Organometals and organometalloids: Occurrence and fate in the environment

Organometals and Organometalloids In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; Am...

Author: F. E. Brinckman | J. M. Bellama

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Organometals and Organometalloids

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Organometals and Organometalloids Occurrence and Fate in the Environment F. E . Brinckman,

EDITOR

National Bureau of Standards J . M . Bellama,

EDITOR

University of Maryland

Based on a symposium sponsored by the Division of Inorganic Chemistry at the 175th Meeting of the American Chemical Society, Anaheim, California, March 13-17,

1978.

ACS SYMPOSIUM SERIES 82

AMERICAN

CHEMICAL

SOCIETY

WASHINGTON, D. C. 1978

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Library of Congress

Data

Organometals and organometalloids. (ACS symposium series; 82 ISSN 0097-6156) Includes bibliographies and index. 1. Organometallic compounds—Environmental as pects—Congresses. I.Brinckman, F. Ε. II. Bellama, Jon M., 1938III. American Chemical Society. Division of Inorganic Chemistry. IV. Title: Organometalloids: occurrence and fate in the environment. V. Series: American Chemical Society. ACS symposium series; 82. QH545.074073 ISBN 0-8412-0461-6

574.5'2 79-24316 ACSMC8-82 1-447 1979

Copyright © 1978 American Chemical Society All Rights Reserved. The appearance of the code at the bottom of the first page of each article in this volume indicates the copyright owner's consent that reprographic copies of the article may be made for personal or internal use or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc. for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to copying or transmission by any means—graphic or electronic—for any other purpose, such as for general distribution, for advertising or promotional purposes, for creating new collective works, for resale, or for information storage and retrieval systems. The citation of trade names and/or names of manufacturers in this publication is not to be construed as an endorsement or as approval by ACS of the commercial products or services referenced herein; nor should the mere reference herein to any drawing, specification, chemical process, or other data be regarded as a license or as a conveyance of any right or permission, to the holder, reader, or any other person or corporation, to manufacture, repro duce, use, or sell any patented invention or copyrighted work that may in any way be related thereto.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ACS Symposium Series Robert F . G o u l d , Editor

Advisory Board Kenneth B. Bischoff

James P. Lodge

Donald G . Crosby

John L. Margrave

Robert E. Feeney

Leon Petrakis

Jeremiah P. Freeman

F. Sherwood Rowland

E. Desmond Goddard

Alan C. Sartorelli

Jack Halpern

Raymond B. Seymour

Robert A. Hofstader

Aaron Wold

James D. Idol, Jr.

Gunter Zweig

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

FOREWORD T h e A C S S Y M P O S I U M SERIES was founded in 1974

to provide

a medium for publishin format of the Series parallels that of the continuing A D V A N C E S IN C H E M I S T R Y SERIES except that in order t ô save time the papers are not typeset but are reproduced as they are submitted by the authors in camera-ready form. Papers are reviewed under the supervision of the Editors with the assistance of the Series Advisory Board and are selected to maintain the integrity of the symposia; however, verbatim reproductions of previously published papers are not accepted. and

Both reviews

reports of research are acceptable since symposia may

embrace both types of presentation.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

To Frederick Challenger

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

EMERITUS

PROFESSOR

O F ORGANIC

CHEMISTRY

UNIVERSITY O F LEEDS

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

DEDICATION he significance of the metal-carbon or metalloid-carbon bond to that Α

rather vague area of descriptive science variously termed "environ

mental chemistry," "bioinorgani now perceived as basic to the assessment of man's activities and future on our planet, and there is one individual who stands out as the pioneer in this field that encompasses so many disciplines. More than 40 years ago, long before chemists recognized the implications of sterically con strained donor sites or enjoyed spectrometric means for virtually non destructive characterization

of trace materials, this researcher single-

handedly applied all available chemical forces to a unified study of the biogenesis of organometalloids. His work still stands as a beacon i n the field, and even today a report rarely appears without citing one or more of the many papers of Professor Frederick Challenger—papers that span 60 years of personal research. Today technological, social, and political pressures give urgency to expanded studies on the occurrence and fate of organometals and their implications for mankind: this volume is an attempt to highlight such work. It is obvious that no attempt to give a topical perspective on our present state of knowledge concerning problems in the field could succeed without the most direct recognition of Professor Challenger s contribu tions and views. The

editors deem themselves and all readers most fortunate that

Professor Challenger, now enjoying more than 90 summers of health, could and would give this symposium volume a keynote paper.

Most

happily, all contributors to this volume take this opportunity as fitting and proper to recognize his past and present primal role in the field of environmental organometallic chemistry. W e dedicate this book to h i m and to his work. F. E .

BRINCKMAN

J. M . B E L L A M A

National Bureau of Standards

University of Maryland

Washington, D C

College Park, M D xi

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

PREFACE he inorganic chemist today is confronted with an intriguing and challenging prospect which will significantly advance our understanding of chemical reactions and transport of toxic elements in the environment.

T h e opportunity lies partly in extending fundamental

studies of bioactive sigma carbon-metal bonds or other similar toxic heteroatomic

combinations that are formed in polar transport

media

such as water. T h e challenge also exists for inorganic chemists to inject their ideas and findings described as "environmental chemistry" and thereby to profit from such an interchange by finding exciting new problems to solve. Our current perception of mobilization and transport of certain combinations of organometals and organometalloids is that certain toxic moieties can be and are relocated on a global scale. Recent unambiguous findings show that even simple, labile methylmetal species occur in the environment as a result of biogenic processes.

Moreover, anthropogenic

inputs of organometals parallel growing technological and agricultural demands. Matching these increased demands are amplified requirements to understand the potential, or lack of it, for wastewater treatment of refractory organometals and organometalloids by chlorination or ozonation, a neglected study area. Similarly, study and discussion are necessary for us to understand the means b y which man introduces organometals and organometalloids into the environment, and the pathways by which the environment can pass on ( return ) such bioactive metal species to the human organism. Consequently, not only from pragmatic environmental quality or public health perspectives, but also from basic needs to understand biogeochemical cycles, participation of inorganic chemists in the dialogue is timely and is needed urgently. T h e symposium on inorganic chemical problems in the environment could not deal with the entire range of such identifiable problems amenable to inorganic research in a brief two-day meeting.

Therefore, the

symposium focused on two main objectives: a) definition, by example, of the latest research concerned with organometal and organometalloid chemistry relevant to environmental concerns, with particular emphasis on aqueous reactions and transport mechanisms; and b) dialogue, with interested and competent colleagues outside the inorganic community, who can best transmit the current needs and consequences of alternative courses for future research relevant to biological implications of organometallic chemistry. xiii In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Therefore, this symposium comprises a series of invited research and review papers by researchers active internationally in both biological and organometallic chemistry. A t the welcome suggestion of reviewers, additional papers were solicited from highly competent colleagues to achieve better balance and topical presentation for this volume. T h e editors assume full responsibility for the fact that additional areas in the title field are not discussed. Such omissions were dictated by our personal biases, constraints of publication costs, and the obvious need to produce similar symposia in the near future. W e have not attempted to arrange papers in chronological order, e.g. in the symposium format.

Rather, we have exercised editorial preroga-

tive and (with apologies to authors) have assembled the volume into three broad categories of needed and ongoing research: biogenesis of organometals and organometalloids try and mechanisms; and the nature of entry, transport, or uptake of organometals and organometalloids into environmental compartments. Clearly, many papers overlap these classifications, just as expected for such an interdisciplinary dialogue. Just as clearly, some readers will find useful a structuring which aids them in placing their own interests into perspective with others. T h e editors also chose to adopt a symposium format which devoted approximately 30%

of available meeting time to discussion.

(Authors

were asked to complete their manuscripts after the symposium to exploit this feedback feature.)

W e have recorded and edited these additional

verbal interactions between symposium participants, and have attached these discussions to the end of each paper. Again, rigorous, and hopefully equitable, editing was imposed to provide the best presentation of each commentator's remarks while adhering to minimum length. T h e editors hope that readers will find the discussions to be useful supplements to the formal papers, particularly from the standpoint of highlighting untouched research topics in this fascinating field. In addition to the authors who have steadfastly supported the attempts of the editors to produce a volume of excellent papers, and the referees (those from the American Chemical Society ( A C S ) as well as those who critically read the individual papers), we owe debts of gratitude to many others.

W e are deeply grateful to S. Sisk (University of

Maryland) and to C . L a m b (National Bureau of Standards ( N B S ) ) who unstintingly provided the secretarial critical to a book in this format.

and professional typing support

W e especially thank our colleagues,

particularly Professors J. M . W o o d , M . L . Good, J. S. Thayer, J. K . Kochi, and W . R. Cullen, who sparked and sustained our effort for so many months. In the final analysis, these colleagues gave their talents to conducting and pacing symposium sessions, without which realization of this volume would have been impossible. xiv In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Finally, we are grateful to our sponsors who both financially a n d spiritually supported our effort. W e thank the A C S for many valuable suggestions and aids i n producing the symposium. W e are indebted to the National Measurements Laboratory, N B S , and the Division of Inorganic Chemistry, A C S , for assistance in organizing and defraying costs for invited authors. F. E . BRINCKMAN

J. M . B E L L A M A

Center for Materials Science

Department of Chemistry

National Bureau of Standards

University of Maryland

Washington, D C 20234

College Park, M D 20742

August, 1978

xv

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1 Biosynthesis of Organometallic and Organometalloidal Compounds FREDERICK C H A L L E N G E R 19 Elm Avenue, Beeston, Nottingham, NG9 1BU, U. K.

I f e e l g r e a t l y honoure Symposium an i n t r o d u c t o r to the proceedings. The programme covers almost every aspect of the b i o l o g i c a l methylation of a l a r g e number of elements and the p r o p e r t i e s of s e v e r a l other o r g a n o - m e t a l l i c compounds e . g . those of tin. C l e a r l y , only a b r i e f survey of c e r t a i n areas of t h i s wide field i s p o s s i b l e , and t h i s paper will be confined to those aspects of the Symposium which approach most c l o s e l y to the work of my students and myself, e s p e c i a l l y on the b i o l o g i c a l m e t h y l a t i o n of compounds of a r s e n i c , selenium, and t e l l u r i u m (1931-1953) at the U n i v e r s i t y of Leeds. A strictly historical treatment takes us back to the o l d l a b o r a t o r i e s at U n i v e r s i t y C o l l e g e , Nottingham (now merged in the Trent P o l y t e c h n i c ) where between 1900 and 1944 Kipping laid the foundations of the organic chemistry of silicon. I t was my privilege to work with him f o r 2½ years and to succeed i n the o p t i c a l r e s o l u t i o n of D , L - d i b e n z y l e t h y l p r o p y l s i l a n e monosulphonic a c i d by means of brucine i n December 1909. The study of the S i - C bond (though strictly speaking silicon i s n e i t h e r metal nor a m e t a l l o i d ) gave me a budding i n t e r e s t i n the metal-carbon link i n general, and p a r t i c u l a r l y i n o r g a n o - d e r i v a t i v e s of bismuth which l a t e r was extended to a r s e n i c . I t i s impossible here f o r me to emphasize s u f f i c i e n t l y my deep indebtedness to Professor F r e d e r i c k Stanley K i p p i n g , which I have endeavoured partially to discharge i n an a p p r e c i a t i o n of the man and h i s work, published i n 1950 and 1951 (1-2). His exacting l a b o r a t o r y methods were based on those of von Baeyer ( i n whose l a b o r a t o r y he had worked) and r e q u i r e d little but beakers, f l a s k s , t e s t tubes and g l a s s r o d s . They were at once the d e s p a i r and the i n s p i r a t i o n of h i s research students. I t was not s o l e l y an i n t e r e s t i n o r g a n o - m e t a l l i c compounds that l e d to our work on the a r s e n i c a l Gosio-gas but an e q u a l l y keen a t t r a c t i o n , m i c r o b i o l o g i c a l chemistry, of which I gained some rudimentary knowledge i n the l a b o r a t o r y of Professor A l f r e d Koch in Gottingen (1910-1912) and maintained i n Manchester. In 1931 i t

0-8412-0461-6/78/47-082-001$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2

ORGANOMETALS AND

ORGANOMETALLOIDS

became p o s s i b l e , w i t h the a s s i s t a n c e of Constance Higginbottom and Louis E l l i s (3),to combine these two i n t e r e s t s . I was a t t r a c t e d by the e a r l y work on the unknown composition of Gosio-gas which was evolved from a r s e n i c a l wallpaper c o n t a i n i n g the m i n e r a l p i g ments Scheele's green and P a r i s green. L a t e r on, t h i s vapour was found by Gosio (4) to be evolved from pure c u l t u r e s of the mould Pénicillium b r e v i c a u l i s (now d e s i g nated S c o p u l a r i o p s i s b r e v i c a u l i s ) c o n t a i n i n g arsenious oxide. At the time i t appeared that the p o s s i b l e i d e n t i f i c a t i o n of Gosio-gas would, w h i l e i n t e r e s t i n g , r e l a t e to a s m a l l area of m y c o l o g i c a l chemistry w i t h , p o s s i b l y , a q u i t e r e s t r i c t e d s i g n i f i c a n c e . When we found that Gosio-gas was pure t r i m e t h y l a r s i n e , we were suddenly e j e c t e d from our s m a l l corner and p i t c h f o r k e d d i r e c t l y i n t o the growing f i e l d of Transmethylation, then i n the e a r l y stages of i t s development i n animals b th fundamental k f Vincent d Vigneaud (5). There we my metaphors are very mixe persona the i n v e s t i g a t i o n s which f o l l o w e d may perhaps be accepted as an excuse Î B i o l o g i c a l M e t h y l a t i o n of A r s e n i t e and Arsenate The e a r l i e s t attempts t o i d e n t i f y Gosio-gas were made by B i g i n e l l i who passed the gases from aerated c u l t u r e s of S^. b r e v i c a u l i s c o n t a i n i n g As^O^ through H g C l i n d i l u t e h y d r o c h l o r i c a c i d . He regarded the r e s u l t i n g p r e c i p i t a t e as (CH^CH^ AsH* 2 H g C l , but a study i n my l a b o r a t o r y at the U n i v e r s i t y of Leeds showed f t to be a mixture of the mono- and d i m e r c u r i c h l o r i d e s of t r i m e t h y l a r s i n e . The f i r s t c l u e to the i d e n t i t y of Gosio-gas was obtained, however, by passage through a l c o h o l i c b e n z y l c h l o r i d e , formation of trimethylbenzylarsonium p i c r a t e , and comparison w i t h an a u t h e n t i c specimen prepared some years p r e v i o u s l y by I n g o l d , Shaw, and Wilson at Leeds i n research (6) on the o r i e n t i n g i n f l u e n c e of posi t i v e poles i n aromatic s u b s t i t u t i o n . The i d e n t i t y was confirmed by the formation of s e v e r a l other d e r i v a t i v e s , see below. Sodium methylarsenate CH^AsO(ONa) and sodium cacodylate (CH^) AsO(ONa) when added to the mould c u l t u r e s on bread crumbs a l s o gave t r i m e t h y l a r s i n e . This r e a c t i o n was, however, ambiguous owing to the p o s s i b i l i t y of the f i s s i o n of the As-C l i n k i n these a c i d s and formation of A s 0 ^ . However, when s e v e r a l mono- or d i a l k y l a r s o n i c a c i d s RAsO(OH) and RR'AsO-OH or t h e i r sodium s a l t s were added t o bread c u l t u r e s of S. b r e v i c a u l i s , m e t h y l a t i o n occurred g i v i n g e t h y l d i m e t h y l a r s i n e , n - p r o p y l d i m e t h y l a r s i n e , a l l y l d i m e t h y l a r s i n e and m e t h y l e t h y l n-propylarsine. These were c h a r a c t e r i z e d by formation of v a r i o u s d e r i v a t i v e s such as the m e r c u r i c h l o r i d e , the b e n z y l t r i a l k y l a r sonium p i c r a t e and the h y d r o x y t r i a l k y l a r s o n i u m p i c r a t e , and comp a r i s o n s w i t h a u t h e n t i c specimens. I t was t h e r e f o r e c l e a r t h a t the methyl group was s u p p l i e d by the mould (7) as summarized i n the scheme below. 2

2

2

2

2

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1.

CHALLENGER

Biosynthesis

B i o l o g i c a l M e t h y l a t i o n of A l k y l and D i a l k y l a r s o n i c A c i d s CH AsO(OH) 3

2

(CH ) As 3

3

(CH ) AsO(OH) 3

2

CH CH As(CH ) 3

RAsO(OH)

2

3

2

> CH CH CH As(CH )

2

3

2

2

3

2

CH :CHCH As(CH )

C H

R

*>sO(OH)

>

3

CH.CH ^As 0

R

y

3

CH CH CH 3

2

2

M e t h y l a t i o n o f Selenate, S e l e n i t e , and T e l l u r i t e S e v e r a l workers had already drawn a t t e n t i o n t o the odourous products evolved from c u l t u r e s of S_. b r e v i c a u l i s c o n t a i n i n g v a r i o u s oxy-acids of selenium and t e l l u r i u m , but without i d e n t i f y i n g them. Using s i m i l a r methods t o those employed f o r a r s e n i c com pounds, the odours were i d e n t i f i e d by Harry North (8) and M a r j o r i e B i r d (9) as due t o d i m e t h y l s e l e n i d e and d i m e t h y l t e l l u r i d e . These were c h a r a c t e r i s e d by v a r i o u s d e r i v a t i v e s such as the m e r c u r i c h l o r i d e , mercuribromide, p l a t i n o c h l o r i d e ( ( C H ) S e - P t C J l ) , hydroxyselenonium n i t r a t e (CH > Se(OH)·Ν0 and the p i c r a t e s prepared u s i n g b e n z y l c h l o r i d e as before. Dimethylselenide and - t e l l u r i d e were a l s o evolved from v a r i o u s c u l t u r e s of Pénicillium chrysogenum, JP. notaturn, and a mould c l o s e l y a l l i e d t o P. notatum. A s p e r g i l l u s n i g e r gave (CH^KSe w i t h s e l e n a t e . D i m e t h y l t e l l u r i d e could only be detected (except by i t s powerf u l odour) when the c u l t u r e s were grown i n t e s t tubes i n s e r i e s t o minimise atmospheric o x i d a t i o n and the minimum of absorbent was used. 3

3

2

2

2

3>

The Metabolism of Some Sulphur Compounds i n Mould C u l t u r e s S t r i c t l y speaking, t h i s subject i s not w i t h i n the purview of t h i s Symposium, but as the r e s u l t s now t o be summarised a r e of r a t h e r general a p p l i c a t i o n , some account of them may be j u s t i f i e d .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4

ORGANOMETALS AND

ORGANOMETALLOIDS

S_. b r e v i c a u l i s was a l s o shown by Alan Rawlings (10), P h i l i p C h a r l ton (11), and Stanley Blackburn (12) to cause f i s s i o n of d i m e t h y l , d i e t h y l , d i - n - p r o p y l and d i - n - b u t y l d i s u l p h i d e s , RS-SR, g i v i n g RSH and RSCïL. No f i s s i o n was observed w i t h d i b e n z y l - and d i p h e n y l d i s u l p h i a e s , i n accord w i t h the r e s u l t s obtained w i t h phenyl-and b e n z y l a r s o n i c a c i d s which g i v e no methylated a r s i n e s i n the mould c u l t u r e s . Another i n t e r e s t i n g f i s s i o n r e a c t i o n was observed by C h a r l t o n (11). b r e v i c a u l i s , i n bread c u l t u r e s , produces a l k y l t h i o l and alkylmethy 1 sulphide from S-methyl-, S - e t h y l - and S-n-prop y l c y s t e i n e s , RSCH CHNH C00H. The sulphur compounds were charact e r i s e d by formation of well-known a u t h e n t i c compounds. These f i s s i o n r e a c t i o n s have w e l l - e s t a b l i s h e d analogies i n animal b i o chemistry. A d d i t i o n of sulphur, Na S0«, Na S„0«, t h i o u r e a , sodium e t h anesulphinate and sulphonate and sodium t h i o d i g l y e o l l a t e S(CH C00Na) , to culture gave no dimethylsulphide and at present the author knows of only one mould which w i l l methy l a t e simple i n o r g a n i c compounds of sulphur, namely Schizophyllum commune, a higher fungus which destroys wood and which was shown by Birkinshaw, F i n d l a y , and Webb (13) to g i v e methane t h i o l and t r a c e s of hydrogen sulphide when grown on a glucose medium cont a i n i n g sulphate. We found a t Leeds t h a t d i m e t h y l s u l p h i d e and - d i s u l p h i d e are a l s o evolved, and t h a t c u l t u r e s on wort or bread without a d d i t i o n of sulphate evolve methanethiol due to sulphur compounds i n the medium. When the c u l t u r e s are almost odourless, a d d i t i o n of sodium selenate gave d i m e t h y l s e l e n i d e i n s m a l l amount. Only f a i n t odours were observed on adding a r s e n i t e , t e l l u r i t e , or methyl- or n-propylarsonic a c i d s to s i m i l a r c u l t u r e s . F i s s i o n to the corresponding t h i o l , RSH, was observed w i t h d i m e t h y l , d i e t h y l , and d i - n - b u t y l d i s u l p h i d e s . With d i m e t h y l d i s u l p h i d e some dimethylsulphide was detected. A c a r e f u l study of the metabolism of t h i s fungus might y i e l d i n t e r e s t i n g r e s u l t s . 2

2

2

2

2

2

Selective Methylation B i r d et a l . (14) s t u d i e d the c a p a c i t y of a number of other moulds to methylate i n o r g a n i c and organic compounds of a r s e n i c , selenium, and t e l l u r i u m . A. n i g e r , V_. notatum and P. chrysogenum i n bread c u l t u r e s gave no t r i m e t h y l a r s i n e w i t h a r s e n i t e , but w i t h methyl- and dimethylarsonic a c i d s as sodium s a l t s , t r i m e t h y l a r s i n e was evolved. A. n i g e r gave e t h y l d i m e t h y l a r s i n e w i t h sodium e t h y l arsonate. The same mould w i t h selenate and the two P e n i c i l l i a w i t h s e l e n i t e gave d i m e t h y l s e l e n i d e . A. v e r s i c o l o r and A. glaucus gave t r i m e t h y l a r s i n e w i t h a r s e n i t e and sodium methylarsonate, but no dimethylselenide or - t e l l u r i d e w i t h s e l e n i t e or t e l l u r i t e . Attempts at an e x p l a n a t i o n of s e l e c t i v e m e t h y l a t i o n were made by B i r d et a l . (14), but no d e f i n i t e c o n c l u s i o n s were reached.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1.

CHALLENGER

Biosynthesis

5

The Development of Ideas on The Mechanism of B i o l o g i c a l M e t h y l ation I n 1887 i t was shown by H i s (15) t h a t p y r i d i n e acetate admin i s t e r e d t o dogs and t u r t l e s i s e x c r e t e d as methylpyridinium ace t a t e . An analogous r e a c t i o n occurs w i t h q u i n o l i n e i n dogs. A s t r o n g g a r l i c odour was observed by Gmelin (15) and by Hansen (16) i n animals and man, r e s p e c t i v e l y , a f t e r doses of potassium t e l l u r i t e . T h i s odour was regarded by Hofmeister (15) as being due t o d i m e t h y l t e l l u r i d e , though without p r o o f . I n h i s a r t i c l e we can recognize the f i r s t r a t h e r vague conception of a p o s s i b l e t r a n s f e r of a methyl group. He suggested that "the methyl group i s a l r e a d y present i n the t i s s u e s which possess the c a p a c i t y f o r m e t h y l a t i o n . I n presence of p y r i d i n e and t e l l u r i u m these are methylated, where as under normal c o n d i t i o n c r e a t i n e are produced. the source of the methyl group. T h i s conception was c a r r i e d much f u r t h e r by R i e s s e r i n 1913 (17) who considered that methyl groups of the (assumed) d i m e t h y l t e l l u r i d e , formed i n the animal body a f t e r t e l l u r i t e a d m i n i s t r a t i o n , probably arose from c h o l i n e or bet a i n e . He based t h i s suggestion p a r t l y on h i s o b s e r v a t i o n t h a t , when t e l l u r i t e was heated w i t h sodium formate and e i t h e r c h o l i n e c h l o r i d e or b e t a i n e h y d r o c h l o r i d e , an odour resembling d i m e t h y l t e l l u r i d e was evolved. Challenger et a l . (18) extended t h i s r e a c t i o n t o i n c l u d e sodium s e l e n i t e and s u l p h i t e , which on h e a t i n g w i t h b e t a i n e f r e e from h y d r o c h l o r i d e and without formate, gave d i m e t h y l s e l e n i d e and-sulphide which were i d e n t i f i e d by formation of d e r i v a t i v e s . Under s i m i l a r c o n d i t i o n s pure b e t a i n e , when heat ed w i t h primary aromatic amines, gave RNHCH^. Phenol and β-napht h o l gave the corresponding methyl e t h e r s , an i m i t a t i o n at h i g h temperatures of many b i o l o g i c a l m e t h y l a t i o n s . In 1935 C h a l l e n g e r and Higginbottom (19) s t a t e d " I t i s not impossible that some i n g r e d i e n t of the c e l l substance c o n t a i n i n g a methylated n i t r o g e n atom may, under the s p e c i a l c o n d i t i o n s ob t a i n i n g i n the c e l l , l o s e a methyl group which i f i t be e l i m i n a t e d w i t h a p o s i t i v e charge could be e a s i l y co-ordinated by the un shared e l e c t r o n s of t e r v a l e n t a r s e n i c o r q u a d r i v a l e n t selenium and t e l l u r i u m . " The u n d e r l i n i n g i n d i c a t e s the degree t o which t h i s suggestion extends those of Hofmeister and R i e s s e r . C h a l l e n g e r , i n s e v e r a l p u b l i c a t i o n s , d i s c u s s e d t h i s conception i n d e t a i l and proposed a s e r i e s of r e a c t i o n s f o r the m e t h y l a t i o n of arsenate or a r s e n i t e , s e l e n a t e o r s e l e n i t e which f o r b r e v i t y may be summarised on the next page. The scheme i n v o l v e s i o n i s a t i o n , r e d u c t i o n , and the c o o r d i n a t i o n of a p o s i t i v e methyl group. The suggested i n t e r m e d i a t e a r s e n i c compounds were not found i n the medium but were a l l conver ted t o t r i m e t h y l a r s i n e i n bread c u l t u r e s of J3. b r e v i c a u l i s . Met h y l a r s o n a t e , however, was found by McBride and Wolfe (20) as an i n t e r m e d i a t e compound i n the b i o l o g i c a l formation of d i m e t h y l a r s i n e by a methanobacterium from c a n a l mud. The potassium s a l t s of methane-, ethane-, and n-propanesel-

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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6

e n i n i c a c i d s , RSeC^H, r e a d i l y gave the corresponding m e t h y l a l k y l s e l e n i d e s i n bread c u l t u r e s o f SL b r e v i c a u l i s . The potassium s a l t s o f methane-, ethane- and n-propaneselenonic a c i d s , RSeC^OH, unexpectedly gave o n l y d i m e t h y l s e l e n i d e due t o h y d r o l y s i s t o s e l e n i t e . Dimethylselenone, (CH«) SeO«, has not been prepared, but methylselenoxide n i t r a t e , (ciL^SefoH)(ONC^), a l s o gave d i m e t h y l selenide. ?

B i o l o g i c a l M e t h y l a t i o n of A r s e n i t e and Selenate

1.

As(OH)

> CH AsO(OH)

3

3

(CH ) AsO 3

2.

Se0 (0H) 2

> (CH > AsO(OH)

2

3

> (CH ) As

3

3

3

> CH SeO(OH)

2

>(CH > Se0

3

(CH ) SeO 3

>

2

3

2

>

2

> (CH ) Se

2

3

2

The r e a c t i o n s s e t out above may be represented as the a d d i t i o n s o f a methylcarbonium i o n , CH +, t o a n e u t r a l molecule, f o l lowed by e x p u l s i o n of a proton: CH

+ 3

+ :As(OH)

> CH As(OH>

3

3

>CH AsO(OH> + H

3

3

+

2

In recent years much a t t e n t i o n has been d i r e c t e d towards methion i n e . I n l i v e r o r kidney enzyme systems which can e f f e c t methyla t i o n , Cantoni (21) found i n 1952 t h a t added methionine forms a sulphonium compound, S-adenosylmethionine, or " a c t i v e methionine", as i t was f i r s t c a l l e d . I t s formula and involvement i n b i o l o g i c a l m e t h y l a t i o n a r e so,well-known as t o need no comment. I f i t i s represented as RR sCH , and i f we assume that methionine i s s i m i l a r l y " a c t i v a t e d " i n moulds the b i o m e t h y l a t i o n of a r s e n i t e could be represented: + + RR SCH + :As(OH) > [ R R S < — CH :As(OH> ] > f

3

f

l

3

3

3

1

RSR + [CH As(OH) ] 3

3

3

> CH AsO(OH> + H 3

+

2

The a t t r a c t i o n of the p o s i t i v e sulphur center f o r the e l e c t r o n s of the -S-CH l i n k might a l l o w n u c l e o p h i l i c a t t a c k on the methyl group by the a r s e n i c atom w i t h i t s unshared e l e c t r o n s . The r e s u l t ing t r a n s i t i o n s t a t e would l e a d t o a n e u t r a l s u l p h i d e (R*S*R ), a p r o t o n , and methylarsonic a c i d without formation of a f r e e p o s i t i v e methyl i o n a t any s t a t e . This e x p l a n a t i o n i s p r e f e r r e d by some of my c o l l e a g u e s . I t was put forward by Challenger i n 1955 3

f

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1.

CHALLENGER

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Biosynthesis

and 1959 i n two reviews (22, 23) and i s s t i l l regarded as a s a t i s f a c t o r y explanation. The f a i l u r e of the author and co-workers (24) i n t h e i r adm i t t e d l y p r e l i m i n a r y experiments of 1935 t o observe any methyla t i o n of mercuric oxide by S^. b r e v i c a u l i s i s e x p l i c a b l e because the Hg^ i o n would not behave as a n u c l e o p h i l e . For the l a t e r r e s u l t s of other workers see p. 16 of t h i s review. I t may, perhaps, be emphasised here that the fundamental demo n s t r a t i o n of the a c t i v a t i o n of methionine p r i o r t o the t r a n s f e r of i t s methyl group (transmethylation) was f i r s t made i n 1952 by Cantoni (21). My suggestion (22, 23) t h a t methionine might be s i m i l a r l y a c t i v a t e d i n moulds and t h a t t h i s might precede the m e t h y l a t i o n of a r s e n i c was an adaption of Cantoni*s work a t a much l a t e r date. This h i s t o r i c a l p o i n t i s n o t , perhaps, made q u i t e c l e a r by R i d l e y , D i z i k e s Cheh, and Wood (26). +

14 M e t h y l a t i o n of Selenium u s i n g Methionine L a b e l l e d w i t h L i q u i d C u l t u r e s of A s p e r g i l l u s n i g e r

C- i n

In an extended i n v e s t i g a t i o n w i t h P h i l i p D r a n s f i e l d and Denis L i s l e (27, 28), the author showed t h a t i n l i q u i d c u l t u r e s of A. n i g e r c o n t a i n i n g sucrose, g l y c i n e , i n o r g a n i c s a l t s , s e l e n a t e , and e i t h e r DL-, L- or D-[Me C]methionine, over 90% of the methyl groups of the evolved d i m e t h y l s e l e n i d e were d e r i v e d from the l a b e l l e d methionine. The d i m e t h y l s e l e n i d e was c o l l e c t e d i n aqueous mercuric c h l o r i d e and counted as the m e r c u r i c h l o r i d e adduct, ( C H ) S e - H g C l , m.p. 153-154°. A. n i g e r does not methylate A s ^ , but i n one experiment w i t h S^. b r e v i c a u l i s i n bread c u l t u r e s cont a i n i n g arsenious oxide and DL-[Me-^C]methionine, the m e t h y l a t i o n percentage was 28.3%, a v e r y much lower f i g u r e than was obtained w i t h A. n i g e r and s e l e n a t e . 3

2

2

Search f o r Methanol i n A r s e n i c a l L i q u i d C u l t u r e s of S. b r e v i c a u l i s I f a f r e e p o s i t i v e CIL group i s the m e t h y l a t i n g agent i n j[. b r e v i c a u l i s c u l t u r e s , i t might be expected t o r e a c t w i t h the water of the medium t o g i v e methanol. Attempts were made t o detect the methanol i n 2-3 l i t r e s of a r s e n i c a l medium upon which the mould had grown f o r 46 days. A f t e r c a r e f u l f r a c t i o n a l d i s t i l l a t i o n , the f i r s t runnings were t e s t e d f o r methanol by Wright's method (29). T h i s depends on o x i d a t i o n t o formaldehyde w i t h potassium permanganate, and i t s d e t e c t i o n by S c h i f f s reagent. The r e s u l t s obtained by Douglas Barnard (30) suggested the presence of not more than 0.001 mL per l i t r e of medium. This f i g u r e was q u i t e i n s u f f i c i e n t to a l l o w any c o n c l u s i o n t o be drawn as to the mechanism of format i o n or even of the a c t u a l presence of methanol. L a t e r experiments by Fernand K i e f f e r (31) were e q u a l l y i n c o n c l u s i v e . More d e l i c a t e methods employed by A x e l r o d and Daly i n 1965 (32, 33) have shown t h a t an enzyme o c c u r r i n g i n the p i t u i t a r y f

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

8

ORGANOMETALLOIDS

XH

gland of s e v e r a l mammals can form methanol from [Me C] -S-adenosylmethionine. I n p a r a l l e l experiments u s i n g the same enzyme p r e p a r a t i o n and [ 2 - ^ C ] S-adenosylmethionine, the demethylated p r o duct [2--^C] S-adenosylhomocysteine was formed. The methanol and the homocysteine d e r i v a t i v e were formed e n z y m i c a l l y and i n s t o i chiometrical proportions. The methanol was detected by conversion to i t s 3 , 5 - d i n i t r o benzoate which was r a d i o a c t i v e and was i d e n t i f i e d by t h i n l a y e r chromatography a f t e r d i l u t i o n w i t h an i n a c t i v e specimen and c r y s t a l l i s a t i o n t o constant s p e c i f i c a c t i v i t y . The authors s t a t e " t h i s r e a c t i o n proceeds by m e t h y l a t i o n of water or by h y d r o l y s i s of S—adenosylmethionine". McBride and Wolfe (20) showed t h a t arsenate i s reduced and methylated under anaerobic c o n d i t i o n s ( i n a hydrogen atmosphere) by c e l l e x t r a c t s and b MoH) i n present of methylcobalami The organism was i s o l a t e d from the mud of a c a n a l near D e l f t . The gaseous product was regarded as d i m e t h y l a r s i n e , and m e t h y l a r s o n i c a c i d CH AsO(OH) was i d e n t i f i e d by e l e c t r o p h o r e s i s . Dimethyla r s o n i c (cacodylic) a c i d was not found i n the medium, but both i t and m e t h y l a r s o n i c a c i d gave d i m e t h y l a r s i n e i n c e l l e x t r a c t s of the bacterium. The r e a c t i o n was shown t o be enzymic. The authors p o i n t e d out t h a t a mixture of CILAslL and (CH-KAs would g i v e the same r a t i o of CH^ t o As as was found by a n a l y s i s of the v o l a t i l e product. However, v a r i a t i o n i n the c o n c e n t r a t i o n of the methyl donor d i d not a f f e c t t h i s r a t i o . In another paper of t h i s symposium Dr. McBride and h i s c o l leagues d i s c u s s t h e i r c o n s i d e r a b l e l a t e r work i n which dimethy1a r s i n e i s produced by anaerobic organisms, and t r i m e t h y l a r s i n e i s produced by a e r o b i c organisms. A l l the b i o l o g i c a l l y methylated a r s i n e s described by Challenger were produced i n w e l l - a e r a t e d mould c u l t u r e s which n e v e r t h e l e s s e x h i b i t e d a s t r o n g reducing a c t i o n . The authors s t a t e t h a t they are not aware of any other references t o the b a c t e r i a l s y n t h e s i s of a r s i n e or i t s a l k y l a t e d d e r i v a t i v e s . T h i s r e c a l l s the n e g a t i v e r e s u l t s of Challenger and Higginbottom (19) w i t h As^O^ and s e v e r a l b a c t e r i a , a p o i n t emphas i s e d by Challenger (34) at the B r u s s e l s Biochemical Congress i n 1955. 3

2

Attempts to Methylate D e r i v a t i v e s of Elements other than A r s e n i c Antimony I n Vienna a case of c h r o n i c antimony p o i s o n i n g occurred i n a house c o n t a i n i n g s i l k c u r t a i n s mordanted w i t h a compound of antimony. A s e r i e s of experiments were performed i n 1913 by K n a f f l - L e n z (35) to detect the p o s s i b l e formation of v o l a t i l e compounds of antimony. Thus, S^. b r e v i c a u l i s was grown on media c o n t a i n i n g one percent of t a r t a r emetic (potassium antimonyl t a r t r a t e , 0=Sb-0-C0·CHOH·CHOH·CO·OK), w i t h the v o l a t i l e products being a s p i r a t e d through concentrated n i t r i c a c i d which was l a t e r t e s t e d f o r antimony w i t h n e g a t i v e r e s u l t s . L a t e r , s i m i l a r work by

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1.

CHALLENGER

Biosynthesis

9

Tiegs (36) and a l s o by Smith and Cameron (36) was a l s o unsuccessf u l . The l a s t named authors s t a t e t h a t antimony compounds do not i n t e r f e r e w i t h the b i o l o g i c a l t e s t f o r a r s e n i c u s i n g j>. b r e v i c a u l i s . Challenger and E l l i s (36) found that bread o r l i q u i d c u l tures of S^. b r e v i c a u l i s c o n t a i n i n g t a r t a r emetic gave no odour or any p r e c i p i t a t e i n a c i d i f i e d mercuric c h l o r i d e s o l u t i o n . When the c u l t u r e s were l e f t ' f o r 9 months, a l a r g e amount of antimony t r i oxide Sb 0^ was deposited i n the mycelium. An attempt t o i s o l a t e t r i m e t h y l s t i b i n e oxide as the p i c r a t e from these mould c u l t u r e s f a i l e d . T a r t a r emetic and Sb 0~ c o n t a i n antimony as a c a t i o n . M e t h y l a t i o n by n u c l e o p h i l i c mechanism analogous to that e x e r t e d by j>. b r e v i c a u l i s i n a r s e n i c a l media would t h e r e f o r e not be expected. In experiments by Barnard (37) w i t h Î5. b r e v i c a u l i s and Έ_. no t a turn c u l t u r e s c o n t a i n i n g p h e n y l s t i b o n i c a c i d C^H^SbOiOH)^ or potassium meta-antimoniate KSbO^ i whic i anion methylation might be expected but non products from the c u l t u r e s i n t o concentrated n i t r i c a c i d , evapor a t i o n of the a c i d and a p p l i c a t i o n of the G u t z e i t or Marsh t e s t to the r e s i d u e gave v a r y i n g r e s u l t s . The amount of v o l a t i l e antimony compound was, however, f a r too s m a l l to a l l o w any c o n c l u s i o n s as t o i t s nature or o r i g i n . The p o s i t i o n does not seem t o have a l t e r e d s i n c e these exper iments were performed i n 1933 and 1947. P a r r i s and Brinckman (38) s t a t e "At t h i s time i t has not been demonstrated that methyls t i b i n e s are m e t a b o l i t e s of microorganisms a c t i n g on i n o r g a n i c antimony compounds, but the e x t e n s i v e s i m i l a r i t y of the chemistry of a r s e n i c and antimony g i v e s reasons t o b e l i e v e t h a t antimony can be b i o l o g i c a l l y methylated." In a l a t e r paper (39) these authors say "There i s no obvious thermodynamic or k i n e t i c b a r r i e r to b i o m e t h y l a t i o n and the chem i c a l s i m i l a r i t i e s between Sb and Sn, Pb, As, Se, and Te, which l i t e r a l l y surround Sb i n the P e r i o d i c Table, and a l l of which have been shown to be s u b j e c t t o b i o m e t h y l a t i o n , would suggest b i o m e t h y l a t i o n pathways f o r antimony." The authors then r e f e r t o the use of i n o r g a n i c and o r g a n i c compounds of antimony along w i t h halogenated hydrocarbons i n f i r e r e t a r d a n t systems. Should b i o m e t h y l a t i o n o c c u r , the antimony i n v a r i o u s commercial products would become more s o l u b l e i n water and become a p o t e n t i a l hazard. The occurrence of arsenious oxide i n antimony p r e p a r a t i o n s should a l s o be borne i n mind. An unusual outbread of antimony p o i s o n i n g (not due, however, t o b i o m e t h y l a t i o n ) occurred s e v e r a l years ago i n a l a r g e shop i n Newcastle-upon-Tyne. On a v e r y hot day the employees were g i v e n lemonade, presumably " s y n t h e t i c " lemonade, i n l a r g e enamelled jugs. The enamel, as i n many other products, contained Sb 0- which d i s solved i n the t a r t a r i c (or c i t r i c ) a c i d of the lemonade to g i v e t a r t a r emetic or an analogous compound. The r e s u l t can be im agined . P a r r i s and Brinckman (38) a l s o r e f e r t o the atmospheric o x i d a t i o n of a s o l u t i o n of t r i m e t h y l a r s i n e i n methanol and the f o r 2

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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ORGANOMETALLOIDS

mation of c a c o d y l i c a c i d and t r i m e t h y l a r s i n e o x i d e , (CH~)~AsO, detected by NMR. This was a l s o observed by E l l i s (36) i n e t h e r . The c a c o d y l i c a c i d was separated and the oxide i s o l a t e d as the p i c r a t e . D i m e t h y l a l l y l a r s i n e behaved i n a s i m i l a r manner. Metabolism

of Selenium Compounds

Any study of the b i o c h e m i s t r y of selenium compounds w i l l i n v o l v e not o n l y t h e i r m e t h y l a t i o n but a l s o t h e i r uptake by p l a n t s and t r a n s f e r to animals. This has been d i s c u s s e d i n very many p u b l i c a t i o n s and need not be d e a l t w i t h i n d e t a i l here. Many selenium analogues of b i o l o g i c a l l y important amino a c i d s c o n t a i n ing sulphur have been found i n p l a n t s growing on s e l e n i f e r o u s soils. The l i t e r a t u r e on seleniu metabolis has been admirably discusse c l o s e l y p r i n t e d pages w i t Mention may here be made of a statement by Cerwenka and Cooper (41) that the odours produced i n animals by a d m i n i s t r a t i o n of s e l e n i t e and of t e l l u r i t e are s i m i l a r . The odour of d i m e t h y l t e l l u r i d e resembles that of t r i m e t h y l a r s i n e which i s , however, q u i t e d i f f e r e n t from that of d i m e t h y l s e l e n i d e . Here i t may be s a i d that the well-known m e t h y l a t i o n of i n o r g a n i c t e l l u r i u m compounds i n man and animals, so much more pronounced at s i m i l a r conc e n t r a t i o n s than that of selenium, w i l l not be d e a l t w i t h f u r t h e r i n t h i s review. I t s h i s t o r y and chemistry have been discussed p r e v i o u s l y by the author (22, 23). The e x h a l a t i o n of d i m e t h y l s e l e n i d e a f t e r i n j e c t i o n of r a d i o a c t i v e ( S e ) sodium s e l e n a t e i n t o r a t s has been reported by McConnell and Portman (42). Much a t t e n t i o n i s now being p a i d t o the e f f e c t of compounds of a second element on the biogenesis of o r g a n o m e t a l l i c or -métalloidal d e r i v a t i v e s . D i p l o c k (40) d i s c u s s e s i n d e t a i l the e f f e c t of a r s e n i c , cadmium, mercury, s i l v e r , and t h a l l i u m on the t o x i c i t y of selenium compounds i n animals. R e s u l t s up to the present are not always easy t o i n t e r p r e t and f u r t h e r advances w i l l be awaited w i t h interest. An important step forward was made by Byard (43) i n the course of a study of the metabolism of sodium s e l e n i t e c o n t a i n i n g t r a c e s of H ^Se0« a f t e r o r a l a d m i n i s t r a t i o n to r a t s . He found that the u r i n e contained the trimethylselenonium i o n Me Se . This ion was i s o l a t e d a f t e r i o n exchange chromatography as tne r e i n e c kate and converted to the c h l o r i d e (CH-^SeCJl. The i d e n t i t y of t h i s s a l t was e s t a b l i s h e d by paper chromatography, NMR, and mass spectrometry. I t was a l s o detected i n the bladder 30 minutes a f t e r i n j e c t i o n of s e l e n i t e and was t h e r e f o r e not a product of b a c t e r i a l a c t i o n . A second compound of selenium was i s o l a t e d but not i d e n t i f i e d . Almost simultaneously, Palmer et a l . (44) i s o l a t e d t r i m e t h y l selenonium c h l o r i d e from the u r i n e of r a t s a f t e r i n j e c t i o n w i t h [ S e ] s e l e n i t e by methods very s i m i l a r t o those employed by 2

75

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CHALLENGER

1.

Biosynthesis

11

Byard. They used the r e i n e c k a t e , and by c o - c r y s t a l l i s a t i o n w i t h the a u t h e n t i c trimethylselenonium s a l t , i d e n t i f i e d t h e i r specimen as the corresponding c h l o r i d e , a c o n c l u s i o n confirmed by the NMR spectrum. In l a t e r s t u d i e s , Palmer elt a l . (45) i n j e c t e d r a t s i n t r a p e r i t o n e a l l y w i t h sodium selenate c o n t a i n i n g H '^SeO^. Several seleno-amino a c i d s were a l s o used. 2

Amino-Acids Containing Selenium

HOOCCH(NH )CH Se-SeCH CH(NH )COOH 2

2

2

2

Selenocystine

Selenomethylselenocysteine HOOCCH(NH )CH CH SeCH 2

2

2

3

Selenomethionine 75 Some of the selenomethionine was l a b e l l e d w i t h Se. Coc r y s t a l l i s a t i o n s of the r e i n e c k a t e s were again used and a l l the selenoamino a c i d s gave the same t r i m e t h y l s e l e n i u m c h l o r i d e , (CH ) SeC£, which was a l s o formed on feeding the r a t s w i t h s e l e n i f e r o u s wheat grown on s o i l c o n t a i n i n g s e l e n i t e o r s e l e n a t e . 3

3

Co-Enzyme M (2-Mercaptoethanesulphonic

Acid)

Recent work by McBride, Wolfe, and t h e i r colleagues (46, 47, 48, 49, 50) has provided much i n f o r m a t i o n about a h e a t - s t a b l e cof a c t o r f o r methyl t r a n s f e r p r i o r t o methane formation i n c e l l ext r a c t s of Methanobacterium s t r a i n M.O.H. grown i n hydrogen. The c o - f a c t o r i s a c i d i c and d i a l y s a b l e . I t a l s o occurs i n rumen f l u i d and has been designated Co-enzyme M. I t contains phosphate when f i r s t i s o l a t e d , and t h i s i s removable by prolonged a c i d h y d r o l y s i s . I t s r e l a t i o n t o the r e s t of the molecule has not been establ i s h e d . A f t e r prolonged p u r i f i c a t i o n of c e l l e x t r a c t s by i o n exchange, o r on a s m a l l e r s c a l e by d i a l y s i s , chemical a n a l y s i s and numerous s p e c t r o s c o p i c s t u d i e s showed t h a t the product was 2 : 2 - d i t h i o d i e t h a n e s u l p h o n i c a c i d ( I ) , a s t r u c t u r e v e r i f i e d by comparison w i t h a s y n t h e t i c specimen prepared from sodium 2-bromoethanesulphonate and H S i n ammoniacal s o l u t i o n . This procedure gave the corresponding -SH compound ( I I ) , which was converted t o the d i s u l p h i d e by gaseous oxygen. By u s i n g methanethiol i n s t e a d of H S, the S-methylated product ( I I I ) was obtained which was i d e n t i c a l w i t h the product formed b i o l o g i c a l l y from Co-enzyme M ,

2

2

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ORGANOMETALS AND ORGANOMETALLOIDS

12

Co-Enzyme M and D e r i v a t i v e s HOS0 CH CH SSCH CH S0 OH 2

2

2

2

2

(I)

2

CH SCH CH S0 OH 3

2

2

(III)

2

HSCH CH S0 OH 2

2

(II)

2

(CH ) t-CH CH S0 5 3

2

2

2

(IV)

2

( t h i o l form) and methyl-B^ i n c e l l e x t r a c t s of the Methanobacterium. The enzyme r e s p o n s i b l e was named methylcobalamin Coenzyme M methyl t r a n s f e r a s e , and was p u r i f i e d 100 times. By r e a c t i o n w i t h methyl i o d i d e i n methanol, the -SCH d e r i v a t i v e gave the corresponding dimethylsulphonium ethanesulphonate (IV). T h i s was found t o be i n e r t as a methyl donor i n the methyl r e d u c t a s e - c a t a l y z e d r e a c t i o n i n i n c u b a t i o n periods up t o 70 minu t e s . No methane production was observed when the onium compound (IV) and the t h i o l form i n the r e a c t i o n medium ate the t h i o l t o y i e l d b i o l o g i c a l l y a c t i v e methylCo-enzyme M ( I I I ) . T h i s s p e c i e s c o u l d not be f u r t h e r methylated by the enzyme methylt r a n s f erase. I t i s probable t h a t the d i s u l p h i d e form of Co-enzyme M (I) i s an a r t i f a c t a r i s i n g d u r i n g the p u r i f i c a t i o n process, and that the e f f e c t i v e Co-enzyme M i s the t h i o l form ( I I ) . I n b i o l o g i c a l systems which o b t a i n i n the mud of swamps, r i v e r s , and l a k e s , t h i s i s methylated t o t h e -SCH compound ( I I I ) which by enzymatic r e d u c t i o n g i v e s methane. 2

3

3

Speculations on the B i o s y n t h e s i s of Co-enzyme M A compound o f c l o s e l y r e l a t e d s t r u c t u r e i s i s e t h i o n i c a c i d H0CH CH «S0 0H. Some s p e c u l a t i o n s on the p o s s i b l e biochemical s i g n i f i c a n c e o f t h i s sulphonic a c i d were made by the author (51, 52) i n 1970 i n another connection. By r e a c t i o n w i t h H S, i s e t h i o n i c a c i d might g i v e the t h i o l form of Co-enzyme M, a r e a c t i o n analogous t o the enzymatic conv e r s i o n of s e r i n e t o c y s t e i n e i n yeast by H S, and the enzyme formerly known as s e r i n e s u l f h y d r a s e . Dagley and Nicholson (53) name the enzyme " L - s e r i n e hydrolyase, adding ILS". The modern name f o r t h i s enzyme (because of one of i t s c h i e f r e a c t i o n s ) i s c y s t a t h i o n i n e 3-synthase[L-serine-hydro-lyase (adding homoc y s t e i n e ) E.G.4.2.1.21.] (54). S i m i l a r l y , O-phosphohomoserine w i t h H S and a s u l f h y d r a s e gives homocysteine (55). I s e t h i o n i c a c i d i s connected w i t h c y s t e i n e by a s e r i e s of r e a c t i o n s s e t out below. Cysteine i s , no doubt, present i n the c e l l p r o t e i n of the methanobacterium. I t can be b i o l o g i c a l l y converted t o t a u r i n e , H ^ C I L ' C H ^ S O ^ H , which y i e l d s i s e t h i o n i c a c i d by enzymatic o x i d a t i v e deamination f o l l o w e d by r e d u c t i o n . Some of these r e a c t i o n s were c i t e d by Challenger i n 1970 (51, 5 2 ) . I have not access t o a l l my f i l e s a t present, but I t h i n k the c o n v e r s i o n of c y s t e i n e t o t a u r i n e i s w e l l e s t a b l i s h e d ; I f o r g e t the circumstances. I t h i n k i t i s described i n M e i s t e r s "Amino-acids"(2nd e d i t i o n ) . 2

2

2

2

2

2

1

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1.

CHALLENGER

Biosynthesis

HSCH CH(NH )COOH 2

> H0 SC^CH (NH ) COOH

2

2

Cysteine

2

2

~ ° s H0 S · CH CH NH C

2

2

Cysteinesulphinic Acid

HOS0 CH CH NH 2

13

2

> [HOS0 CH CHO]

2

2

2

2

2

Hypotaurine

>HOS0 CH CH OH — 2 —

2

2

Taurine

2

Isethionic

2

acid

-> HOS0 'CH CH SH 2

2

2

Co-enzyme M

Taurine i s a produc J>. s u b t i l i s mutant (56). T h i s i s i n t e r e s t i n g i n view o f the f o r mation o f Co-enzyme M i n e x t r a c t s of s o n i c a t e d c e l l s o f Methanobacterium. When t a u r i n e i s present as s o l e source o f sulphur i n A. n i g e r c u l t u r e s , i s e t h i o n i c a c i d i s formed (57). Another p o s s i b l e (though not e s t a b l i s h e d ) source o f i s e t h i o n i c a c i d and so of Co-enzyme M i s 3 - L - s u l f o l a c t i c a c i d , HO^SCHp·CHOH*COOH, which has been p r o v i s i o n a l l y i d e n t i f i e d i n 1969 as a major sulphur compound i n jB. s u b t i l i s spores by Bonsen e t a l . (58). By a w e l l recognized b i o c h e m i c a l r e a c t i o n t h i s might g i v e formic a c i d and HO^S'CH'CHO which by r e d u c t i o n would y i e l d i s e t h i o n i c a c i d . I have not f o l l o w e d the f u r t h e r work ( i f any) on s u l f o l a c t i c a c i d , but the c l e a r a s s o c i a t i o n of s u l p h o n i c a c i d s w i t h c e l l w a l l s , d i s r u p t e d c e l l s , and spores suggests f u r t h e r study o f these r e l a t i o n s h i p s . I have always thought that i s e t h i o n i c a c i d i s worthy o f more a t t e n t i o n by b i o c h e m i s t s , and the f a c t s set out above may be s a i d to strengthen t h i s view. T h i s i s , I t h i n k , t r u e f o r s u l f o n i c a c i d s i n general. A b i l i t y of Metals f o r I n c o r p o r a t i o n i n t o L i v i n g Systems In a most u s e f u l p u b l i c a t i o n (59) summarising t h e r e s u l t s o f s i x o r seven y e a r s work, Wood d i s c u s s e s t h e a v a i l a b i l i t y o f numerous metals f o r i n c o r p o r a t i o n i n t o l i v i n g systems. He p o i n t s out that t i t a n i u m and aluminum are not so a v a i l a b l e because of the i n s o l u b i l i t y of t h e i r hydroxides ; and that n i c k e l and chromium a r e almost absent from b i o l o g i c a l systems, owing t o t h e s t a b i l i t y o f these c a t i o n s i n o c t a h e d r a l s i t e s i n s i l i c a t e s . These l a s t two elements do not form complexes w i t h p r o t e i n s f o r g e o m e t r i c a l reasons. The l i m i t s imposed by space and t h e s u b j e c t o f h i s r e view, " B i o l o g i c a l Cycles f o r Elements i n the Environment", unf o r t u n a t e l y do not permit him t o d i s c u s s these i n t e r e s t i n g observ a t i o n s i n d e t a i l . He r e f e r s , however, t o ten metals which, a f t e r 1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

14

ORGANOMETALS AND

ORGANOMETALLOIDS

t r a n s p o r t i n t o the c e l l by s u i t a b l e c h e l a t i n g agents, bind to v a r i o u s l i g a n d s , and mentions the molybdenum-phosphorus l i n k . This r e c a l l s the ready formation of the y e l l o w phosphomolybdate p r e c i p i t a t e i n q u a l i t a t i v e a n a l y s i s . The requirements of many enzyme systems f o r magnesium, z i n c , and manganese are w e l l - r e c o g n i z e d . Having d i g r e s s e d s l i g h t l y i n t o the realm of i n o r g a n i c b i o chemistry, d e t a i l e d reference may now be made to a somewhat s i m i l a r i n v e s t i g a t i o n i n t o some aspects of the behaviour of t o x i c metals i n s o i l s . The r e s u l t s were p u b l i s h e d i n 1975 and only very r e c e n t l y came to the author's n o t i c e . Much v a l u a b l e work was published i n 1975 (60, 61) as the r e s u l t of a survey of the metal content of the s o i l of the s i t e f o r a s a t e l l i t e town at Beaumont-Leys, two m i l e s from L e i c e s t e r . P r i o r to 1964 the s i t e was used as a sewage farm, a f t e r which i t was l e t to farmers. In 1970, i vie f i t impendin investiga t i o n by the N a t i o n a l A g r i c u l t u r a c o n c e n t r a t i o n of heavy metals y copper on the s i t e . A v a l u e , based on the content of these three metals, known as the z i n c e q u i v a l e n t was used f o r a s s e s s i n g t h e i r content i n the s o i l , and 250 p a r t s per m i l l i o n (ppm) was regarded as perm i s s i b l e . Maximum values of 1000-6000 ppm were obtained f o r s o i l s from Beaumont-Leys. Moreover, the z i n c content of g r a i n grown on the e s t a t e was found to be 115 ppm, the maximum p e r m i s s i b l e v a l u e being 50 ppm. The study was then extended to i n c l u d e other more poisonous metals such as cadmium, a r s e n i c , and l e a d . The r e s u l t s were of p a r t i c u l a r i n t e r e s t because of the imminent development of the s i t e which was known to be contaminated (a) w i t h sewage sludge and (b) by sewage e f f l u e n t which flowed o f f a f t e r d e p o s i t i o n of the sludge. The r e s u l t s of t h i s i n v e s t i g a t i o n , r e p r e s e n t i n g much ext e n s i v e and d e t a i l e d work by E. R. P i k e , the L e i c e s t e r s h i r e County A n a l y s t , Miss L. C. Graham ( h i s deputy), and M. W. Fogden, are s e t out (60, 61) i n two p u b l i c a t i o n s . P a r t I deals w i t h z i n c , copper, and n i c k e l , P a r t I I w i t h l e a d , cadmium, a r s e n i c , and chromium. Some of the c o n c l u s i o n s w i l l be discussed l a t e r . In consequence, a r e - d i s t r i b u t i o n of the proposed s i t e s f o r houses and gardens, r e l a t i v e to other non-domestic b u i l d i n g , was found necessary. The q u e s t i o n of the uptake of t o x i c elements by vegetables a l s o had to be considered. I am g r e a t l y indebted to Mr. P i k e and h i s colleagues f o r sending me r e p r i n t s of t h e i r two papers and a l i s t of r e f e r e n c e s . The m i c r o b i o l o g i c a l and biomethy l a t i o n aspects of the s u b j e c t were not i n v e s t i g a t e d . The main l i n e s of study pursued by P i k e et a l . i n c l u d e d (1) determination of t o t a l metal p o l l u t i o n i n the s o i l by (a) sewage sludge d e p o s i t s and (b) sewage e f f l u e n t ; (2) determination of " a v a i l a b l e " metal i n the s o i l by e x t r a c t i o n w i t h 0.5 M a c e t i c a c i d . The " n o n - a v a i l a b l e " metal i s probably h e l d by r e a c t i o n w i t h the organic matter of the s o i l . Most of the analyses were c a r r i e d out by atomic a b s o r p t i o n spectrophotometry. A t h i r d l i n e of i n v e s t i g a t i o n i n v o l v e d the determination of t o x i c metal content i n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1.

CHALLENGER

Biosynthesis

15

vegetables grown on both (a) and (b) types of s o i l , both at Beaumont-Leys and on s i t e s remote therefrom. For d e t a i l s r e g a r d i n g most metals, r e f e r e n c e must be made t o the o r i g i n a l papers, but because of work on the uptake of cadmium by an American o y s t e r (62) and by c e r t a i n b a c t e r i a (63), r e s u l t s obtained f o r t h i s metal may be given i n some d e t a i l . At Beaumont-Leys, however, z i n c appears t o be present i n the g r e a t e s t c o n c e n t r a t i o n . The symptoms of the I t a i - I t a i d i s e a s e (Japan, 1939-1945) are d e s c r i b e d and a t t r i b u t e d to the cadmium content of r i v e r water t h a t r e c e i v e d waste\from a z i n c , l e a d , and cadmium mine and which was used f o r d r i n k i n g purposes and f o r i r r i g a t i o n of r i c e f i e l d s . The symptoms are probably due t o an i n h i b i t i o n of enzymes r e q u i r i n g z i n c . Cadmium hazards i n Great B r i t a i n have a r i s e n from fumes produced d u r i n g the welding of cadmium i n badly v e n t i l a t e d p l a c e s . I t has been found i n f o o d s t u f f d i huma t i s s u e s wher i t i n c r e a s e w i t h age, causin ease. The cadmium conten given as 0.01-5.00 ppm. In s p i t e of the h i g h z i n c content of s o i l at Beaumont-Leys, the t o t a l cadmium ranged from l e s s than 5 ppm ( e f f l u e n t area) t o 50 ppm i n the sludge areas. The corresponding f i g u r e s f o r a v a i l a b l e cadmium were l e s s than 5 ppm, r i s i n g to 25 ppm, on sludge ground. Those f i g u r e s were based on a v e r y l a r g e number of samples (sludge areas over 1200 samples, e f f l u e n t areas over 1700 samples). The r a t i o of a v a i l a b l e t o t o t a l cadmium (30%), and the t o t a l cadmium do not a l t e r g r e a t l y w i t h the depth of the s o i l . Lead presents a d i f f e r e n t p i c t u r e w i t h a p o s s i b l e a v a i l a b l e percentage of only 1.0. The mode of f i x a t i o n of compounds of metals to p r o t e i n and humus of the s o i l and t o v a r i o u s a c i d s , e.g. phosphoric, or t o s i l i c a t e s would present an i n t e r e s t i n g s u b j e c t f o r a l e i s u r e l y study beginning w i t h the s i m p l e s t analogues. The cadmium content of many garden and a l l o t m e n t s o i l s remote from Beaumont-Leys i s l i t t l e d i f f e r e n t from t h a t of the s o i l s which have r e c e i v e d e f f l u e n t , but much lower than t h a t i n those r e c e i v i n g sludge. As regards the uptake of cadmium by v e g e t a b l e s , a c a r e f u l study of seven garden v a r i e t i e s grown i n s o i l s c o n t a i n i n g cadmium r e v e a l e d a content of 0.05 to 0.5 ppm, but u s u a l l y nearer the lower l i m i t . The f i g u r e s obtained a t Beaumont-Leys and elsewhere may represent a normal cadmium content. A r s e n i c does not appear t o be a problem a t Beaumont-Leys. The h i g h e s t observed f i g u r e i s 59 ppm and then o n l y i n the areas h e a v i l y p o l l u t e d by sludge. I t s c o n c e n t r a t i o n i n the s o i l of most of the area i s s i m i l a r t o t h a t i n the gardens and a l l o t m e n t s a l r e a d y mentioned as remote from the s i t e . On c a r e f u l a n a l y s i s of 10 types of vegetab l e s grown on p l o t s at Beaumont-Leys only t r a c e s of a r s e n i c were found i n l e t t u c e s and r a d i s h e s and no d e t e c t a b l e amounts i n the others. The r e s u l t s at Beaumont-Leys c o n f i r m those c i t e d by MonierW i l l i a m s (64) t h a t only n e g l i g i b l e amounts of a r s e n i c are taken up by p l a n t s even from h i g h l y a r s e n i c a l s o i l s .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

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ORGANOMETALLOIDS

Lead The a n a l y t i c a l r e s u l t s of a study of the d i s t r i b u t i o n of l e a d on the Beaumont-Leys s i t e are i l l u s t r a t e d by two maps f o r (1) t o t a l and (2) a v a i l a b l e l e a d . Land r e c e i v i n g only e f f l u e n t t r e a t ment had a lead content not g r e a t l y d i f f e r e n t from the 200 ppm g i v e n by Swaine (65) f o r n a t u r a l s o i l . H i s s t u d i e s on the metal content of s o i l s are f r e q u e n t l y quoted by P i k e et a l . I t seems t h a t i t i s the content of " a v a i l a b l e " l e a d which i s s i g n i f i c a n t i n the uptake of t h i s metal by p l a n t s , much l e a d becoming i n s o l u b l e due t o r e a c t i o n w i t h p r o t e i n and other compounds present i n the s o i l a f t e r sludge d e p o s i t i o n . The presence of l e a d appears t o be confine d t o the f i r s t two f e e t of s o i l , below which the f i g u r e approaches that of the normal l e a d content of the area. The " a v a i l a b l e " l e a d can, however increas w i t h depth probabl owin to a decrease i n the organi The lead content o uptak by the u s u a l vegetables employed i n t h i s study, and i n a l l cases was much l e s s than the 2 ppm allowed f o r lead i n Food R e g u l a t i o n s (48, 53, 66). The paper presented t o the Symposium by Dr. G. K. Pagenkopf on the t r a n s p o r t of ions of t r a n s i t i o n and heavy m e t a l s , mediated by f u l v i c and humic a c i d s , i s v e r y r e l e v a n t t o the quest i o n of " a v a i l a b l e " and " n o n - a v a i l a b l e " metals ions t o which P i k e et a l . make such frequent r e f e r e n c e i n t h e i r d i s c u s s i o n of the Beaumont-Leys s o i l . Although Pagenkopf appears t o be concerned mainly w i t h r e a c t i o n s i n aqueous media, h i s f u l l paper w i l l be read w i t h much i n t e r e s t by a l l a g r i c u l t u r i s t s . The B i o l o g i c a l Degradation of Organo-derivatives of Mercury Wood (59), when r e f e r r i n g t o h i s well-known work on the m e t h y l a t i o n of compounds of mercury by methyl-B-^* p o i n t s out t h a t m e t h y l a t i o n proceeds more r a p i d l y than degradation by other organisms. Nelson, Brinckman et a l . (67), working i n a c l o s e d system, f i n d that benzene and mercury vapours are produced from phenylmercury (C^H HgOCOCH ) by c u l t u r e s of m e r c u r y - r e s i s t a n t b a c t e r i a . Under n a t u r a l c o n d i t i o n s the mercury so produced may p o s s i b l y , owing t o i t s v o l a t i l i t y , escape i n t o the atmosphere. D e t a i l s are given of the c u l t i v a t i o n of m e r c u r y - r e s i s t a n t b a c t e r i a on media c o n t a i n i n g mercuric c h l o r i d e and phenylmercury a c e t a t e , and a l s o r e f e r e n c e s t o t h e i r i d e n t i f i c a t i o n as t o genus. The phenylmercury a c e t a t e was l a b e l l e d w i t h H g and f u l l d e t a i l s of the analyses f o r Hg and benzene are provided and the apparatus d e s c r i b e d . References are a l s o given t o the conversion of C.H^HgOCOCH^ to mercury and diphenylmercury by a e r o b i c b a c t e r i a , which a l s o conv e r t CH«Hg and C H H g t o methane, ethane, and mercury. The work of Spangler et a l . (68) has shown t h a t , i n l a k e sediments c o n t a i n i n g Hg , formation of CH Hg occurs followed by a f a l l i n c o n c e n t r a t i o n and formation of m e t a l l i c mercury. Four p u r i f i e d c u l t u r e s of what appeared to be a Pseudomonas were 2 0 3

+

2

5

+

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1.

CHALLENGER

Biosynthesis

17

+

i s o l a t e d from the sediment. These a l s o converted CH~Hg t o methane and mercury. These products were i d e n t i f i e d i n the head-space gases by flame i o n i s a t i o n gas chromatography and mass spectromet r y , r e s p e c t i v e l y , thus e x p l a i n i n g why CILHg " has been so d i f f i c u l t t o i d e n t i f y i n n a t u r a l sediments o r r i v e r s . Methane formation was only observed w i t h c u l t u r e s that degraded CHgHg under i d e n t i c a l c o n d i t i o n s . Somewhat s i m i l a r r e s u l t s were obtained by Edwards and McBride (69) who s t u d i e d the b i o s y n t h e s i s and degradation o f CH^Hg " i n human f e c e s . Formation o f methane i s mentioned s e v e r a l times but an extended d i s c u s s i o n of i t s o r i g i n would have been i n t e r e s t i n g . 4

+

4

The N a t u r a l Occurrence of Methylated

Compounds of A r s e n i c :

Braman and Forebac senate, a r s e n i t e , methylarsonate ate) i n many environmental samples i n c l u d i n g s e a - s h e l l s , egg s h e l l s , n a t u r a l waters and human u r i n e . The methods o f a n a l y s i s devised f o r the purpose a r e discussed and a l s o e a r l i e r methods s u i t a b l e only f o r t o t a l a r s e n i c . A r s e n i t e i s reduced t o AsH^ by sodium borohydride a t pH 4-9. Arsenate i s s t a b l e t o t h i s reagent and must f i r s t be reduced t o a r s e n i t e by sodium cyanoborohydride a t pH 1-2, followed by r e d u c t i o n w i t h NaBH^ a t pH 1-2. Methylarsonate and cacodylate gave the corresponding a r s i n e s w i t h NaBH, a t pH 1-2. The AsH^, CILAsIL, and ( C H ^ A s H were c o l l e c t e d i n g l a s s beads cooled i n l i q u i d n i t r o g e n and then passed a f t e r f r a c t i o n a l v o l a t i l i s a t i o n through an e l e c t r i c a l discharge g i v i n g a r s e n i c emission l i n e s which were examined p h o t o m e t r i c a l l y . Methylarsonic a c i d and/or c a c o d y l i c a c i d were s i m i l i a r l y found i n human u r i n e , and the authors suggest t h a t i n o r g a n i c a r s e n i c i s methylated by methylcobalamin or methionine i n the body. A l l these a r s e n i c compounds were found i n nanogram q u a n t i t i e s . The m e t h y l a t i o n of i n o r g a n i c a r s e n i c t o v o l a t i l e d i - o r t r i m e t h y l a r s i n e i n the human body has, t o the author's knowledge, never been r i g i d l y e s t a b l i s h e d . M e t h y l a t i o n may, o f course, cease at the c a c o d y l i c a c i d s t a t e , o r the methylarsines may be o x i d i s e d i n the body. The evidence was discussed i n 1945 by Challenger (71), and l a t e r work may have escaped h i s n o t i c e . The author would a p p r e c i a t e any references which h i s colleagues might send him. At the most the amount v o l a t i l i s e d must be minute as m e d i c i n a l doses of a r s e n i t e produce h a r d l y any odour, whereas that a r i s i n g from absorption o f t r a c e s o f t e l l u r i t e i s i n t e n s e . 4

Acknowledgement s I need h a r d l y say how much I am indebted t o my research c o l l a b o r a t o r s , the r e s u l t s o f whose labours f o r over 20 y e a r s , o f t e n w i t h unpleasant compounds, have added so g r e a t l y t o my enjoyment of U n i v e r s i t y l i f e and work.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18

ORGANOMETALS AND ORGANOMETALLOIDS

Dr. D. Barnard has k i n d l y allowed me to mention some of h i s unpublished work on antimony compounds, and h i s research f o r meth a n o l i n mould c u l t u r e s [Ph.D. T h e s i s , U n i v e r s i t y of L e e d s ] . My thanks are a l s o due to D r . P . A . B r i s c o e and the l a t e D r . J . W. Baker f o r v a l u a b l e d i s c u s s i o n s on t h e o r e t i c a l p o i n t s . D i s c u s s i o n i n t h i s review on the development of ideas on b i o l o g i c a l m e t h y l a t i o n i s based on p a r t s of pages 164 and 170-173 of the a u t h o r ' s book "Aspects of the Organic Chemistry of S u l f u r " . I am indebted to my p u b l i s h e r s , Messrs. Butterworths, London, f o r permission to use t h i s m a t e r i a l . In c o n c l u s i o n , may I once more thank the o r g a n i s e r s of t h i s Symposium f o r a s k i n g me t o w r i t e t h i s review, and p a r t i c u l a r l y D r . Brinckman, Professor Woo ment and help they hav

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34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50.

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Discussion J . S. THAYER ( U n i v e r s i t y of C i n c i n n a t i ) : I would l i k e t o add j u s t a b i t of h i s t o r i c a l p e r s p e c t i v e i n p o i n t i n g out that C h a l l e n g e r s work had o r i g i n i n the r e a l problem that "Gosio-gas" was emitted i n p o o r l y v e n t i l a t e d housing, and q u i t e a number of people d i e d or s u f f e r e d from a r s e n i c p o i s o n i n g . In England, i n 1930, there was a r a t h e r n o t o r i o u s case t h a t l e d d i r e c t l y to C h a l l e n g e r s i n t e r e s t i n t h i s area. He t r i e d t o methylate mercury u s i n g t h i s same route and u n f o r t u n a t e l y f a i l e d by a very narrow margin; otherwise, the s i t u a t i o n that developed i n the 50 s and l a t e r might have a t l e a s t been a n t i c i p a t e d . 1

1

1

J . M. WOOD ( U n i v e r s i t y of Minnesota): I n 1945, Challenger wrote a review [Chem. Rev not o n l y i n terms of th t o r y of the Gosio-gas p o i s o n i n g cases. [ I t d e s c r i b e d the] h i s t o r y of c h i l d r e n i n the Forest of Dean who were poisoned by t r i m e t h y l a r s i n e when a farmer put some a r s e n i c compounds i n a p a r t i c u l a r area i n the f o r e s t . He g i v e s d e t a i l s of the c l i n i c a l h i s t o r y as w e l l as the chemistry. That review i s almost as long as h i s present paper, but i t ' s worth the e f f o r t to s i t down and read i t . W. R. CULLEN ( U n i v e r s i t y of B r i t i s h Columbia): Yes, I can add t h a t the r e f e r e n c e to a r s e n i c i n concrete was t h a t the house the c h i l d r e n were l i v i n g i n had a r s e n i c i n the f l y ash used f o r the concrete. T h i s i s what the molds worked on t o produce t r i methylarsine. F. E. BRINCKMAN ( N a t i o n a l Bureau of Standards): From C h a l lenger s h i s t o r y and commentary on h i s n u c l e o p h i l i c r e a c t i o n shown i n F i g u r e 2, I'd l i k e to address a simple question t h a t ' s of great i n t e r e s t to us. In the f i n a l step he p o i n t s out formation of t r i m e t h y l a r s i n e , which i s the observed v o l a t i l e product. There i s a t r i m e t h y l a r s i n e oxide intermediate step and t h i s of course i n v o l v e s the two e l e c t r o n r e d u c t i o n t o form u l t i m a t e l y the observed v o l a t i l e s p e c i e s . Dr. P a r r i s and I , s e v e r a l years ago, looked at the r a t e s of o x i d a t i o n of t r i m e t h y l a r s i n e i n aqueous media and i n a i r [Environ. S c i . Technol. (1976), 10, 1128]. I t was f a i r l y c l e a r t h a t w h i l e comparatively slow as a chemical r e a c t i o n , i t proceeded r a p i d l y compared to b i o l o g i c a l r a t e s of f o r m a t i o n , a t l e a s t our estimates of b i o l o g i c a l r a t e s of formation. I'm r a t h e r c u r i o u s i f anybody has a comment on t h a t f i n a l r e d u c t i o n s t e p , whether t h a t i s an a b i o t i c or whether i t i s a b i o g e n i c step. 1

CULLEN: I t h i n k I can answer t h a t q u e s t i o n . We have a c t u a l l y used t r i m e t h y l a r s i n e oxide as a s u b s t r a t e f o r Candida humicola and have obtained t r i m e t h y l a r s i n e from i t . So there i s some f u n g a l r e d u c t i o n anyway. I t h i n k we can comment f u r t h e r on t h a t when P r o f e s s o r McBride speaks l a t e r today.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

22

ORGANOMETALS AND ORGANOMETALLOIDS

F. CHALLENGER (in absentia): Regarding the matter of p o s s i b l e b i o m e t h y l a t i o n of antimony, the question of i t s charge i n t a r t a r emetic bears f u r t h e r note. R e i h l e n and Hezel [Ann. (1931) 487, 213], a f t e r much experimental work, have proposed a formula f o r t a r t a r emetic

i n which antimony appears i n the anion. This work escaped my n o t i c e u n t i l r e c e n t l y . The few experiments o f Barnard were i n s u f f i c i e n t t o a l l o w f o r a d i s c u s s i o n o f the i m p l i c a t i o n s o f t h i s f o r mula f o r the p o s s i b l e m e t h y l a t i o n o f antimony, [ c f . paper by G.E. P a r r i s i n t h i s volum Sb and p o t e n t i a l f o r m e t h y l a t i o F. CHALLENGER (in absentia): Regarding methylation of i n organic a r s e n i c i n t h e body, a f u r t h e r comment i s a p p r o p r i a t e . I n a s e r i e s of important s t u d i e s , C r e c e l i u s [Environmental Health Pers p e c t i v e s (1977) 19, 147] demonstrated, f o r example, that human i n g e s t i o n of A s ^ - r i c h wine r e s u l t s w i t h i n 5-10 hours i n about a 5 - f o l d increase i n u r i n a r y l e v e l s of A s and As , methylarsonic a c i d (MAA), and dimethy l a r s o n i c a c i d (DMAA). Most (~ 80%) of the ingested a r s e n i c i s excreted i n u r i n e over s e v e r a l days. Other experiments r e v e a l t h a t both As and A s ^ a r e excreted from t h e body, c h i e f l y i n methylated forms. I n g e s t i o n o f "marine a r s e n i c " i n crab meat r e s u l t s i n u r i n a r y e l i m i n a t i o n , but the o r g a n i c a l l y bound As e n t e r i n g t h e body apparently undergoes no m e t h y l a t i o n . I n a l l of these s t u d i e s , the r e d u c t i v e v o l a t i l i z a t i o n method of Braman and Forelock [ c f . reference 70] was used. Consequently, my e a r l i e r statement that methylation of i n o r g a n i c a r s e n i c t o v o l a t i l e d i - or t r i m e t h y l a r s i n e i n the human body i s not e s t a b l i s h e d cannot y e t be r e v i s e d . +

J

+

RECEIVED September 15, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2 Biotransformations οf Sulfur as Evolutionary Prototypes for Metabolism of Metals and Metalloids GEORGE E. PARRIS Division of Chemical Technology HFF-424, Food and Drug Administration, Washington, DC 20204

Sulfur, like phosphorus earth's crust and sulfu early in the process of evolution. Some non-metals and metalloids ( e . g . , Se, Te, As) have chemical properties similar to metabolicly active forms of sulfur and/or phosphorus. There is always a possibility that an organism w i l l encounter an element, compound or ion in its environment which will act as a pseudo-sulfur or pseudo-phosphorus nutrient. Pseudo-nutrients may or may not be actively toxic, but they can inhibit c e l l functions as they compete with true nutrients in respiration and assimilation. It is observed that pseudo-nutrients are often transformed in vivo into products which no longer encumber the c e l l ' s function. Ideally, such a transformation w i l l produce a material which has few labile valences capable of combining with enzymes, nucleic acids or constituents of the cytoplasm, is not i t s e l f a mimic of a normal metabolite, and has low polarity so that i t can passively diffuse directly out of the cytoplasm through the c e l l membrane. Whether these transformations are merely serendipitous or are evolved specifically for the purpose of dealing with pseudonutrients may be debatable. Because the analogy between the chemistry of S, Se and Te is rather obvious and has been reviewed at length (1), attention in this manuscript is focused on arsenic and other elements where current understanding is relatively incomplete. Evolution of Respiration Chains It is convenient to f i r s t consider biotransformation of sulfur in the respiration of cells which obtain energy from the oxidation of sulfur compounds. In 1 9 4 5 » Horowitz ( 2 J stated a hypothesis which is summarized as follows: The primordial organism is assumed to be capable of a simple form of respiration

0-8412-0461-6/78/47-082-023$05.00/0 © 1978 American Chemical Society

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

24

i n v o l v i n g one enzyme.

Within the environment o f the organism

substrate a

Enzyme A

»

products + energy

there are other substances such as s u b s t r a t e "b" which could be converted to substrate " a " , but the primordial organism cannot u t i l i z e substrate " b " . There may be, however, spontaneous mutants of the primordial s t r a i n which possess the genetic b l u e p r i n t f o r "Enzyme B" which could convert "b" to " a " i n t r a c e l l u l a r ^ , perhaps even with a small r e l e a s e o f useful energy. Under the s t r e s s o f Malthusian growth, the primordial organisms become so numerous that s u b s t r a t e " a " i s consumed as f a s t as i t enters the organisms' environment. When the a v a i l a b i l i t y of substrate " a " becomes c r i t i c a l , the b a s i c s t r a i n o f the primordial organism becomes e x t i n c t and i s replaced cal transformations. Thus, a chain o f r e s p i r a t o r y enzymes i s R

b —

A

a

» .products

+

energy

g r a d u a l l y b u i l t up. G e n e r a l l y , the primeval enzyme systems w i l l be r e t a i n e d i n more h i g h l y evolved and s p e c i a l i z e d organisms. However, a new group o f enzymes, F , G, H, e t c . , may evolve that i s capable o f c a r r y i n g out these o r other e n e r g y - r e l e a s i n g r e a c t i o n s without r e s o r t i n g to use o f the primeval enzyme system A, B, C, e t c . In such a c a s e , an e n t i r e l y new r e s p i r a t o r y system may evolve as the n o w - s u p e r f i c i a l primeval system i s l o s t p i e c e meal i n subsequent mutations ( 2 , 4 , 5 , ) . Unlike the development o f a products

+

energy

r e s p i r a t i o n sequence i n an e v o l v i n g f a m i l y o f organisms, the i n t r o d u c t i o n o f a defensive d e t o x i f i c a t i o n system can l o g i c a l l y s p r i n g from any o f the e x i s t i n g enzymes. A l s o , the organisms w i l l seldom be so lucky as to be able to d e r i v e any net useful energy from d e t o x i f i c a t i o n and i t i s l i k e l y t h a t d e t o x i f i c a t i o n w i l l a c t u a l l y amount to a considerable tax on the normal energy pools o f the organism. There are two types o f biochemical o x i d a t i o n r e a c t i o n s : dehydrogenations and oxygen i n s e r t i o n s . Dehydrogenations are b e l i e v e d to have evolved i n the time before molecular oxygen was a v a i l a b l e i n q u a n t i t y i n the atmosphere. Oxygen i n s e r t i o n r e a c t i o n s could not have been o f much importance u n t i l a f t e r the e v o l u t i o n o f photosynthetic blue-green a l g a e . The dehydrogenation process o f most organisms are s i m i l a r . T y p i c a l l y , an organism has a r e s p i r a t o r y chain which f a c i l i t a t e s dehydrogenation o f some s u b s t r a t e (DH ) ( £ ) . Each time the hydride (H:~ or H- + e") i s 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2.

PARRIS

25

Biotransformations of Sulfur carrier 2 red.

c a r r i e r 1 red. enzyme 1

c a r r i e r η red.

enzyme 2

carrier 1 oxid.

enzyme η

c a r r i e r 2 oxid.

carrier η oxid.

1

t r a n s f e r r e d , chemical p o t e n t i a l i s made a v a i l a b l e t o the c e l l . This chemical p o t e n t i a l i s u t i l i z e d by coupling the o x i d a t i o n steps t o phosphorylation steps which u l t i m a t e l y form ATP from ADP + Ρ · (inorganic phosphate). The f i r s t e l e c t r o n c a r r i e r s i n the r e s p i r a t i o n chain are adapted to the type o f substrate being o x i d i z e d ( e . g . , dehydrogenated). Nicotinamide adenine d i n u c l e o t i d e (NAD , Figure 1 ) i s a common r e c e p t o r which functions as a coenzyme i n the o x i d a t i o n o f many organic compounds. NAD"" can be reduced t o NADH by t r a n s f e r o f a hydrid nicotinamide. A very s i m i l a r coenzyme NADP has a t h i r d phosphate group a t the C - 2 hydroxy! group o f the ribose moiety o f the adenine p o r t i o n o f the i o n . There are d i f f e r e n t enzymes and coenzyme receptors f o r o x i d a t i o n o f d i f f e r e n t s u l f u r species (e.g., sulfur, sulfide, thiosulfite, sulfite). Once the e l e c t r o n s have been removed from the s u b s t r a t e , they can be passed i n t o a c a r r i e r chain which i s made up o f a s e r i e s o f cytochromes. Cytochromes are complexes o f metals (such as i r o n o r copper) which have convenient o x i d a t i o n p o t e n t i a l s and favorable e l e c t r o n t r a n s f e r k i n e t i c s f o r enzymatic coupling to phosphorylation r e a c t i o n s producing ATP. As discussed above, the major elements of t h i s chain may be common to many s p e c i e s . Complexes o f Ί

+

Substrate A — » C« Substrate Β Substrate

C,

C— • C — *

C-| · CoQ

C —• C 2

3

C — » 0, n

Substrate Ν — » C , Ν ubiquinones (coenzyme Q) with cytochromes are known t o be the focal point f o r e l e c t r o n s a r r i v i n g from d i f f e r e n t s u b s t r a t e branches o f r e s p i r a t o r y chains (]J. Respiration in T h i o b a c i l l i There are several genera o f b a c t e r i a which o x i d i z e i n o r g a n i c s u l f u r compounds. The genus T h i o b a c i l l u s has been the most thoroughly s t u d i e d . T h i o b a c i l l i o b t a i n T l l t h e i r carbon from C 0 and a l l t h e i r energy from r e a c t i o n o f various reduced forms o f

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

26

ORGANOMETALS AND ORGANOMETALLOIDS

s u l f u r (Sg, S " , S O 3 " , S 2 O 3 " ) with oxygen or an oxygen donor ( N O 3 - ) to form o x i d i z e d forms o f s u l f u r ( S Û 4 " ) ( 8 ) . T h i o b a c i l l u s thiooxidans derives i t s energy a u t o t r o p h ! c l y by o x i d i z i n g elemental s u l f u r to s u l f a t e . The e f f i c i e n c y with which 2

2

2

2

1/8 S

+

g

3/2 0 =

AG

2

+

H0 J = ±

H S0

2

2

4

-596 kJ

t h i s energy f i x e s carbon to form c e l l u l a r material has been c a l c u l a t e d to be about 6%. Nearly 32 gm o f s u l f u r are o x i d i z e d f o r every gram o f carbon a s s i m i l a t e d i n t o c e l l components. Cytochromes and coenzyme Q have been i d e n t i f i e d i n T . thiooxidans and i t has been observed t n a t low concentrations o f c y a n i d e , azide or carbon monoxide ( a l l o x i d a t i o n i n t h i s organism to be comparable t o t h a t i n b a c t e r i a which are not s p e c i a l i z e d sulfur oxidizers. Thus, the cytochrome-!inked phosphorylation was concluded to be an i n t e g r a l part o f the r e s p i r a t o r y machinery o f the organism (9,10). T h i o b a c i l l u s t h i o p a r u s , u n l i k e T . t h i o o x i d a n s , does not appear capable o f using n a t i v e s u l f u r as a substrate s i n c e when i t i s grown on t h i o s u l f a t e , i t accumulates elemental s u l f u r and produces s u l f a t e . A cytochrome (cyt s , t e n t a t i v e l y c l a s s i f i e d as a c - t y p e cytochrome) has been i s o l a t e d from T . t h i o p a r u s . Nonetheless, evidence seems to i n d i c a t e t h a t the c l a s s i c a l cytochrome-!linked o x i d a t i v e phosphorylation chain may have been supplemented, i n the course o f e v o l u t i o n a r y s p e c i a l i z a t i o n , by a d i r e c t o x i d a t i o n sequence which involves formation o f high energy AP^S (APS, adenosine 5*-phosphosulfate). Notice that i n 8

(1)

S 0=

+

?

c

2 H

+

+

2 e"

0

(2)

2 HS

(3)

SO

+

2

=

+

0 AMP

2

thiosulfate^ reductase

sulfide o x i d a s

e >

S

2

2 e~

+

s

=

o

+

J

H

S c

2 H 0 2

cyt

(ox)

II

0

APS

APS-reductase 2 e" ρ c y t (red)

r e a c t i o n 3 a high energy s u l f a t e bond has been formed i n APS" analogous to ADP . The h y d r o l y s i s of APS to AMP + S. i s s a i d to be about 42 kJ more exothermic than the h y d r o l y s i s of ADP to AMP + P j . While f o r some energy r e q u i r i n g functions of the c e l l , APS may be used d i r e c t l y , a more conventional view i n d i c a t e s t h a t APS i s p r i m a r i l y used as a substrate to form ADP . Ultimately, =

=

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2.

(4)

PARRIS

APS

27

Biotransformations of Sulfur

=

+

P.

ADP-sulfurylase

A

Ί

D

p

+

s

-

=

1

the conventional c e l l u l a r energy source ATP i s formed. (5)

2 ADP

adenylic kinase

Peck and

AMP + ATP

F i s h e r and Stulberg noted t h a t reactions 3 and 4 may be capable o f s u p p l y i n g the necessary ATP f o r a l l c e l l u l a r energy requirements (11,12). However, i t i s u n l i k e l y t h a t cvtochrome-1inked phosphorylation ( i n i t i a t e d i n r e a c t i o n 3) i s completely supplanted

(11,14).

Involvement of Arsenic i A r s e n i t e i s not only a p s e u d o - s u l f i t e n u t r i e n t , i t i s very t o x i c to c e l l s because i t combines i n d i s c r i m i n a t e l y with t h i o l groups causing mass d i s r u p t i o n i n metabolism. Arsenate i s a pseudo-phosphate n u t r i e n t , but s i n c e i t does not r e a d i l y r e a c t with t h i o l s , i t only " c l o g s - u p " c e r t a i n phosphate-processing enzymes r a t h e r than rendering enzymes n o n f u n c t i o n a l . T h u s , the o x i d a t i o n o f a r s e n i t e to arsenate can be viewed as a defensive mechanism. The f i r s t report o f b a c t e r i a l o x i d a t i o n o f a r s e n i t e t o arsenate dates to 1918 when an organism known as B a c i l l u s arsenoxydans was observed i n c a t t l e d i p p i n g preparations based on arsenite. However, the organism was never s t u d i e d s y s t e m a t i c l y and has s i n c e been l o s t . In 1949 Turner (15,16) r e i n v e s t i g a t e d organisms responsible f o r the o x i d a t i o n o f a r s e n i t e t o arsenate i n sheep d i p and i s o l a t e d f i f t e e n s t r a i n s o f h e t e r o t r o p h i c b a c t e r i a which both t o l e r a t e d up t o 0.1 M a r s e n i t e and accomplished the o x i d a t i o n to arsenate. The b a c t e r i a were b e l i e v e d t o be s t r a i n s of Pseudomonas. The biochemical functions o f one s t r a i n were studied. An optimal pH f o r c e l l growth was found to be between 6.0 and 6.5 where a r s e n i t e i s protonated (pK 9 . 1 2 ) . The optimum o x i d a t i o n rate was 90 μΜ a r s e n i t e per hour per mg dry weight o f cells. Oxidation was completely i n h i b i t e d o u t s i d e pH 3 - 1 1 . The a r s e n i t e oxidation was i n h i b i t e d by c y a n i d e , azide and carbon monoxide. The i n h i b i t i o n by CO was only i n the dark. These observations are t y p i c a l o f cytochrome e l e c t r o n t r a n s f e r systems. In p a r t i c u l a r , they are suggestive o f the s o - c a l l e d P-450 cytochrome system. The r e v e r s i b l e i n h i b i t i o n by CO i s due to the e q u i l i b r i u m below. The a c t i v e s i t e o f P-450 i s b e l i e v e d to a

P-450(Fe ) 2+

C

Q

»

P-450(Fe )-C0 2+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

28

ORGANOMETALS AND

ORGANOMETALLOIDS

i n v o l v e a pentacoordinate i r o n moiety which has been r e c e n t l y discussed (17,18^19.)· While e l e c t r o n s given up by As ( 111 ) i n t h i s process are apparently funneled i n t o the normal cytochrome r e s p i r a t i o n c h a i n , there was no evidence that any useful energy i s derived from a r s e n i t e o x i d a t i o n as measured by growth rate o f cultures. Turner regarded the transformation as purely defensive. In a study r e l a t e d to b i o l o g i c a l o x i d a t i o n o f a r s e n i t e to arsenate, Johnson and Pi 1 son (20) have examined o x i d a t i o n o f a r s e n i t e i n s t e r i l i z e d sea water. The s t e r i l i z a t i o n was accomplished by f i l t r a t i o n (0.1 micron) to remove l i v e c e l l s . Thus, the sea water can be regarded as a d i l u t e c e l l - f r e e e x t r a c t s i n c e rupture o f nonviable c e l l s i n a population under natural c o n d i t i o n s undoubtedly frees a whole range o f enzymes. The observed a b i o t i c ( i . e . , e x t r a - c e l l u l a r ) o x i d a t i o n rate o f As(111) was s u f f i c i e n t to account f o r most of the a r s e n i c i n sea water each year (0.023 micromole At t h i s time no organism has been found which o x i d i z e s a r s e n i t e f o r r e l e a s e o f useful energy. Arsenate i s an uncoupler o f o x i d a t i v e phosphorylations. I t i s b e l i e v e d t h a t i n (unadapted) c e l l s arsenate i s mistaken f o r phosphate and unstable ADP^As products are formed which are hydrolyzed before they can be used as ATP (ADP^P) analogues. In the t h i o s u l f a t e o x i d i z i n g b a c t e r i a T. t h i o p a r u s , arsenate was b e l i e v e d to function i n place o f pïïosphate i n the l i b e r a t i o n o f S 0 from APS (see Reaction 4 ) . 4

[Ado-0P0 0S0 ] 2

3

+

=

As0

4

=

ADP-sulfurylasç

^

A M P

^

+

A s

S

0

4

=

There has apparently been no i n v e s t i g a t i o n o f the p o s s i b l e o x i d a t i o n of a r s e n i t e by J \ thioparus i n analogy to s u l f i t e oxidation. Thermodynamicly the o x i d a t i o n o f s u l f i t e i s s l i g h t l y more favorable than the o x i d a t i o n o f a r s e n i t e . H S0 2

+

3

H As0 3

Reduction of

1/2 0 +

3

> H S0

2

2

1/2 0

2

»

H

3

A

s

0

A G = -205 kJ

4

δ

4

6

"

=

1 3 0

k J

Sulfate

Adenosine-5'-phosphosulfate (APS) a l s o plays a c e n t r a l r o l e in the a s s i m i l a t i o n of s u l f a t e ( $ · ) Q 4 ) . Reaction 6 l i e s very Ί

(6) '

ATP

+

x

S. ι

*

" = ATP-sulfurylase Λ Τ Π

Ί Χ

APS

+

PP. ι

much i n favor of ATP + S. ( A G * + 4 6 k J ) . Some o f t h i s energy can be recouped ini vivo by h y d r o l y s i s o f ΡΡ ·. Regardless, APS i s Ί

( 7 )

P P

i

=

+

¥

pyrophosphatase'

2

V

+

2

H +

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2.

PARRIS

29

Biotransformations of Sulfur

trapped i n a usable form f o r a s s i m i l a t o r y reactions by phosphorylation o f the 3 h y d r o x y l . Reaction 8 i s favored by 1

(8)

APS +

ATP • χ , . *PAPS * APS-kinase

+ ADP

Λ η

about 21 kJ* Reactions 6 and 8 are found i n a l l c e l l s which utilize 3*-Phosphoadenosine-5'-phosphosulfate (PAPS, Figure 2) can be reduced by NADPH to s u l f i t e . (9)

PAPS

+

NADPH

*PAP PAPS-reductase

+

S0

o

+

=

NADP

PAPS i s also the s u l f u r source i n formation o f s u l f a t e R-OH

+

PAPS

+

+

H

+

ό

esters.

»

An inorganic reduction o f s u l f i t e to s u l f i d e has been p o s t u l a t e d by Wool fork (21):

(10)

0 0 it II * "0-S—S-0

2 HSO "

+

H«0

0 (metabisulfite) -0 (11)

SJ) *

+

H

0

y

9

S-S

0

4

V

+

H 0 9

(dithionite) (12)

S 0 2

4

2

"

+

H

2

>

S 0 2

3

2

*

+

H 0 2

(thiosulfate) (13)

S 0 2

3

2

"

+

H

2

>

HS0 " 3

+ HS"

2S i m i l a r pathways i n v o l v i n g t r i t h i o n a t e S 0 c have a l s o been proposed (22). An enzymatic scheme f o r s u l f a t e reduction t o enzyme bound -SH v i a PAPS has been o u t l i n e d (23). 3

Reduction o f Arsenate L i t t l e i f any biochemical experimentation has been d i r e c t e d at b i o l o g i c a l reduction o f arsenate, or formation o f a r s e n i c

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

30

hydrogen bonds. Many s u l f a t e reducing b a c t e r i a ( D e s u l f o v i b r i o ) are known. The production of hydrogen s u l f i d e i s usually observed under anaerobic c o n d i t i o n s . Reduction o f arsenate to a r s e n i t e commonly occurs i n aerobic media, though formation of (CH ) AsH has only been reported under anaerobic c o n d i t i o n s (24,25,26;. Johnson and Pi 1 son (20,27) have pointed out that the presence o f a r s e n i t e i n sea water i s undoubtedly due to a c t i v i t y of arsenate reducers. The absence o f any organism which produces A s H i s probably due to the f a c t t h a t t h i s compound i s one of the most potent biochemical toxins known. 3

3

3

A l k y l a t i o n o f Metals and M e t a l l o i d s With regard to the c r i t e r i a l i s t e d i n the i n t r o d u c t i o n f o r an ideal d e t o x i f i c a t i o n process d e s i r a b l e f o r b a c t e r i a an (metal = Sn,Pb,Sb,Hg) and c a r b o n - m e t a l l o i d ( m e t a l l o i d = S e , T e , A s , S i ) bonds u s u a l l y unreactive towards -OH, -SH and -NH groups i n the cytoplasm of c e l l s , organometal and organometallofds are f r e q u e n t l y l i p o p h i l i c enough to d i f f u s e through the c e l l ' s membrane and escape more o r l e s s permanently from the c e l l ' s environment. In complex organisms, l i p o p h i l i c i t y leads to undesirable t o x i c e f f e c t s s i n c e f a t - s o l u b l e compounds breach the body's compartmentalization o f s e n s i t i v e systems. The non-methyl c a r b o n - s u l f u r bonds i n p r o t e i n s are formed by r e a c t i o n s i n which carbon-oxygen bonds are d i s p l a c e d . The s u l f u r n u c l e o p h i l e i s g e n e r a l l y s u l f i d e ( S ) or hydrosulfide (HS~)(V4). These powerful n u c l e o p h i l e s are produced i n t r a c e l l u l a r ^ by enzymatic reduction o f s u l f i t e . NADPH i s the most common reducing coenzyme. L i t t l e i s known about the d e t a i l s o f the r e a c t i o n because the s u l f u r intermediates are u s u a l l y p r o t e i n bound. T h i o s u l f a t e may be i n v o l v e d . Reactions 11 and 12 account f o r the introduction of s u l f i d e into proteins. 2

=

(14)

HO-protein

+

(15)

AcO-pro te i n

acetylCoA +

HS 2

>

AcO-protein

%» HS-protein enzyme^

0

r

e n z y m e

+

AcOH

r

The formation of m e t h y l - s u l f u r bonds i s a common biochemical transformation and i t appears t h a t biomethylation of metals can be t r a c e d t o the methylation o f s u l f u r . The b i o s y n t h e s i s o f methionine from aspartate by way o f c y s t e i n e has been o u t l i n e d by Mahler and Cordes (28). For the c u r r e n t d i s c u s s i o n , only the l a s t major transformation i n which homocysteine i s methylated to form methionine i s important. HSCH CH CHNH C0 " 2

2

3

homocysteine

+

2

CH SCH CH CHNH C0 " 3

2

2

3

+

2

methionine

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2.

PARRis

Biotransformations of Sulfur

31

There are a t l e a s t two enzymatic pathways by which t h i s methylat i o n occurs. In species o f organisms which lack vitamin Βτο» there are r e l a t i v e l y i n e f f i c i e n t transmethylases which bind methyl donor p o l y - L - g l u t a n a t e - N - m e t h y l t e t r a h y d r o f o l a t e (N -methyl-H4f o l a t e ( G l U ] , G l U o , e t c . ) Figure 3) and homocysteine and promote methyl t r a n s f e r t o form methionine and t e t r a h y d r o f o l a t e (hLfolate). Most enzyme systems o f t h i s type do not f u n c t i o n with the m o n o - L - g l u t a m a t e - N - m e t h y l - H - f o l a t e . The main function o f the glutanate moieties appears to be to provide a s u i t a b l e binding s i t e f o r the methyl donor to the enzyme. There i s l i t t l e i f any information a v a i l a b l e concerning the l a b i l i z a t i o n o f the methyl group i n t h i s t r a n s f e r . The turnover rate f o r one o f these d i r e c t transmethylase r e a c t i o n s i s only 14 moles o f N -methyl groups per minute per mole o f enzyme (0.25 mole/sec-mole enzyme)(29). The second and more e f f i c i e n t transmethylase enzyme system depends upon vitamin Β ^ of vitamin B ^ chemistry (30). In vitamin B i ? , c o b a l t i s complexed by a porphyrin-iTîce c o r r i n r i n g . The f i f t h c o o r d i n a t i o n s i t e i s occupied by a 5,6-benzimidazole (Bz) r i n g and the s i x t h s i t e can be occupied by a methyl group o r a v a r i e t y o f other ligands. Unlike the d i r e c t methyl transferase described above, the CHj-B-jp mediated methyl t r a n s f e r process requires a reducing (anaerobic) mediurn. The CHo-B^-enzyme system t r a n s f e r s methyl groups from N - m e t h y l - H a - f o l a t e (Glu-i, e t c . ) to homocysteine a t a steady rate o f about 800 moles per mi η per mole o f enzyme (13 mole CH /sec-mole enzyme)(31). Weissbach and T a y l o r (32) summarized the work o f a number o f others t o describe the r o l e o f vitamin B-J2 the synthesis o f methionine. The scheme which evolved from a v a r i e t y o f e x p e r i mental observations i s o u t l i n e d i n Figure 4. Here 'ΈΝΖ" stands f o r the " N - m e t h y l t e t r a h y d r o f o l a t e homocysteine cobalamin methyl t r a n s f e r a s e " which has a molecular weight o f about 140,000 and has u s u a l l y been i s o l a t e d from s t r a i n s of E. c o l i . The enzyme i t s e l f may o r may not be involved i n any other biomethylation r e a c t i o n s ; but the o v e r a l l scheme, where "ENZ" stands f o r some other enzyme and di f f e r e n t methyl donors and r e c e i v e r s are i n v o l v e d , appears t o be adaptable to many s i t u a t i o n s where the methyl group i s donated as an i n c i p i e n t carbon c a t i o n producing a reduced form o f the Βίο-enzyme complex ( B ^ s ) - The mode o f B - E N Z binding i n the methionine synthetase system has been discussed by Law and Wood (33) who point out t h a t the p h o t o s t a b i l i t y o f the CHo-Co bond i n t h i s C F ^ - B ^ - E N Z complex weighs against a s u l f u r Tigand r e p l a c i n g the benzimidazole base i n s p i t e o f the f a c t that CH3-B12 w i l l not bind t o the enzyme i f a l l the enzyme's s u l f h y d r y l groups have been p r e v i o u s l y blocked. The r o l e o f S-adenosylmethionine (SAM), i n t h i s scheme, i s to provide a r e l a t i v e l y high-energy methyl donor which, i n the presence o f a s u i t a b l e reducing agent, w i l l methyl ate the o x i d i z e d , i n a c t i v e , enzyme-bound Β ^ · SAM w i l l also methyl ate the r e d u c e d - r e a c t i v e , enzyme-bound B moiety but i t i s more than 1 0 times slower than 5

5

5

4

5

5

3

i

n

5

12

1 2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

32

ORGANOMETALS A N D ORGANOMETALLOIDS

Figure 1. Nicotinamide adenine dinu cleotide (NAD")

0

0

"0- S-O-P-0—CH,

II Figure 2. 3'-Phosphoadenosine5'phosphosulfate (PAPS )

ADENINE

A. 0 I

OH P 0

3~

Figure 3. Tetrahydrofolic acid

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2.

ρARRIS

Biotransformations of Sulfur

33

N f - m e t h y l - H - f o l a t e i n t h i s r e a c t i o n . Thus, i n the presence o f N - m e t h y l - H 4 - f o l a t e , l i t t l e SAM i s consumed except to regenerate the a c t i v e methyl-B-jo-ENZ from the o x i d i z e d form. It i s note worthy t h a t SAM can be replaced by other a l k y l a t i n g aaents such as CH3I i n the presence o f a s u i t a b l e reducing agent (34). 4

5

Formation o f Carbon-Metal and Carbon-Metalloid Bonds Alkylcobalamins are a t t r a c t i v e models f o r b i o l o g i c a l a l k y l donors where the a l k y l r e c e i v e r i s a metal o r m e t a l l o i d . Depending upon the a b i l i t y o f the ligands ( e . g . , enzyme) bound to cobalt t o s t a b i l i z e the product o x i d a t i o n s t a t e ( C o , C o o r Co ) , the a l k y l - c o b a l t bond can be broken i n three ways (35*36, 37): 1

1 1

1 1 1

R-B

1 2

Ν

»

R.

+

B

1 2 r

>

R"

+

B

1 2

(Co ) n

(Co

l n

)

The a b i l i t y o f C H - B to y i e l d an i n c i p i e n t methyl anion may mean that cobalamin p l a y s a unique r o l e as a coenzyme i n the b i o m e t h y l a t i o n - o f metals i n high o x i d a t i o n s t a t e s ( e . g . , Hg , Sn4 , S b , P t , P b * ) . In v i t r o transmethylations i n v o l v i n g C H o - B have been studied e x t e n s i v e l y . In these cases the methyl i s t r a n s f e r r e d as a carbon anion i n an S 2 type mechanism. The o v e r a l l r e a c t i o n 3

1 2

1

+

5 +

2

4

+

1 2

E

M -CH I

3

+

M

+

\

H

Γ CH Π L M ' " ^ M J

+

M

r

, +

+

CH -M 3

has an i n t e r e s t i n g complication i n that the metals which have been studied as methyl receptors compete with the c o b a l t f o r the benzimidazole l i g a n d . This r e a c t i o n has an e q u i l i b r i u m constant CH 3

B L 1 £

BZ

+

M

-J±CH -B 3

1 2

k^Bz-M base-on

base-off

on the order o f 10 and the " b a s e - o f f " complex i s formed more r a p i d l y than methyl t r a n s f e r from the "base-on" complex to the metal M. The " b a s e - o f f " complex i s probably a c u l - d e - s a c s i n c e , with the e l e c t r o n donating benzimidazole group gone, the c o b a l t would develop a very high e f f e c t i v e p o s i t i v e charge d e n s i t y i f the methyl group l e f t as an anion. Thus, the ultimate productive reaction i s hampered by the d i v e r s i o n o f the r e a c t i v e substrate ( C H B j base-on)(38). Hughes has discussed the observation t h a t the alEylcobalamins behave as though they are Co(II) r a t h e r than 3

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

34

Co(III) s i n c e l i g a n d exchange a t the f i f t h c o o r d i n a t i o n s i t e i s r a p i d and there appears t o be an e q u i l i b r i u m between 5 and 6 coordinate species i n the alkylcobalamins. Normally, Co(III) has very slow l i g a n d exchange and i t i s s t r i c t l y 6 coordinate (39). There i s a host o f p o t e n t i a l coenzymes f o r t r a n s f e r o f i n c i p i e n t a l k y l cations to metals and m e t a l l o i d s i n low o x i d a t i o n s t a t e s ( e . g . , A s 3 , S b , S n , P t , H g ° , P b , d i v a l e n t S , Se and T e , and I"). The mechanism most l i k e l y to account f o r a l k y l t r a n s f e r i n these cases can be c a l l e d " o x i d a t i v e a d d i t i o n " and presumably i s r e l a t e d to the well-known non-enzymatic S 2 mechanisms (40). In t h i s r e a c t i o n a l e a v i n g group (X) on carbon i s d i s p l a c e d with i t s e l e c t r o n s as a n u c l e o p h i l e (N) forms a new +

3 +

2 +

2 +

2 +

N

R

bond t o carbon. The t r a n s i t i o n s t a t e i s s t a b i l i z e d by p o l a r i z a b l e Ν and X groups which can form r e l a t i v e l y strong bonds even when the N-C and X-C bond distances are rather l o n g . Bulky s u b s t i t u ents (R) on carbon i n h i b i t the r e a c t i o n by s t e r i c crowding. S-Adenosylmethionine (Figure 5) comes t o mind i n t h i s c l a s s of C H donating coenzymes. There has been some work which suggests t h a t the enzymatic t r a n s f e r o f methyl from S - a d e n o s y l methionine to 3,4-dihydroxyacetophenone by r a t l i v e r e x t r a c t i n v o l v e s a r a t e l i m i t i n g S^2 s t e p . I t i s not known whether o r not the methyl i s t r a n s f e r r e d to the enzyme at any p o i n t during the r e a c t i o n (41)· ATP a l k y l a t e s (adenosylates) methionine with ΡΡΡ · a c t i n g as a l e a v i n g group (42). Other phosphate e s t e r s may have s i m i l a r a l k y l a t i n g p o t e n t i a l . Acetate has been mentioned as a po t e n t i a l l e a v i n g group ( r e a c t i o n 15 above). S u l f a t e e s t e r s , R0S0 ; would appear t o be p o t e n t i a l l y very good R donor coenzymes. N - m e t h y l - f y - f o l a t e (Figure 3) has been mentioned as a methyl donor i n n o n - B formation o f methionine (29). E t h y l a t i o n has not been s e r i o u s l y considered s i n c e Challenger refuted G o s i o ' s c l a i m f o r d i e t h y l a r s i n e formation by fungi (43,44). G o s i o ' s proposal might not have been so r e a d i l y o v e r t u r n e d T f the production o f e t h i o n i n e by E . c o l i (45) and the formation o f S-adenosylethionine (46) had been recognized i n 1930. The nature o f the metal o r m e t a l l o i d n u c l e o p h i l e i s as important as the l e a v i n g group i n a l k y l t r a n s f e r s . March (40) and Pocker and Parker (47) should be consulted f o r general d i s c u s s i o n s about n u c l e o p h i l i c i t y . S u l f u r seems to be b i o a l k y l a t e d only a f t e r reduction to a powerful RS" o r HS" n u c l e o p h i l e (Equation 12 and Figure 5 ) . Selenium and t e l l u r i u m may a l s o be reduced t o the d i v a l e n t s t a t e p r i o r t o d i s p l a c i n g a l e a v i n g group from carbon. The reduction o f a r s e n i t e to arsenide does not seem to be l i k e l y . I t i s noteworthy that s u l f i t e i s a n u c l e o p h i l e which i s capable 3

+

Ί

3

5

1 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2.

PARRIS

35

Biotransformations of Sulfur

PPP,

ATP

8AM sγ

v

reoucod r levin

EN Ζ Homocysteine

N-methyl-tj^folete

Bthlonine -

oxidatio

Figure 4.

B

lg

System for methyhtion of homocys teine

ADENINE

Figure 5. S-Adenosylmethionine

Figure 6. Structure of anti mony (III) tartrate showing pseudotrigonal bipyrimid (ψtbp) coordination

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

36

ORGANOMETALS AND ORGANOMETALLOIDS

of displacing halides from alkyl halides (48,49). Sel enite, t e l l u r i t e and arsenite should have similar nucleophilic capabilities, and they are reasonable choices as alkyl acceptors in biological systems. Antimonite probably is less nucleophilic than arsenite because its lone pair of electrons tends to be in a more s-type molecular o r b i t a l . Nonetheless, trimethyl stibine displaces halogens from alkyl halides (50), even though the lone pair of electrons is in an orbital with somewhat more than 25% s character and the bonding orbitals C-Sb have somewhat more than 75% ρ character ( e . g . , C-Sb-C a n g l e s « 1 0 9 ° ) ( 5 1 ) . The polarizability of the low oxidation states of heavy metals ( e . g . , Pb2 , Sb3 ) may make them reasonably nucleophilic when the lone pair occupies a pseudo-pendent site on the coordinated metal ion, e.g., as in antimony tartrat to observe biomethylatio taken too negatively since trimethyl stibine wouTJ not survive long enough in the aerobic systems investigated to allow detection by the usual technique of headspace gases analysis (55). +

+

Literature Cited 1.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

15.

Klayman, D. L. and Gunther, W. Η. Η . , "Organic Selenium Compounds: Their Chemistry and Biology", John Wiley and Sons, New York, N . Y . , 1973. Horowitz, Ν. H . , Proc. Natl. Acad. S c i . U.S. (1945) 31, 153157. Foster, J . W., "Chemical Activities of Fungi", 207-208, Academic Press, New York, N . Y . , 1949. Calvin, M . , Amer. Scientist (1975) 63, 169-177. Lock, D. Μ., "Enzymes-The Agents of Life", 177-207, Crown Publishers, New York, N . Y . , 1969. Mahler, H. R. and Cordes, Ε. Η . , "Biological Chemistry, 2nd Ed.", 632, Harper and Row, New York, N . Y . , 1971. Mahler, H. R. and Cordes, Ε. H . , loc. cit., 778-781. Zajic, J . Ε., "Microbial Biogeochemistry", 46-78, Academic Press, New York, N . Y . , 1969. Cook; T. M. and Umbreit, W. W., Biochem. (1963) 2, 194-196. London, J., Science (1963) 140, 409-410. Peck, H. D . , J r . and Fisher, E., Jr., J . Biological Chem. (1962) 237, 190-197. Peck, H. D . , J r . and Stulberg, M. P . , J. Biological Chem. (1962) 237, 1648-1652. Bowen, T. J., Happold, F. C. and Taylor, B. F., Biochim. Biophys. Acta (1966) 118, 566-576. Peck, H. D . , Jr., Sulfur Requirements and Metabolism of Microorganisms,"Symposium: Sulfur in Nutrition", Muth, O. H. and Oldfield, J . Ε., editors, 61-79, Avi Publishing C o . , Westport, Conn., 1970. Turner, A. W., Nature (1949) 164, 76-77.

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2.

PARRIS

16. 17.

Turner, A. W., A u s t r a l . J. B i o l o g i c a l Sci. (1954) 7 , 452. Collman, J. P . , Sorrell, T . N. and Hoffman, Β. Μ., J. Amer. Chem. Soc. (1975) 9 7 , 913-914. Koch, S . , Tang, S. C., Holm, R. H. and F r a n k e l , R. Β . , J. Amer. Chem. Soc. (1975) 9 7 , 914-916. Koch, S . , Tang, S. C., Holm, R. Η . , F r a n k e l , R. B. and I b e r s , J. Α . , J. Amer. Chem. Soc. (1975) 97, 916-918. Johnson, D. L. and P i l s o n , M. E . Q . , E n v i r o n . L e t s . (1975) 8, 157-171. Woolfork, C. Α . , J. B a c t e r i o l . (1962) 84, 659. F i n d l e y , J. E . and A k a g i , J. Μ., Biochem. Biophys. Res. Commun. (1969) 36, 266. Roy, A. B. and T r u d i n g e r , P. Α . , "The Biochemistry o f Inorganic Compounds o f S u l f u r " , 256, Cambridge a t the U n i v e r s i t y Press, London, 1970. Z a j i c , J. E., l o c Johnson, D. L., Nature (1972) 240, 44-45. McBride, B. C. and Wolf, R. S., Biochemistry (1971) 10, 4312-4317. Pilson, M. E . Q . , Limnol. Oceanog. (1974) 19, 339-341. Mahler, H. R. and Cordes, Ε. H . , l o c . cit., 778-781. W h i t f i e l d , C. D. and Weissbach, H . , J. Biol. Chem. (1970) 245, 402. P r a t t , J. Μ., "Inorganic Chemistry o f Vitamin B ", Academic P r e s s , New York, N . Y . , 1972. T a y l o r , R. T . and Hanna, M. L., A r c h . Biochem. Biophys. (1970) 137, 453. Weisbach, H. and T a y l o r , R. T., Roles o f Vitamin B and F o l i c A c i d i n Methionine S y n t h e s i s , "Vitamins and Hormones", H a r r i s , R. S., Munson, P. L. and P i c z f a l u s y , E., e d i t o r s , 415-440, Academic P r e s s , New York, N . Y . , 1970. Law, P. Y. and Wood, J. Μ., J. Amer. Chem. Soc. (1973) 95, 914-919. Penley, M. W., Brown, D. G. and Wood, J. Μ., Biochem. (1970) 9, 4302-4310. B r o d i e , J. D . , Proc. N a t l . Acad. Sci. U.S. (1969) 6 2 , 461.

18. 19. 20. 21. 22. 23.

24. 25. 26. 27. 28. 29. 30. 31. 32.

33. 34. 35. 36. 37. 38. 39.

40. 41. 42. 43.

Biotransformations of Sulfur

37

12

12

Schrauzer, G. Ν . , Accounts Chem. Res, (1968) 1, 9 7 103. Silverman, R. B. and Dolphin, D . , J. Amer. Chem. Soc. (1974) 96, 7094-7096. S c o v e l l , W. Μ., J. Amer. Chem. Soc. (1974) 9 6 , 3451-3456. Hughes, M. N . , "The Inorganic Chemistry o f B i o l o g i c a l P r o c e s s e s " , 186-187, John Wiley and Sons, New York, N . Y . , 1972. March, J., "Advanced Organic Chemistry", 251-375, McGraw-Hill Book C o . , New York, N . Y . , 1968. Hegazi, M. F., Borchardt, R. T . and Schowen, R. L., J. Amer. Chem. Soc. (1976) 9 8 , 3048-3049. Mahler, H. R. and Cordes, Ε. H . , loc. cit., 382. Gosio, Β . , Arch. Ital. B i o l . (1893) 18, 253.

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ORGANOMETALS AND ORGANOMETALLOIDS

38

44. 45. 46. 47. 48. 49. 50. 51. 52. 53.

54. 55.

Challenger, F . , Higginbottom, C. and Ellis, L., J. Chem. Soc. (1933), 95-101. Fisher, J . F. and Mallette, M. F., J. Gen. Physiol. (1961) 45, 1. Farber, E., Adv. Cancer Res. (1963) 7, 383 Pocker, Y. and Parker, A. J., J. Org. Chem. (1966) 31, 1526. March, J., loc. cit., 330. Gilbert, Ε. Ε., "Sulfonation and Related Reactions", 136-163, Interscience Publishers, Inc., New York, N . Y . , 1965. Parris, G. E. and Brinckman, F. E., J. Org. Chem. (1975) 40, 3801-3803. B r i l l , Τ. Β., Parris, G. E., Long, G. G. and Bowen, L . Η . , Inorg. Chem. (1973) 12, 1888-1891. Poore, M. C. and Russell, D. R . , J. Chem. Soc. A (1971), 18. Cotton, F. A. and Wilkinson G . "Advanced Inorgani Chemistry; 3rd E d . " N.Y., 1972. Challenger, F. and Ellis, L., J. Chem. Soc. (1935), 396. Parris, G. E. and Brinckman, F. Ε., Environ. S c i . Tech. (1976) 10, 1128-1134.

RECEIVED August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

3 Occurrence of Biological Methylation of Elements in the Environment Y. K. CHAU and P. T. S. WONG

Canada Centre for Inland Waters, Burlington, Ontario, Canada

Biological methylatio ing biochemical processes involved wit l i v i n g systems s phenomenon was observed in the early nineteenth century (1815) when several cases of arsenical poisoning occurred in Germany due to the use of domestic wallpapers containing arsenic pigments. In 1839 Gmelin (1) noted that a garlic odor was present in rooms associated with the incident. The mystery was not thoroughly unveiled until 1893 when Gosio (2) observed the evolution of a garlic odor gas from a mould-infected sample of mashed potato on exposure to a i r . The gas was called Gosio gas which was later identified by Challenger as trimethylarsine. The term "biological methylation" was f i r s t used by Challenger (3) to describe the replacement of the οxy-groups of arsenic, selenium and tellurium compounds by methyl groups through the action of moulds, resulting in the formation of organometalloids or organometallic compounds. It has since been shown that bio logical methylation is a general process for l i v i n g organisms (4). Available information indicates that microorganisms, especially bacteria and fungi play an important role in the transformation. While the biological function of methylation is not clearly known, it has been proposed to be a detoxification process. Alternately, it may be energetically preferable for some organisms to trans methyl ate metal rather than to synthesize methane (5). Studies on the environmental impacts of biological methyla tion have gained much momentum since the discovery that micro organisms in a natural lake sediment were able to methylate mercury to a highly-neurotoxic methylmercury species (6). Because methylmercury is produced at a rate faster than organisms can accomplish its degradation, i t may accumulate in fish and so poses a threat to public health (7). Indeed, several incidents of environmental catastrophies caused by mercury have been documented f8.9). Methylation in the environment results in the formation of organometalloids or organometals which are generally more toxic and easily bioaccumulated; it plays an important role in the mobilization of elements from sediment to water; i t may cause 0-8412-0461-6/78/47-082-039$05.00/0 © 1978 American Chemical Society

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

40

organometals and organometalloids

transmethylation of other elements. Attempts have been made to predict the p o s s i b i l i t y of methylation of other elements by the relative ease of formation of metal-carbon bonds (7) and by the reduction potential of the elements (10). The metals Hg, Sn, Pd, Pt, Au and T l and metalloids As, Se, Te and S have been postulated to accept methyl groups from methyl-cob alamin in biological systems. However, Pb, Cd and Zn have been predicted not to be methylated because of the extreme i n s t a b i l i t y of their monoalkyl derivatives in aqueous systems. Methylation studies pertaining to environmental impact began when Jensen and Jernelov (6) investigated the transformation of HgCl in bottom sediments from freshwater aquaria. Then Cox and Alexander (11) studied the transformation of methylated arsenic and selenium compounds from their inorganic salts by fungi isolated from raw sewage and grow (12,13) investigated methylatio species isolated from Chesapeake Bay. A l l these investigations were carried out with environmentally originated microorganisms grown in laboratory media. More r e a l i s t i c approaches were adopted by Bramen (14), Langley (15), and Wong et a l . (16) who used systems containing natural waters and sediments to investigate respectively the methylation of As, Hg, and Pb. A l l these investigations, however, bear certain relevance and significance to the environment and can be extrapolated to living ecosystems. Methylation of mercury in the environment has been well established and documented by other workers. 2

Experimental A sediment-lake water system is used for the investigation of methylation of metals and metalloids in the aquatic environment. In each study, 50 g of sediment and 150 ml of lake water were placed in a 250 ml f i l t e r flask. Nutrient broth (0.5%), glucose (0.1%), and yeast extract (0.1%) were added to stimulate microbial growth. The compounds to be tested for methylation were added to the sediment (5 mg/Jt) and the flasks were capped and incubated at 20°C for 7-10 days. The headspace gas was analyzed for volatile methylated compounds and the lake water was analyzed for the presence of methylated species of the element. A specially-developed Gas Chromâtograph-Atomic Absorption technique was used for the analyses of volatile alkyllead compounds (17), methyl selenides (18), methylarsines and methylarsenic acids (19). Sediments from several lakes in Ontario were used for the studies. In a l l these experiments, appropriate controls were prepared either by omitting the test compounds or by s t e r i l i z i n g the medium by autoclaving. The toxicity of the v o l a t i l e alkyl metals (Pb) and metalloids (As, Se) on algal growth was investigated by using the biologically generated alkyls since most of the methylated products are highly

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

3.

CHAU AND WONG

Biological Methylation

41

v o l a t i l e and i n s o l u b l e i n water, making the dosing o f the compounds t o b i o t a d i f f i c u l t . The b i o l o g i c a l generator (Figure 1) c o n s i s t s o f a 4 £ c u l t u r e f l a s k c o n t a i n i n g a b a c t e r i a l inoculum (Aeromonas sp. 150 ml) and 1350 ml o f the f r e s h n u t r i e n t medium w i t h and without the d e s i r e d compound (at 5 ppm l e v e l as the element) f o r generation o f the v o l a t i l e methylated products. When sediment was used, 500 g sediment and one l i t r e of l a k e water w i t h and without the compound were incubated w i t h glucose (0.1%). A f t e r about 10 days i n c u b a t i o n , the headspace gases were analyzed f o r the presence of the methyl d e r i v a t i v e s before the c u l t u r e f l a s k was connected t o a t e s t f l a s k (4 l i t r e ) c o n t a i n i n g 1.4 £ o f f r e s h CHU-10 medium and 100 ml of a l g a l inoculum. The b i o l o g i c a l l y - g e n e r a t e d methylated product was sucked through the a l g a l c u l t u r e f l a s k by a p e r i s t a l t i c pump. The setup without the a d d i t i o n o f the compound was used as a c o n t r o l . product on a l g a l growt Results and

Discussion

Methylation of lead. Wong et a l . (16) presented the f i r s t evidence that under l a b o r a t o r y c o n d i t i o n s microorganisms i n s e d i ments from s e v e r a l Canadian lakes would transform c e r t a i n i n o r g a n i c and organic lead compounds i n t o a v o l a t i l e and h i g h l y t o x i c tetramethyllead. I t was a l s o observed t h a t i n c u b a t i o n o f c e r t a i n lake sediments produced Me^Pb even without the a d d i t i o n o f extraneous lead compound. There was no d i r e c t r e l a t i o n s h i p between lead concentrations i n the sediment and the amount o f Me^Pb produced (Table I ) . The conversion o f MeaPbOAc to Me^Pb was observed i n a l l experiments but that o f lead n i t r a t e was only sporadic. Subsequently, J a r v i e et a l . (20) confirmed the methylation o f MeaPbOAc t o Mei*Pb and proposed a mechanism i n v o l v i n g hydrogen s u l f i d e complexed w i t h MeaPbOAc f o l l o w e d by decomposition t o Mei*Pb. These workers suggested t h a t lead methylation was a chemical process, without c o n s i d e r i n g the m i c r o b i a l production o f s u l f i d e i n sediment as being a b i o l o g i c a l process. Later Schmidt and Huber (21) demonstrated t h a t not only t r i m e t h y l l e a d , but a l s o lead a c e t a t e , could be methylated t o t e t r a m e t h y l l e a d i n aquarium water. The mechanism o f methylation i s yet to be established. Chemical d i s p r o p o r t i o n a t i o n r e a c t i o n s o f Me3Pb s a l t s are known to produce Me^Pb. The experiments s e t up t o determine the p o r t i o n o f Mei+Pb due t o chemical d i s p r o p o r t i o n a t i o n r e a c t i o n s c o n s i s t e d of a s e r i e s of c u l t u r e of Aeromonas species i n n u t r i e n t b r o t h w i t h a d d i t i o n o f 0-100 mg Pb/£ o f Me PbOAc. An i d e n t i c a l set o f samples was s t e r i l i z e d f o r determining the MeiiPb produced by chemical d i s p r o p o r t i o n a t i o n r e a c t i o n s . A f t e r three weeks i n c u b a t i o n , the b a c t e r i a growth was measured and the amounts o f Me^Pb produced i n the headspace of the chemical and b i o l o g i c a l systems were q u a n t i f i e d . The amounts o f Me^Pb generated +

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4.7 4.0 21.0 7.6 2.4 1.4 6.4

0.09 1.10 0.14 2.10 0.55 0 0 0.13

0 1.80 0.16 0 0.71 0 0 0.01

116 285 47 48 47 48 43

Long Lake

K e l l y Lake

Lunch Lake

Robinson Lake

D i l l Lake

Norway Lake

Babine Lake

Hamilton Harbor

4.

5.

6.

7.

8.

9.

10.

11.

50 gm sediment ( w e t w t . ) , 150 ml l a k e water, 0.5% n u t r i e n t broth and 0.1% glucose with and without the a d d i t i o n o f 1 mg Pb as Pb (NO3)2 o r Me PbOAc. F i n a l Pb c o n c e n t r a t i o n 5 ppm.

3

8.6

0

0

69

P o r t Stanley

3.

273

2.9 5.2

0

0

60

E r i e a u Harbor

2.

4.7

2.20

1.20

110

3

Me PbOAc

M i t c h e l Bay

2

Pb(N0 )

No a d d i t i o n 3

yg Me^Pb generated from sediment supplemented w i t h

(mg/kg dry wt.)

T o t a l Pb cone. i n sediment

M e t h y l a t i o n o f l e a d i n l a k e sediments.

1.

Lake

Table I .

3.

CHAU AND WONG

43

Biological Methylation

b i o l o g i c a l l y and c h e m i c a l l y a t d i f f e r e n t concentrations o f MeaPbOAc and t h e i r r e l a t i o n s h i p s t o b a c t e r i a l growth a r e i l l u s t r a t e d i n Figure 2. At any c o n c e n t r a t i o n o f MeaPbOAc where t h e microorganisms were a c t i v e l y growing, the Me^Pb generated chemic a l l y only represented about 15-20% o f t h e t o t a l MeifPb produced i n the b i o l o g i c a l system. When growth was i n h i b i t e d a t 100 ppm o f MeaPbOAc, the Me^Pb generated i n the system was s o l e l y due t o chemical d i s p r o p o r t i o n a t i o n . U l t r a v i o l e t i r r a d i a t i o n d i d n o t cause f u r t h e r chemical conversion o f Me PbOAc t o Me^Pb i n t h e absence o f microorganisms. D i r e c t chemical s y n t h e s i s o f methyllead compounds through a l k y l a t i o n o f i n o r g a n i c lead i s very d i f f i c u l t because o f t h e extreme i n s t a b i l i t y o f t h e p o s t u l a t e d f i r s t i n t e r m e d i a t e monoa l k y l l e a d s a l t ( M e P b ) . The d i f f i c u l t i e s have a l s o been e x p l a i n e d i n terms o f o x i d a t i o n - r e d u c t i o b i o m e t h y l a t i o n (10). However i t i s not e n t i r e l y unreasonable t o envisage l i g a n d systems which could form s t a b l e monomethyllead complexes before t h e s u c c e s s i v e methylation steps occur. Such may have been the case i n t h e observations o f methylation o f lead n i t r a t e and lead c h l o r i d e t o Me^Pb i n some sediments. The t o x i c i t y o f Mei*Pb on an a l g a (Scenedesmus quadricauda) was s t u d i e d by b u b b l i n g t h e b i o l o g i c a l l y - g e n e r a t e d Mei»Pb i n t o t h e c u l t u r e medium (22). I t was estimated t h a t l e s s than 0.5 mg (as Me^Pb) had passed through t h e c u l t u r e medium. The primary product i v i t y ( C technique) and c e l l growth (dry weight) decreased by 85% and 32%, r e s p e c t i v e l y , as compared w i t h t h e c o n t r o l s without exposure t o Mei*Pb. Furthermore, c e l l s exposed t o Me»»Pb tended t o clump together. S i m i l a r r e s u l t s were obtained w i t h Ankistrodesmus f a l c a t u s . To o b t a i n s i m i l a r e f f e c t s , t w i c e as much lead i n t h e form o f MesPbOAc, and twenty times as much lead n i t r a t e would be required. Lead methylation i s analogous t o mercury i n s e v e r a l aspects. I t i s dependent on temperature, pH and m i c r o b i a l a c t i v i t i e s o f t h e medium but independent o f t h e c o n c e n t r a t i o n o f l e a d i n t h e sediment. So f a r t h e r e are o n l y three r e p o r t s o f l a b o r a t o r y experiments on lead methylation. Evidence o f i t s occurrence i n t h e environment i s s t i l l l a c k i n g . However, e x i s t e n c e o f s i g n i f i c a n t l y h i g h r a t i o s o f t e t r a a l k y l l e a d t o t o t a l lead i n c e r t a i n f i s h e r y products i n d i c a t e s the p o s s i b i l i t y o f methylation i n sediment o r i n f i s h t i s s u e s (23). The f a c t o r s and t h e occurrence o f i n s i t u l e a d methylation i n t h e environment and t h e mechanisms o f methylation a r e being f u r t h e r investigated. 3

+3

llf

M e t h y l a t i o n o f Selenium. The production o f v o l a t i l e selenium compounds by microorganisms has been acknowledged f o r decades (24). I t i s known t h a t v o l a t i l e selenium compounds (Me Se and Me Se ) a r e produced through methylation by f u n g i , b a c t e r i a , r a t s , and h i g h e r p l a n t s (25). Not much i s known about t h e methylation o f selenium i n the a q u a t i c environment. Under l a b o r a t o r y c o n d i t i o n s , Chau e t 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2

2

ORGANOMETALS AND ORGANOMETALLOIDS

VOLATILE ALKYL-METAL GENERATOR Figure 1.

O

BIOASSAY FLASK

PUMP

Biological generation of volatile methyl alkyls for algal toxicity testing

20

40

Meg Pb OAc (mg

60

80

100

Pb-Γ)

Figure 2. Production of Me Ph by chemical disproportionation and by biological methylation and their rehtionships to growth of Aeromonas species. Growth was measured by optical density. h

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

3. CHAU AND WONG

45

Biological Methylation

a l . (26) observed the production of Me Se and Me Se from s e v e r a l sediment and soil samples w i t h and without enrichment w i t h the f o l l o w i n g selenium compounds: sodium s e l e n i t e , sodium s e l e n a t e , s e l e n o c y s t i n e , selenourea, and selenomethionine. In many cases, an u n i d e n t i f i e d v o l a t i l e selenium compound was produced w i t h a r e t e n t i o n time between t h a t o f Me Se and Me Se i n the gas chromatogram. The production o f v o l a t i l e selenium compounds was observed to be a s s o c i a t e d w i t h m i c r o b i o l o g i c a l growth and was temperature dependent. A summary o f the i n v e s t i g a t i o n s w i t h l a k e sediments w i t h and without a d d i t i o n of sodium s e l e n i t e and s e l e n ate i s given i n Table I I . I t has been shown t h a t s i g n i f i c a n t concentrations of selenium e x i s t i n both f r e s h and s a l t water f i s h (27). In studying the r e l a t i v e t o x i c i t y o f organic and i n o r g a n i c selenium compounds t o f i s h , N i i m i and LaHam (28 selenium l e v e l s i n the t e s t o the m i c r o b i a l methylation o f the i n o r g a n i c selenium t o a v o l a t i l e organoselenium compound which was more t o x i c t o f i s h . Selenium i s of p a r t i c u l a r i n t e r e s t as a p o t e n t i a l environmental t o x i c a n t because o f the small s a f e t y margin between the l e v e l s necessary i n the d i e t and the concentrations hazardous t o man (29). Organic selenium compounds are more t o x i c and have longer r e t e n t i o n times than the i n o r g a n i c selenium s a l t s (30). Thus i t i s of considerable i n t e r e s t t o study the methylation o f selenium i n the aquatic environment. 2

2

2

2

2

2

Methylation of arsenic. M e t h y l a t i o n o f a r s e n i c by f u n g i and b a c t e r i a has been known f o r s e v e r a l decades. Challenger and co-workers (3) e x t e n s i v e l y i n v e s t i g a t e d the a b i l i t y o f S c o p u l a r i opsis b r e v i c a u l i s t o methylate organic and i n o r g a n i c a r s e n i c compounds. Cox and Alexander (11) found 3 sewage f u n g i t h a t would methylate v a r i o u s a r e s e n i c compounds used as p e s t i c i d e s t o form t r i m e t h y l a r s i n e . McBride et_ a l . (31) a l s o showed that aerobic microorganisms produced t r i m e t h y l a r s i n e whereas the anaerobic methanogenic b a c t e r i a produced d i m e t h y l a r s i n e when incubated i n the presence of pentavalent and t r i v a l e n t a r s e n i c d e r i v a t i v e s . In our experiments w i t h lake water and sediment, we have demonstrated t h a t i n c e r t a i n sediments c o n t a i n i n g high a r s e n i c l e v e l s , such as those from the Moira R i v e r area i n O n t a r i o , nonv o l a t i l e methylated a r s e n i c compounds are detected i n the overl a y i n g lake water without the a d d i t i o n of extraneous a r s e n i c compounds (Table I I I ) . In other sediments w i t h low a r s e n i c l e v e l s , a d d i t i o n o f a r s e n i c compounds was r e q u i r e d f o r methylation. However i n most o f these experiments, no v o l a t i l e methylated a r s i n e s were detected i n the headspace of the i n c u b a t i o n f l a s k s . I n s e v e r a l experiments w i t h the sediments from the Moira R i v e r , v o l a t i l e methylated a r s i n e s (Me AsH,, Me3As) were detected. Factors which c o n t r o l a r s e n i c methylation are not completely understood. Adenosine t r i p h o s p h a t e and hydrogen were found t o be e s s e n t i a l f o r the formation of d i m e t h y l a r s i n e by c e l l e x t r a c t s o f 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

i

0.90

3.Kelley

4.Long

2

0

0

0

0

6.3

0

0.65

0.67

0.44

0.53

0.55

0.67

7. Windy

8. Moose

9. Kukagami

lO.Nepewassi

11.Johnnie

12.George

0

0.52

0

1.7

2.7

0

34

6.Vermillion

16.28

1.64

20.48

2.Ramsey

0.48

5.Simons

3

No A d d i t i o n 3

0

0

0

0

0

0

0

0

0

3.3

0

0

2

0

3.7

0

0

0

0

0

0

0

2.3

0

3.3

yg/g dry ( C H ) S e (CH )ζSe Unknown wt.

1.Elbow

Lake

Se i n Sediment 2

56.8

43.3

25.3

33.3

5

12.3

20.3

18.7

27.3

14

0

33.3

3

(CH ) Se 3

0

16.5

0

0

0

0

0

0

0

0

0

0

2

(CH ) Se 2

Na s e l e n i t e 3

2

8.7

0

0

0

0

0

18

0

0

0

0

94.7

94.6

28.7

23.4

10.5

0

9.7

20

24.7

20

33.6

34

11

19.4

0

0

0

0

8

4.7

0

3.3

0

0

3

2

Unknown ( C H ) S e ( C H ) S e

Na selenate

Table I I . M e t h y l a t i o n o f selenium compounds i n 12 Sudbury area l a k e sediment samples.

2

7.3

54.8

0

0

2

0

5.3

19.7

0

5.3

0

3.3

Unknown

£2-

5 g?

2.

Sample

3* CD

ET —*

20.40 3.73

3.96

arsenite

17.92 7.19

arsenate

8.89

6.03

none

7.59

trimethy1 a r s i n e oxide

2.93 0.63

0.52

3.27

0.50

0.45

arsenate

arsenite

2.29

7.84

9.57

3.25

dime t h y l a r s i n i c acid

3.75

0.80

1.03

2.14

methylarsonic acid

1.16

0.80

1.92

As(III) As(V)

none

arsenite

arsenate

* - below 0.1 ng d e t e c t i o n l i m i t

Pond sediment

ça q *2 ~ R i v e r sediment

§

CD

3

R~

Ο

none

Arsenic a d d i t i o n (5 mg/1)

A r s e n i c i n medium (ug/l)

Table I I I . Methylations o f a r s e n i c compounds i n sediment samples from Moira R i v e r area, O n t a r i o .

2?La -, Lake sediment 3 I 3

"•"*· cr%

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

limit

dimethylarsinic acid

-

9.10

arsenite

methylarsonic a c i d

4.89

arsenate

dimethylarsinic acid

-

0.14 3.76

12.60

-

1.18

-

1.0

0.40

-

0.5

1.1

-

0.4

-

0.6

0.2

0.5

0.8

Arsine

-

-

-

trimethyl arsine oxide

10.9

-

—

113.0

-

Trimethyl-

V o l a t i l e As i n headspace (ng)

6.15

0.47

-

11.73

1.79

1.67

0.09

8.09

arsenite

methylarsonic a c i d

0\51

0.08

7.61

arsenate

below 0.1 ng d e t e c t i o n

Flavobacterium sp

E. C o l i

2.72

-

2.88

-

9.63

dimethylarsinic acid

*

0.78

-

dimethylarsinic acid

_

8.92

arsenite

-

methylarsonic acid

(mg/£)

me t h y l a r s o n i c a c i d

8.59

arsenate

Aeromonas sp

As(III) As (V)

As i n medium

o f a r s e n i c compounds by pure b a c t e r i a .

Arsenic addition (10 mg/£)

Methylation

Bacterial species

Table IV.

ο

> ο

Ο Ο » Ο

>

r

g >

> ο

w ο

Ο

3.

CHAU AND WONG

49

Biological Methylation

Methane-bacterium (32). Phosphate, s e l e n a t e and t e l l u r a t e , however, i n h i b i t e d the conversion o f arsenate t o t r i m e t h y l a r s i n e by a fungus (11). Since sediment i s a complex b i o l o g i c a l and chemical mosaic, i t i s d i f f i c u l t t o understand what organisms(s) and r e a c t i o n s are r e s p o n s i b l e f o r the a r s e n i c m e t h y l a t i o n . In an attempt t o s i m p l i f y the s i t u a t i o n , we have found two pure b a c t e r i a l c u l t u r e s Aeromonas and Flavobacterium sp., i s o l a t e d from lake water and another bacterium E s c h e r i c h i a c o l i , commonly found i n the i n t e s t i n e o f an organism and i n p o l l u t e d water, had the a b i l i t y t o methylate a r s e n i c compounds when grown i n a medium o f 0.5% n u t r i e n t b r o t h , 0.1% glucose and 10 mg/£ a r s e n i c compound (as As) at 20°C under aerobic c o n d i t i o n s (Table I V ) . Results show t h a t the a d d i t i o n s o f a r s e n i c compounds t o the medium would g e n e r a l l y r e s u l t i n the formation o f d i m e t h y l a r s e n i a c i i medium Trimethylarsin oxide was seldom detected a r s i n e and t r i m e t h y l a r s i n e were a l s o found i n the headspace o f the culture flasks. The t o x i c i t y o f a mixture o f b i o l o g i c a l l y - g e n e r a t e d v o l a t i l e a r s i n e s on an a l g a ( C h l o r e l l a pyrenoidosa) was i n v e s t i g a t e d by the p r e v i o u s l y mentioned technique. The primary p r o d u c t i v i t y ( C technique) and c e l l growth ( c e l l count) decreased by 45% and 44%, r e s p e c t i v e l y , as compared w i t h the c o n t r o l algae without exposure to a r s i n e s . Chemical analyses o f the a l g a l c e l l s r e v e a l e d t h a t the t o t a l As l e v e l s i n the exposed c e l l s were 10 times more than t h a t i n the unexposed c e l l s . McBride et a l . (31), u s i n g c e l l - f r e e e x t r a c t s o f the a e r o b i c s o i l organism, Candida humicola, demonstrated t h a t i n the presence o f S-adenosylmethionine and NADPH, the e x t r a c t s could s y n t h e s i z e a r s e n i t e , methylarsonate and d i m e t h y l a r s i n a t e from arsenate. Whether such r e a c t i o n s occur i n sediments r e q u i r e s f u r t h e r investigation. llf

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

50

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L.J.

and Wood, J . M .

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Cox, D . P . and Alexander, M. (1973) 9, 84.

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Huey, C., Brinckman, F.E., Grim, S. and I v e r s o n , W.P. Proc. I n t . Conf. "Transport o f P e r s i s t e n t Chemicals in A q u a t i c Ecosystems". O.N. LeHam, Ed. ( N a t i o n a l Research Council o f Canada, Ottawa 1974) pp. 73-78.

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Huey, C., Brinckman, F.E., I v e r s o n , W.P. and Grim, S.O. Abst. I n t . Conf. Heavy Metals Environ. Toronto, Ont. (1975) Paper C214.

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Braman, R . S .

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"Arsenical Pesticides",

pp. 108-123.

Amer. Chem. Soc.

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Washington, D.C. (1975).

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Langley, D.G. J. Water

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Wong, P.T.S., Chau, Y . K . and Luxon, P . L . Nature (1975) 253, 263. Chau, Y.K., Wong, P . T . S . and Goulden, P . D . A n a l . Chim. Acta (1976) 85, 421.

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In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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51

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Chau, Y.K., Wong, P . T . S . and Goulden, P . D . (1975) 47, 2279.

A n a l . Chem.

19.

Wong, P.T.S., Chau, Y.K., Luxon, P . L . and Bengert, G.A. Proc. 11th Ann. Conf. "Trace Substances i n E n v i r o n . Health X I " M i s s o u r i . Ed. D.D. H e m p h i l l , pp. 100-106 (1977).

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Nature

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Schmidt, U . and Huber, F .

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22. 23.

S i l v e r b e r g , B.A., Wong P . T . S d Chau Y . K A r c h E n v i r o n Contam. T o x i c o l S i r o t a , G.R. and Uthe, J.F. A n a l . Chem. (1977) 49, 823.

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Schroeder, H.A., F r o s t , D.A. and B a l a s s a , J.J. J . Chronic Disease (1970) 23, 227. McBride, B.C., Reimer, M.M. and C u l l e n , W.R. 175th ACS N a t i o n a l Meeting, Anaheim, Calif. (1978) A b s t r a c t o f Papers, I n o r g a n i c , no. 116.

32.

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Discussion J . M . WOOD ( U n i v e r s i t y of M i n n e s o t a ) : One of the t h i n g s I f i n d p u z z l i n g about the m e t h y l a t i o n of l e a d i s what s o r t of comp l e x has to be formed i n b i o l o g i c a l systems to s t a b l i z e a s i n g l e lead-carbon bond i n water? T h i s i s a tremendous problem from a thermodynamic p o i n t of v i e w . Y e t , i t appears that somehow t h i s happens because t e t r a m e t h y l l e a d i s produced. I wonder whether

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

52

ORGANOMETALS AND

ORGANOMETALLOIDS

anybody here has any idea on what s o r t of l i g a n d i s l i k e y t o coo r d i n a t e lead to s t a b l i z e a s i n g l e lead-carbon bond i n water. CHAU: We are working on a number of b i o l o g i c a l l i g a n d s , name l y , g l u t a t h i o n e p o l y c a r b o x y l i c a c i d s , and s u l f u r l i g a n d s , t r y i n g t o s t a b l i z e the monomethyllead complex. F. HUBER ( U n i v e r s i t y of Dortmund): Did you add v i t a m i n B t o your s o l u t i o n s when studying the production of t e t r a m e t h y l l e a d from l e a d ( I I ) compounds? 1 2

CHAU: Yes, we d i d add B^» use no B^2«

but i n our general experiments we

HUBER: So there i s no i n f l u e n c e on the t e t r a m e t h y l l e a d d u c t i o n when you add v i t a m i CHAU: No,

pro

there was no enhancement.

HUBER: This i s about the same r e s u l t we got, e s p e c i a l l y when we t r i e d i t w i t h t h a l l i u m . You t a l k e d about the problem of the p r o p o r t i o n where you found about 15%-20%; we f i n d about 80% chemi c a l l y produced t e t r a m e t h y l l e a d . I t might be p o s s i b l e that the compositions of the s o l u t i o n s are d i f f e r e n t . We show t h a t , depending on the composition of the s o l u t i o n , there i s a tremendous i n f l u e n c e on the r a t e of r e d i s t r i b u t i o n r e a c t i o n s of organolead compounds· J . J . ZUCKERMAN ( U n i v e r s i t y of Oklahoma): In some cases you s p e c i f i e d the a c e t a t e ; I take i t that these were s o l u b l e l e a d compounds , and t h a t these engaged i n the r e d i s t r i b u t i o n r e a c t i o n . Did you t r y c o l l o i d a l or i n s o l u b l e lead compounds to see i f they could be m o b i l i z e d by the b i o l o g i c a l species i n these r e a c t i o n s ? CHAU: We t r i e d s e v e r a l i n s o l u b l e compounds, such as l e a d hydroxide , lead c h l o r i d e , and s p a r i n g l y s o l u b l e l e a d carbonate. There was no m e t h y l a t i o n . But even w i t h l e a d n i t r a t e we had d i f f i c u l t y g e t t i n g c o n s i s t e n t r e s u l t s , so I'm not s u r p r i s e d that those i n s o l u b l e compounds d i d n ' t r e a c t . W. P. RIDLEY ( U n i v e r s i t y of Minnesota): I'm i n t e r e s t e d i n your experiments on the methylation of l e a d i n f i s h i n t e s t i n e s . Have you examined the t r a n s p o r t of the methylated a r s e n i c species across the i n t e s t i n a l w a l l of the f i s h ? CHAU: No, we haven't. We used f i s h i n t e s t i n e cut i n t o pieces and mixed i t w i t h an i n o r g a n i c a r s e n i c s o l u t i o n . The b a c t e r i a from the f i s h i n t e s t i n e could transform the arsenate and a r s e n i t e i n t o methyl and dimethyl a r s e n i c compounds.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

3.

CHAU AND WONG

Biological Methyfotion

53

K. IRGOLIC (Texas A & M U n i v e r s i t y ) : You showed data on a r s e n i c compounds which you i d e n t i f i e d as d i m e t h y l a r s i n i c and met h y l a r s o n i c a c i d s . As you pointed out, i t i s not n e c e s s a r i l y t r u e t h a t the d i m e t h y l a r s i n e or monomethylarsine you detected need come from these compounds. They could come from an arsenobetaine. I would l i k e t o warn that use of d i m e t h y l a r s i n i c a c i d or methylars o n i c a c i d as a standard i n a n a l y t i c a l procedures does not mean t h a t you have these compounds i n s o l u t i o n . I would l i k e to ask what k i n d of s t r u c t u r e was suggested f o r the v o l a t i l e unknown selenium intermediate i n the methylation of the selenium. WOOD: I n a model system, we were l o o k i n g at the methylation of selenium by dimethylmercury. Under the r i g h t c o n d i t i o n s , you can get methyl t r a n s f e r from dimethylmercury. We i s o l a t e d and c h a r a c t e r i z e d a seleniu f a c t , the predominant produc r a p i d l y converted to dimethylselenide by b e t a - e l i m i n a t i o n . Dr. Chau had i s o l a t e d something s i m i l a r and I sent him the mass spect r a l data and the mar data. I j u s t learned today when you t a l k e d t h a t these t h i n g s are i d e n t i c a l . CHAU:

Yes, they are i d e n t i c a l .

E. BEVAGE ( U n i v e r s a l O i l P r o d u c t s ) : I s i t your o p i n i o n t h a t the m e t h y l a t i o n of these elements i s given by a wide number o f species of b a c t e r i a or do you f e e l i t i s l i m i t e d t o f a i r l y few? I n o t i c e d you had data on E. c o l i . CHAU: Dr. Wong has i d e n t i f i e d s e v e r a l b a c t e r i a l s p e c i e s , namely Aeromonas and Pseudomonas, very common i n l a k e sediments. They do c a r r y out methylation. I t h i n k we have i d e n t i f i e d f o u r s p e c i e s of b a c t e r i a which could c a r r y out t h i s m e t h y l a t i o n . It is more f a v o r a b l e i n anaerobic s i t u a t i o n s . Sometimes m e t h y l a t i o n occurs w i t h e i t h e r aerobic or anaerobic c o n d i t i o n s as w i t h a r s e n i c . RECEIVED August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4 Kinetic and Mechanistic Studies on B -Dependent Methyl Transfer to Certain Toxic Metal Ions 12

Y.-T. FANCHIANG, W. P. RIDLEY, and J. M . WOOD Freshwater Biological Institute/Department of Biochemistry, College of Biological Sciences, University of Minnesota, P.O. Box 100, Navarre, M N 55392 Introduction In the 1930's Challenger discovered the biomethylation of arsenic, and provided us with the f i r s t example of how biological systems possess the capability for synthesizing very toxic organo-arsenic compounds from less toxic inorganic substrates [1,2]. Even in those early days Challenger recognized that biomethylation could only present a local environmental hazard, if the methylated product is produced in significant concentration so as to exert its toxic effect and if the methylated product is stable to hydrolysis. Oxidation-reduction reactions were not well understood in the 1930's; in fact, they are not too well understood to this day, especially in biological systems. For example, biochemists and chemists do not understand the fundamental processes of nitrogen fixation, hydrogen evolution and fixation, photosynthesis, sulfite and n i t r i t e reduction, e t c . , etc. These processes all use electron transfer systems which contain transition metal ions such as molybdenum, iron, manganese, e t c . , for catalysis, and most of these systems are sensitive to molecular oxygen. A major, as yet unanswered question i s : "How did such a great variety of single electron transfer reactions evolve and remain active in a global system which is bathed in molecular oxygen?" Clearly, the "redox" conditions in a specific environment must select for the preferred reaction mechanism, but also control the kinetics for environmentally significant reactions such as biomethylation. Dynamic aspects of these reactions are of c r i t i c a l importance, because even though most methylated metals are thermodynamically unstable in water, many of them are kinetically stable. In fact, i t can be shown that metals which are lower in their periodic groups form metal-alkyls which are kinetically more stable. For example, mercury, platinum and possibly lead offer potentially stable systems whereas palladium, chromium and cadmium do not. In this brief report we examine the different mechanisms for 0-8412-0461-6/78/47-082-054$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4.

F A N C H i A N G E T AL.

55

B n-Dependent Methyl Transfer

Bj^-dependent m e t h y l - t r a n s f e r t o a s e l e c t e d group o f t o x i c e l e ments p l a c i n g s p e c i a l emphasis on "redox" c o n d i t i o n s . Four i n v i t r o mechanisms have been e l u c i d a t e d f o r B^2""dependent m e t h y l - t r a n s f e r to date: (1) h e t e r o l y t i c cleavage o f the Co-C bond w i t h t h e t r a n s f e r o f a carbanion t o the a t t a c k i n g metal i o n ; ( 2 ) h e t e r o l y t i c cleavage o f the Co-C bond w i t h the t r a n s f e r o f a carbonium ion t o an a t t a c k i n g n u c l e o p h i l e ; ( 3 ) homolytic cleavage o f t h e Co-C bond w i t h t r a n s f e r o f a m e t h y l - r a d i c a l t o an a t t a c k i n g f r e e r a d i c a l ; and ( 4 ) "Redox-Switch", a mechanism where metal ions complex w i t h the c o r r i n macrocycle t o l a b i l i z e the Co-C bond t o a t t a c k by weak e l e c t r o p h i l e s [ 3 , 4 , 5 , 6 ] . The t r a n s f e r o f CH3" o r CH3* have been found t o be the most predominant r e a c t i o n mecha nisms f o r a number of metals and m e t a l l o i d s . (1) E l e c t r o p h i l i M e t h y l - t r a n s f e r from methyI bond. The methyl t o c o b a l t bond can break under d i f f e r e n t con d i t i o n s t o g i v e a carbanion, a r a d i c a l o r a carbonium i o n (Figure 1). We have shown that the carbanion and r a d i c a l forms are the p r i n c i p a l species i n v o l v e d i n m e t h y l - t r a n s f e r t o metals and m e t a l l o i d s [7J . The r e a c t i o n between mercuric i o n and methyl c o r r i n o i d s i s an example o f carbanion m e t h y l - t r a n s f e r ( F i g u r e 2 ) . Because mercuric i o n i s a good e l e c t r o p h i l e , i t a l s o coordinates t o t h e n i t r o g e n of the 5,6-dimethylbenzimidazole base t o g i v e a mixture of "base o f f " and "base on" methy1-Βχ2. The "base on" species r e a c t s 1000 times f a s t e r than the "base o f f " s p e c i e s t o g i v e methylmercury as the product [ 3 J ( F i g u r e 2 ) . Other metals which are known t o r e a c t w i t h methyI-B12 by a s i m i l a r mechanism t o mercuric i o n are l e a d ( P b ) , t h a l l i u m ( T l ) and p a l l a d i u m (Μ") Γ8.9.10Ί. The r e a c t i o n s d e s c r i b e d above a l l i n v o l v e the displacement of a carbanion from the c o b a l t atom o f methy l - B - ^ . These r e a c t i o n s occur under aerobic c o n d i t i o n s w i t h r a t e constants i n the order o f m i l l i s e c o n d s . I t i s apparent t h a t metals which r e a c t by e l e c t r o p h i l i c a t t a c k on the Co-C bond (SE2 mechanism) occur w i t h the more o x i d i z e d s t a t e of the metal ( i . e . P b , T l , Hg , Pd , etc.). I V

1 1 1

I V

1 1 1

1 1

1 1

(2) Free R a d i c a l A t t a c k on the Co-C bond o f Methyl-Βτ 9 . A second general mechanism f o r b i o m e t h y l a t i o n i n v o l v e s the d i s placement o f a methyl r a d i c a l from methyI-B12 by the a t t a c k i n g m e t a l l i c s p e c i e s . Homolytic cleavage o f the Co-C bond occurs w i t h the t r a n s f e r o f the methyl r a d i c a l . This r e a c t i o n can be viewed as one e l e c t r o n o x i d a t i v e a d d i t i o n [ 5 , 7 ] . Reactions o f t h i s k i n d r e q u i r e the generation o f a r a d i c a l i n t e r m e d i a t e . This r a d i c a l intermediate can be produced under anaerobic c o n d i t i o n s i n the l a b o r a t o r y e i t h e r by adding a s i n g l e e l e c t r o n oxidant t o a metal i o n i n the reduced s t a t e o f a redox couple (e.g. Sn-*-* — > S I I I + e) o r by adding a s i n g l e e l e c t r o n reductant t o a m e t a l n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

Codll)

α u\ ϋ

A N D ORGANOMETALLOIDS

•

CHi

+

CH *

•

CH

CHl

Codll)

1

θζ

C o d I)

Χ

1

3

Βζ

Co(l)

ί—Βζ Βζ = 5,6-dimethylbenzimidazole Figure 1. Methyl transfer from methyl-B requires cleav age of the Co-C bond. The methyl-to-cobalt bold can break under different conditions giving a carbanion, a radical, or a carbonium ion. 12

CH

CH

3

3

H 0 + Hg > >Co+: Κ 1

2

N

H'° H L

BzHg

2+

Fast reaction

ν

+

-Hg'

H

s

Slow reaction

Η +

>Co< + CH Hg + Hg

CH Hg +

2+

3

3

L

Bz

Figure 2. The reaction between mercuric ion and methyl corrinoids is an example of carbanion methyl transfer.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4.

B12-Dependent Methyl Transfer

FANCHiANG E T AL.

57 1

1

i o n i n the o x i d i z e d s t a t e o f a redox couple (e.g. A u * + e — > A u ) [11]. I n the case o f t i n we have shown that r e d u c t i v e Co-C bond cleavage of methy l - B ^ occurs by a t r a n s i e n t Sn*** r a d i c a l which i s generated by one e q u i v a l e n t o x i d a t i o n o f Sn** (Figure 3) [5*7]. I n the case o f gold we have shown that cleavage o f the Co-C bond r e q u i r e s the generation of Au** by s i n g l e e l e c t r o n r e d u c t i o n of Au*** (Figure 4) [11]. For t h i s r e a c t i o n preincubat i o n o f the Au*** s a l t w i t h the Fe** s a l t i s r e q u i r e d before a r e a c t i o n w i t h methyl-B^2 proceeds. S i m i l a r r e a c t i o n mechanisms have been demonstrated f o r methy1-transfer t o s u i f h y d r y 1 groups [12] and t o chromium (Cr**) [13]. The standard r e d u c t i o n p o t e n t i a l s (E° v o l t s ) f o r elements known t o be methylated by methyl-B^2 shown i n Table I . I t i s c l e a r t h a t those metals w i t h a h i g h r e d u c t i o n p o t e n t i a l ( o x i d i z i n g agents) r e a c t by a those w i t h a low r e d u c t i o a r e d u c t i v e mechanism (Type I I ) [5,7]. This connection between standard r e d u c t i o n p o t e n t i a l and mechanism f o r b i o m e t h y l a t i o n seems h i g h l y r a t i o n a l , because E° d e s c r i b e s the r e l a t i v e thermodynamic tendency f o r the metals i n v o l v e d t o accept or donate electrons. 11

v

a

r

e

Table I . R e l a t i o n s h i p Between Standard Reduction P o t e n t i a l (E°) and the Mechanism of M e t h y l a t i o n f o r Selected Elements. Redox Couple Pb(IV)/Pb(II) T1(III)/T1(I) Se(VI)/Se(IV) a c i d Pd(II)/Pd(0) Hg(II)/Hg(0) Au(III)/Au(I) Pt(IV)/Pt(II) As(V)/As(III) acid Au(III)/Au(II) Sn(IV)/Sn(II) Se(VI)/Se(IV) base Cys-S-S Cys/2Cys-SH Cr(III)/Cr(II) A s ( V ) / A s ( I I I ) base

E° ( v o l t s ) +1.46 +1.26 +1.15 +0.987 +0.854 +0.805 +0.760 +0.559 +0.50* +0.154 +0.05 -0.22 -0.41 -0.67

Mechanism of M e t h y l a t i o n Type I [7,8] Type I [9]

* The A u ( I I I ) / A u ( I I ) couple i s estimated

Type I [10] Type I [3,7] Redox Switch [14] Redox Switch [14] Type I I [ 6 J Type I I [5,7] Type I I [12] Type I I [13]

[19].

Those metals which r e a c t by e l e c t r o p h i l i c a t t a c k (Type I mechanism) have standard r e d u c t i o n p o t e n t i a l s g r e a t e r than +0.80 v o l t s , whereas those metals which r e a c t by r e d u c t i v e homolytic cleavage (Type I I mechanism) tend to have standard r e d u c t i o n p o t e n t i a l s l e s s than +0.56. Reactions which are not c l e a r l y defined occur c l o s e t o the standard r e d u c t i o n p o t e n t i a l f o r molecular oxygen (+0.68 v o l t s ) , and t h i s group o f metals have been c a l l e d "Redox

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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Switch" metals [14] because both o x i d a t i o n s t a t e s of the metal are r e q u i r e d f o r b i o m e t h y l a t i o n to occur. I n the f o l l o w i n g sec t i o n we w i l l present recent data on t h i s "Redox S w i t c h " mechanism. (3) The "Redox Switch" Mechanism f o r A t t a c k on the Co-C Bond of Methyl-B-p. In 1972, Brown and Wood [15] showed t h a t 2 3 - i s o p r o p y l i d e n e - 5 - d e o x y - 3 - ( D ) r i b o x y l cobinamide c o u l d e x i s t as two s t a b l e c o r r i n - r i n g isomers. This i s o m e r i z a t i o n was shown to be pH dependent and s o l v e n t dependent. The y e l l o w c o l o r e d isomer (Y) had a X at 420 nm and the Co-C bond was shown t o be s t a b l e to v i s i b l e l i g h t , but the red isomer (R) had a X at 475 m\i and was shown t o be p h o t o l a b i l e . A 220 MHz NMR study of these two isomers gave markedly d i f f e r e n t s p e c t r a . For (R) the v i n y l proton at C^Q was assigned at σ = 6.7 s h i f t i n g t o α = 7.48 i n the (Y) form. The (Y r e v e r s i b l e . T h i s researc i n f l u e n c e of c o r r i n - r i n g conformation on the s t a b i l i t y of the Co-C bond. At that time we suggested t h a t the i n t e r a c t i o n of Βχ2 w i t h p r o t e i n s could lead t o c o r r i n - r i n g i s o m e r i z a t i o n s which may represent an important f e a t u r e i n understanding s u b s t r a t e directed l a b i l i z a t i o n of the Co-C bond i n the Bi2-enzymes [15]« Certainly, i t seems reasonable t h a t the propionamide s i d e chains on Βχ2" coenzymes could hydrogen bond to p r o t e i n s to cause some d i s t o r t i o n of the c o r r i n macrocycle. In 1975, f i r s t Hogenkamp et a l . , [16] and then Cockle et a l . , [17] used 270 MHz NMR to demonstrate that a s i m i l a r r e d - y e l l o w s h i f t t o t h a t observed by Brown and Wood [15] could be e x p l a i n e d by c o r r i n - r i n g i s o m e r i z a t i o n of cobalamins. R e c e n t l y , Abeles et a l . , [18] showed t h a t a red to y e l l o w isomer i z a t i o n occurs i n the Bj^-enzyme d i o l dehydrase when a mono-ester d e r i v a t i v e of Bi2~coenzyme i s s u b s t i t u t e d f o r 5'deoxyadenosylcobalamin. This mono-ester coenzyme analog shows a s u b s t r a t e dependent red t o y e l l o w t r a n s i t i o n , and the y e l l o w form of the coenzyme analog i s about 5% as a c t i v e as 5 deoxyadenosylcobalamin itself. Each of the above examples demonstrate t h a t the red (R) to y e l l o w (Y) i s o m e r i z a t i o n r e a c t i o n f o r f r e e Βχ2 analogs as w e l l as f o r a Bi2 analog bound to the enzyme d i o l dehydrase, r e s u l t s i n s t a b i l i z a t i o n of the Co-C bond to h o m o l y t i c cleavage. Recently we have shown t h a t P t H C l ^ - forms a one to one complex w i t h the c o r r i n macrocycle and l a b i l i z e s the Co-C bond to a t t a c k by weak e l e c t r o p h i l e s such as P t , A s and S e ( F i g u r e 5 ) . No r e a c t i o n occurs w i t h P t , A s or S e alone. U s i n g 270 MHz NMR together w i t h a d e t a i l e d k i n e t i c and e q u i l i b r i u m study of t h i s r e a c t i o n the f o l l o w i n g f e a t u r e s emerge: 1. P t ^ C l ^ " forms a one t o one "outer sphere" complex w i t h methyI-B12· 2. There i s no displacement or i n t e r a c t i o n w i t h the benz i m i d a z o l e moiety nor any other r e g i o n of the molecule which pro j e c t s below the plane of the c o r r i n macrocycle. 3. The pKa f o r the displacement of benzimidazole i n c r e a s e s 1

f

1

m a x

m a x

1

I V

I V

v

v

V I

V I

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Β ι'-Dependent

FANCHiANG ET AL.

FE11

+

SN

ς n

+

/ ^

d

FE*

Figure 3. Reductive Co-C bond cleavage of methyl-B, occurs by a transient Sn radicflZ which is generated by one equivalent oxidation of Sn . 2

h \ · 0

ν ^

*

L- Bz

FE

•

Η

v

•m S

• SN*

1

Methyl Transfer

ch

3

Sn

L-5

+ Au

m

111

x

11

Z

* Au*

Figure 4. Cleavage of the Co-C bond requires the gen eration of Au by single-elec tron reduction of Au . 11

m

IL Q_

CH*

Co 1 1

+

PT C L É

= ^

Bz

H

Co

L

B

z

H H

CHz

_ ο

\ Ι**/Ρτ C L É

Y

«κ 9-

Co^

+

Ρτ θ |

+

Η

2

0 - ^

L^BZ

^Βζ

-π 5 -

Co^ +

Ρ Α ή

+

Ε CH3PT

CL§

+

CL"

V

Figure 5. Vt Cl?~ forms a one-to-one complex with the corrin macrocycle and labilizes the Co—C bond to attack by weak electrolytes such as ?t , As , and Se . u

IV

v

VI

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

60

ORGANOMETALS AND ORGANOMETALLOIDS

I

2

by 0.6 u n i t s i n the P t * C l 4 ~ - m e t h y l - B i 2 complex. 4. Complex formation i s s e n s i t i v e to both i o n i c s t r e n g t h and the nature of the anion i n s o l u t i o n . 5. A downfield s h i f t of 0.064 ppm i s observed f o r the methyl group σ bonded t o the c o b a l t atom of M e B ^ - P t ^ C l ^ - com p l e x i n d i c a t i n g a change i n e l e c t r o n d e n s i t y on the methyl-group making i t more s u s c e p t i b l e t o e l e c t r o p h i l i c a t t a c k . 6. The Co-C bond i n the Ρt^Cl^'-methyl-Bj^ complex i s more p h o t o l a b i l e than f o r methy1-Βχ2 alone ( i . e . the bond i s a p p r o x i mately h a l f as s t a b l e t o l i g h t i n the complex). A d e t a i l e d r e p o r t on the k i n e t i c s and mechanism f o r methylt r a n s f e r to platinum i s i n press [ 6 J . The major f e a t u r e s of the r e a c t i o n mechanism are presented i n F i g u r e 5. Although we do not know the d e t a i l e d s t r u c t u r e of the P t C l 4 " - m e t h y l - B i 2 complex, i t i s c l e a r that a c t i v a t i o formation of t h i s complex MHz NMR study of t h i s i n t e r a c t i o n i s underway w i t h a view to determination of the p r e c i s e s t r u c t u r e of t h i s " a c t i v a t e d " methy1-B^2 s p e c i e s . 2

II

2

Conclusions The mechanisms f o r Β-^-dependent m e t h y l - t r a n s f e r to a number of metals and m e t a l l o i d s are shown t o be determined by the s t a n dard r e d u c t i o n p o t e n t i a l (E°) f o r the a t t a c k i n g i n o r g a n i c s a l t . The standard r e d u c t i o n p o t e n t i a l f o r molecular oxygen separates those complexes which cleave the Co-C bond by h e t e r o l y s i s from those which cleave t h i s bond by homolysis. I n the case of p l a t i num, which has an E° f o r the P t ^ / P t couple c l o s e t o that f o r molecular oxygen, we have discovered the formation of an "outer sphere" complex between the P t s a l t and the c o r r i n macrocycle which l a b i l i z e s the Co-C bond t o e l e c t r o p h i l i c a t t a c k by P t . This mechanism has been c a l l e d a "Redox Switch" and has many s i m i l a r i t i e s t o current mechanisms being proposed f o r l a b i l i z a t i o n of the Co-C bond i n the B^-enzymes. We b e l i e v e that a fundamen t a l study of k i n e t i c s and mechanism f o r B^-dependent methylation of metals and m e t a l l o i d s has not only helped t o d e f i n e e n v i r o n mental c o n d i t i o n s f o r b i o m e t h y l a t i o n r e a c t i o n s , but has a l s o shed some l i g h t on the p r e r e q u i s i t e s r e q u i r e d f o r " a c t i v a t i o n " of the Co-C bond i n Bi2-enzyme c a t a l y z e d r e a c t i o n . 1 1

1 1

i v

Acknowledgements Some of the research supported i n t h i s report was s u b s i d i z e d by the U.S. P u b l i c Health S e r v i c e AM 18101, the I n t e r n a t i o n a l Lead Z i n c Research O r g a n i z a t i o n and the Northwest Area Foundation.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4. FANCHIANG ET AL.

B -Dependent 12

Methyl Transfer

61

References 1. C h a l l e n g e r , F . Chem. Rev. (1945) 36, 315. 2. R i d l e y , W . P . , Dizikes, L.J., Cheh, Α . , and Wood, J.M. Env. Health P e r s p e c t i v e s (1977) 1 9 , 4 3 . 3. DeSimone, R.E., P e n l e y , M.W., Charbonneau, L., Smith, S.G., Wood, J.M., Hill, H . A . O . , Pratt, J.M., R i d s d a l e , S . , and W i l l i a m s , R.J.P. Biochim. Biophys. A c t a (1973) 304, 851. 4. Schrauzer, G.N., Sibert, J . W . , and Windgassen, R.J. J. Amer. Chem. Soc. (1968) 90, 6681. 5. D i z i k e s , L.J., R i d l e y , W . P . , and Wood, J.M. J. Amer. Chem. Soc. (1978) 1 0 0 : 3 , 1010. 6. Fanchiang, Y.-T., R i d l e y , W . P . , and Wood, J . M . J. Amer. Chem. Soc. (1978) 100, 1010. 7. R i d l e y , W . P . , Dizikes, L.J., d Wood J.M. Scienc (1977) 197, 329. 8. Wood, J.M. (1978) ceedings of an I n t e r n a t i o n a l Conference on Lead in the Marine Environment. R o v i n j , Y u g o s l a v i a . M . B r a n i c a , e d i t o r . 9. Agnes, G., Hill, H . A . O . , Pratt, J.M., R i d s d a l e , S.C., Kennedy, F.S., and W i l l i a m s , R.J.P. Biochim. Biophys. A c t a (1971) 252, 207: 10. S c o v e l l , W.H. J. Amer. Chem. Soc. (1974) 96, 3451. 11. Fanchiang, Y.-T., R i d l e y , W . P . , and Wood, J.M. Chem. Communs (1978) (submitted) March. 12. F r i c k , T., F r a n c i a , M . D . , and Wood, J.M. Biochim. Biophys. A c t a (1976) 428, 808. 13. Espenson, J.H., and S e e l e r s , T . D . J . Amer. Chem. Soc. (1974) 96, 94. 14. Agnes, G., Bendle, Β., Hill, H . A . O . , W i l l i a m s , F.R., and Williams, R.J.P. Chem. Communs. (1971) 850. 15. Brown, D.G., and Wood, J.M. S t r u c t u r e and Bonding (1972) 11, 47. 16. Hogenkamp, H.P.C., V e r g a m i n i , P.J., and Matwiyoff, N . A . J. Chem. Soc. D a l t o n Trans. (1975) 2628. 17. C o c k l e , S.A., Hensens, O . D . , Hill, H . A . O . , and W i l l i a m s , R.J.P. J . Chem. Soc. D a l t o n Trans. (1975) 2633. 18. A b e l e s , R . H . Current Status of the Mechanism of B -coenzyme. B i o l o g i c a l Aspects o f I n o r g a n i c Chemistry. Wiley I n t e r s c i e n c e , E d . D . H . Dolphin 1977) 245. 12

19.

R i c h , R.L., and Taube, H . J. Phys. Chem. (1954) 58, 1,6.

Discussion J . J . ZUCKERMAN ( U n i v e r s i t y of Oklahoma): I s there evidence for b i o a l k y l a t i o n where the a l k y l group i s other than methyl? WOOD: On the question of B^-dependent r e a c t i o n s , e t h y l c o balamin has been i s o l a t e d and c h a r a c t e r i z e d as a n a t u r a l product by a group of German workers, but i t ' s there i n v e r y s m a l l concen-

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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t r a t i o n s . I t may be p o s s i b l e t o get e t h y l t r a n s f e r r e a c t i o n s . I f t h a t ' s the case, I would t h i n k that ethylmercury should have been t u r n i n g up i n some b i o l o g i c a l systems; however, i t ' s only been t u r n i n g up where people have s p i l l e d e t h y l l e a d . I f you have a c h l o r i n e p l a n t next t o an a l k y H e a d - p r o d u c i n g p l a n t , you get d i s p r o p o r t i o n a t i o n i n the s y n t h e s i s of ethylmercury compound. ZUCKERMAN: I r e c a l l that marsh gas has an odor and i s proba b l y a mixture of a l a r g e number of hydrocarbons. Are these d i r e c t l y incorporated onto a r s e n i c by b i o l o g i c a l organisms? WOOD: The s y n t h e s i s o f the a r s i n e s and the s y n t h e s i s o f v o l a t i l e selenium compounds i s w e l l known; the s y n t h e s i s of v o l a t i l e dime thy lmercury i s w e l l known. So, v o l a t i l i z a t i o n o f metal and m e t a l l o i d a l k y l s i n thes occurs. A l s o , Brinckman' methyItins. [Proc. I n t e r n a t . Con. on Transport o f P e r s i s t e n t Chemicals i n Aquatic Ecosystems. N a t i o n a l Research C o u n c i l , Ottawa, Canada, 1974, p.11-73.] ZUCKERMAN: With respect t o the a l k y l a t i o n o f t i n , has i t been demonstrated t o occur i n environmental c o n d i t i o n s of pH, tempe r a t u r e , etc? F. E. BRINCKMAN ( N a t i o n a l Bureau of Standards): There i s a c o m p l i c a t i o n here. S a l i n i t y i s a very l a r g e f a c t o r , but the r e s u l t s of a change i n the m i c r o b i a l p o p u l a t i o n may be more important as C o l w e l l showed [ M i c r o b i a l Ecology (1975), 1, 191]. She made i t q u i t e c l e a r that the Pseudomonas p o p u l a t i o n , which i s the p r i n c i p l e a c t o r i n t h i s p a r t i c u l a r case i n v o l v i n g the mercury o r the t i n t r a n s f o r m a t i o n s , was very s u s c e p t i b l e t o such changes. So I t h i n k there i s an a d d i t i o n a l f a c t o r o f the a v a i l a b i l i t y o f growth. The growth k i n e t i c s of the microorganisms themselves w i l l then of course a f f e c t the apparent r a t e even f o r the e x o c e l l u l a r production of methylcobalamin. I t i s not y e t c l e a r whether the methylcobalamin might be i n v o l v e d i n the e n d o c e l l u l a r o r an exoc e l l u l a r v i s - a - v i s these metal ions such as t i n o r mercury. ZUCKERMAN: I f I r e c a l l your paper i n J . Amer. Chem. Soc. [(1978) 100, 1010] the c o n d i t i o n s were r a t h e r more severe than b i o l o g i c a l environmental c o n d i t i o n s . WOOD: The k i n e t i c s experiments were run a t low pH f o r the obvious reason o f keeping the t i n i n s o l u t i o n . For the t i n t a r t r a t e complex, s i m i l a r k i n e t i c s are obtained f o r r e a c t i o n s a t amb i e n t pH and temperature. We chose t o do the study under these c o n d i t i o n s so t h a t we could do k i n e t i c s more r e a d i l y w i t h t i n i o n . I t i s not a simple problem, but i f you make the t a r t r a t e complex you can do i t . There are many complexes i n b i o l o g y t h a t could mimic t a r t a r i c a c i d .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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Bi>-Dependent Methyl Transfer

63

G. E. PARRIS (Food & Drug A d m i n i s t r a t i o n ) : With regard t o the formation of other a l k y l m e t a l compounds, I read an ACS p u b l i c a t i o n e n t i t l e d "Chemical Carcinogens" [ACS "Advances", No. 173]. In a s e c t i o n r e g a r d i n g n a t u r a l l y o c c u r r i n g carcinogens, i t was r e ported that E. c o l i produced e t h i o n i n e and even the adenosyl der i v a t i v e of e t h i o n i n e analogous to methionine, which a l s o p r o v i d e s another p o s s i b l e a l k y l a t i n g agent. WOOD: I n that case, you have to l o o k a t some n u c l e o p h i l e . So the m e t a l l o i d s would be good candidates f o r r e a c t i o n s of that k i n d . PARRIS: I f i t i s a b i m o l e c u l a r n u c l e o p h i l i c r e a c t i o n , as the methyl t r a n s f e r might be i n e i t h e r enzymatic or non-enzymatic cases, the e t h y l t r a n s f e r would s u f f e r c o n s i d e r a b l y , r e l a t i v e t o methyl t r a n s f e r , i n term f WOOD: When you do these k i n e t i c s s t u d i e s , you f i n d the e t h y l always s u f f e r s a p p r e c i a b l y . PARRIS: I t h i n k t h e r e i s an i m p l i c a t i o n t h a t cobalamin i s preeminent i n the methyl t r a n s f e r r e a c t i o n i n v i v o , as w e l l as i n i n v i t r o s t u d i e s you have done. Would you comment? WOOD: Yes, I can put t h i s i n p e r s p e c t i v e . Many microorgan isms do i n f a c t produce Β ^ · Almost a l l of the blue-green algae s y n t h e s i z e l a r g e amounts of B ^ . M e t h y l - B ^ has been shown t o be a coenzyme i n a number of enzyme-catalyzed r e a c t i o n s . Therefore, t h i s coenzyne does t u r n over, and so you have t h i s c o n s t a n t l y r e generated m e t h y l a t i n g agent j u s t l i k e you have w i t h S-adenosylmethionine. B a s i c a l l y , i f you want t o look a t m e t h y l a t i o n problems i n the environment, you are always chasing the k i n e t i c parameters. The i n t r i g u i n g t h i n g about methylcobalamin i s that you are l o o k i n g at r e a c t i o n s w i t h r e s p e c t a b l e r e a c t i o n r a t e s . In f a c t , the r e a c t i o n r a t e f o r the m e t h y l a t i o n of mercury i s a l i t t l e b e t t e r than the turnover number f o r B-^-dependent methionine s y n t h e s i s , which i s a c r u c i a l B^-dependent enzyme. T h i s means every time a mer cury i o n gets i n the v i c i n i t y of methyl-B-^ bound i n the methionine enzyme, you are more l i k e l y t o make methylmercury than you are methionine. PARRIS: With regard t o metals other than the e l e c t r o p h i l i c mercury, or m e t a l l o i d s , do you regard B ^ preeminent methyl donor, or would you then regard S-adenosylmethionine as more l i k e l y source of methyl? a

s a

WOOD: I t h i n k i t ' s v e r y important t o do these experiments w i t h i s o t o p e s . We do model s t u d i e s and we ask that people working i n the environmental s c i e n c e s do t h i s , f o r example, w i t h l e a d . I f you want to f i n d out whether lead i s methylated, see where the C ^ -methyl group comes from i n these extremely complex experiments

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where you have complex media i n v o l v i n g mixed b a c t e r i a l c u l t u r e s , sludge, e t c . I t ' s c r i t i c a l l y important to do i s o t o p e experiments to f i n d out where the methyl group i s coming from. I f t h a t ' s done, then you can w r i t e a t e n t a t i v e mechanism. I f you can w r i t e a tent a t i v e mechanism, you can t e s t i t . What we t r y t o do i s t o g i v e people a c l u e about the s o r t of mechanism that may occur i n the environment so t h a t they can go and see whether i t does. That has always been our p o s i t i o n . 1

PARRIS: One l a s t comment w i t h regard to the other a l k y l groups. I n support of the suggestion that t r a n s f e r from something l i k e S-adenosylmethione t o a m e t a l l o i d would be a n u c l e o p h i l i c r e a c t i o n . There i s one p u b l i c a t i o n i n _J. Amer. Chem. Soc. [(1976), 98, 3048] concerning the o - a l k y l a t i o n of dihydroxyacetophenone, and i n t h a t case the autho i u s i n deuteriu i s o t o p e suggested that the r e a c t i o the c r i t i c a l step i n the r e a c t i o n was b i m o l e c u l a r . WOOD: That's the only example i n the l i t e r a t u r e . RECEIVED

August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5 Aqueous Chemistry of Organolead and Organothallium Compounds in the Presence of Microorganisms F. HUBER, U. SCHMIDT, and H. KIRCHMANN Chemistry Department, University of Dortmund, D 4600 Dortmund 50, Federal Republic of Germany

Organocompounds o corresponding compound following the decreasing strength of the central atom-carbon bond. Their stability is strongly dependent on the nature and also on the number of the organic groups, R, bound to lead. Alkyllead compounds are, i n general, d i s t i n c t l y less stable than aryllead compounds, and their s t a b i l i t y decreases with decreasing number of R. In aqueous solution, tri- and dialkyllead compounds, R PbX and R PbX (X = anion), show a more or less marked tendency to decompose, and monoalkyllead compounds, RPbX are actually unknown [there is only one report that Pb(OAc ) (OAc = acetate) reacts with alkylpentafluorosilicates to give (impure) RPbF (R = CH , C H , CH =CH) (1)]. Tetraalkyllead compounds are only very s l i g h t l y soluble i n water. For a general review see (2). Alkylthallium compounds, R T1X and RT1X , are i n general more stable than the corresponding lead compounds, but only a rather limited number of monoalkylthallium compounds, RT1X , are known. Trialkylthallium compounds, R T1, hydrolyze to give R T1 + OH and RH (3). 3

2

2

3

4

3

3

2

5

2

2

2

2

3

+

-

2

Decomposition of Organolead Compounds i n Water Me^PbXg. We have investigated quantitatively the decompos i t i o n of Me PbX (Me = CH ) i n aqueous solution and i n aqueous salt solutions between 20 and 60°C (4). The reaction proceeds i r r e v e r s i b l y according to equation [1] 2 Me PbX 2

2

Me PbX + PbX 3

2

+ MeX

[1]

and the stoichiometry i s not influenced by the type or the concentration of s a l t added to the solution. (The redistribution of Me ~PbX [see below] i s much slower, so i t does not appreciably interfere with [1].) The reaction rate, which i n a l l cases corresponds to f i r s t order, increases strongly with increasing salt concentration, the anions displaying much stronger influence 0-8412-0461-6/78/47-082-065$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

66

ORGANOMETALS AND ORGANOMETALLOIDS

than the c a t i o n s . The anions arranged according t o t h e i r a b i l i t y to i n c r e a s e the r e a c t i o n r a t e k g i v e a s e r i e s r e f l e c t i n g t h e i r polarizability: X : OAc V" Cl~ / k

:

C10

0 , 0 2

<

° ·

NO3

4

η κ

°·

2 0

Cl

N0

2

Br

SCN

I 4

< 1-0 < 2.4 < 130 < (>130) < (~10 )

(Concentrations^-0.036 mol Me PbX«.L "S NaX and KX r e s p e c t i v e l y 2.7 - 0.7 mol.lT ). The r e s u l t s i n d i c a t e that MeJPbX i n a f i r s t step g i v e s an intermediate which i s bridged by anions X and/or s o l v e n t molecules L: ?

2

L/X , X/L I ^X/L^| 2 M e

2

P b X

solvent _ 2 molecules t

e

X / ^

e

In a second rate-determining s t e p , t r a n s a l k y l a t i o n i s e f f e c t e d when t h i s intermediate r e d i s t r i b u t e s t o give Me^PbX and MePbX~; the l a t t e r decomposes immediately and i r r e v e r s i b l y t o PbX and MeX. B r i d g i n g i n organolead compounds i s not unusual; e.g., P h P b C l (5) or Ph PbX (Ph = C ^ ; X = CI, Br) (6) are h a l i d e bridged polymers i n the s o l i d s t a t e ; a l s o , emf measurements w i t h the system P h P b / i " i n d i c a t e d the formation of b i n u c l e a r complexes, e.g. P h P b I , P l ^ P b ^ , o r P h P b I i n a d d i t i o n t o the u s u a l mononuclear complexes ( 7 ) . 2

2

2

3

2 +

2

2 +

4

MeJPbXto [2]

2

2

4

2

4

Me^PbX r e d i s t r i b u t e s i n aqueous s o l u t i o n according

J

3

2Me.PbX

a t b

Me,Pb + Me PbX 0

2

0

[2]

2

Me PbX i s an educt of [ 1 ] , but s i n c e [2] i s r e v e r s i b l e , [2b] competes w i t h [ 1 ] . The i r r e v e r s i b i l i t y of [ 1 ] , however, f i n a l l y causes the decomposition of Me^PbX according t o [3] (=[2]+[l]) 2

2

3Me PbX + 2Me,Pb + PbX + MeX 3 4 2 0

0

[3]

The r e a c t i o n r a t e s o f [2a] and of [3] a r e a p p r e c i a b l y s m a l l e r than t h a t of [1] so the c o n c e n t r a t i o n of Me PbX« i s always s m a l l i n such s o l u t i o n s . [2b] i s much f a s t e r tnan f l ] . The r a t e law i s r a t h e r complicated, as d i s s o c i a t i o n and complex e q u i l i b r i a p l a y an important r o l e . The r a t e o f [3] i s increased i n the same way as mentioned f o r [ 1 ] , the dependency on the type of anion, however, being s m a l l e r . This can be explained by the f a c t t h a t the comproportionation [2b] i s i n f l u e n c e d by the same a c c e l e r a t i n g f a c t o r s . R e s u l t s of experiments on r e d i s t r i b u t i o n r e a c t i o n s of m e t h y l t h a l l i u m compounds s h a l l be discussed i n a subsequent chapter.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5. HUBER E T AL.

Organolead and Organothallium

67

T o x i c i t y of Organolead and Organothallium Compounds During our r e d i s t r i b u t i o n experiments, we became i n t e r e s t e d i n the t o x i c i t y o f organolead and o r g a n o t h a l l i u m compounds toward b a c t e r i a . The two t o p i c s , apparently having nothing t o do w i t h each o t h e r , f i n a l l y brought us t o study b i o m e t h y l a t i o n . Organolead Compounds. Organolead compounds act as b i o c i d e s (8, 9 ) ; i n the main, i n t e r e s t i n i n v e s t i g a t i o n o f t h i s property had been d i r e c t e d towards determining minimum concentrations necessary t o prevent m i c r o b i a l o r f u n g a l growth, and very few data are a v a i l a b l e on e f f e c t s o f s u b l e t h a l doses and on the chemical f a t e o f the organolead s p e c i e s . Even l e s s was known regarding the t o x i c i t y o f o r g a n o t h a l l i u m compounds. For our measurement C u l t u r e media were prepared i n BOD b o t t l e s . Lead compounds and n u t r i e n t s (peptone, yeast e x t r a c t ) d i s s o l v e d i n d i l u t i o n water (10, 11) were p i p e t t e d i n t o the f l a s k s , simultaneously i n o c u l a t e d w i t h 10 m l o f aquarium water ( c e l l d e n s i t y 10^ - 10-* c e l l s / m L ; from an aerated aquarium, which was repeatedly i n o c u l a t e d w i t h s u r f a c e water from a freshwater l a k e ) , f i l l e d w i t h d i l u t i o n water to the top, and s e a l e d . The b o t t l e s stood i n the dark a t 20 C. R e s u l t s o f the BOD- and BOD measurements are l i s t e d i n t a b l e I . I n other experiments, d i s s o l v e d 0 was analyzed c o n t i n u o u s l y w i t h an oxygen e l e c t r o d e . As growth parameters we determined the

Table I . Dependency o f I n h i b i t i o n o f B a c t e r i a l Growth a f t e r 5 Days (or 24 h*) on Type o f Lead Compound Added t o C u l t u r e ( N u t r i e n t : peptone, 5 mg/L; i n 24 h experiments 15 mg/L) Compound

N.I. T.I. [mg Pb/L]

Compound

Me^PbCl Me PbCl Et^PbOAc

1 0.5 % 1 0.05

Et PbCl Et PbCl

°· * 0.01

Bu Pb0Ac J Bu Pb(0Ac) PluPbCl PtuPbCl, Pb6l

3

2

2

(a)

o

1

?

0 1

2

10

2

Me - CH , E t = C H , Bu = n - C ^ , 3

2

2

5

N.I. [mg * 0.05 0.1 0.01 0.01 0.1 1

T.I. Pb/L] * 5 10 5-8 10 (a) 50

Ph = C ^ , OAc = CH C00 3

N.I. = no i n h i b i t i o n , T.I. = t o t a l i n h i b i t i o n (a) No t o t a l i n h i b i t i o n i n s a t u r a t e d s o l u t i o n o f organolead s a l t ( S o l u b i l i t i e s a t 20°C: Me PbCl ça. 130 g Pb/L, Ph PbCl ça. 0.5 g Pb/L) 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

68

ORGANOMETALS AND

ORGANOMETALLOIDS

d u r a t i o n of the i n i t i a l l a g phase and the slope of the 0 consumption r a t e during the beginning of the l o g phase, l i n e a r l y approximated. A t y p i c a l set of growth curves i s shown i n F i g . 1; data of growth parameters at v a r i o u s l e a d and n u t r i e n t concentrations are given i n t a b l e I I . 9

At comparatively low l e a d concentrations the l a g phase i s prolonged, w h i l e the l o g phase seems to be u n a f f e c t e d ; the c e l l count of 10 - l C r cells/mL a f t e r 24 h i s equal t o Pb-free samples. At medium l e a d c o n c e n t r a t i o n s , the l a g phase i s more prolonged; the l o g phase slope decreases and up t o 20% n e c r o t i c c e l l s are observed a f t e r 24 h. I t i s important t o note t h a t the l a g phase sometimes i s so prolonged, t h a t short term BOD values would I n d i c a t e t o t a l i n h i b i t i o n exponential acceleratio to about 10"* cells/mL (ca. 50% n e c r o t i c ) and decreases a f t e r about 2 days. 2+ The measurements show t h a t Pb i s l e s s t o x i c than organol e a d compounds and t h a t , i n g e n e r a l , R^PbX^ compounds are more t o x i c than R^PbX compounds, though there are e x c e p t i o n s . The e f f e c t of Me PbCl i s a s t o n i s h i n g l y s m a l l , compared w i t h t h a t of other compounds. Tetraorganoleads are more t o x i c than R-PbX or R^PbX^; the corresponding e f f e c t s on b a c t e r i a l growth were observed at concentrations one or two orders of magnitude lower ( i n the case of P b , at concentrations one order of magnitude h i g h e r ) . The r u l e that the t o x i c i t y of organolead compounds i n c r e a s e s w i t h i n c r e a s i n g c h a i n lengths of R (8) proved not to be t r u e under a l l c o n d i t i o n s ; apparently n u t r i e n t and a l s o organol e a d concentrations are of a p p r e c i a b l e i n f l u e n c e (see t a b l e I I ) . 2 +

Organothallium Compounds. The r e s u l t s of the measurements of the t o x i c i t y of T l compounds showed a s t o n i s h i n g d i f f e r e n c e s compared to the r e s u l t s w i t h Pb compounds. T l i s more t o x i c than the R^TIX compounds i n v e s t i g a t e d ; the s m a l l e s t c o n c e n t r a t i o n at which i n h i b i t i o n was observed i s 0.01 mg T l /L, t o t a l i n h i b i t i o n was found at 1000 mg T l /L. As F i g . 2 shows, the i n h i b i t i o n of b a c t e r i a l growth i n v a r i o u s cases was greater at lower R T1X c o n c e n t r a t i o n s , and there a l s o i s no s t r a i g h t f o r w a r d r e l a t i o n s h i p of c h a i n length of R and t o x i c i t y . 2

2+ Biomethylation of Pb

and Organolead Compounds.

Considering the f a c t s t h a t organolead compounds r e d i s t r i b u t e i n s o l u t i o n and t h a t d i f f e r e n t species show d i f f e r e n t t o x i c i t i e s , i t was convient to study the i n f l u e n c e of r e d i s t r i b u t i o n on the t o x i c i t y and v i c e v e r s a t o c o n t r o l the s t o i c h i o m e t r y of the r e d i s t r i b u t i o n reactions i n a nonsterile solution.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

HUBER E T AL.

Organolead and Organothallium

mg CWt 1 g peptone/l

Figure 1, Typical growth curves at various Et PbCl concentra tions showing Ο consumption as a function of time a

g

lagphase [h] 20

(Nutrient

cone

: 1g/l

)

/ /

15 /

/

I 10 n-Prop

/

Me/ i-Prop

/ /

01

1

10

100

C o n c e n t r a t i o n of R T l 2

Figure 2.

+

1000

Img/l]

Inhibition of bacterial growth by diorganothallium compounds

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

70

ORGANOMETALS AND ORGANOMETALLOIDS

TABLE I I . I n h i b i t i o n of B a c t e r i a l Growth by Organolead Compounds at Various Lead and N u t r i e n t Concentrations Concentr. a

3 PbCl lag log M e

b

Pb >

Nu >

0 0 0.1 0.1 1 1 10 10 100 100

0.2 1 0.2 1 0.2 1 0.2 1 0.2 1

7 5 7

2.9 3.7 3.4

12

2.9

80 30

0. 0.8

Me PbCl 2

lag

Et PbCl

2

log

7 5 20 10 45 23

2.9 3.7 2.4 2.2 2.7 2.6

95

0.4

Et : P b C l

3

lag 6 6.5 10 6.5 13 12 25

2

log 1.3 2.4 0.5 2.4 0.36 1.1 0.25

2

lag

log

6 6.5 18 8 30 15 50

1.3 2.4 1.4 0.84 0.23 0.64 0.14

0.06

0.05

l a g = p e r i o d of l a g phase ( h ) ; l o g = slope of l o g phase (mg 0 /L-h) 9

a) b)

Concentration of l e a d compound (mg Pb/L) Concentration o f n u t r i e n t (g/L)

In no case was there a n o t i c e a b l e e f f e c t o f r e d i s t r i b u t i o n on the growth curves, and w i t h r a t h e r low c e l l d e n s i t i e s no remark a b l e i n f l u e n c e on r e d i s t r i b u t i o n was observed. But i n c o n t i n u a l l y aerated c u l t u r e s w i t h h i g h e r c e l l d e n s i t i e s , e.g., correspond ing t o those i n the a c t i v a t e d sludge o f a sewage p l a n t , a very a p p r e c i a b l e i n c r e a s e i n the r e d i s t r i b u t i o n r a t e was observed. T h i s was accompanied by o x i d a t i v e degradation o f 50 - 60% o f the added methyllead s p e c i e s t o Pb . T h i s could be i n t e r p r e t e d as a detox i f i c a t i o n by the b a c t e r i a , as Pb i s l e s s t o x i c than the added Me^PbX o r Me PbX . Under discontinuous c o n d i t i o n s ( i n BOD f l a s k s ) the o x i d a t i v e degradation amounted t o about 15 - 20%. 2

2

2+ B i o m e t h y l a t i o n of Pb . When we f o l l o w e d t h e r e d i s t r i b u t i o n of Me^PbX i n anaerobic c u l t u r e s ( b a c t e r i a from the s u r f a c e of a n a t u r a l l a k e , grown under N2, o r from the anaerobic sedimen^ of a s m a l l pond), we a l s o observed a r a t e i n c r e a s e , but l e s s Pb and more Me,Pb than were expected from the s t o i c h i o m e t r y of equation [31.

2

+

I n f e r r i n e from the d e f i c i t of Pb and the e x t r a amount o f Me^b t h a t Pb might have been methylated by b a c t e r i a , we added Pb [as P b ( 0 A c ) J t o anaerobic c u l t u r e s i n gas wash b o t t l e s and c u l t i v a t e d these c u l t u r e s under N i n t h e dark a t 30 C. A f t e r 7 to 14 days v o l a t i l e products were f l u s h e d w i t h N i n t o a 0.2 Ν methanolic I scrubber s o l u t i o n . Ten mL ΚΙ·Ι s o l u t i o n were added t o ensure q u a n t i t a t i v e t r a n s f o r m a t i o n o f organolead species 2 +

2

2

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5.

HUBER E T A L .

Organolead and Organothallium

71

toPb .The l a t t e r was determined p h o t o m e t r i c a l l y a f t e r r e d u c t i o n of I w i t h Na«SO« i n ammoniacal b u f f e r s o l u t i o n and a f t e r complexa t i o n w i t h PAR [ 4 - ( 2 - p y r i d y l a z o ) - r e s o r c i n o l ] (12, 13). A blank and a l s o a s t e r i l e s o l u t i o n c o n t a i n i n g Pb o r methyllead compounds showed no Pb content i n the methanolic s o l u t i o n a f t e r the same treatment. We t h e r e f o r e concluded t h a t Me/Pb was the v o l a t i l e species produced i n the b i o m e t h y l a t i o n of P b by b a c t e r i a (14). We could f u r t h e r prove the i d e n t i t y of Me^Pb i n the head-space gas above the c u l t u r e s by GC a n a l y s i s . The production r a t e of Me^Pb was about 2.5 yg Pb/d. 2

9 + -

2 +

2+ The b i o m e t h y l a t i o n of Pb proceeded r e p r o d u c i b l y , provided a) the P b c o n c e n t r a t i o n was c o n t r o l l e d ( t a k i n g i n t o c o n s i d e r a t i o n the r e s u l t s of the t o x i c i t y measurements) b) the concentrat i o n of s u l f u r compound wise ELjS produced by th a c o n c e n t r a t i o n o f P b which i s too s m a l l f o r the generation of d e t e c t a b l e amounts of Me^Pb), c ) the inoculum was not more than 6 - 7 weeks o l d . Optimum r e s u l t s were obtained w i t h glucose and urea o r amino a c i d s as n u t r i e n t s (supply of s u l f u r i s maintained by SO," i n the d i l u t i o n water) and a t concentrations of 1 - 10 yg Pb2+ 7mL. Only s l i g h t l y s m a l l e r production r a t e s were u s u a l l y observed u s i n g concentrations o f ca. 100 yg P b /mL [ca. 15 mg Pb(OAc) /100 mL]. I t was f a v o r a b l e t o add CaCO^ t o avoid greater decrease of pH. 2 +

2 +

2 +

2

Biomethylation o f Me PbX. On a d d i t i o n of Me PbX t o the ana e r o b i c c u l t u r e s , the Me.Pb p r o d u c t i o n was much higher than from c u l t u r e s c o n t a i n i n g P b , and a l s o higher than from the r e d i s t r i b u t i o n of Me^PbX i n s t e r i l e s o l u t i o n s . T h i s i n d i c a t e d a h i g h prop o r t i o n o f Me^Pb production by chemical r e d i s t r i b u t i o n . A f t e r we had obtained these r e s u l t s , Wong, Chau and Luxon reported (15) that they had detected Me.Pb above the sediment o f a l a k e , and that a d d i t i o n o f MeaPbOAc and, i n some cases, of P b ( N 0 ) o r PbC^, increased Me^Pb p r o d u c t i o n ; pure species of b a c t e r i a l i s o l a t e s , however, were not able t o produce Me.Pb from PbX«. Another paper presented a c o n t r o v e r s i a l e x p l a n a t i o n denying a l k y l a t i o n o f P b by microorganisms (16): Me.Pb and Et.Pb (Et = CJH^) should be products of chemical a l k y l a t i o n of Me PbOAc and Et PbOAc, r e s p e c t i v e l y , i n an anaerobic sediment system. As a p o s s i b l e mechanism, i n i t i a l formation of ( R P b ) S f o l l o w e d by decomposition t o g i v e R^Pb as one product was proposed. 3

3

2 +

3

9

2

3

3

2

Our r e s u l t s e x p l a i n the observations u n e q u i v o c a l l y (see f i g u r e 3); i n an anaerobic b a c t e r i a l c u l t u r e , P b i s methylated t o g i v e Me.Pb ( r e a c t i o n [4] i n F i g . 3 ) . Since a l k y H e a d compounds r e d i s t r i b u t e i n aqueous s o l u t i o n according t o [1] and [2] t o g i v e Me^Pb and P b , i n a b a c t e r i a l c u l t u r e both chemical and b i o l o g i c a l production o f Me,Pb occurs. I n media c o n t a i n i n g h i g h concen2 +

2 +

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

72

ORGANOMETALS AND ORGANOMETALLOIDS

t r a t i o n s o f s u l f u r compounds (which was the case i n the work of r e f . [16]), r e d i s t r i b u t i o n o f ILPbX proceeds r a t h e r f a s t , as s u l f i d e present has a h i g h p o l a r i z a b i l i t y ; P b , though produced s i multaneously i n a p p r e c i a b l e amounts, i s p r e c i p i t a t e d as PbS. Therefore, t h e amount o f Me^Pb produced by b i o m e t h y l a t i o n o n l y can be r a t h e r low i n such systems, and the Me^Pb p r o d u c t i o n e s s e n t i a l l y i s caused by chemical r e d i s t r i b u t i o n . 2 +

A rough estimate o f the r a t i o o f c h e m i c a l l y and b i o l o g i c a l l y produced Me^Pb from our c u l t u r e s (100 mL s o l u t i o n , c o n t a i n i n g 200 mg g l u c o s e , 10 mg urea; 56 mg Me^PbCl were added a f t e r 1 week o f i n c u b a t i o n ) i s p o s s i b l e by comparing concentrations o f Me^Pb, Me^PbX and PbX^, which were a) analyzed and b) c a l c u l a t e d from equations [2] and [ 3 ] : a f t e r 7 days we found 5.3 ymol Me^Pb; i n the s o l u t i o n 0.3 ymol Me Pb * analyzed (13) which a c c o r d i n t o [2] correspond t o 0. 2.1 ymol P b , which a c c o r d i n g [3] correspon amount o f 4.2 ymol Me^Pb produced c h e m i c a l l y . (The sediment cont a i n e d no d e t e c t a b l e amount of Pb.) The d i f f e r e n c e between the analyzed and the c a l c u l a t e d amount of Me^Pb i s 0.8 ymol. T h i s amount, however, must s t i l l be c o r r e c t e d i n two r e s p e c t s . Any Pb transformed b i o l o g i c a l l y t o Me,Pb was produced c h e m i c a l l y t o gether w i t h Me^Pb; on the other hand, one has t o make allowance f o r a c e r t a i n amount of Me^Pb produced by immediate b i o m e t h y l a t i o n of Me^PbX (see below). We assume that these two q u a n t i t i e s a r e about s i m i l a r . One t h e r e f o r e can estimate that not more than 0.8 ymol Me^Pb have been produced b i o l o g i c a l l y a f t e r 7 days, i . e . , not more than about 16% of the t o t a l amount of Me^Pb found. From f o u r a d d i t i o n a l experiments we obtained s i m i l a r estimates of 15, 16, 17, and 19% f o r the p o r t i o n of Me,Pb which was produced b i o l o g i c a l l y . The p r o d u c t i o n r a t e o f Me,Pb from s t e r i l e n u t r i e n t s o l u t i o n s (100 mL s o l u t i o n , c o n t a i n i n g 200 mg g l u c o s e , 10 mg u r e a , amino a c i d s ; 0.1 and 10 mg Pb r e s p e c t i v e l y , added as MeJPbCl o r MeJPbCl ) a f t e r 7 days was 2.9 and 3.4 yg Pb/d (Me PbCl) and 3.1 and 3.3 Ug Pb/d ( M e P b C l ) . I n analogous experiments s i m i l a r r a t e s were observed; i n autoclaved c u l t u r e s maximum r a t e s o f 6 - 8 yg Pb/d have been measured. The p r o d u c t i o n of MeJPb from c u l t u r e s c o n t a i n i n g MeJPbCl (56 mg Me PbCl/100 mL = 40 mg Pb/100 mL) and MeJPbCl (60 mg Me PbCl /100 m l ) , r e s p e c t i v e l y , v a r i e d between 85 and 157 yg/d and between 45 and 124 yg/d. 24

2 +

2

3

2

2

3

2

2

2

Biomethylation of Et^PbX. To check whether R~PbX i s a l s o b i o methylated by anaerobes, we added E t ^ P b C l (up t o 100 mg Pb/L) t o a 4 L c u l t u r e and observed a maxmium p r o d u c t i o n r a t e of 500 yg Pb/d. As n u t r i e n t , a s o l u t i o n of 0.1 g NH,C1, 0.052 g K HP0,'3H 0, 0.1 g MgCl '6H 0, 1 g EtOH i n d i l u t i o n water (10, 11) w i t h added amino a c i d s was used. The gas above the c u l t u r e s o l u t i o n was s l o w l y passed (using a slow N stream) through petroleum e t h e r t o absorb the t e t r a a l k y l l e a d compounds. The s o l u t i o n , which was separated by GC on a Chromosorb column w i t h Apiezon (15%), contained b e s i d e s 2

2

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2

73

Organolead and Organothallium

HUBER E T A L .

5.

s o l v e n t Et^Pb (83%), Et MePb (13%) and Me,Pb ( 3 - 4 % ; t o t a l amount of R _ R P b « 100%). P r a c t i c a l l y , n e i t h e r Et Me Pb nor EtMe Pb were found. (The composition o f the products from other e x p e r i ments was d i f f e r e n t . ) To exclude the p o s s i b i l i t y t h a t any com pounds i n the c u l t u r e s c a t a l y z e the r e d i s t r i b u t i o n of mixtures of Et^Pb and Me^Pb, 0 5 ml o f these compounds were placed i n s t e r i l e n u t r i e n t s o l u t i o n s and autoclaved c u l t u r e s ; a f t e r 2 weeks no change i n the composition o f the R^Pb mixture had occurred. Ac c o r d i n g t o these r e s u l t s which are summarized i n f i g u r e 4, Et^PbX i s biomethylated d i r e c t l y t o Et^MePb. Et,Pb i s produced chemical l y by r e d i s t r i b u t i o n of Et^PbX; E t P b X , the other r e d i s t r i b u t i o n product which could not be detected (13) i n the f i l t e r e d s o l u t i o n , apparently r e d i s t r i b u t e s (according t o [1])so f a s t , that no appre c i a b l e amount i s a v a i l a b l e f o r b i o m e t h y l a t i o n . P b , one of the f i n a l products of r e d i s t r i b u t i o n Considering the d i f f e r e n Et^MePb and Me^Pb b i o l o g i c a l l y ) the percentage of the d i f f e r e n t t e t r a a l k y l l e a d species i n the mixture roughly corresponds t o the estimate of c h e m i c a l l y and b i o l o g i c a l l y produced Me^Pb from c u l t u r e s c o n t a i n i n g Me^PbX. 3

4

n

n

2

2

3

?

2

2

2 +

Biomethylation o f T l * . An i n t r i g u i n g problem r a i s e d by the d i s c o v e r y of b i o m e t h y l a t i o n of P b i s the i n c r e a s e of the formal o x i d a t i o n number of Pb during i t s b i o l o g i c a l t r a n s f o r m a t i o n t o Me^Pb. For t h i s and other obvious reasons we sought t o f i n d out whether T l , i s o e l e c t r o n i c w i t h P b , i s a l s o subject t o biomethyl a t i o n i n anaerobic mixed b a c t e r i a l c u l t u r e s , during which process i t too increases i t s formal o x i d a t i o n number. I n the l i t e r a t u r e there were no r e p o r t s on b i o m e t h y l a t i o n o f T l . Model experiments showed that methylcobalamin i s not demethylated by T1(I) (17), y e t i s demethylated by T l ( I I I ) (17, 18); from s p e c t r a l t i t r a t i o n s i t was concluded t h a t M e T l i s produced (19). 2 +

+

2 +

2 +

+

The experimental c o n d i t i o n s we used t o biomethylate T l essen t i a l l y corresponded t o those we had a p p l i e d d u r i n g b i o m e t h y l a t i o n of P b . I n 250 mL gas wash b o t t l e s we incubated three types of s o l u t i o n s which had been i n o c u l a t e d w i t h 5 g anaerobic sediment. The s o l u t i o n s were prepared from 100 ml d i l u t i o n water (10, 11) and contained 1 g peptone ( s o l u t i o n A) o r 0.1 g NH.Cl, 0.052 g Κ ΗΡ0 ·3Η 0, 0.01 g MgCl -6H 0 and e i t h e r 1.0 g C a ( 0 A c ) ( s o l u t i o n B) o r 1.0 g C j OH ( s o l u t i o n C). 1.9 g s o l i d CaC0 were added t o n e u t r a l i z e a c i d from metabolic processes. Starting at the t h i r d day of i n c u b a t i o n , 100 mg TlOAc were added during 7 days. A f t e r 2-3 weeks, M e 2 T l could be detected i n samples as w e l l as T l ; that M e 2 T l was the only methylated t h a l l i u m species found i s understandable i n view o f the normal behavior of a l k y l t h a l l i u m compounds: MeTlX compounds i n general are unstable or tend t o decompose i n aqueous s o l u t i o n (20, 21): ΜββΤΙ decomposes i n s t a n t a neously i n water t o form s t a b l e M e T l and methane ( 3 ) . To determine the amount of M e 2 T l produced by b i o m e t h y l a t i o n 2 +

2

4

2

2

2

2

3

+

+

+

2

+

2

+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

j 4 Me PbX 3

JiL

2 Me2PbX

+

2

2 Me^Pb

!

Bacteria alkylate η 3 M^PbX

Figure S.

Et PbCl

*

(2*n) Me^Pb • (1-n)PbX + MeX 2

Sources of Me Fb in an anaerobic bacterial culture k

R E D I S T R I B U T I 0 N

3

•

PbCl

BIOMETHYLATION

Figure 4.

2

•

EtCl

Et^Pb

•

ELMePb

Biomethylation of Et PbCl 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5.

Organolead and Organothallium

HUBER E T A L .

75

+

of T l , 10 mL samples a f t e r f i l t e r i n g through a diaphragm were mixed w i t h EDTA t o mask T l . Then l - ( 2 - p y r i d y l a z o ) - 2 - n a p h t h o l (PAN) was added a t pH 10-12 t o complex M e T l , and a f t e r e x t r a c t i o n w i t h CHClg the Me Tl-PAN c o n c e n t r a t i o n was measured photomet r i c a l l y a t 570 nm. [Masking of T l i s necessary as T l forms a complex w i t h PAN (22) which a l s o absorbs a t 570 nm.] +

+

2

2

+

+

The r e s u l t s showed t h a t i n the c u l t u r e s o f s o l u t i o n s Β and C a f t e r 21 days, 10 yg and 36 yg Me Tl /mL, r e s p e c t i v e l y , had been formed. I n s o l u t i o n A only about 1 - 2 yg Me Tl /mL were detected a f t e r 21 days; a low y i e l d of methylated species from c u l t u r e s c o n t a i n i n g peptone as n u t r i e n t was a l s o observed i n b i o m e t h y l a t i o n experiments w i t h Pb^+. +

2

+

2

+

+

The observation tha T l i biomethylated T l unde i n crease of the o x i d a t i o i s not unique w i t h P b an i n c r e a s e i n o x i d a t i o n number occurs a l s o during b i o m e t h y l a t i o n of As compounds (23). 2 +

Mechanistic

Considerations

The o v e r a l l process of the i n v i v o methylation of metal ions i s c e r t a i n l y complex. Hence, use o f r e s u l t s of mechanistic i n v i t r o experiments t o p o s t u l a t e general i n v i v o mechanisms should be done only w i t h great care. Moreover, well-founded knowledge i s s t i l l too scarce t o a l l o w one of the v a r i o u s pathways which a r e conceivable f o r " o x i d a t i v e m e t h y l a t i o n " t o be favored. One might assume t h a t m e t h y l a t i o n i n v o l v e s methylcobalamin which conveys Me" t o an e l e c t r o p h i l i c t h a l l i u m o r l e a d s p e c i e s ; a p r i n c i p a l question i s then whether o x i d a t i o n occurs f i r s t f o l l o w e d by m e t h y l a t i o n , o r v i c e v e r s a ; the two steps could a l s o be s i m u l taneous. I t i s hard t o see which o x i d i z i n g agent could overcome the h i g h o x i d a t i o n p o t e n t i a l of T l and P b (24), and t h e r e f o r e i t seems reasonable t o t h i n k o f m e t h y l a t i o n as the f i r s t s t e p , p a r t i c u l a r l y s i n c e MePb was r e c e n t l y reported as a product of the r e a c t i o n of a dimethylcobalt complex and Pb (25). I n t h i s case the primary methylation product of P b and T l could d i s p r o p o r t i o n a t e t o g i v e M e P b o r M e T l and the element. Since we could not detect elementary Pb o r T l i n the samples, we conclude t h a t dimethyl species are not formed by d i s p r o p o r t i o n a t i o n of interme d i a t e MePb* o r MeTl. We t h e r e f o r e would p r e f e r t o assume that T l and P b , present i n a p p r o p r i a t e complexed form a t s p e c i f i c s i t e s of the c e l l , are simultaneously o x i d i z e d and methylated t o M e T l ( I I I ) and MePb(IV) m o i e t i e s which are s t a b i l i z e d by complexa t i o n . The importance and e f f e c t i v e n e s s of complexation f o r s t a b i l i z i n g unstable monoorganolead compounds i s known: Organolead t r i h a l i d e s , RPbX (Χ φ F ) , are unknown; however, i t i s p o s s i b l e t o prepare r a t h e r s t a b l e complex d e r i v a t i v e s M [PhPbX4] and +

2 +

+

+

2 +

2 +

2

+

+

2

+

2 +

3

f

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

76

ORGANOMETALS AND ORGANOMETALLOIDS

M^[PhPbX ] (Μ' « P h P , Ph As; M" = Me^N; X = CI, Br) (26). 5

4

4

Another pathway might s t a r t w i t h an e l e c t r o p h i l i c a t t a c k by CK^ , which c o u l d e a s i l y s o l v e the problem of o x i d a t i o n . I n t h i s case the r e a c t i o n of the " o x i d i z i n g agent" CHL w i t h the metal i o n ( i n a s p e c i f i c a l l y complexed form, mainly w i t h negative l i g a n d s ) would l e a d f o r m a l l y t o M e T l o r MePb . These could d i s p r o p o r t i o n a t e , o r , being s t r o n g electrophilés, could be f u r t h e r methylated a t a s p e c i f i c CH "-conveying methylating s i t e of the c e l l system. +

2 +

Behavior o f MeTlX^ i n S o l u t i o n . I n order not t o end t h i s paper w i t h s p e c u l a t i o n , some r e a c t i o n s i n aqueous s o l u t i o n r e l e vant t o c o n s i d e r a t i o n s on methyl t r a n s f e r i n b i o l o g i c a l systems by r e d i s t r i b u t i o n w i l l be described Decomposition of MeTlXp Monomethylthalliu compound unstable i n aqueous s o l u t i o n . The decomposition of MeTl(OAc) f o l l o w s a f i r s t order r a t e law (X = OAc) (21) and produces, accordi n g t o the r e a c t i o n sequence [ 5 ] , 2

MeTl(OAc) + TlOAc + CH.COOCH. 9

1

CH COOCH + H 0 t CH COOH + GT^OH 3

3

2

J

3

TlOAc, CH COOCH , and, as products of h y d r o l y s i s of the l a t t e r , CH COOH and CH OH (21, 27). Based on k i n e t i c and conductometric data and by comparison w i t h data c a l c u l a t e d from d e r i v e d r a t e equ a t i o n s , a b i m o l e c u l a r S 2 mechanism w i t h a r a t e determining step of the a t t a c k o f OAc" a t the Tl-bonded Me-group of the very e l e c t r o p h i l i c MeTlOAc*" could be e s t a b l i s h e d (21). Other n u c l e o p h i l i c agents a l s o a t t a c k MeTl (OAc) and can thereby be methylated: pyri d i n e and other N-bases r e a c t w i t h MeTl (OAc) t o N-methylated compounds a c c o r d i n g t o [ 6 ] : 3

3

3

3

N

2

2

MeTl (OAc )

0 2

+ N^ t \

Met"" + OAc" + TlOAc X

[6]

Since the n u c l e o p h i l i c c h a r a c t e r o f these N-bases i s higher than that o f OAc"", CH COOCH i s formed only i n minor amounts (28, 2 9 ) . 3

3

In methanolic s o l u t i o n MeTl (OAc) decomposes over a p e r i o d of s e v e r a l weeks t o TlOAc and CH COOCH (28). I f t h i o a n i s o l e i s added, the decomposition i s complete i n 2-3 days. This " c a t a l y t i c e f f e c t " i s caused by a two-step r e a c t i o n (29). A t f i r s t , MeTl (OAc) methylates t h i o a n i s o l e according t o [ 7 ] : 2

3

3

2

MeSPh + MeT10Ac

+

ί

+

[ M e S P h ] + TlOAc

and i n the second s t e p , OAc according t o [ 8 ] :

2

i s methylated

[7] by S-methy 1 t h i o a n i s o l e

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5.

HUBER E T AL.

Organolead and

+

[Me SPh] + OAc"

î

2

Organothallium

MeSPh + CH COOCH 3

77 [8]

3

T h i s behavior of MeTl(OAc) , which i s shown f o r o t h e r monomethylt h a l l i u m compounds (28, 30;, a l s o helps to e x p l a i n why experiments t o prepare MePbX were doomed t o f a i l u r e : MePb^ , being s t i l l more e l e c t r o p h i l i c than M e T l , methylates most e f f e c t i v e l y s o l vent molecules or/and anions and i s decomposed d u r i n g t h i s r e a c t i o n to P b ; t h i s r e a c t i v i t y i s h i g h l y promoted by the " i n e r t p a i r effect". 2

+

3

2 +

2 +

D i s p r o p o r t i o n a t i o n of MeTlX^. D i s p r o p o r t i o n a t i o n r e a c t i o n s of monoalkylthallium compounds have not yet been r e p o r t e d i n the l i t e r a t u r e . In s o l u t i o n s of MeTl (OAc) i n CD C0CD /CH 0H (5:1; composition chosen to optimize c o n d i t i o n s f o r NMR measurements), the e q u i l i b r i u m c o n c e n t r a t i o n disproportion a t i o n according to equatio 2

2 MeTl (OAc)

2

Ζ

3

Me Tl(0Ac) + T l ( 0 A c ) 2

3

3

[9]

3

are too s m a l l to be detected. However, i f one adds a reducing agent to remove Tl(0Ac)«, one gets q u a n t i t a t i v e t r a n s f o r m a t i o n of MeTl (OAc) to Me Tl(0AcJ (30) according t o [ 9 ] . The r e a c t i o n of T l ( 0 A c ) ~ and (Meu)^P proceeds according t o [10]: 2

2

T l ( 0 A c ) + (MeO) P + CH 0H 3

3

TlOAc + (Me0) P0 +

3

3

HOAc + CH COOCH 3

[10]

3

The r e a c t i o n products have been i d e n t i f i e d by NMR spectroscopy and by GC. Equations [9] and [10] add to g i v e the o v e r a l l r e a c t i o n [11]: 2 MeTl (OAc)

+ (Me0) P + CH 0H +

2

3

3

[ η ]

Me Tl(0Ac) + TlOAc + (MeO) PO + HOAc + CH C00CH 2

3

3

3

Reaction [10] i s instantaneous, w h i l e [11] i s complete o n l y a f t e r some minutes. We t h e r e f o r e conclude t h a t the exchange of the methyl groups i n the r e d i s t r i b u t i o n r e a c t i o n [9] i s r a t e determin ing. Regarding the behavior of MeTl (OAc ) i n s o l u t i o n s , and p r e supposing that M e T l i s an intermediate of b i o m e t h y l a t i o n of T l , one a r r i v e s a t an important c o n c l u s i o n concerning the open ques t i o n as t o which pathways might be of s i g n i f i c a n c e . There are i n p r i n c i p l e two p o s s i b i l i t i e s f o r the t r a n s f o r m a t i o n of M e T l to M e T l , one chemical and one b i o l o g i c a l (the v e r t i c a l and the h o r i zontal branch r e s p e c t i v e l y of the f o l l o w i n g scheme) i n which [12] and [13] f o r m a l l y symbolize the complexation of the monomethylt h a l l i u m species i n s o l u t i o n : 2

2 +

+

2 +

+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

>

78

+ +Me+

π

Tl

-2

e"

ORGANOMETALS A N D ORGANOMETALLOIDS

+ Me"

MeTl2* •X"

+>

Me2Tl+

[12]

MeTlX* MeTlX

^113]

[5]

MeX • T l X

2+ If one assumes t h a t methylations o f MeTl and o f the i s o electronic H g (31) proceed at. a s i m i l a r r a t e , the chemical path way f o r the formation of Me«Tl ( r e d i s t r i b u t i o n according t o [ 9 ] ) _ has no a p p r e c i a b l e chance o f competing w i t h the b i o t r a n s f e r of Me (via methylcobalamin), s i n c e the r a t e of [9] i s comparatively s m a l l , even i f T l X ^ i s removed extremely r a p i d l y from the e q u i l i b rium. An eventual c o m p e t i t i o n of the decomposition [5] (being f a s t e r than the non-catalyzed r e a c t i o n [9]) and b i o m e t h y l a t i o n (presumably much f a s t e r than [5]) can be neglected j u s t as w e l l . So, according t o these c o n s i d e r a t i o n s f o r the t r a n s f o r m a t i o n of M e T l t o M e T l i n b a c t e r i a l c u l t u r e s , b i o l o g i c a l pathways should be favored over chemical ones. 2 +

2 +

+

2

Analogous c o n s i d e r a t i o n s apply f o r the d i s c u s s i o n of d i f f e r ent pathways of the b i o m e t h y l a t i o n of P b . Since M e P b i s s t i l l more e l e c t r o p h i l i c than MeTl +, the r a t e of i t s m e t h y l a t i o n of Me might be s t i l l h i g h e r , as might the r a t e o f i t s decomposition. One can t h e r e f o r e expect that the b i o m e t h y l a t i o n of P b i s a l s o , on the whole, a stepwise b i o l o g i c a l m e t h y l a t i o n i n v o l v i n g no chemical steps v i a d i s p r o p o r t i o n a t i o n r e a c t i o n s . 2 +

3+

2

2 +

+ 2+ S i g n i f i c a n c e of B i o m e t h y l a t i o n o f T l and Pb +

+

Me«Tl compounds are l e s s t o x i c t o b a c t e r i a than T l , so b i o m e t h y l a t i o n of T l appears as a d e t o x i f i c a t i o n of the b a c t e r i a l environment (but only i n a r e l a t i v e sense, s i n c e T l remains i n the s o l u t i o n ) . This aspect, however, must not of n e c e s s i t y be the determining reason f o r the occurrence of m e t h y l a t i o n , as biometh y l a t i o n of P b leads t o Me^Pb, which i s much more t o x i c t o bac t e r i a l c u l t u r e s than P b . However, the s o l u b i l i t y o f Me^Pb i n water i s extremely low, and Pb i s t h e r e f o r e f i n a l l y removed from +

2 +

2 +

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5.

HUBER ET AL.

Organolead and Organothallium

79

the s o l u t i o n . Concerning c o n c l u s i o n s on the e c o l o g i c a l s i g n i f i c a n c e of the b i o m e t h y l a t i o n of T l and P b . one should remember that biomethy l a t i o n only has been observed i n an anaerobic medium, and that r e s u l t s on t h i s r e a c t i o n and those on t o x i c i t y of T l and Pb compounds were obtained from l a b o r a t o r y experiments and should be t r a n s f e r r e d to n a t u r a l c o n d i t i o n s o n l y w i t h great care and not without s p e c i f i c experimental examination. N e v e r t h e l e s s , one should be a l e r t t o (and i n v e s t i g a t e ) the p o s s i b i l i t y that P b ^ and T l , i n anaerobic regions of metal-contaminated n a t u r a l w a t e r s , are methylated and are t r a n s p o r t e d as o r g a n o m e t a l l i c compounds to other regions of the n a t u r a l system, there showing the d i f f e r e n t behavior of o r g a n o m e t a l l i c species or being reconverted t o P b ^ and Tl . +

2 +

+

+

+

+

Acknowledgement The support of t h i s work by Deutsche Forschungsgemeinschaft and Herbert-Quandt-Stiftung i s g r e a t f u l l y acknowledged. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

S h a p i r o , H., F r e y , F . W . , "The Organic Compounds of Lead", W i l e y - I n t e r s c i e n c e , New Y o r k , 1968. M ü l l e r , R . , R e i c h e l , S . , Dathe, C., I n o r g . N u c l . Chem. L e t t e r s (1967) 3, 125. H a r t , C . R . , I n g o l d , C.K., J. Chem. Soc. (1964) 4372 Haupt, H.-J., Huber, F., Gmehling, J., Z. anorg. allg. Chem. (1972) 390, 3 1 . Mammi, M., Busetti, V., D e l P r a , Α . , I n o r g . Chim. A c t a (1967) 1, 419. P r e u t , H., Huber, F., Z. anorg. allg. Chem. (1977) 435, 234. S t a f f o r d , S . , Haupt, H.-J., Huber, F., I n o r g . Chim. A c t a (1974) 1 1 , 207. Van der Kerk, G.J.M., B i o d e t e r i o r . M a t e r . , P r o c . I n t e r n a t . B i o d e t e r i o r . Symp. (1971, p u b l . 1972) 1. Lorenz, J., B i o d e t e r i o r . M a t e r . , P r o c . I n t e r n a t . B i o d e t e r i o r . Symp. (1971, p u b l . 1972) 443. Standard Methods f o r the Examination of Water and Wastewater, 13th ed., 489 ( e d i t , by APHA, AWWA, WPCF, Washington, 1971) Deutsche E i n h e i t s v e r f a h r e n zur Wasseruntersuchung, H 5, 6; L 12 ( e d i t , by GDCh, Fachgruppe Wasserchemie, V e r l a g Chemie, Weinheim, 1972) D a g n a l l , R . M . , West, T.S., Young, P., T a l a n t a (1965) 12, 583. Schmidt, U., Huber, F., A n a l . Chim. Acta (1978) 98, 147. Schmidt, U., Huber, F., Nature (1976) 259, 157. Wong, P.T.S., Chau, Y.K., Luxon, P.L., Nature (1975) 253, 263.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

80 16. 17. 18.

19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.

ORGANOMETALS AND ORGANOMETALLOIDS

J a r v i e , A.W.P., M a r k a l l , R.M., P o t t e r , H.R., Nature (1975) 255, 217. Agnes, G., Bendle, S., Hill, H.A.O., W i l l i a m s , F.R., W i l l i a m s , R.J.P., Chem. Comm. (1971) 850. Agnes, G., Hill, H.A.O., Pratt, J.M., R i d s d a l e , S.C., Kennedy, F.S., W i l l i a m s , R.J.P., Biochim. Biophys. A c t a (1971) 252, 207. Abley, P., Dockal, E.R., Halpern, J., J. Amer. Chem. Soc. (1973) 95, 3166. Lee, A.G. "The Chemistry o f T h a l l i u m " , Elsevier, Amsterdam, London, New York, 1971. P o h l , U., Huber, F., J. Organometal. Chem. (1976) 116, 141. Cheng, K.L., Bray, R.H., A n a l . Chem. (1955) 27, 782. C h a l l e n g e r , F., Chem. Rev. (1945) 36, 315. R i d l e y , W.P., D i z i k e s 197, 329. Witman, M.W., Weber, J.H., Inorg. Chem. (1976) 15, 2375. Lindemann, Η., Huber, F., Z. anorg. allg. Chem. (1972) 394, 101. Kurosawa, H., Okawara, R., J. Organometal. Chem. (1967) 10, 211. P o h l , U., Huber, F., J. Organometal. Chem. (1977) 135, 301. K n i p s , U., Huber, F., unpublished r e s u l t s . P o h l , U., Huber, F., unpublished r e s u l t s . DeSimone, R.E., Penley, M.W., Charbonneau, L., Smith, S.G., Wood, J.M., Hill, H.A.O., Pratt, J.M., R i d s d a l e , S., W i l l i a m s , R.J.P., Biochim. Biophys. A c t a (1973) 304, 851.

Discussion J . H. WEBER ( U n i v e r s i t y o f New Hampshire): Concerning some of t h e products you got i n your r e a c t i o n s , p a r t i c u l a r l y w i t h the m i c r o b i o l o g i c a l a l k y l a t i o n o f l e a d , i f you a l k y l a t e d l e a d ( I I ) you could have an u n s t a b l e species o f d i m e t h y l l e a d ( I I ) . This i s not a well-known species and i s considered a t r a n s i e n t s p e c i e s which de composes t o t e t r a m e t h y l l e a d and l e a d metal. Have you thought o f t h i s p o s s i b i l i t y and looked f o r l e a d metal i n your r e a c t i o n s ? HUBER: Yes, we d i d and we d i d not f i n d l e a d . d i d not f i n d m e t a l l i c t h a l l i u m .

S i m i l a r l y , we

J . M. WOOD ( U n i v e r s i t y o f Minnesota): Do you assume 10 days i s a good time f o r steady s t a t e when you determine how much i s b i o l o g i c a l and how much i s chemical d i s p r o p o r t i o n a t i o n ? HUBER: I t i s a time which g i v e s r e p r o d u c i b l e r e s u l t s . Ex periments over a longer p e r i o d were s i m i l a r , so we chose t h e s h o r t e r time.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5.

HUBER E T A L .

Organolead and Organothallium

81

WOOD: The microbes were i n the s t a t i o n a r y phase, and they were j u s t s i t t i n g there when you had these d i f f e r e n t chemical species i n s o l u t i o n a t the time you d i d the analyses? [HUBER: Y e s ] . Now, I t h i n k i t i s c r i t i c a l l y important t o s t a r t i s o t o p e experiments w i t h C-14 l a b e l s , probably C - 1 4 - l a b e l l e d methionine which should get i n t o the c e l l s . This w i l l e s t a b l i s h what s o r t o f methyl t r a n s f e r i s o c c u r r i n g i n these systems. I have a d i f f i c u l t y i n t r y i n g t o r a t i o n a l i z e a mechanism without knowing what the b i o l o g i c a l methyl donor i s i n the system. Do you p l a n t o do some i s o t o p e experiments and f i n d out? HUBER: Yes, we p l a n t o do so. We are s t u d y i n g the t h a l l i u m compound. C u r r e n t l y we are u s i n g methylcobaloxime and methylcobalamin t o see i f m e t h y l a t i o n occurs w i t h a d d i t i o n of an oxidant f o r the P b ^ and Sn^ . W negative r e s u l t s w i t h P +

+

WOOD: When you add t h a l l i u m ( I ) t o a complex system, have you any i d e a what the o x i d a t i o n s t a t e i s o f the a c t i v e t h a l l i u m species? We can r a t i o n a l i z e methyl t r a n s f e r of t h a l l i u m ( I I I ) . I n f a c t the r e a c t i o n goes q u i t e w e l l . T h a l l i u m ( I ) i s unusual; i f you look a t the standard r e d u c t i o n p o t e n t i a l idea f o r t h a l l i u m ( I I I ) t o t h a l l i u m ( 1 } , i t i s f a i r l y h i g h . I f , f o r example, methyl Β were i n v o l v e d i n your r e a c t i o n c o n d i t i o n s , I'm sure t h a t c o n d i t i o n s a r e so extreme t h a t the o x i d i z i n g agent would c e r t a i n l y break the cobalt-carbon bond anyway. Therefore, there i s a r e a l d i f f i c u l t y w i t h a CHg suggestion. 2

HUBER: I f we s t a r t w i t h t h a l l i u m ( I ) we cannot p o s t u l a t e t h a t we have an o x i d a t i o n i n the f i r s t p l a c e f o l l o w e d by m e t h y l a t i o n , because the o x i d a t i o n would g i v e T l ( I I I ) , and T l ( I I I ) would o x i d i z e the methylcobalt compound. Therefore, we have some k i n d o f simultaneous methylation and o x i d a t i o n , where two e l e c t r o n s a r e taken away and some k i n d of CH^~ r e s u l t s t o g i v e MeTl^"*". We have attempted t o r a t i o n a l i z e t h i s p o s s i b i l i t y i n a way which i s con s i s t e n t w i t h our experimental r e s u l t s , as shown i n the Scheme on page 12. RECEIVED

August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

6 Bioorganotin Chemistry: Stereo- and Situselectivity in the Monooxygenase Enzyme Reactions of Cyclohexyltin Compounds RICHARD H. FISH, JOHN E. CASIDA, and ELLA C. KIMMEL Pesticide Chemistry and Toxicology Laboratory, College of Natural Resources, Wellman Hall, University of California, Berkeley, CA 94720 The in vitro reaction oxygenase enzymes utilizin studied with tributyltin derivatives (1a,b). The results from that study confirmed carbon-hydroxylation as the primary bio chemical reaction occurring with these compounds. Furthermore, the tin-carbon sigma electrons were implicated in the possible stabilization of carbon free radicals generated on the α and β carbon atoms to the tin atom. Additionally, by using several criteria, we established that the metabolism of these tributyltin derivatives involved the interesting and biologically important cytochrome P-450 dependent monooxygenase enzyme system (1a). Recent studies on this system have concluded that a l l the available evidence points to a heme-iron-monooxygen complex which converts carbon-hydrogen bonds to carbon-hydroxyl bonds (2), Figure 1. The reaction has been shown to be highly stereospecific 3+ 3+ Fe

+

RH

- R H

>**' .RH

3+

2+ 2+

Fe " 1

[+o

- R O H

+ Fe:= Q 1 i

RH

2

2+ Fe0

+2H+ -H 0

_RH

2

2

RH

Figure 1. Mechanism of Cytochrome P-450 en zyme hydroxyhtion reaction

(3); however, surprisingly few investigations have been concerned with the cyclohexyl ring system (4). Our work i n this area was logically extended to cyclohexyltin compounds for several reasons. F i r s t l y , these compounds are used as agricultural miticides on 0-8412-0461-6/78/47-082-082$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

6.

FISH E T A L .

Bioorganotin Chemistry

83

food crops and a study o f t h e i r monooxygenase enzyme r e a c t i o n s would be important f o r b i o l o g i c a l and t o x i c o l o g i c a l reasons. Secondly, we wanted t o a s c e r t a i n the s t e r e o as w e l l as s i t u s e l e c t i v i t i e s o f these r e a c t i o n s w i t h a p p r o p r i a t e c y c l o h e x y l t i n model compounds, s i n c e t h i s aspect, as f a r as we c o u l d e s t a b l i s h w i t h t h e cytochrome P-U50 monooxygenase enzyme system, has n o t been e l u c i d a t e d i n a d e f i n i t i v e manner. We decided i n i t i a l l y (j?) t o study c y c l o h e x y l t r i p h e n y l t i n , ^ because we found i n an e a r l i e r i n v e s t i g a t i o n ( l b ) t h a t the t r i p h e n y l t i n d e r i v a t i v e s were not h y d r o x y l a t e d under i n v i t r o r e a c t i o n c o n d i t i o n s . More i m p o r t a n t l y , the s y n t h e s i s o f potent i a l m e t a b o l i t e s , which w i t h the c y c l o h e x y l system i n v o l v e s t h e c i s - and t r a n s - h y d r o x y c y c l o h e x y l t i n isomers i n the 2,3> and *Jp o s i t i o n s ( t r i p h e n y l t i n being p o s i t i o n l ) , would be more conveni e n t u s i n g the t r i p h e n y l t i A d d i t i o n a l l y , the e x t e n s i o J^, would o n l y i n v o l v e e l e c t r o p h i l i c cleavage o f a phenyl group i n order t o prepare p o t e n t i a l m e t a b o l i t e s f o r t h i s model substrate ( 7 ) . A d i s c u s s i o n o f the s t e r e o and s i t u s e l e c t i v i t y i n v o l v e d i n the P-lj-50 monooxygenase r e a c t i o n s o f 1 and and the consequence o f t h e i r conformation a t the a c t i v e sTte w i l l be presented. Results The p r e p a r a t i o n o f [ l - ^ C ] c y c l o h e x y l t r i p h e n y l t i n , j ^ , was r e a d i l y accomplished by the r e a c t i o n o f [ l - ^ l e y c l o h e x y l magnesium bromide w i t h t r i p h e n y l t i n c h l o r i d e i n 3 3 $ y i e l d w i t h a s p e c i f i c a c t i v i t y o f 1 . 2 6 mCi/mmole (Eq l ) . The use o f [ C ] 1 4

h /

-

=

y f ^ B r

h»

1) Mg/THF 2>(©)snCI

/

^

- ^ 7 ^ S n ( ^

(1) 1

l a b e l l e d o r g a n o t i n s u b s t r a t e s i s mandatory i n these metabolism s t u d i e s , s i n c e the amount of metabolism i s g e n e r a l l y t o t h e extent o f 10% o f t h e s t a r t i n g r a d i o l a b e l l e d s u b s t r a t e . Thus, compound 1 ( 0 . 0 5 pmole) was incubated w i t h our source o f c y t o chrome P - Ç 5 0 , r a t l i v e r microsomes ( l a ) ( 1 0 . 6 mg p r o t e i n ) , f o r 1 h r a t 3 7 ° i n 2 . 0 ml phosphate b u f f e r (pH 7·*0 c o n t a i n i n g ΝΑΌΡΗ (2 Mmole) the e s s e n t i a l c o f a c t o r . A f t e r chloroform e x t r a c t i o n , we u t i l i z e d t h i n l a y e r chromatography (TLC) t o separate the m e t a b o l i t e s and l i q u i d s c i n t i l l a t i o n counting t o q u a n t i f y them. They were i d e n t i f i e d by a combination o f TLC cochromatography, p r e p a r a t i v e TLC i n c o n j u n c t i o n w i t h 360 MHz % FT nmr s p e c t r o scopy and by s p e c i f i c degradation r e a c t i o n s (Eq 2 ) . The

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

84

ORGANOMETALS

•Sn(®)

pH 7.4,

Ih

A N D ORGANOMETALLOIDS

3

H

I

g (85.6%)

(2) 3 (6.5%)

4 (3.0%)

•Sn(®)

6 (1.9%)

3

+

5 (1.6%)

/ ^ ^ S n ( © )

3

7 (1.4%)

percentages i n Eq 2 represen m e t a b o l i t e s and account f o r 8 $ o f s t a r t i n g s u b s t r a t e , ^ The remainder was 1 ( 7 0 $ ) and u n i d e n t i f i e d m a t e r i a l s ( 2 2 $ ) . One important aspect of t h i s type o f work i s the a b i l i t y t o synthesize p o t e n t i a l m e t a b o l i t e s and t o understand t h e i r subsequent chemistry. This f a c i l i t a t e s t h e i r u l t i m a t e i d e n t i f i c a t i o n and allows t h e use o f cochromatography as one c r i t e r i o n f o r t h i s purpose. A l l the m e t a b o l i t e s , 2,-£, were separated from one another u s i n g n e u t r a l TLC s o l v e n t systems (5) and then cochromatographed w i t h s y n t h e t i c standards ( 6 j j ) . Furthermore, compound 2 was p u r i f i e d by p r e p a r a t i v e TLC and a 360 MHz % FT nmr spectrum was obtained ( 1 3 , 6 0 0 acquisitions,CDC1-> TMS) conf i r m i n g t h a t the major m e t a b o l i t e ( 8 5 . 6 $ ) was trans-4-hydroxyc y c l o h e x y l t r i p h e n y l t i n , 2 . The nmr spectrum showed t h e a x i a l methine proton on the carbon (ck) bearing the h y d r o x y l group as a 9 u n e m u l t i p l e t ( 3 . 5 8 ppm, J - J = 11.1 Hz; J - J = h.O Hz) c o n s i s t e n t w i t h a spectrum or the a u t h e n t i c compound 2 ( 6 , 7 ) · We were a b l e t o detect the corresponding c i s isomer o f ^15y t h i s nmr technique; however, none was observed i n the nmr spectrum of metabolite 2 . The c i l f - and trans-3-hydroxy m e t a b o l i t e s , ^ and j ^ , were i d e n t i f i e d o n l y by TLC cochromatography w i t h a u t h e n t i c compounds, because o f the low amounts produced i n the b i o l o g i c a l o x i d a t i o n r e a c t i o n . I n t h i s regard, we are c o n f i d e n t o f t h e i r assigned s t r u c t u r e s , s i n c e both isomers are r e a d i l y separable by t h i s technique. M e t a b o l i t e 5 was i d e n t i f i e d by TLC cochromatography and by a s p e c i f i c degradation r e a c t i o n . The m e t a b o l i t e mixture was a c i d i f i e d w i t h g l a c i a l a c e t i c a c i d and TLC a n a l y s i s showed the disappearance o f m e t a b o l i t e 5 . Experiments w i t h a u t h e n t i c ^ r e v e a l e d t h a t t h i s trans-2-Kydroxy compound undergoes a f a c i l e 1 , 2 - d e o x y s t a n n y l a t i o n r e a c t i o n g i v i n g cyclohexene, t r i p h e n y l t i n a c e t a t e and water. In agreement w i t h t h i s , we assume t h a t m e t a b o l i t e 5 r e a c t e d s i m i l a r l y under a c i d i c c o n d i t i o n s (Eq 3 ) · a

x

a x

e q

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

6.

FISH E T A L .

Bioorganotin Chemistry

85

The t r a n s m e t a b o l i t e , but not t h e corresponding c i s isomer o f 5, can form eycloiiexene, s i n c e a t r a n s d i a x i a l con formation ( I ) i s needed f o r r e a c t i o n t o take p l a c e . The

corresponding c i s-methyl e t h e r , a model f o r t h e c i s - a l c o h o l we were not able t o s y n t h e s i z e , d i d not r e a c t even a f t e r t h r e e days w i t h g l a c i a l a c e t i c a c i d (Eq k).

^ H

CH

3

S n

(@),

HOAc Ίί^

hs.

3days

Η

_ ( @ ) SnOAc + CH OH /

+

Λ

3

(4)

Η

These r e s u l t s a r e a l s o c o n s i s t e n t w i t h those found w i t h t h e corresponding c i s - and t r a i i s - 2 - h y d r o x y c y c l o h e x y l t r i m e t h y l s i l i c o n d e r i v a t i v e s under weakly a c i d c o n d i t i o n s ( 8 ) . A c c o r d i n g l y , any cis-2-hydroxy m e t a b o l i t e t h a t might form would have been detected and was not. We a l s o found t h a t t h e ketones and J£ from t h e alcohols and ^ were produced, and v e r i f i e d t h i s r e s u l t by TIC cochromatography, but again, we a r e c o n f i d e n t o f t h e i r assigned s t r u c t u r e s u s i n g t h i s technique. Compound j ^ , 1 - h y d r o x y c y c l o h e x y l t r i p h e n y l t i n , a m e t a b o l i t e t h a t might a l s o be formed, c o u l d not be detected because o f i t s probable low c o n c e n t r a t i o n and experimental d i f f i c u l t i e s a s s o c i ated w i t h q u a n t i f y i n g i t . We found t h a t 1 - h y d r o x y a l k y l t i n d e r i v a t i v e s undergo e l e c t r o p h i l i c cleavage r e a c t i o n s o f t h e t i n carbon bond b e a r i n g t h e h y d r o x y l group w i t h h y d r o c h l o r i c a c i d t o g i v e t h e a l c o h o l and t h e corresponding d e a l k y l a t e d t i n d e r i v a t i v e ( l a ) . Consequently, r e a c t i o n o f j3 i f present w i t h hydro c h l o r i c a c i d would provide [ l - M2 ]cycïohexanol and t r i p h e n y l t i n c h l o r i d e (Eq 5)· I n c o n t r o l experiments w i t h [ l - ^ C l c y c l o h e x a nol,determined as i t s phenylcarbamate d e r i v a t i v e , we c o u l d detect l e v e l s o f t h i s d e r i v a t i v e down t o 2$ but not lower. S i m i l a r experiments w i t h t h e r e a c t i o n mixture gave no d e t e c t a b l e phenylcarbamate o f [ l - ^ C Jcyclohexanol and thus we r a t i o n a l i z e d 1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

86

£ = J - H m

3

JSL

+

M

AND

ORGANOMETALLOIDS

S N C (

3

8 |©-N=C=0

(5)

t h a t < 2 $ o r none o f 8 was formed. The study o f [ l - J ^ C ] c y c l o h e x y l d i p h e n y l t i n a c e t a t e , in those monooxygenase enzyme r e a c t i o n s was accomplished by conv e r t i n g compounds J^-J^, p h e n y l t i n bromides. Fo propanol/chloroform t o g i v e an e x c e l l e n t y i e l d o f [ l - l ^ C ] c y c l o h e x y l d l p h e n y l t i n bromide (Eq 6 ) . P r e p a r a t i v e TLC u s i n g d i i s o -

p r o p y l e t h e r / a c e t i c a c i d (^9:1) converted t h e bromide t o t h e acetate, as analyzed by 90 MHz hi nmr spectroscopy. Reaction o f £ w i t t i * r a t l i v e r microsomes, as w i t h 1 , gave t h e f o l l o w i n g r e s u l t s a f t e r a c i d i f i c a t i o n o f the r e a c t i o n mixture and e x t r a c t i o n w i t h chloroform (Eq 7 ) . The percentages i n Eq 7 represent

(7)

normalized v a l u e s o f i d e n t i f i e d m e t a b o l i t e s which account f o r 1 0 $ o f s t a r t i n g compound, 9 . The remaining m a t e r i a l s were (82$) as w e l l as 8 $ u n i d e n t i f i e d compounds.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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The corresponding ketones from and although a v a i l a b l e , were not p o s i t i v e l y i d e n t i f i e d as m e t a b o l i t e s because o f i n t e r f e r i n g compounds and i n c o n s i s t e n t cochromatography r e s u l t s , r e s p e c t i v e l y , upon TLC a n a l y s i s . We a l s o analyzed f o r [ l - ^ ! ] c y c l o h e x a n o l , as p r e v i o u s l y d e s c r i b e d f o r 1-hydroxycyclohexylt r i p h e n y l t i n , j ^ , but were not a b l e t o detect t h i s compound as i t s phenylcarbamate due t o experimental d i f f i c u l t i e s . Thus, l - h y d r o x y c y c l o h e x y l d i i ) h e n y l t i n acetate was not determined u s i n g t h i s method. Compounds and J £ were i d e n t i f i e d by TLC cochromatography, but u n f o r t u n a t e l y , s e p a r a t i o n o f both the c i s - and t r a n s - 3 or -U-hydroxyl isomers was not s u c c e s s f u l by TLC and t h e r e f o r e no assignments c o u l d be made. The t r a n s stereochemistry o f was a s c e r t a i n e d , as w i t h J^, by r e a c t i o n w i t h g l a c i a o f compounds ^ j ) - ^ was 10 c o u l d not be d i r e c t l y analyzed as was done w i t h m e t a b o l i t e 5· tïônsequently, t r a p p i n g o f the [ l - ^ C l c y c l o h e x e n e was e s s e n t i a l * * f o r q u a n t i f i c a t i o n o f JJjh T h i s was accomplished by r e a c t i o n o f the [ l - ^ C J c y c l o h e x e n e w i t h mercuric a c e t a t e i n methanol t o g i v e the oxymercuration product, 3^, which c o u l d be r eery s t a l i i zed t o constant s p e c i f i c a c t i v i t y and q u a n t i f i e d (Eq 8 ) . 1

13 Discussion Cytochrome P-^50 monooxygenase enzyme r e a c t i o n s have been w i d e l y s t u d i e d ; however, the use o f monosubstituted c y c l o h e x y l d e r i v a t i v e s as s u b s t r a t e s has r e c e i v e d o n l y l i m i t e d a t t e n t i o n . One such i n v i t r o study (k) concerned methylcyclohexane, ijjb and i t was shown t h a t P-^50 enzyme h y d r o x y l a t i o n gave the

14 f o l l o w i n g s i t u s e l e c t i v i t y on a per hydrogen b a s i s , i . e . , C^ : C : C : C o f 5 : 5 : 1 : 1 1 . No stereochemical l

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assignments were made, u n f o r t u n a t e l y , t h u s , t h i s important aspect cannot be compared t o our r e s u l t s . In c o n t r a s t t o the observed s i t u s e l e c t i v i t y f o r j ^ , compound ] ^ presents a d r a m a t i c a l l y d i f f e r e n t r e s u l t . Thus, t h e s i t u s e l e c t i v i t y f o r 1 on a per hydrogen b a s i s f o r : C-d : C£ : C± i s 1 0 9 : 7 : 1 Τ 0 . T h i s s t r i k i n g s i t u s e l e c t i v i t y f o r 1 i s a l s o complemented by a h i g h degree o f s t e r e o s e l e c t i v i t y f o r predominantly e q u a t o r i a l h y d r o x y l a t e d m e t a b o l i t e s , w i t h compounds 2> ^ and representing 95$ o f the m e t a b o l i t e s formed and g i v i n g an e q u a t o r i a l / a x i a l r a t i o o f 59· While s t e r i c e f f e c t s c o u l d be invoked t o e x p l a i n the s i t u s e l e c t i v i t y d i f f e r e n c e s between ] ^ an<J i t should be noted t h a t the c a r b o n - t i n bond l e n g t h i s 2 . 1 8 A as compared t o a c a r bon-carbon bond l e n g t h o f 1.5*4- Κ and t h i s should a l l e v i a t e the s t e r i c b u l k o f the t r i p h e n y l t i account f o r the s i t u s e l e c t i v i t by which must b i n d t o t h e membrane i n p r o x i m i t y t o the P-^-50Fe=0 complex. By v i e w i n g D r i e d i n g models o f i t was r e a l i z e d t h a t the t r i p h e n y l t i n group c o u l d p r o v i d e a template f o r the p o s s i b l e p o s i t i o n i n g o f the c y c l o h e x y l group towards the Fe=0 complex as shown i n F i g u r e 2 .

Figure 2. One possible confor mation of 1 at the active un

i n t e r e s t i n g l y , removal o f one phenyl group, i . e . , compound £s p r o v i d e s a v a s t l y d i f f e r e n t s i t u s e l e c t i v i t y , w i t h the r a t i o per hydrogen f o r C V : CQ : C being 1 . 2 : 1 : 2 . 9 . E v i d e n t l y , the conformation o f Jg, w i t h respect t o b i n d i n g i n p r o x i m i t y t o the Fe=0 complex i s d i f f e r e n t than 1. I t i s h i g h l y conceivable t h a t w i t h the t r i o r g a n o t i n d e r i v a t i v e a t e t r a h e d r a l configura t i o n r a t h e r than a t r i g o n a l - b i p y r a m i d a l c o n f i g u r a t i o n i s more important. Since has a r e p l a c e a b l e a c e t a t e group, b i n d i n g may be d e p i c t e d as i n F i g u r e 3 . T h i s would make hydrogens on the 2 , 2

Figure 3. One pos sible conformation of 9 at the active enzyme site

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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and 3 carbon atoms o f Jg, more a c c e s s i b l e than f o r comparable hydrogens i n ^ ( F i g u r e " 2 ) . We wished t o l e a r n more about the b i n d i n g d i f f e r e n c e s between compounds ] ^ and j ^ . V i s i b l e spectrophotometry has been u t i l i z e d t o determine the "finding c h a r a c t e r i s t i c s o f a wide v a r i e t y o f compounds i n p r o x i m i t y t o o x i d i z e d ( F e 3 ) F-k^O ( 9 ) . We thought s i m i l a r s p e c t r a might show the u s u a l o p t i c a l d i f f e r e n c e s a s s o c i a t e d w i t h type I and I I b i n d i n g . F i g u r e k shows t h e o p t i c a l d i f f e r e n c e s p e c t r a f o r compounds and as w e l l as f o r t r i p h e n y l t i n and t r i b u t y l t i n c h l o r i d e s a t ~ 1 . 5 "x 1 0 " % w i t h r a t l i v e r microsomes (0Λ3 nmole F-k^O/ml phosphate b u f f e r , pH 7·*0· Compounds and Jg. showed troughs a t 3 8 6 - 3 8 9 nm and a peak a t * 4 l 8 nm. T h i s was somewhat s i m i l a r t o t r i p h e n y l t i n c h l o r i d e , 385 and klk nm, but o p p o s i t e t o t r i b u t y l t i n c h l o r i d e which had a peak a t klO nm and a trough a ^25 type I I s p e c t r a (troug w h i l e the l a t t e r gave a s h i f t e d type I curve (peak a t 3 8 5 - 3 9 0 and trough a t ^-16-^20 nm). These dramatic d i f f e r e n c e s between the a r y l - and a l k y I t i n compounds might p r o v i d e one e x p l a n a t i o n as t o why the t r i p h e n y l t i n group does not get h y d r o x y l a t e d , i . e . , the b i n d i n g p l a c e s t h i s group away from the Fe=0 complex (Figure 2). The s p e c t r a l f e a t u r e s o f jL and ^ w h i l e s l i g h t l y d i f f e r e n t , cannot be d e f i n i t i v e l y i n t e r p r e t e d as evidence f o r the p o s s i b l e b i n d i n g changes we e n v i s i o n f o r both s u b s t r a t e s (Figures 2 and 3 ) · The s t e r e o s e l e c t i v i t y provides a t each carbon atom the thermodynamic a l l y most s t a b l e e q u a t o r i a l h y d r o x y l a t e d isomer. I n our previous s t u d i e s w i t h the t r i b u t y l t i n d e r i v a t i v e s , we p o s t u l a t e d from the observed s i t u s e l e c t i v e h y d r o x y l a t i o n p a t t e r n and other c r i t e r i a t h a t a f r e e r a d i c a l mechanism was o p e r a t i v e i n these b i o l o g i c a l o x i d a t i o n r e a c t i o n s ( l a ) . The present r e s u l t s w i t h compounds 1 α c l e a r l y demonstrate t h a t t h i s f r e e r a d i c a l process can be h i g h l y s s t e r e o s p e c i f i c (Eq 9 ) · +

S

In regards t o t h i s s p e c i f i c i t y , a r e c e n t l y r e p o r t e d r e s u l t (12.) u s i n g a p u r i f i e d P-l+50 enzyme p r e p a r a t i o n from r a b b i t l i v e r microsomes w i t h exo-D^-norbornane r e v e a l s a pronounced s t e r e o s e l e c t i v i t y f o r exo hydrogen a b s t r a c t i o n (k exo/k endo = 7 )

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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Cyclohexyltriphenyltin +0.01-1

418 OH 386 -0.01 -L 350 nm

500 nm

Cyclohexyldiphenyltin Acetate +0.01· 418

1

-0.0I- 350 nm

389 500 nm Triphenyltin Chloride 414

+0.01 -ι

-0.01-L 350 nm

500 nm

Tributyltin Chloride +0.01 410

-0.0 l-L 350 nm Figure 4.

500 nm

Optical difference spectra with P-450 (Fe *) oxidized enzyme 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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and a l a r g e k i n e t i c i s o t o p e e f f e c t (k^/k^ = 1 1 ) . Groves et a l . (10) i n t e r p r e t e d these r e s u l t s i n terms o f a homolytic C-H bond s c i s s i o n g i v i n g a l o n g l i v e d f r e e r a d i c a l capable o f e p i m e r i z i n g , i . e . , endo hydrogen a b s t r a c t i o n t o g i v e exo a l c o h o l (25$ o f exonorborneol had r e t a i n e d a l l deuterium). The important q u e s t i o n i n our case i s whether the Fe=0 complex h o m o l y t i c a l l y removes e q u a t o r i a l hydrogens i n a t o t a l l y s t e r e o s p e c i f i c r e a c t i o n (as i m p l i e d i n F i g u r e 2) or whether some o f the e q u a t o r i a l products come from a x i a l hydrogen a b s t r a c t i o n and can o n l y be a s c e r t a i n e d w i t h s p e c i f i c deuterium l a b e l l i n g . Our r e s u l t s and t h a t o f Groves et a l . (10) make the f r e e r a d i c a l h y d r o x y l a t i o n w i t h the V-k^O Fe=0 complex a v i a b l e pathway and our r e s u l t s show t h a t t h i s can occur w i t h h i g h s t e r e o s e l e c t i v i t y . I n c o n c l u s i o n , the r e a c t i o n s o f c y c l o h e x y l t i n compounds, and 2j w i t h a P-^50 monooxygenas cyclohexyl metabolites i n d i c a t e t h a t the conformational aspects o f the s u b s t r a t e , upon b i n d i n g near the Fe=0 complex, can c o n t r o l these b i o t r a n s f o r m a tions . Abstract The r e a c t i o n s o f a cytochrome P-^50 monooxygenase enzyme system from r a t l i v e r microsomes w i t h c y c l o h e x y l t r i p h e n y l t i n and c y c l o h e x y l d i p h e n y l t i n a c e t a t e were s t u d i e d . The s t e r e o and s i t u s e l e c t i v i t y w i t h c y c l o h e x y l t r i p h e n y l t i n showed a strong preference f o r e q u a t o r i a l h y d r o x y l a t i o n o c c u r r i n g predominately a t the ^ - p o s i t i o n ( t r a n s - ^ - h y d r o x y c y c l o h e x y l t r i p h e n y l t i n ) . Thus, the conformation o f the c y c l o h e x y l group i n p r o x i m i t y t o the P-^50 f e r r y l oxygen complex seems t o be an important f a c t o r i n determining the s i t u s e l e c t i v i t y . Furthermore, by removing one p h e n y l group, i . e . , c y c l o h e x y l d i p h e n y l t i n a c e t a t e , the p a t t e r n o f carbon-hydroxylation i s more e q u a l l y d i s t r i b u t e d on the 2 , 3 and k carbon p o s i t i o n s . The stereochemistry i n the case o f t h i s l a t t e r system was o n l y v e r i f i e d f o r the trans-2-hydroxyc y c l o h e x y l d i p h e n y l t i n a c e t a t e m e t a b o l i t e . The r e s u l t s w i t h c y c l o h e x y l d i p h e n y l t i n a c e t a t e f u r t h e r s u b s t a n t i a t e the conformat i o n a l f a c t o r as c r i t i c a l f o r the observed s i t u s e l e c t i v i t y . Acknowledgment s We wish t o thank Dr. W. W. Conover o f the S t a n f o r d Magnetic Resonance Laboratory f o r o b t a i n i n g the 360 MHz H nmr spectrum o f m e t a b o l i t e 2 . SMRL i s supported by grants NSF GR 23633 and NIH RR 0 0 7 1 1 . * * The work r e p o r t e d h e r e i n was supported by the N a t i o n a l I n s t i t u t e o f Environmental H e a l t h Sciences (Grant P01 ES0CKA-9).

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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References 1. a. R. H. Fish, E. C. Kimmel, J. E. Casida, J. Organometal. Chem. (1976) 118, 41. b. E . C. Kimmel, R. H . Fish, J. E. C a s i d a , J. A g r . Food Chem. (1977) 25, 1. 2 . J . H . Dawson, J. R. Trudell, G. B a r t h , R. E . Linden, E . Bunnenberg, C. Djerassi, R. C h i a n g , L . P . Hager, J. Amer. Chem. Soc. (1976) 98, 3707 and references t h e r e i n . 3· K. R. Hanson, I. A. Rose, Accounts Chem. Res. (1975) 8, 1. 4. U . Frommer, V . Ullrich, H . Staudinger, Hoppe-Seyler's Ζ. Physiol. Chem. (1970) 351, 903. 5. R. H . Fish, J. Lett. (1977 6. R. H . Fish, B . M . Broline, J. Organometal. Chem. (1977) 136, C41. 7. R. H. Fish, Β. M. Broline, I b i d . (1978) in p r e s s . 8. 9. 10.

M. De J e s u s , O. R o s a r i o , G. L . Larson, I b i d . (1977) 132, 301. A . P . K u l k a r n i , R. B . Mailman, E . Hodgson, J. A g r . Food Chem. (1975) 23, 177 and references t h e r e i n . J . T. Groves, G. A . McClusky, R. E . White, M . J. Coon, Biochem. Biophys. Res. Comm. (1978) 81, 154.

Discussion J . J . ZUCKERMAN ( U n i v e r s i t y of Oklahoma): Could there be another pathway w i t h the cleavage of the cyclohexane group from t i n , and would you know anything about the steps along that route? FISH:

You mean without h y d r o x y l a t i o n ?

ZUCKERMAN:

With or w i t h o u t , but w i t h s e p a r a t i o n from the

tin? FISH: I t h i n k t h a t you need h y d r o x y l a t i o n i n order to sepa r a t e the c y c l o h e x y l group; e i t h e r 1 - h y d r o x y l a t i o n (which we d i d n ' t see) t h a t would r e s u l t i n the l o s s of t i n or the c y c l o h e x y l group, and/or formation of the 2-hydroxy compound which i s a l s o l a b i l e under p r o t i c c o n d i t i o n s . F . HUBER ( U n i v e r s i t y of Dortmund): I would l i k e to comment on the mechanism you proposed. I f e e l a b i t uneasy that you p r o pose a c o o r d i n a t i o n number of f i v e (a t r i g o n a l bipyramid) when you have the h y d r o x y l a t i o n of the t r i p h e n y l t i n compound, and you p r o pose only a t e t r a h e d r a l c o o r d i n a t i o n when you have a d i p h e n y l t i n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

6.

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FISH E T A L .

1

a c e t a t e . I t s normal i n the gan ο t i n compounds that there dination with tetraorganotin d i n a t i o n increases when you at the t i n center.

93

c o o r d i n a t i o n chemistry o f these o r i s no great tendency f o r pentacoorcompounds, and the tendency f o r coor reduce the number o f organic l i g a n d s

FISH: You mean the mechanism o f the b i n d i n g ( c f . Figures 2 and 3 ) . I t h i n k t e t r a o r g a n o t i n compounds can, i n f a c t , form t r i gonal bipyramidal-type intermediates i n s o l u t i o n o r on a p r o t e i n s u r f a c e . You do b e l i e v e that the t r i o r g a n o t i n compounds can b i n d the way I depicted? HUBER: Yes, they c e r t a i n l y can but they show much g r e a t e r tendency t o have a t r i g o n a l b i p y r a m i d a l c o n f i g u r a t i o n than t h e other ones. ZUCKERMAN: We have i s o l a t e d a complex o f a t e t r a a l k y l t i n compound w i t h a bromide i o n . I t h i n k Dr. F i s h has t h i s interme d i a t e as a step i n a k i n e t i c pathway, and maybe i t wouldn't have to l a s t very long t o do i t s j o b . HUBER: I t ' s the same problem we have when we study r e a c t i o n s of t e t r a o r g a n o - t i n o r ^-lead compounds. We have t o assume some k i n d o f c o o r d i n a t i o n f o r a short time. A. J . CANTY ( U n i v e r s i t y o f Tasmania): You mentioned t h a t the phenyl groups do not get hydroxylated and t h i s has a l s o been shown f o r phenylmercury compounds i n r a t l i v e r . I s t h i s a general phe nomenon f o r a r y l organometallics? FISH: I'm not sure. I don't t h i n k a wide spectrum o f phen y l m e t a l compounds has been s t u d i e d . One of the problems i s t h e b i n d i n g ; i . e . , i n d i s c r i m i n a t e b i n d i n g a t other s i t e s . I t a l s o could be the mechanism o f h y d r o x y l a t i o n . J . M. WOOD ( U n i v e r s i t y o f Minnesota): The h y d r o x y l a t i o n of aromatic compounds by P450 i n the l i v e r i s w e l l known, i . e . , hy d r o x y l a t i o n of the s t e r o i d s . I t could be t h a t l i v e r i s a bad choice w i t h these metal complexes. I'm sure you could f i n d some m i c r o b i a l communities t h a t w i l l produce P450 and hydroxylate aromatic r i n g s attached t o metal i o n s . FISH: I t may happen i n v i v o , where we see t r i p h e n y l t i n being metabolized t o d i p h e n y l o r monophenyl, but i t ' s not apparent what the mechanism i s i f we can't do i t i n v i t r o . RECEIVED

August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7 Anaerobic and Aerobic Alkylation of Arsenic BARRY C. McBRIDE, HEATHER MERILEES, WILLIAM R. CULLEN, and WENDY PICKETT Departments of Microbiology and Chemistry, University of British Columbia, Vancouver, British Columbia, V6T 1W5 Canada

Arsenic and i t s derivatives are important as herbicides and are used in, or are by-products of, many industrial processes. Large quantities of this potentially toxic compound are mobilized and placed i n new environments where they accumulate in concentrations which may exceed the normal arsenic burden of these ecosystems. The microflora i n these environments possess the metabolic machinery to transform these compounds into gaseous arsines. Challenger (1) described the formation of trimethylarsine by fungi. Cox and Alexander (2) have shown that s o i l organisms w i l l produce trimethylarsine and McBride and Wolfe (3) reported that the anaerobic methane bacteria synthesized dimethylarsine. A consequence of this microbial activity i s the modification of arsenic to new compounds possessing different chemical, physical, and biological properties. Methanogenic B a c t e r i a The methanogenic b a c t e r i a a r e a unique group of m i c r o organisms which produce methane as their principal m e t a b o l i c end product. They a r e found in l a r g e numbers in anaerobic ecosystems when o r g a n i c matter is decomposing. As a group they are morphol o g i c a l l y d i v e r s e , embracing c o c c a l , b a c i l l a r y and s p i r a l forms. They a r e extremely s e n s i t i v e t o 0 » a f a c t o r which has c o n t r i b uted t o our l i m i t e d understanding o f t h e i r biochemical a c t i v i t i e s . A r e s t r i c t e d number o f s u b s t r a t e s can be reduced t o methane these i n c l u d e : C 0 , formate, a c e t a t e , and methanol. Hydrogen i s the p r e f e r r e d source o f e l e c t r o n s . The p e r t i n e n t c h a r a c t e r i s t i c s of the methane b a c t e r i a a r e summarized i n Table I . There a r e s e v e r a l (4-8) reviews o f these organisms which d e a l w i t h t h e i r i s o l a t i o n , c h a r a c t e r i z a t i o n and b i o c h e m i s t r y . The methane b a c t e r i a f u n c t i o n as the t e r m i n a l members o f the 2

2

0-8412-0461-6/78/47-082-094$05.50/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7.

MCBRiDE E T A L .

Aïkylation of Arsenic

95

Table I . C h a r a c t e r i s t i c s of the Methanogenic B a c t e r i a Organisms

Habitat

Morphology

Substrates

Methanobacterium ruminantium

rume sludge

short rods

formate

Methanobacterium s t r a i n M.oH

mud sludge

irregularly curved rods

H2+CO2

Methanobacterium formicicum

mud, sludge

irregularly curved rods

H2+CO2

Methanobacterium mobilie

rumen

short r o d , motile

H2"KX)2

Methanosarcina barkerii

mud, sludge

Methanococcus vannielii

mud

Methanospirilium hungatii

mud,sludge

sarcina

formate H2+CO2

methanol, acetate m o t i l e coccus

H2+CO2

formate

mud, sludge Methanobacterium thermoautotrophicum hot s p r i n g s

spirillum

H2+CO2

formate irregularly curved r o d

H2+CO2

formate

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

96

ORGANOMETALS

AND

ORGANOMETALLOIDS

anaerobic food c h a i n , scrubbing the environment of p o t e n t i a l l y t o x i c components and r e l e a s i n g a non-toxic end product which e v e n t u a l l y escapes i n t o oxygenated environments. A g e n e r a l i z e d scheme (6) i l l u s t r a t i n g the e s s e n t i a l steps r e q u i r e d to synthesize a molecule of methane i s summarized i n F i g . 1. The scheme accounts f o r a l l the known methane precursors and i n d i c a t e s the r e a c t i o n s r e q u i r e d to form a completely reduced carbon molecule. Compound X i s a c a r r i e r which may represent one or more molecular s p e c i e s . Our understanding of the steps i n methane b i o s y n t h e s i s i s sketchy and i s almost e n t i r e l y l i m i t e d to the t e r m i n a l methyl t r a n s f e r r e a c t i o n s . No intermediates between CO2 and X - C H 3 , have been i d e n t i f i e d . The c a r r i e r molecule X has been p o s t u l a t e d to be r e q u i r e d because no f r e e reduced C - l intermediates have been i d e n t i f i e d . Progress has been mad i understandin th mechanis f th methyl t r a n s f e r r e a c t i o n s demonstrated that methy methane b i o s y n t h e s i s i n c e l l e x t r a c t s of Methanosarcina b a r k e r i i . Subsequently Wo l i n et_ a l (10) found that methylcobalamin was a s u b s t r a t e f o r methane b i o s y n t h e s i s i n Methanobacterium o m e l i a n s k i i . B l a y l o c k was able to r e s o l v e the Methanosarcina (11) system i n t o a number of components,one of which was a c o r r i n o i d c o n t a i n i n g p r o t e i n . Wood (12) was s u c c e s s f u l i n i s o l a t i n g a cobalamin c o n t a i n i n g p r o t e i n from M. o m e l i a n s k i i . The p r o t e i n s t i m u l a t e d CHi+ production when added to c e l l e x t r a c t s (13) of the organism. These s t u d i e s suggested that B12 might be the X f a c t o r i n v o l v e d i n methyl t r a n s f e r . This seemed p a r t i c u l a r l y f e a s i b l e i n l i g h t of the r o l e of C H 3 - B 1 2 i n the CH3 t r a n s f e r r e a c t i o n s l e a d i n g to methionine b i o s y n t h e s i s . U n f o r t u n a t e l y , Wood s c u l t u r e was found to c o n s i s t of two organisms; a. methanogen (Methanobacterium s t r a i n M.oH) which reduced CO2 to CHi* and a second organism which s u p p l i e d e l e c t r o n s f o r methanogenesis by o x i d i z i n g ethanol to acetate and hydrogen (14). R e s u l t s from i n v e s t i g a t i o n s w i t h the mixed c u l t u r e must be viewed w i t h c a u t i o n because i t i s impossible to i d e n t i f y w i t h c e r t a i n t y the g e n e t i c o r i g i n of the B12 p r o t e i n which s t i m u l a t e d methanogenesis. Biochemical s t u d i e s have been complicated by the l a b i l i t y of the e x t r a c t s and u n t i l a few years ago i t was not p o s s i b l e to f r a c t i o n a t e the c e l l s or r e s o l v e them f o r s p e c i f i c components of the methane s y n t h e s i z i n g system. As a consequence i t was necessary to use s t i m u l a t i o n of CHif b i o s y n t h e s i s as the assay f o r c o n s t i t u e n t s which had been f r a c t i o n a t e d from other e x t r a c t s . In t h i s type of assay the r e a c t i o n mixture was complete and would support a l i m i t e d amount of CHi* b i o s y n t h e s i s . Fractionated c e l l e x t r a c t was then added to the r e a c t i o n mixture and i f i t s t i m u l a t e d CHi* production i t was i m p l i c a t e d i n the t e r m i n a l methyl t r a n s f e r r e a c t i o n s . A d i f f i c u l t y w i t h t h i s type of assay i n a complex m u l t i s t e p r e a c t i o n i s that one can only measure s t i m u l a t i o n of a r a t e l i m i t i n g r e a c t i o n . In methane b i o s y n t h e s i s , 1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7.

97

Alkyhtion of Arsenic

MCBRIDE E T A L .

s t i m u l a t i o n could r e s u l t from i n c r e a s e d e l e c t r o n t r a n s p o r t , a c t i v a t i o n o f ATP,or t r a n s f e r of methyl groups. Thus the i m p l i c a t i o n o f a c o r r i n o i d p r o t e i n i n CHi» b i o s y n t h e s i s by Μ· o m e l i a n s k i i was based on r a t h e r tenuous evidence, but c e r t a i n l y the best evidence that could be developed a t that time. The isolâtion,of the pure c u l t u r e o f M.oH f a c i l i t a t e d the study of methanogenesis; c e l l e x t r a c t s were not as l a b i l e and c a t a l y z e d CHi* formation a t an i n c r e a s e d r a t e . I n a d d i t i o n these e x t r a c t s reduced C 0

t o CHi*

2

(7) .

Attempts t o i s o l a t e the c o r r i n o i d p r o t e i n from M.oH have been unsuccessful (15). I n f a c t no B 1 2 c o n t a i n i n g enzymes appear to be present i n t h i s organism. The red p r o t e i n i s o l a t e d by Wood was shown t o be synthesized by the non-methanogenic contaminant (15) and thus could not be a p a r t o f the i n v i v o methane s y n t h e s i z i n g system. Th cast some doubt on the importanc transfer reactions. The question was answered w i t h the discovery o f the methyl donor, C H 3 - C 0 M . CoM i s a low m o l e c u l a r weight, heat s t a b l e c o f a c t o r found i n a l l methane b a c t e r i a that have been examined (16). Chemically CoM i s 2,2 - d i t h i o d i e t h a n e s u l f o n i c a c i d (17). I t can be reduced and methylated c h e m i c a l l y o r b i o l o g i c a l l y t o form 2-(methylthio) e t h a n e s u l f o n i c a c i d . I n the presence of c e l l e x t r a c t , ATP, and H ,CH -CoM i s r e d u c t i v e l y cleaved t o y i e l d CH^ and CoM ( F i g . 2 ) . E x t r a c t s can be r e s o l v e d f o r CoM by anaerobic d i a l y s i s and w i l l synthesize CHi* only i f they a r e s u p p l i e d w i t h CoM. I t seems reasonable t o assume that Βχ2 i s n o t i n v o l v e d i n CHi» b i o s y n t h e s i s i n MoH, and that t h i s r e a c t i o n i s c a t a l y z e d by CoM. I t i s not c l e a r a t t h i s time whether Methanosarcina depends on B 1 2 , as t h i s organism has been shown t o possess CoM i n a d d i t i o n t o a c o r r i n o i d p r o t e i n . P o s s i b l y t h i s organism possesses 2 methane s y n t h e s i z i n g pathways,one dependent and one independent of Β 1 2 · f

2

3

A l k y l a t i o n o f Metals M.oH has been i m p l i c a t e d as an organism which w i l l a l k y l a t e mercury (18) and a r s e n i c ( 3 ) . A l k y l a t i o n o f metals by M.oH could t h e o r e t i c a l l y occur a t any b i o s y n t h e t i c step which generated a C - l group. Because the methanogenic b a c t e r i a process l a r g e numbers of C - l u n i t s i t i s not unreasonable to assume that the CH^ b i o s y n t h e t i c pathway could be important i n these r e a c t i o n s , and that CoM would be a molecule of i n t e r e s t . I t would be unwise t o f o r g e t that methyl groups must be generated f o r the s y n t h e s i s of methionine and that intermediates i n t h i s r e a c t i o n could be i n v o l v e d i n metal a l k y l a t i o n . Two methionine b i o s y n t h e t i c pathways operate i n b a c t e r i a . One system i n v o l v e s t r a n s f e r o f a methyl group from N -methyl-tetrahydrofolic acid (N , CH3THFA) to B and then t o homocysteine. The methylation of homocysteine r e q u i r e s c a t a l y t i c 5

5

1 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

98

AND

ORGANOMETALLOIDS

amounts of S-adenosyl methionine (SAM). The second system r e q u i r e s N , CH -THFA t r i - g l u t a m a t e and SAM. The i n a b i l i t y to f i n d a c o r r i n o i d p r o t e i n i n M.oH suggests that the l a t t e r mechanism may operate i n these organisms. 5

3

Arsine Biosynthesis C e l l e x t r a c t s of M.oH produce a s t r o n g g a r l i c odor when they are incubated w i t h arsenate. The f o l l o w i n g s e c t i o n of t h i s paper w i l l d e a l w i t h the b i o c h e m i c a l s t u d i e s which l e d to the i d e n t i f i c a t i o n of the g a r l i c s m e l l i n g compound and to a scheme f o r i t s b i o s y n t h e s i s . This w i l l be f o l l o w e d by a study of a r s e n i c t r a n s f o r m a t i o n i n n a t u r a l anaerobic systems . A l k y l a r s i n e Assays. The r e a c t i o n v e s s e l and c o n d i t i o n s used f o r the b i o s y n t h e s i s of a l k y l a r s i n e s i m i l a t thos described f o r methane b i o s y n t h e s i v e s s e l was connected by polyethylen g glas contained 2 mL of 2M HNO3. The t r a p p i n g tube was placed i n an e t h a n o l - i c e bath. A slow stream of H2 was passed i n t o the r e a c t i o n f l a s k and the v o l a t i l e a l k y l a r s i n e s were swept i n t o the n i t r i c a c i d , where they were condensed and trapped by o x i d a t i o n to n o n - v o l a t i l e a c i d s (20). The contents of the t r a p were assayed f o r a r s e n i c by atomic a b s o r p t i o n spectrometry and f o r C by counting i n Bray's s c i n t i l l a t i o n f l u i d . The i s o t o p e , *As was used to f o l l o w the formation of v o l a t i l e a l k y l a r s i n e . E x t r a c t s were incubated w i t h [ A s ] N a 2 H A s 0 i * and the v o l a t i l e methylated As was measured. Advantage was taken of the property of a l k y l a r s i n e s to r e a c t w i t h the red-rubber serum stoppers which were used to s e a l the r e a c t i o n f l a s k s . At the a p p r o p r i a t e times the r e a c t i o n mixture was i n a c t i v a t e d by h e a t i n g on a steam cone. The f l a s k s were then incubated f o r an a d d i t i o n a l 20 min to ensure t h a t a l l the v o l a t i l e d i m e t h y l a r s i n e was adsorbed onto the rubber stopper. The serum stopper was removed from the f l a s k , r i n s e d i n water, cut i n h a l f , and placed i n a s c i n t i l l a t i o n v i a l together w i t h 15 mL of Bray's s c i n t i l l a t i o n f l u i d . T h i s mixture was e i t h e r counted d i r e c t l y , as the rubber stopper d i d not quench the high-energy 3 p a r t i c l e s emitted by ks, or the stopper was removed a f t e r the **As had been leached from the rubber (1 h r . ) . The rubber stopper technique was found to be an e f f i c i e n t and s p e c i f i c means of s e p a r a t i n g [ C] dime thy l a r s i n e from [ C]CHi . lh

7l

7lf

7lf

7k

llf

1If

t

Requirements f o r B i o s y n t h e s i s . Conditions f o r the b i o s y n t h e s i s of a l k y l a r s i n e d e r i v a t i v e s are d e s c r i b e d i n Table I I . In these experiments c e l l e x t r a c t s were incubated under anaerobic c o n d i t i o n s w i t h [ * A s ] N a 2 H A s 0 i , and the formation of v o l a t i l e *ks compounds was measured. A methyl donor, H 2 , ATP, and arsenate were r e q u i r e d f o r the r e a c t i o n ; w i t h the exception of arsenate these same components are r e q u i r e d i n the CHi*s y n t h e s i z i n g system. A t o t a l of 34 yg of a r s e n i c was found i n 7l

f

7t

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7.

MCBRiDE E T A L .

Alkyfotion of Arsenic

99

an a l k y l a r s i n e t r a p l i n k e d to a r e a c t i o n f l a s k which contained arsenate and c e l l e x t r a c t , p r o v i d i n g evidence that a v o l a t i l e a l k y l a r s i n e was b e i n g s y n t h e s i z e d . V o l a t i l e a l k y l a r s i n e compounds were not d e t e c t e d i n a s i m i l a r c o n t r o l r e a c t i o n mixture which contained arsenate and b o i l e d e x t r a c t . S u b s t r a t e s . C H 3 - B 1 2 and CO2 were shown to be methyl donors f o r a l k y l a r s i n e s y n t h e s i s . Arsenate, a r s e n i t e and m e t h y l a r s o n i c a c i d were reduced to d i m e t h y l a r s i n e i n the presence of a C - l donor. C a c o d y l i c a c i d was reduced i n the absence of a C - l donor. M e t h y l a r s o n i c a c i d was found i n e x t r a c t s incubated w i t h AsOi* "and a C - l donor. Whole C e l l s . The a b i l i t y of whole c e l l s to s y n t h e s i z e a l k y l a r s i n e i s shown i an a c t i v e l y growing c u l t u r 12-L fermentor and was incubated a n a e r o b i c a l l y under a H : C 0 atmosphere. 2

2

A n a l y s i s of the A l k y l a t e d A r s i n e . The s t r u c t u r e of the a l k y l a r s i n e formed i n c e l l e x t r a c t s was i n d i c a t e d by two experimental procedures. I n one procedure N a 2 H A s 0 i f was incubated w i t h [ C]methylcobalamin, and the trapped a l k y l a r s i n e was analyzed f o r a r s e n i c and C. The r e s u l t s of two such experiments are presented i n Table I I I . D i s s o l v e d [^CjCHt, was removed by b u b b l i n g CHi* through the t r a p p i n g s o l u t i o n a f t e r i t had been disconnected from the r e a c t i o n f l a s k . The number of methyl groups i n the trap was c a l c u l a t e d from the s p e c i f i c a c t i v i t y of [ C ] C H 3 - B i 2 . T h i s v a l u e was d i v i d e d by the amount of a r s e n i c to o b t a i n a methyl group to a r s e n i c r a t i o . The r a t i o s obtained (1.8:1 and 1.9:1) i n d i c a t e that the compound i s dimethylarsine. These r e s u l t s were s u b s t a n t i a t e d by a d o u b l e - l a b e l i n g experiment i n which [ *As]Na2HAs0if and [ C]methylcobalamin were s u b s t r a t e s . The r e s u l t s of two such experiments are shown i n Table IV. A l k y l a r s i n e was separated from contaminating [ C]CHi by t r a p p i n g i n a rubber serum stopper as d e s c r i b e d p r e v i o u s l y . The s p e c i f i c a c t i v i t y of the s u b s t r a t e s was used to c a l c u l a t e the micromoles of a r s e n i c as w e l l as methyl groups. The r a t i o s of methyl groups to a r s e n i c (2.1:1 and 1.9:1) suggest that the g a r l i c - s m e l l i n g compound i s d i m e t h y l a r s i n e . A pathway f o r d i m e t h y l a r s i n e s y n t h e s i s has been proposed (3) F i g . 4. Arsenate i s f i r s t reduced to a r s e n i t e which i s then methylated to form m e t h y l a r s o n i c a c i d . T h i s compound was found i n r e a c t i o n mixtures when e x t r a c t s were incubated w i t h e i t h e r arsenate o r a r s e n i t e and C H 3 - B 1 2 . M e t h y l a r s o n i c a c i d i s reduced and methylated to form d i m e t h y l a r s i n i c a c i d . The a c i d i s then reduced to form dime t h y l a r s i n e . A l l i n t e r m e d i a t e s have been shown to be converted to d i m e t h y l a r s i n e by c e l l e x t r a c t s . T h i s pathway i s based on s t u d i e s i n which C H 3 - B 1 2 was used as methyl llf

llf

7l

llf

llf

f

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

A N D ORGANOMETALLOIDS

CO + XH a

ι X-COOH

ι ». X-CHO

1 I>

CH,OH

XCH OH 2

h

ChLCOOH

X-CH

Figure 1. Possible pathway for methane biosynthesis. C-2 of ace tate is preferentially reduced to methane.

3

H X + CH

(-S-CH CH S03 ) 2

1

2

h

<

HS-CHgC^SO^ 2

CH^-S-Ch^CH^SO^

—

"2 Mg*2 CH

4

+

HS-CH^Ch^SO^

Figure 2. Role of CoM in methane biosyn thesis. (1) 2,2'-dithiodiethane sulfonic acid; (2) 2-mercaptoethane sulfonic acid; (3) 2(methylthio)ethane sulfonic acid.

Figure 3. Synthesis of alkyhrsine by whole cells of Methanobacterium strain M.oH. Each reaction mixture contained whole cells, As-Na HAsO,„ and H -CO (80:20). 74

2

g

x

40 60 80 MINUTES

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4

7.

Alkylation of Arsenic

MCBRiDE E T A L .

Table III·

101

I d e n t i f i c a t i o n of Dime t h y l a r s i n e .

Each r e a c t i o n f l a s k contained: potassium phosphate b u f f e r , aden o s i n e t r i p h o s p h a t e , [ C ] C H - B i 2 , N a 2 H A s 0 i * , crude c e l l e x t r a c t ; the a r s i n e s were trapped i n 2 Ν HNO3 and assayed f o r a r s e n i c by atomic a b s o p r t i o n spectrometry and f o r r a d i o a c t i v i t y by s c i n t i l l a t i o n counting i n Bray's s o l u t i o n . C a l c u l a t e d from s p e c i f i c a c t i v i t y of [ * C ] C H 3 - B i 2 added. Determined by atomic a b s o r p t i o n spectrometry. l f |

3

1,

Volatile As (cpm) 7k

Flask

Omissions

1

None

2

-CH3-B12

3

-H

4

-ATP

5

- C e l l extract

0

6

None ( r e a c t i o n mixture b o i l e d )

0

13,400

0

2

3,600

Table I I . Requirements f o r D i m e t h y l a r s i n e Synthesis by C e l l E x t r a c t s of Methanobacterium S t r a i n M.O.H. Complete r e a c t i o n mixture contained; TES b u f f e r , adenosine t r i phosphate, C H 3 - B 1 2 , crude c e l l e x t r a c t , [ * Α 8 ] Ν 3 Η Α 8 θ ι * , H , a i r replaced H i n f l a s k 3; F l a s k 6 was heated f o r 5 min. i n a b o i l ing-water bath p r i o r t o i n c u b a t i o n . 7

2

2

2

Expt

CH3 Groups (ymole)

1

0.058

0.033

1.90

2

0.096

0.053

1.81

0

0

Control

As (ymole)

Ratio CH :As 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

102

donor; i t i s p o s t u l a t e d t h a t methylation r e d u c t i o n f o l l o w s the same scheme.

AND

ORGANOMETALLOIDS

by the product of

C0

2

A r s e n i c transformation i n anaerobic ecosystems. The s t u d i e s on pure c u l t u r e s of M.oH proved that the organism could make dime thy l a r s i n e . I t then became of i n t e r e s t to determine i f the methanogenic b a c t e r i a would s y n t h e s i z e the molecule i n a n a t u r a l ecosystem. Sewage sludge from an anaerobic d i g e s t e r was chosen as the methanogenic source because i t i s an area of intense b i o l o g i c a l a c t i v i t y , populated by l a r g e numbers of methanogenic b a c t e r i a a c t i v e l y s y n t h e s i z i n g methane. Sludge was c o l l e c t e d f r e s h d a i l y from an anaerobic d i g e s t e r * exposure to oxygen was minimized. The sludge was t r a n s f e r r e d to 18 mm t e s t tubes and amended w i t h [ As]Na2HAs0i . The tube was then gassed w i t h 0 f r e rubber stopper. S t r i p the sludge were used as a r s e n i c t r a p s . The traps were removed at designated i n t e r v a l s , washed thoroughly to remove unreacted As, and then placed i n Bray's s c i n t i l l a t i o n f l u i d and counted immediately. The transformation of arsenate to a form which w i l l r e a c t w i t h a rubber stopper i s described i n F i g . 5. As can be seen, transformation i s r a p i d and complete w i t h i n 8 hours. There was no transformation to a rubber r e a c t i v e d e r i v a t i v e when the sludge was heated to 90 f o r 15 min. p r i o r to adding the arsenate. The s e n s i t i v i t y of the system to heat suggests that t r a n s f o r m a t i o n i s a b i o l o g i c a l process r e q u i r i n g l i v i n g c e l l s and i s not l i k e l y to be a r e a c t i o n mediated by compounds present i n the sewage. The r e a c t i o n was dose dependent; a d d i t i o n of i n c r e a s i n g l e v e l s of arsenate r e s u l t e d i n a corresponding increase i n the amount of transformed a r s e n i c . I t was not p o s s i b l e to i d e n t i f y the a r s e n i c compound i n the rubber stoppers using the methodology employed i n pure c u l t u r e s t u d i e s because the l e v e l s of carbon precursors could not be a c c u r a t e l y e s t a b l i s h e d . Attempts were made to i s o l a t e the products by a n a e r o b i c a l l y e x t r a c t i n g the sewage mixture at v a r i o u s p o i n t s during the r e a c t i o n . Rubber stoppers were l e f t out of the r e a c t i o n i n the hope that the transformed metal would remain f r e e and thus be a v a i l a b l e f o r chemical a n a l y s i s . None of the e x t r a c t i o n procedures produced d e t e c t a b l e l e v e l s of a l k y l a t e d a r s e n i c . I t seemed p o s s i b l e that the transformed a r s e n i c , which i s b e l i e v e d to be an a r s i n e , was r e a c t i n g w i t h some other c o n s t i t u e n t i n the sewage sample and was f u r t h e r transformed before i t was e x t r a c t e d . To t e s t t h i s hypothesis an experiment was designed i n which traps were placed i n the r e a c t i o n mixture at v a r i o u s times a f t e r a d d i t i o n of the arsenate and then a l l the traps were removed at the same time. The c o n t r o l experiment i n which stoppers were i n the r e a c t i o n mixture when arsenate was added and were removed at v a r i o u s times show the t y p i c a l r e s u l t of i n c r e a s i n g i n c o r p o r a t i o n of the transformed a r s e n i c ( F i g . 6 ) . ?lf

t

2

?if

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7.

MCBRiDE E T A L .

Alkylation of Arsenic

HO-As-OH

ο

103

As-OH

1

^ ' H Q - A s - OH

u

methv! donor

ο

2 Ç3 H

CH ÂS-CH3 3

r e ( J u c t

HO-AS-CH3

'°

n

,

6

4

Η

5

Figure 4. Proposed pathway for the biosyn thesis of dimethyl arsine. (1) arsenate; (2) ar senite; (3) methyl arsonic; (4) cacodylic acid; (5) dimethyl arsine.

Figure 5. Transformation of arsenic in sludge. Sewage sludge was mixed with As-Na HAsO,, and incubated anaerobi cally. Rubber traps were removed at the specified intervals, washed, and counted. Experimental, ·; sludge was boiled for 15 min prior to adding ^As-NagHAsOt, O . 74

E

Figure 6. Lability of transformed arsenic. Rubber traps added at zero time and re moved at times indicated, Φ; Rubber traps added at times indicated and removed at 18 hr,m-

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

104

ORGANOMETALS

AND

ORGANOMETALLOIDS

In the experimental s i t u a t i o n , there i s a decrease i n the number of counts i n the traps which c o r r e l a t e s w i t h the time when the traps were placed i n the r e a c t i o n mixture. I t can be concluded from t h i s experiment that a r s e n i c i s transformed to a l a b i l e product which r a p i d l y l o s e s i t s a b i l i t y to b i n d to rubber stoppers. This experiment p o i n t s out the d i f f i c u l t i e s of d e f i n i n g metal transformation i n n a t u r a l systems and i n d i c a t e s that the f i n a l product i n an ecosystem may represent the c u l m i n a t i o n of a number of b i o l o g i c a l a c t i v i t i e s o c c u r r i n g i n a s p e c i f i c sequence. I t i s important to know the nature of the intermediate products because they may have s i g n i f i c a n t l y d i f f e r e n t p h y s i c a l , chemical or b i o l o g i c a l p r o p e r t i e s than e i t h e r the s t a r t i n g m a t e r i a l or the f i n a l product. A knowledge of the intermediates may help e x p l a i n how a metal w i l l move through th food c h a i n Nature of the Transforme g compoun synthesized was dime thy l a r s i n e and t h a t t h i s compound was a l k y l a t e d by methanogenic b a c t e r i a , an experiment was designed which took advantage of the f a c t t h a t C-2 of acetate i s the p r i n c i p l e precursor of CHi» i n sewage sludge (21) . Reactions were set up as described p r e v i o u s l y but i n t h i s case C - a c e t a t e was added as a methyl donor. The r e s u l t s are shown i n Table V. L a b e l from 2- ^ - a c e t a t e i s i n c o r p o r a t e d i n t o the t r a p s i n s i g n i f i c a n t amounts only when there i s concurrent a d d i t i o n of arsenate. There i s l i t t l e endogenous arsenate to act as a receptor f o r the methyl groups. Acetate l a b e l l e d i n C - l d i d not l a b e l the arsenate as e f f i c i e n t l y presumably because i t was d i l u t e d by e q u i l i b r a t i o n w i t h endogenous C O 2 . I t i s a good c o n t r o l showing t h a t acetate i t s e l f i s not incorporated i n t o the traps or i n t o a r s e n i c . While t h i s data can i n no way be construed as proof that the transformed a r s e n i c i s an a l k y l a r s i n e we f e e l t h a t i t i s a t l e a s t h i g h l y suggestive that t h i s i s the case. llf

1

Role of Methanogenic B a c t e r i a . The f a c t t h a t the methyl carbon of acetate i s r e a d i l y i n c o r p o r a t e d i n t o a r s e n i c i n the sludge mixture suggests that methanogenic b a c t e r i a are i n v o l v e d i n the b i o t r a n s f o r m a t i o n r e a c t i o n . Further proof that t h i s i s the case was provided by an experiment i n which CHCI3 was used to s e l e c t i v e l y poison the methane b a c t e r i a . Methanogenic b a c t e r i a are p a r t i c u l a r l y s u s c e p t i b l e to halogenated hydrocarbons (22) at l e v e l s which do not i n t e r f e r e w i t h the metabolic a c t i v i t y of other organisms. When CHCI3 (10~ M) i s incubated w i t h sewage i n the presence of arsenate and 2- C-acetate, CH^ b i o s y n t h e s i s i s i n h i b i t e d as i s the b i o s y n t h e s i s of a r s i n e . The c o r r e l a t i o n between CHi* b i o s y n t h e s i s and formation of C - l a b e l l e d a r s e n i c was noted i n other experiments i n which the sludge had decreased methanogenic a c t i v i t y . 6

lif

1 I f

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7.

MCBRiDE E T A L .

105

Alkijlation of Arsenic

A r s e n i c Transformation i n Other Anaerobic Ecosystems. Samples from a number of anaerobic ecosystems were incubated w i t h arsenate to determine i f they would produce a rubber r e a c t i v e d e r i v a t i v e . As shown i n Table VI the ecosystems which produced CHif a l s o transformed arsenate. P a r t i c u l a r note should be made of rumen f l u i d which i s p a r t i c u l a r l y e f f e c t i v e at transforming arsenate. This has important i m p l i c a t i o n s f o r animals which feed on a r s e n i c t r e a t e d foods and s u b s t a n t i a t e s the suggestion of Peoples (23) that a r s e n i c compounds are transformed i n the rumen. In summary we can say t h a t the c e l l e x t r a c t s of methanogenic b a c t e r i a w i l l convert arsenate to d i m e t h y l a r s i n e . An a r s i n e i s produced by whole c e l l s of t h i s organism but the nature of the a r s e n i c d e r i v a t i v e has not been determined. The methanogenic b a c t e r i a appear to p l a y an important r o l e i n the b i o t r a n s f o r m a t i o n of arsenate i n anaerobi The nature of the a r s e n i probably an a l k y l a r s i n e which r e a c t s r a p i d l y w i t h u n i d e n t i f i e d c o n s t i t u e n t s i n the environment. Aerobic M e t h y l a t i o n of A r s e n i c Challenger and h i s coworkers (1) showed that t r i m e t h y l a r s i n e was the v o l a t i l e g a r l i c - s m e l l i n g product, "Gosio gas", obtained when the mould S c o p u l a r i o p s i s b r e v i c a u l i s growing on bread crumbs i s exposed t o a r s e n i t e . They a l s o found t h a t S. b r e v i c a u l i s methylates, arsenate, methylarsonate, and cacod y l a t e to t r i m e t h y l a r s i n e , a n d that other a l k y l a r s o n i c and d i a l k y l a r s i n i c a c i d s are methylated to the appropriate methylarsine, e.g. (C H )(C H )AsO(OH) y i e l d s ( C H ) ( C H ) A s ( C H ) . Challenger a l s o e s t a b l i s h e d that aerobic a l k y l a t i o n by other microorganisms i s s u b s t r a t e dependent. Thus Pénicillium notaturn does not methyl a t e arsenate. In an i n t e r e s t i n g example of the same phenomenon the a l k y l a t i o n of benzene a r s o n i c a c i d to ( C H ) A s ( C H ) by Candida humicola proceeds w i t h ease (24) yet the same s u b s t r a t e i s unaffected by S. b r e v i c a u l i s (1). This r e s u l t i s p a r t i c u l a r l y p e r t i n e n t i n view of the wide spread use of aromatic a r s o n i c a c i d s as food a d d i t i v e s f o r chickens, turkeys, and swine (25) and the r e p o r t of g a r l i c l i k e odors above s o i l s t r e a t e d w i t h these compounds (26,27). C. humicola was f i r s t i n v e s t i g a t e d as an a r s e n i c methylating agent by Cox and Alexander (2^25) who found that i t acted on the same i n o r g a n i c and methyl a r s e n i c a l s u b s t r a t e s as S. b r e v i c a u l i s (1). More recent work shows that t h i s organism a l s o methylates longer chain a l i p h a t i c a r s o n i c a c i d s such as C^HgAsOiOH^. This r e s u l t i s seen i n experiment 14, Table V I I (28). For these e x p e r i ments C. humicola was grown i n l i q u i d c u l t u r e and the a r s i n e evolved from the added a r s e n i c a l was u s u a l l y trapped and examined by VPC/mass spec, or by d i r e c t i n j e c t i o n i n t o a mass spectrometer. In a number of experiments L-methionine-methyl-d , CD SCH CH CH(NH )C00H,was added and the r e s u l t s show considerable i n c o r p o r a t i o n of the CD l a b e l i n the evolved a r s i n e . S i m i l a r 2

5

3

7

2

5

3

7

3

6

5

3

3

3

2

2

2

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2

106

ORGANOMETALS

AND

ORGANOMETALLOIDS

Table IV- I d e n t i f i c a t i o n of Dimethylarsine. Each r e a c t i o n f l a s k contained: potassium phosphate b u f f e r , aden osine t r i p h o s p h a t e , crude c e l l e x t r a c t , [ jNaaHAsOi», [ C]CH3-Bi2, H , atmosphere. A r s i n e was trapped i n the serum stopper, serum stoppers were washed, placed i n Bray's s c i n t i l l a t i o n f l u i d f o r 1 h r . and then removed. The s c i n t i l l a t i o n f l u i d was counted simultaneously on two channels i n a Mark I I I s c i n t i l l a t i o n counter (Nuclear-Chicago). llf

2

Expt

Compound

Volatile

cpm

1

7

-As

28.0 χ

10

3

2

7

"As

16.7 χ

10

3

4.26 χ

10

mole of CH3 Groups or As

3

Ratio C: *As

lk

7t

0.0036

1.9

0.0020

2.1

0.0044

Table V. I n c o r p o r a t i o n of **C from C- -acetate i n t o A r s e n i c . Sewage sludge was incubated a n a e r o b i c a l l y . The rubber t r a p s were removed a f t e r 8 h r s . washed and counted. 1

lk

lk

C

(CPM χ

Heated

10 ) k

Unheated

lif

0

210

llf

0

7800

11+

0

75

ll

0

500

2- C-Acetate 2- C-Acetate + Arsenate 1- C-Acetate l- *C-Acetate + Arsenate

Table VI. Transformation of A r s e n i c i n Anaerobic Ecosystems. Samples from anaerobic ecosystems were placed i n a H2:C02(80:20 v/v) atmosphere and mixed w i t h N a 2 A s 0 i t ; a rubber trap was placed f o r CHi* and the t r a p f o r A s . C o n t r o l assays were per formed on samples which had been heated to 80 f o r 30 min. p r i o r to the a d d i t i o n of the i s o t o p e and the t r a p . As (CPM) CH*(nmoles) Unheated Heated Heated Unheated 7 t f

7if

sewage

70

7900

0

7000

marine mud

120

200

0

-7

rumen

900

4500

0

1200

compost

100

1524

0

5

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1 3

9

2

b

a

b

b

a

2

3

3

2

2

3

3

3

2

3

3

9

3

2

3

3

3

2

3

9

3

2

2

2

2

3

3

3

3

2

2

3

3

2

3

3

3

3

3

3

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

3

2

3

3

2

2

f

Arsenic compound

Candida humicola As 0 l a CH As0 Na CD As0 Na 3 CD As0 Na 4 (CH ) As0 H 5 (CH ) As0 H 6 (CH ) As0 H 7 (CH ) As0 H 8 a (CH ) As0 H (CH ) As0 H 10 (CH ) As0 H ll (CH ) As0 H 12 b (CH ) As0 H n-Ci*H As0 Na 14 (CH ) As0 H 15 Scopulariopsis brevicaulis 16b CD As0 Na CH As0 Na 17 (CH ) As0 H 18 n-Ci*H As0 Na 19 (CH ) As0 H 20 G l i o c l a d i u m roseum CH As0 Na 21* n-Ci*H9As0 Na 22

Expt. number

b

C

2.5 1.25 2.0c 2.5 2.5

5 5

-1.25

0.5 1 0.1 5 2.5 1.0 0.5 1.0 2.5 2.5

-5

2 2 2

2

2.5 2.5 2.5 2.5 2.5

5 5 5 5 5 5 1 1 5 5 5 5 0.5 5 5

2

3

2

Substrates (mM) L-CD SCH CH CH(NH )C00H 3

3

f

3

-

-

5.2 no a r s i n e s detected

23

-

2

73

e

e

2

9

3

3

-

—

7.5 0.8

—

83 13.3 3.2 7.8 84.7 6.8 2.7 10.1 87 — 92 -3.6 80.5 3.2 39 2.6 1.4 — 71.4 — 40.7 82.5 2.4 2.7 85.3 2.1 1.0 78 0.6 1.4 74 0.7 0.7 - no a r s i n e s detected 16.1 77.9 - no a r s i n e s detected -

3

— 95.7 25.7 10.3 41.3 24 54 45.9* no a r s i n e s detected

d

3

β

4.3 56.5 33.9

-

6.06

0.6 0.7 <1 8 12.6 57 28.6 59.3 12.1 11.6 20 24.5

3

d

Deuterated species (%) (CH ) As CD As(CH ) (CD ) AsCH (CD ) As

e

s

Table VIL Volatile Arsines Produced by Microorganisms. Samples were collected during the fourth and fifth days after inoculation. * VPC/mass spec determination. Substrate added two days after inoculation. Ethionine. C^HgAsfCHs)». C^H As(CH!i)(CD ). CjHgAsfCDs),. * Collection was made over a 7-day period.

ORGANOMETALS AND ORGANOMETALLOIDS

108

i n c o r p o r a t i o n are found f o r S. b r e v i c a u l i s and f o r G l i o c l a d i u m roseum (28). The Mechanism of the Aerobic Methylation of A r s e n i c The r e s u l t s i n Table V I I s t r o n g l y i n d i c a t e that methionine, or S-adenosylmethionine, SAM, i s the source of the methyl group i n the b i o l o g i c a l a l k y l a t i o n o f a r s e n i c . They support the f o l l o w i n g o x i d a t i o n - r e d u c t i o n pathway i n v o l v i n g carbonium ions o r i g i n a l l y suggested by Challenger ( 1 ) . 3

V " 2e As 0^ — A

f i l l 3s 0

C H

3

3

+

2

γ " > CH As 0 3

3

-o "2

9p f_>

3

·· τ τ τ CH As O

2

i l J

3

V Ϊ (CH ) As 0 3

3

>

2

2e ——f

. ·· I I I (CH )As 3

-o 2

T h i s scheme was proposed on the b a s i s of the a b i l i t y of S. b r e v i c a u l i s t o produce t r i m e t h y l a r s i n e from a l l the arsenic(V) p r e cursors and t o produce l a b e l e d t r i m e t h y l a r s i n e from a r s e n i t e when C l a b e l e d D,L-methionine, *CH SCH CH CH(NH )C00H, was added to the c u l t u r e medium. The mechanism i s e s s e n t i a l l y the same as that of F i g . 4 except that the methyl donor i s i d e n t i f i e d as the chemically reasonably (29) methyl carbonium i o n and that the r e a c t i o n pro ceeds f u r t h e r , before the f i n a l r e d u c t i o n , i n the aerobic system. Challenger r e p o r t s that crude c e l l e x t r a c t s of S. b r e v i c a u l i s do not produce t r i m e t h y l a r s i n e when exposed t o a r s e n i c a l s . T h i s and other experiments (1) i n d i c a t e d that b i o l o g i c a l methylation by t h i s organism i s confined t o the mould c e l l , and does not take p l a c e i n the medium. I n t h i s connection some recent work on c e l l e x t r a c t s o f C. humicola a r e o f considerable i n t e r e s t (30). I t i s found that when the e x t r a c t i s incubated w i t h As l a b e l e d arsenate, SAM as methyl source, and NADPH as reducing agent, and the r e s u l t i n g supernatant l i q u i d a p p l i e d t o a Dowex 1 i o n exchange column, s e v e r a l d i s t i n c t a r s e n i c c o n t a i n i n g f r a c t i o n s can be e l u t e d as shown i n F i g . 7. These can be i d e n t i f i e d f o l l o w i n g e l e c t r o p h o r e s i s and autoradiography as being l a r g e l y a r s e n i t e , c a c o d y l i c a c i d , methylarsonic a c i d , and arsenate i n f r a c t i o n s 1 t o 4 r e s p e c t i v e l y . Experiments of t h i s s o r t can be r e f i n e d f u r t h e r and r e v e a l the presence o f other a r s e n i c c o n t a i n i n g f r a c t i o n s i n c l u d i n g t r i m e t h y l a r s i n e oxide. Thus, p r o v i d i n g SAM i s added, a l l the arsenic(V) intermediate i n Challenger's scheme can be i d e n t i f i e d i n c e l l e x t r a c t s of an organism which i s known to produce t r i m e t h y l a r s i n e . 11+

1I

3

2

2

2

7I+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7.

MCBRIDE E T

Alkylation of Arsenic

AL.

109

The r e s u l t of experiment 15, Table V I I i s p a r t i c u l a r l y i n t e r e s t i n g s i n c e , when e t h i o n i n e i s added i n place of methionine, no a r s i n e s are produced. The absence of e t h y l a r s i n e s argues a g a i n s t a p u r e l y chemical t r a n s f e r of an a l k y l group from sulphur to a r s e n i c , and the absence o f t r i m e t h y l a r s i n e argues s t r o n g l y f o r a methionine based enzyme i n v o l v e d s y n t h e t i c path s i n c e e t h i o n i n e i s a w e l l known antagonist to methionine (31). Along the same l i n e s i t has been found (.2,25) that phosphates i n h i b i t s the f o r mation of t r i m e t h y l a r s i n e from arsenate, a r s e n i t e , and methylarsonate, but not from cacodylate, by growing c u l t u r e s of C. humicola. The same organism can be p r e c o n d i t i o n e d by cacodyl a t e to produce t r i m e t h y l a r s i n e at a g r e a t e r than u s u a l r a t e from both arsenate and cacodylate (32). This i s seen i n F i g . 8. On the other hand,using the same organism, p r e c o n d i t i o n i n g w i t h arsenate r e s u l t s i n a dramati production from cacodylat production from arsenate. Model Studies Each step i n Challenger's mechanism i s c h e m i c a l l y reasona b l e . Indeed the a l k y l a t i o n steps are r e l a t e d to the w e l l known Meyer r e a c t i o n (20,32), which uses methyl i o d i d e or d i m e t h y l sulphate as the source of C H 3 + . Since SAM i s a sulphonium compound (34) other simpler analogues have been s t u d i e d w i t h respect to t h e i r a b i l i t y to methylate a r s e n i c (35). At pH 12 and 80°C (CH ) P"hPF ~ can be used f o r a l l the steps i n Challenger's scheme which i n v o l v e C H (these r e a c t i o n s can be monitored by NMR t e c h niques s i n c e the r e a c t a n t and products have d i s t i n c t chemical s h i f t s ) and each a r s e n i c ( V ) compound i n the scheme can be reduced to the a p p r o p r i a t e a r s e n i c ( I I I ) d e r i v a t i v e using S 0 . Thus the whole sequence can be e a s i l y d u p l i c a t e d . Methyl methionine i s o f t e n invoked as a model f o r SAM (34) and t h i s compound s l o w l y but i n c o m p l e t e l y , methylates CH AsO^~ at 25°C and a t the more r e a l i s t i c pH of 5.8. However a methyl sulphonium d e r i v a t i v e of CH -CoM under the same c o n d i t i o n s f a i l e d to t r a n s f e r i t s methyl group. 3

3

6

+

3

2

3

3

A r s e n i c Cycle i n the Environment Studies w i t h aerobic and anaerobic organisms have shown t h a t the former produce t r i m e t h y l a r s i n e whereas the l a t t e r produce the more c h e m i c a l l y r e a c t i v e d i m e t h y l a r s i n e . Taking these observat i o n s i n t o account, i t i s p o s s i b l e to p o s t u l a t e t h a t there i s an a r s e n i c c y c l e i n nature, a c y c l e that r e l i e s upon both b i o l o g i c a l and a b i o t i c r e a c t i o n s . Such a scheme i s o u t l i n e d i n F i g . 9. I t i s important not to view the r e a c t i o n s as being confined to sediment, water, or a i r but r a t h e r to ecosystems which are e i t h e r a e r o b i c or anaerobic because i t i s the a v a i l a b i l i t y of oxygen which w i l l determine the nature of the m i c r o b i a l f l o r a and w i l l i n f l u e n c e the f a t e and subsequent movement of the a r s i n e . Arsenate, a r s e n i t e , and methylarsonate r e a c t i n a s i m i l a r manner

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

AND

ORGANOMETALLOIDS

1400 1300 1000 ftoo

ο 4c «oo 400

1

Λ

200

0

/V'

10

30

20

AJ 40

50

4

60

FRACTION

Figure 7. Ion-exchange separation of C. humicola extracts incu bated with As-Na HAsOi, SAM, and NADPH. Peaks 1-4 are arsenite, cacodylic acid, methylarsonic acid, and arsenate, respec tively. 74

2

(CH ) As(nmote) 3 3

400"

Figure 8. Amount of (CH ) As in the headspace above growing 300· cultures of C. humicola precondi tioned in cacodylate (C and D) and not preconditioned (A and B). In Curves A and C the arsenical substrate is arsenate, in Β and D 0 it is cacodylate. s

s

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

7.

MCBRIDE E TA L .

Alkylation of Arsenic

ARSENIC

111

CYCLE

(

C H

a) * 3

,

"•(CH ) AiO(OH) 3

^

A»0(OH^=^A.(OH)3—•CH,>UO(OH) =*(CH^A.io(OH)—i a

2

I •(CH,)^A«H (CH,)i.-S^X

ί Figure 9. Biological arsenic cycle. (=) aerobic or anaerobic; (· - -) aerobic biotic or abiotic; ( ) anaerobic; ( ) aerobic; (++) these reactions are prob ably abiotic.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

112

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i n both a e r o b i c and anerobic ecosystem. Cacodylate i s an important branch p o i n t ; aerobes reduce and methylate t h i s compound t o form t r i m e t h y l a r s i n e , anerobes reduce i t t o d i m e t h y l a r s i n e . The t r i m e t h y l a r s i n e i s e v e n t u a l l y o x i d i z e d t o cacodylate which can be i n c o r p o r a t e d d i r e c t l y i n t o the c y c l e o r f u r t h e r m o d i f i e d t o methylarsonate o r arsenate by m i c r o b i a l a c t i v i t y . D i m e t h y l a r s i n e can be o x i d i z e d t o cacodylate but i t may r e a c t w i t h other chemical c o n s t i t u e n t s i n i t s environment and thus i n i t i a t e an e n t i r e l y new s e t o f r e a c t i o n s . The l a t t e r i s a reasonable hypothesis when one considers the r e a c t i v i t y o f the a r s i n e and the e n v i r o n ment i n which i t i s produced. Acknowledgements T h i s paper i s a c o n t r i b u t i o n from the B i o i n o r g a n i c Chemistry Group supported i n p a r grants from N.R.C. andM.R.C BIBLIOGRAPHY 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

C h a l l e n g e r , F. (1945). Chem. Rev., 36, 315. Cox, D.P. and Alexander, M. (1973). A p p l i e d M i c r o . 25, 408. McBride, B.C. and Wolfe, R.S. (1971). B i o c h e m i s t r y , 10, 4312. Wolfe, R.S. (1971). Adv. in Microb. P h y s i o l . 6, 107. Stadtman, T.C. (1967). Ann. Rev. Microbiol. 21, 121. Barker, H.A. (1956). " B a c t e r i a l Fermentations", P. 1 John Wiley and Sons, I n c . , New York. McBride, B.C. and Wolfe, R.S. (1971). Adv. in Chem. S e r . 105, 11. Zeikus, J.G. (1977). B a c t e r i o l . Rev. 41, 514. B l a y l o c k , B.A. and Stadtman, T.C. (1966). Biochem. Biophys. Res. Commun. 11, 34. W o l i n , M.J., Wolin, E.A. and Wolfe, R.S. (1963). Biochem. Biophys. Res. Commun. 12, 465. B l a y l o c k , B.A. (1968). Archs. Biochem. Biophys. 124, 314. Wood, J.M. and Wolfe, R.S. (1966). Biochemistry 5, 3598. Roberton, A.M. and Wolfe, R.S. (1969). Biochim. Biophys. A c t a . 192, 420. Bryant, M.P., Wohn, E.A., Wolin, M.J. and Wolfe, R.S. (1967). Arch. M i k r o b i o l . 59, 20. McBride, B.C. (1970). D i s s e r t a t i o n . U n i v e r s i t y o f Illinois, Urbana, Illinois. McBride, B.C. and Wolfe, R.S. (1971). Biochemistry 10, 2317. T a y l o r , C.P. and Wolfe, R.S. (1974). J. Biol. Chem. 249, 4879. Wood, J.M., Kennedy, F.S. and Rosen, C.G. (1968). Nature 220, 173. Wolin, E.A., Wolin, M.J. and Wolfe, R.S. (1963). J. Biol. Chem. 238, 2882.

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20.

21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34.

35.

MCBRIDE

ET

AL.

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113

R a i z i s s , G.W. and Gavron, J.L. (1923). Organic a r s e n i c a l compounds, New York, N.Y. The Chemical Catalog Co., pp. 38-49. Smith, P.H. and Mah, R.A. (1966). A p p l . M i c r o . 14, 368. Bauchop, T. (1967). J . Bact. 94, 171. Peoples, S.A. (1975). A r s e n i c a l P e s t i c i d e s A.C.S. Symposium S e r i e s #7, p. 1. A v e l i n o , N., C u l l e n , W.R., McBride, B.C. Unpublished results. Woolson, E.A., Ed. (1975). A r s e n i c a l P e s t i c i d e s A.C.S. Symposium S e r i e s #7, Washington, D.C. Woolson, E.A. and Kearney, P.C. (1973). E n v i r o n . Sci. Technol. 7, 47. Isensee, A.R., Kearney, P.C., Woolson, E.A., Jones, G.E. and W i l l i a m s , V.P (1973) E n v i r o n Sci. Technol 7, 841 C u l l e n , W.R., Froese D.J. and Reimer, M. (1977). J. Organometal. Chem. 139, 61. Zingaro, R.A. and Irgolic, K . J . (1975). Science 187, 7651. C u l l e n , W.R., McBride, B.C. and Pickett, A.W. Unpublished results. Simmonds, S., Keller, E.B., Chandler, J.P. and duVigneaud, V. (1950). J. Biol. Chem. 183, 191. C u l l e n , W.R., McBride, B.C. and Reimer, M. Bull. E n v i r o n . Contam. T o x i c o l . , in p r e s s . Quick, A.J. and Adams, R. (1922). J . Amer. Chem. Soc. 44, 805. S a l v a t o r e , F. Borek, E., Zappia, V., Williams-Ashman, H.G., Schlenk, F., Eds. (1977). The Biochemistry o f Adenosyl methionine, Columbia U n i v e r s i t y P r e s s , New York, 1977. Chopra, A.K., C u l l e n , W.R., D o l p h i n , D. Unpublished r e s u l t s .

Discussion J . M. WOOD ( U n i v e r s i t y of Minnesota): I want t o ask t h i s question on b e h a l f of P r o f e s s o r C h a l l e n g e r , because i n h i s review a r t i c l e he a l l u d e s t o the p o s s i b l e r o l e o f coenzyme M i n methyl a t i o n of a r s e n i c by Methanobacteria. He has a s p e c u l a t i v e p a r a graph i n which he suggests t h a t the dimethylsulphonium d e r i v a t i v e would be a very good candidate f o r m e t h y l a t i o n of a r s e n i c . The methyl coenzyme M i t s e l f i s a bad candidate. Have you any i d e a whether h i s suggestion i s a good one? McBRIDE: enzyme M.

We haven't t r i e d any other compound on methyl c o

W. R. CULLEN ( U n i v e r s i t y of B r i t i s h Columbia): I n model s y s tems, t h a t methyl t r a n s f e r does take p l a c e from the methyl coen zyme M t o a r s e n i c ( I I I ) . Any sulphonium compound w i t h a methyl transfers to arsenic.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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G. Ε. ΡARRIS (Food and Drug A d m i n i s t r a t i o n ) : Do you have k i n e t i c data f o r t h i s t r a n s f e r that you are t a l k i n g about?

this.

CULLEN: Yes, we have attempted t o measure some k i n e t i c s on I t ' s a v e r y d i f f i c u l t system t o work on.

M. 0. ANDREAE ( S c r i p p s I n s t i t u t e of Oceanography): Do you have evidence f o r the formation of l a r g e r compounds ; would you see them i f they were formed? McBRIDE:

By l a r g e r compounds do you mean complexes?

ANDREAE:

Yes, arseno-betaine or something l i k e t h a t .

McBRIDE: We don't hav d evidence but r e c e n t l ran a Sephadex column, a c t i v e f r a c t i o n t h a t i n d i c a t e s a h i g h molecular weight. ANDREAE: D i d you do a mass balance t h a t w i l l t e l l you how much of the l a b e l can be accounted f o r by arsenate and other com pounds? McBRIDE:

Yes, we can account f o r 100%.

ANDREAE: In your experiments w i t h the marine mud, were you u s i n g a rubber t r a p t o assay f o r the a r s i n e or was t h a t determined by head space a n a l y s i s ? McBRIDE:

No, there was a t r a p .

F. E. BRINCKMAN ( N a t i o n a l Bureau of Standards): I'm i n t r i g u e d by t h i s apparent complexation on the Dowex column. I s i t engendered by the b i o a c t i v i t y ? That i s , might there be a t h i r d component t h a t leads t o complexation of these a r s e n i c species? [McBRIDE: Yes] T y p i c a l l y , under the c o n d i t i o n s you use f o r e l u t i o n , these are an i o n i c species from the pKa v a l u e s . In our l a b o r a t o r y , f o r HPLC, we use both weak and s t r o n g anion and c a t i o n columns and can make s a t i s f a c t o r y s e p a r a t i o n s of demethylated me t a b o l i t e s from s o i l b a c t e r i a i n v o l v i n g the m e t h y l a r s e n i c a l p e s t i c i d e s . We see no evidence of t h i s k i n d of complexation. We are concerned about higher molecular weight e l u a n t s because of your work and t h a t of P r o f e s s o r I r g o l i c concerning the b e t a i n e or other p o s s i b l e a n i o n i c species w i t h a l a r g e molecule pendant. McBRIDE: I t seems t o be r e a l , and i t seems to be a s s o c i a t e d w i t h a b i o l o g i c a l l y a c t i v e e x t r a c t . I f you i n a c t i v a t e the e x t r a c t you don't see these. You can use l a b e l s (C-14 c a c o d y l , C-14 meth y l a r s o n i c a c i d , As-74 arsenate) and you do not see these complexes form. E v e r y t h i n g e l u t e s at the a p p r o p r i a t e p o i n t , but when you have a b i o l o g i c a l l y a c t i v e system, then you see t h i s change t o

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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what we t h i n k i s a complex formation. I t ' s very dramatic when you look at C-14 cacodyl as a s u b s t r a t e r a t h e r than as arsenate. A l most 99% of the m a t e r i a l moves i n t o a f r a c t i o n which e l u t e s w i t h water. BRINCKMAN: This i s a very c l e a r demonstration that c a u t i o n should be e x e r c i s e d i n s p e c i a t i n g these t r a c e m a t e r i a l s , metabol i t e s p a r t i c u l a r l y , when u s i n g methodology l i k e Braman's technique of r e d u c t i v e v o l a t i l i z a t i o n to form h y d r i d e s . You may l o s e a r a t h e r c r i t i c a l molecule which i s important f o r c o u p l i n g s e v e r a l i o n i c species and which may be i n d i c a t i v e of the mechanistic pathway. K. J . IRGOLIC (Texas A & M u n i v e r s i t y ) : You a l l u d e to the p o s s i b l e transformation f t r i m e t h y l a r s i n dimethylarsini acid i n some of your systems c o n d i t i o n s , i t ' s a r e l a t i v e l y slo r e a c t i o n , but you brea dow the compound, l o s e one methyl group, and end up w i t h d i a l k y l a r s i n i c s from t r i a l k y l a r s i n e s . ANDREAE: Your marine mud produces h a r d l y any methane. Where d i d you get t h a t mud? Some marine muds produce methane, some do not. McBRIDE: We d i d n ' t f i n d any marine mud that was producing l o t of methane although o b v i o u s l y they e x i s t . ANDREAE: i n the core?

Was

your mud

a

sample from a r e l a t i v e l y shallow l e v e l

McBRIDE: No, we went f a i r l y deep. There was a l o t of s u l f u r i n these muds, whether t h a t was i n f l u e n c i n g what was going on, I don't know. RECEIVED

August

22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

8 Arsenic Uptake and Metabolism by the Alga Tetraselmis Chui N. R. BOTTINO—Department of Biochemistry and Biophysics, Texas A & M University, College Station, TX 77843 E. R. COX—Department of Biology, Texas A & M University, College Station, TX 77843 1

K. J. IRGOLIC, S. MAEDA , W. J. McSHANE, R. A. STOCKTON, and R. A. ZINGARO—Department of Chemistry, Texas A & M University, College Station, TX 77843 Not too many years ag s c i e n t i f i c concern about substances present in very low concentrations in the a i r , water or soil. Knowledge about their presence was not at hand. Now, because of the efforts of many analytical chemists a number of these trace elements and their compounds have been identified and quantified. We know now that a whole spectrum of compounds i s present at trace level concentrations in the environment. We also know that many of them are, or may be potentially harmful. Arsenic i s one of the elements which is widely distributed in the earth's environment. Arsenic has a complicated chemistry. It forms a great variety of organic and inorganic compounds of variable potency with regard to their effects on l i v i n g organisms. Arsenic compounds are amenable to chemical transformation through interactions with biological systems. It has been known for almost one hundred years, that molds convert the arsenic present in green paint pigments into a volatile arsenic compound which was identified as trimethylarsine (1). The biological methylation of arsenic compounds producing methylarsines is now a well-established fact (2, 3, 4, 5). Methylcobalamin has been implicated as the methyl donor (2), but recently, Cullen and coworkers (5a) have made the Tmportant discovery that when L-methionine-methyl-d is added to certain microbial cultures, the CD label is incorporated into the evolved arsenic. This is good evidence that S-adenosylmethionine i s involved in the biological methylation process. Lunde (6) found arsenic compounds in the lipids of marine and limnetic organisms. Acid hydrolysis of the arsenic-containing l i p i d fractions produced water soluble, organic arsenic compounds. The isolation of arsenobetaine from rock lobsters was reported by Edmonds et al. (7) in 1977. These findings prove that transformations more complex than simple methylation do occur to 3

3

Present Address: Department of Applied Chemistry, Faculty of Engineering, Kagoshima University, Kagoshima 890, Japan. 1

0-8412-0461-6/78/47-082-116$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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systems.

A r s e n i c Incorporation and Algal Growth. Three years ago an i n v e s t i g a t i o n on the metabolism o f arsenate by marine algae was i n i t i a t e d a t Texas A&M U n i v e r s i t y . The goal o f the project was and s t i l l i s the i s o l a t i o n , i d e n t i f i c a t i o n and c h a r a c t e r i z a t i o n o f organic a r s e n i c compounds formed by the algae from arsenate under c a r e f u l l y c o n t r o l l e d c o n d i t i o n s . Preliminary experiments with a v a r i e t y o f marine algae l e d to the use o f Tetraselmis ehui, a green f l a g e l l a t e (Chlorophyta), as a convenient experimental organism. This alga grows w e l l , takes up a r s e n i c e f f i c i e n t l y and i s r a t h e r i n s e n s i t i v e toward mechanical shock which accompanies the harvesting o p e r a t i o n s . T. ehui was found to t o l e r a t e well exposure to 10 ppm As(arsenate) when grown i n a r t i f i c i a l sea water, and i n f a c t , at the beginning o f the s t a t i o n a r y phase the growth medium contained The a r s e n i c uptake by T. ehui depended on the l i g h t i n t e n s i t y . At a l i g h t i n t e n s i t y o f 12,500 lux the a r s e n i c content o f the c e l l s increased f i r s t to a pronounced maximum w i t h i n several days and then decreased r a p i d l y to a very low l e v e l . At 7000 lux the a r s e n i c l e v e l i n the c e l l s remained at h a l f the concentration reached at 12,500 l u x . The d e t a i l e d causes f o r t h i s behavior remain unknown, but i t can be p o s t u l a t e d that s i n c e arsenate absorption i s an endergonic process (9) i t might compete with c e l l growth f o r the a v a i l a b l e photosynthetic energy. Large-Scale Algal Growth and A r s e n i c - P r o t e i n I n t e r a c t i o n s . The c h a r a c t e r i z a t i o n o f the a r s e n i c - c o n t a i n i n g compounds present i n τ. ehui r e q u i r e d the i s o l a t i o n o f 300-500 mg amounts o f these compounds f o r f u r t h e r p u r i f i c a t i o n and a n a l y s i s . This could not be done with the t e s t - t u b e c u l t u r e s used i n the preceding ex periments. Consequently, an alga growing f a c i l i t y was con s t r u c t e d t o r a i s e T. ehui under c o n t r o l l e d c o n d i t i o n s i n c l u d i n g p r o t e c t i o n from other organisms such as b a c t e r i a . The f a c i l i t y c o n s i s t s o f a converted c o l d storage room, which houses four 1 5 0 0 - l i t e r tanks. This c u l t u r e room i s a i r - c o n d i t i o n e d , well i n s u l a t e d and i s kept under p o s i t i v e a i r pressure. Ultraviolet l i g h t s are s t r a t e g i c a l l y placed to minimize b a c t e r i a l contamin ation. The tanks are i l l u m i n a t e d by banks o f f l u o r e s c e n t l i g h t s . B a l l a s t s are mounted outside the c u l t u r e room t o reduce the heat load on the a i r c o n d i t i o n e r . The growth medium i s mixed i n a c o n t r o l room. The tanks can be f i l l e d , i n o c u l a t e d , aerated, sampled and harvested without e n t e r i n g the c u l t u r e room, through an appropriate system o f pipes and v a l v e s . Each large tank produces approximately one l i t e r o f t i g h t l y packed algae w i t h i n 20 days. Figure 1 i l l u s t r a t e s the t y p i c a l type o f experiments run with the l a r g e - s c a l e growing f a c i l i t y . When A s - l a b e l e d d i s sodium hydrogen arsenate was added to the growth medium at the same time as the inoculum, the algae reproduced r a p i d l y f o l l o w i n g 7 4

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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A N D ORGANOMETALLOIDS

lure 1. Large-scale growth and arsenic uptake by T. ehui instant ocean medium containing 10 ppm As (arsenate) added at the time of inoculation

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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an i n i t i a l l a g p e r i o d , i n a r t i f i c i a l sea water c o n t a i n i n g 10 ppm arsenate. In separate experiments, the arsenate was added to the growing c u l t u r e s during t h e i r exponential phase o r s t a t i o n a r y phase. In the experiment depicted i n Figure 1 the arsenate was added at zero time, i . e . , at the time the medium was i n o c u l a t e d . The curves show p e c u l i a r , but recurrent f l u c t u a t i o n s r e s u l t i n g from changes i n the rate o f i n c o r p o r a t i o n and e f f l u x o f a r s e n i c i n t o and out o f the c e l l s . The two phenomena seem to reach an e q u i l i b r i u m a t the time the a l g a l c e l l s reach the s t a t i o n a r y phase o f growth (about day 14). Other experiments (not shown) i n d i c a t e d that intake and e f f l u x o f ^ A s e q u i l i b r a t e d at approx imately the same l e v e l shown i n Figure 1, whether the ^ a r s e n a t e was added a t the time o f i n o c u l a t i o n , during the exponential growth phase, or during the s t a t i o n a r y phase. The a l g a l c e l l s were a l s o grown i n the presence o f arsenate, then c o l l e c t e d at a tim c e l l s per ml and the c e l l population d i d not change a p p r e c i a b l y for two or three days. The c e l l s were then c e n t r i f u g e d and washed repeatedly with an A s - f r e e medium to remove any arsenate adhering to the c e l l s u r f a c e s . The a l g a l c e l l s were then homogenized i n chloroform/methanol (2:1 v/v) and e x t r a c t e d repeatedly with t h i s solvent mixture u n t i l a l l the green pigments had been removed and the residue assumed a grayish-white appearance. Approximately one h a l f o f the a r s e n i c was i n the organic e x t r a c t ; the other h a l f remained i n the r e s i d u e . The a r s e n i c d i s t r i b u t i o n between these two phases v a r i e d somewhat from batch to batch. When the residue was t r e a t e d with 1 M HC1 and the r e s u l t i n g s o l u t i o n was d i s t i l l e d , a l l the a r s e n i c remained i n the d i s t i l l a t e as a r s e n i t e as i n d i c a t e d by polarography and by reduction to a r s i n e . Hot.water e x t r a c t e d considerable amounts o f a r s e n i c from the r e s i d u e . When four ml o f methanol were added t o one ml o f aqueous e x t r a c t the p r e c i p i t a t e contained a l l the a r s e n i c . When i n c r e a s i n g amounts o f Na2HAsÛ4 were added t o f i x e d volumes o f the water e x t r a c t and the r e s u l t i n g s o l u t i o n s were mixed with methanol, a l l the arsenate p r e c i p i t a t e d q u a n t i t a t i v e l y when 500 yg o f As or l e s s were added. A r s e n i c added i n excess o f 1 mg remained i n the supernatant. The a r s e n i c content of the p r e c i p i t a t e reached a maximum value o f approximately 1 mg As (Figure 2 ) , i n the p r e c i p i t a t e obtained from one ml of the aqueous e x t r a c t . Most o f the a l g a l growth experiments were c a r r i e d out with arsenate tagged with the gamma-emitting A s isotope. When the p r e c i p i t a t i o n s with methanol a f t e r a d d i t i o n o f n o n - r a d i o a c t i v e Na£HAs04 were repeated, but only the ' ^ A s - c o n t e n t o f the p r e c i p i t a t e s and the supernatants determined, the r e s u l t s summarized i n Figure 3 were obtained. Exchange o f n o n - r a d i o a c t i v e arsenate f o r the r a d i o a c t i v e a r s e n i c compounds occurred only a f t e r approximately 500 yg As(arsenate) had been added t o one ml o f aqueous e x t r a c t . Both the p r e c i p i t a t e formed upon methanol a d d i t i o n , and the supernatant gave p o s i t i v e ninhydrin and b i u r e t t e s t s i n d i c a t i n g the presence o f 7

7 4

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Figure 2. The arsenic content of the precipitates and supernatants obtained upon addition of arsenate and then methanol to the aqueous arsenic-containing extracts of the residue from the CHCls/CH OH extraction of T. ehui s

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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121

Figure S. The distribution of As activity between the precipitates and supernatants obtained upon addition of arsenate and then methanol to the aqueous arsenic-containing extracts of the residue from the CHCl /CH OH extraction of T. ehui 74

s

s

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amino groups and p r o t e i n . These observations are c o n s i s t e n t with the working hypothesis that arsenate forms a complex with a p r o t e i n located i n the algal c e l l membrane p r i o r to i t s chemical transformation by the biochemical apparatus o f the c e l l . The separation o f t h i s complex by chromatographic techniques i s i n progress. I s o l a t i o n and C h a r a c t e r i z a t i o n o f A s - C o n t a i n i n g L i p i d s . The combined organic s o l u t i o n s obtained by homogenizing the a l g a l c e l l s i n chloroform/methanol were dark green. The removal o f these pigments from the a r s e n i c compounds was d i f f i c u l t . The separation scheme which l e d t o the i s o l a t i o n o f an a r s e n i c - c o n t a i n i n g l i p i d f r a c t i o n free o f green compounds i s summarized i n Figure 4. A d d i t i o n o f water t o the e x t r a c t produced a chloroform l a y e r which contained a l with acetone removed th the chloroform phase (10). Gel f i l t r a t i o n chromatography on Sephadex LH-20 o f the green p r e c i p i t a t e produced green, a r s e n i c c o n t a i n i n g bands, which were then chromatographed on DEAE C e l l ulose employing a sequence o f solvents ranging from chloroform, chloroform/methanol, (9:1 v/v) chloroform/methanol/acetic a c i d (3:1:1 v/v/v) to a c e t i c a c i d . The brownish-green a r s e n i c f r a c t i o n s were f u r t h e r p u r i f i e d by preparative high pressure l i q u i d chromatography on S i l i c a gel with chloroform/methanol/ a c e t i c acid/water (17:3.5:2:1 v/v/v/v). A s l i g h t l y brown o i l was obtained. A n a l y t i c a l HPLC o f t h i s o i l on S i l i c a gel using a Hitachi Zeeman Graphite Furnace Atomic Absorption Spectrometer as an a r s e n i c - s p e c i f i c detector showed that a t l e a s t two a r s e n i c compounds were present (Figure 5). T h i n - l a y e r chromatography on S i l i c a gel H using a mixture o f chloroform methanol a c e t i c a c i d water ( 5 0 : 2 5 : 8 : 4 , v/v) (11_) as the developing solvent showed two major a r s e n i c - c o n t a i n i n g com pounds with Rf values o f 0.41 (compound A) and 0.61 (compound B) and one major component without a r s e n i c (compound C) with an Rf o f 0.85. F r a c t i o n A was the l a r g e s t , followed by f r a c t i o n s Β and C. Compound A co-chromatographed with phosphatidyl c h o l i n e , compound Β with phosphatidyl s e r i n e and compound C with phospha t i d y l ethanolamine and monogalactosyl d i g l y c e r i d e . A standard o f sulfoquinovosyl d i g l y c e r i d e was not a v a i l a b l e at the time these experiments were r u n , but i t s Rf i n the solvent system used would have been considerably lower than 0.41. Further experiments are i n process which involve the use o f other solvent systems, appropriate standards and c o l o r reactions f o r the r e c o g n i t i o n o f s p e c i f i c chemical groups. The f a t t y a c i d compositions o f compounds A, Β and C were determined by g a s - l i q u i d chromatography and are shown i n Table I. The most remarkable c h a r a c t e r i s t i c o f these data i s the extremely low l e v e l o f C20 to C22 h i g h l y unsaturated f a t t y a c i d s . Such acids have been found at much higher concentrations i n the phospholipids o f several algae (12). It i s p o s s i b l e that the

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

BOTTiNO E T A L .

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TETRASELMIS CHUI centrifugation

l ! =

ι Growth Medium

CELLS

homogeniz at i o n C/M 2:1

E = = ^

J

Water/Methanol

Filtrate

g e l - f i l t r a t i o n LH-20 C/M 3:1

I Discard

e

» As-CONTAINING BANDS

DEAE C e l l u l o s e Ion exchange C; C/M; C/M/A; A

1»

C M A W

= = = •

Chloroform Methanol Acetic Acid Water

Figure 4.

As-CONTAINING FRACTIONS s i l i c a gel C/M/A/W prep. HPLC H Discard

discard

ARSENIC COMPOUNDS

Scheme for the chromatographic isolation of an arsenic-containing phospholipid fraction

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

A N D ORGANOMETALLOIDS

Figure 5. Chromatographic separation and detection of two arsenic compounds in a phospholipid fraction isolation from T. ehui. (HPLC Microporosil (25 cm); CHCl /CH OH/CH COOH/H O, 17:3.5:2:1;flowrate, 0.5 mL min^/l-min fractions; Hitachi-Zeeman AA Model 170-70,193.6 nm.) s

s

s

t

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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Arsenic Uptake by Alga

Table I . Major F a t t y Acids o f P o l a r L i p i d s from Tetraselmis ehui

Weigh Percent TLC f r a c t i o n s y

Unfractionated

d/

A

Β

d/ C

3.6

5.5

4.3

5.2

18:0

3.8

18.3

10.5

24:0

2.6

1.4

0.9

28.5

10.4

11.3

29.6

Fatty Acid 14:0

d/

16:0

13:1

12.8

e/ 16:1 w7 e/ 18:1 w9

17.5

20:1 w9

10.2

18:2 20:4

1.7 11.9 2.8

3.9

5.7

0.4

3.1

17.4

5.4

8.3 21.2 2.0

17.0 1.8

7.4

1.2 3.3 0.1

2.3 1.8

f/ UNKNOWN

— .Only f a t t y a c i d s present a t a l e v e l o f 2% o r more are i n c l u d e d . — Chain l e n g t h : number o f double bonds, w = p o s i t i o n o f f i r s t i double bond counting from the methyl end. — TLC = t h i n - l a y e r chromatography w i t h a mixture o f chloroform: methanol:acetic acid:water (50:25:8:4, v/v) as developing solvent. ~^R o f Fractions*. A = 0.41; Β = 0.61; C = 0.85. T / l t may c o n t a i n other isomers. — R e t e n t i o n time r e l a t i v e t o 18:1 = 0.60, on s i l i c o n i z e d d i e t h y l e n e g l y c o l s u c c i n a t e p o l y e s t e r a t 170°C. f

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prolonged e x t r a c t i o n procedure might have caused t h e i r l o s s . Elemental analyses o f the a r s e n i c - c o n t a i n i n g l i p i d s a f t e r chromatography on S i l i c a gel (Figure 4) showed a r s e n i c present at a l e v e l o f 0.5 percent and confirmed the presence of C, Η, Ρ and Ν i n r a t i o s c h a r a c t e r i s t i c o f those in phosphatidyl c h o l i n e . Pure phosphatidyl arsenocholine would have an a r s e n i c content o f 8.8 percent. HPLC separation and enzymatic and chemical h y d r o l y s i s experiments are in progress to i s o l a t e the a r s e n i c - c o n t a i n i n g components from the a l g a l l i p i d f r a c t i o n . In 1976 at the I n t e r n a t i o n a l Conference on Environmental Arsenic at Fort Lauderdale, we suggested (13) that a r s e n i c could replace nitrogen i n c h o l i n e . The arsenocholine I could then become part of a l i p i d 2 bonded to the phosphate group of a phosphatidyl r e s i d u e .

CH.

CH.

CH -As-CH C00 3 i c

CH -As^CH CH -0H o

2

o

2

o

CH.

CH.

CH -0-C-R 2

i

I

CH-O-C-R CH -0-f-0-CH CH -As(CHj) 2

2

2

3

0

The r e s u l t s obtained thus f a r with the a l g a l l i p i d s are c o n s i s t e n t with t h i s hypothesis. The i s o l a t i o n by Edmonds e t a l _ . , o f arsenobetaine 3 from rock l o b s t e r s (7) shows that an a r s e n i c

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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compound very s i m i l a r to arsenocholine e x i s t s i n nature. I t has been observed (14, 15) that a r s e n i c - c o n t a i n i n g compounds from various organisms would y i e l d v o l a t i l e a r s i n e s upon reduction with sodium borohydride, but only a f t e r the sample had been d i gested with 2H sodium hydroxide. We subjected s y n t h e t i c samples o f arsenobetaine and arsenocholine f i r s t to sodium hydroxide d i g e s t i o n and then to sodium borohydride reduction t o determine i f methylarsines were generated. Arsenocholine, under these c o n d i t i o n s , was found to produce, at b e s t , only t i n y traces o f dimethylarsine or t r i m e t h y l a r s i n e , but arsenobetaine d i d r e a d i l y . The a r s e n i c - c o n t a i n i n g l i p i d s i s o l a t e d from T. ehui do form dimethylarsine or t r i m e t h y l a r s i n e under these c o n d i t i o n s . Be cause betaine i s not a common c o n s t i t u e n t o f l i p i d s , i t i s un l i k e l y that a r s e n i c i s incorporated i n t o l i p i d s i n the form o f arsenobetaine. Arsenocholine might, however, be capable o f being converted t o arsenobetaine conversion i s s i g n i f i c a n t i n organisms, can be answered a f t e r the a r s e n i c - c o n t a i n i n g l i p i d s have been i d e n t i f i e d . The chemical s t r u c t u r e o f the a r s e n i c compounds formed by T. ehui from arsenate should soon be known. The s t a r t i n g mat e r i a l and the end products o f t h i s b i o l o g i c a l conversion w i l l then have been i d e n t i f i e d . Future work w i l l have to be c a r r i e d out to e l u c i d a t e the biochemical pathway o f t h i s transformation. I n v e s t i g a t i o n s o f t h i s nature w i l l f i n a l l y lead to the develop ment o f metabolic charts f o r a r s e n i c and other t r a c e elements s i m i l a r to those now a v a i l a b l e f o r l i p i d s , carbohydrates, n u c l e i c acids and p r o t e i n s . U n t i l such t r a c e element metabolic pathways have been worked o u t , the d e t a i l s o f the i n t e r a c t i o n s o f t r a c e elements with l i v i n g organisms cannot be understood. Basic r e search that would e v e n t u a l l y achieve t h i s important goal has been i n i t i a t e d i n several laboratories. Acknowledgement: These i n v e s t i g a t i o n s were supported by the National I n s t i t u t e o f Environmental Health Sciences (Grant No. 5 ROI ES01125), by the Robert A. Welch Foundation o f Houston, Texas, and by the Texas A g r i c u l t u r a l Experiment S t a t i o n . Literature Cited 1. 2. 3.

4. 5.

Challenger, F . , Chem. R e v . , (1945) 36, 315. McBride, B. C., and Wolfe, R. S., Biochemistry, (1971) 10, 4312. Schrauzer, G. N . , Seek, J. Α . , H o l l a n d , R. J., Beckham, T . Μ., Rubin, Ε. Μ., and S i b e r t , J. W., B i o i n o r q . Chem., (1972) 2, 93. R i d l e y , W. P . , D i z i k e s , L., Chek, Α . , and Wood, J. Μ., Environ. Health P e r s p e c t . , (1977) 19, 43. Wood, J. Μ., S c i e n c e , (T974) 183, 1049.

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5a. C u l l e n , W. R., Froese, C. L . , L u i , Α., McBride, B. C., Patmore, D. J., and Reimer, Μ., J. Organometal. Chem., (1977) 139, 61. 6. Lunde, G . , E n v i r o n . Health P e r s p e c t . , (1977) 19, 47. 7. Edmonds, J. S., F r a n c e s c o n i , Κ. Α . , Cannon, J. R., Raston, C. L . , S k e l t o n , B. W., and White, Α. Η., Tetrahedron L e t t . , (1977) (18) 1543. 8. B o t t i n o , N. R., Newman, R. D . , Cox, E . R., S t o c k t o n , R., Hoban, Μ., Zingaro, R. A. and Irgolic, K. J., J. Exp. Mar. Biol. Ecol., in p r e s s . 9. B l a s c o , F., P h y s i o l . V e g . , 13 (1975) 185. 10. Kates, Μ., "Techniques o f L i p i d o l o g y : I s o l a t i o n , Analysis and I d e n t i f i c a t i o n o f L i p i d s " . American E l s e v i e r P u b l i s h i n g Co., New York, Ν. Υ . , 1972; p. 393. 11. S k i p s k i , V. P . , Peterson, R. F., and B a r c l a y , Μ., Biochem. J., (1964) 90, 374 12. N i c h o l s , B. W., "Comparative L i p i d Biochemistry o f Photo s y n t h e t i c Organisms", i n Harborne, J. B . , e d . , "Phyto chemical Phylogeny". Academic P r e s s , London, 1970, p. 105. 13. I r g o l i c , K. J., Woolson, Ε. Α . , S t o c k t o n , R. Α . , Newman, R. D . , B o t t i n o , N. R., Zingaro, R. Α . , Kearney, P. C., P y l e s , R. Α . , Maeda, S . , McShane, W. J. and Cox, E. R., Environ. Health P e r s p e c t . , (1977) 19, 61. 14. C r e c e l i u s , Ε. Α . , Environ. Health P e r s p e c t . , (1977) 19, 147. 15. Edmonds, J. S . , and F r a n c e s c o n i , Κ. Α . , Nature, (1977) 265, 436.

Discussion Y. K. CHAU (Canada Centre f o r Inland Water Research): How do you separate the methylation due t o b a c t e r i a which generate the n e t h y l a r s e n i c compounds from c o n c e n t r a t i o n o f a r s e n i c a l s by algae? IRGOLIC: F i r s t of a l l , we t r y t o keep the b a c t e r i a out of the algae. We checked whether any t r i m e t h y l a r s i n e i s formed i n our a l g a l c u l t u r e s . We couldn't f i n d any w i t h As-74 t r a c e r s . These c u l t u r e s a r e not completely b a c t e r i a f r e e , but we b e l i e v e most of the transformation i s done w i t h i n the a l g a l c e l l and not by b a c t e r i a . M. 0. ANDREAE (Scripps I n s t i t u t e o f Oceanography): A word o f c o n f i r m a t i o n . We t r i e d t o see i f there i s a c o n t r i b u t i o n by bac t e r i a by comparing c u l t u r e s and monocultures of the same organism, rhere was no measurable d i f f e r e n c e , so I t h i n k that b a c t e r i a do aot c o n t r i b u t e s i g n i f i c a n t l y i n the k i n d of systems that you use. Did you make any attempt t o i d e n t i f y t h e substance that was released by your a l g a l system a f t e r 5 days o r whenever that b i g peak occurred? IRGOLIC: No, but there i s one experiment which I d i d n ' t de s c r i b e . We took these algae, grew them i n 10 p a r t s per m i l l i o n arsenate, and then determined t h e i r a r s e n i c l e v e l . We then r e suspended the algae i n arsenate-free medium and found that between 50% and 75% of the a r s e n i c comes r i g h t out. We would l i k e t o know

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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what form the a r s e n i c i s ; i t could simply be arsenate. The a r s e nate has t o go through the c e l l w a l l , perhaps t o form an arsenate complex there. The c e l l does the t r a n s f o r m a t i o n ; i t i n c o r p o r a t e s the a r s e n i c perhaps i n t o the l i p i d s . I f you d i s t u r b the c e l l , the arsenate can migrate r i g h t back out. We i n t e n d t o do t h i s ; we have now the s e n s i t i v i t y t o determinate t h i s arsenate by p o l a r ography. ANDREAE: Did you t r y t o deacylate the f r a c t i o n i n your l i p i d s o l u b l e e x t r a c t and see i f i t could be i d e n t i f i e d by e l e c t r o p h o r e s i s o r chromatography? IRGOLIC: We t r i e d some phospholipases w i t h the a r s e n i c act i v i t i e s p a r t i t i o n e d between the organic phase and the aqueous phase. We have not yet i n t e r p r e t e d th r e s u l t s ANDREAE: We t r i e d some d e a c y l a t i o o a l g a l i p i d s , and used the water e x t r a c t . C o e l e c t r o p h o r e s i s w i t h arsenocholine o r a r senobetaine was u n s u c c e s s f u l . G. E. PARRIS (Food and Drug A d m i n i s t r a t i o n ) : I s there any comment o r suggestion regarding formation o f a bond between a r s e n i c and the two-carbon u n i t i n b e t a i n e o r arsenobetaine o r a r senocholine? How does i t occur? IRGOLIC: Somehow we have t o go from arsenate t o whatever that organic compound i s . I f i t ' s arsenocholine o r arsenobetaine, t h a t i s s i m i l a r . But i f there are many steps i n between, we r e a l l y can't t a l k i n t e l l i g e n t l y about what i s happening unless we understand that metabolic pathway. There i s some i n d i c a t i o n t h a t organoarsenic compounds produced by transformations i n marine o r ganisms, e.g., shrimp o r c r a b s , do not seem t o be t o x i c when i n gested by man, as shown by Dr. C r e c e l i u s ["Methods and Standards f o r Environmental Measurement", W. H. K i r c h h o f f , ed., Proc. E i g h t h M a t e r i a l s Res. Symp., NBS Spec. P u b l . 464, Washington, D.C., 1977, p. 495]. W. R. CULLEN ( U n i v e r s i t y o f B r i t i s h Columbia): A compound i s o l a t e d from A t l a n t i c f i s h by Environment Canada was repeatedly p u r i f i e d , and we got back an a n a l y s i s r e c e n t l y ; i t had no a r s e n i c i n i t . B a s i c a l l y , i t was b e t a i n e o r something very l i k e b e t a i n e . We suggest that somehow there i s probably an arsenate that gets a s s o c i a t e d w i t h the b e t a i n e i n some way and can be l o s t through purification. IRGOLIC: I t was i n t e r e s t i n g t o hear Dr. McBride mention the a s s o c i a t i o n which then breaks up. We might see something l i k e t h i s i n some o f the c e l l w a l l s ( e x t r a c t r e s i d u e s ) . U n f o r t u n a t e l y , I t h i n k we are i n the dark about these a s s o c i a t i o n s . RECEIVED

August 2 2 ,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

9 The Chemistry of Organometallic Cations in Aqueous Media R. STUART TOBIAS Department of Chemistry, Purdue University, West Lafayette, IN 47907

A number of organometalli moderately stable in aqueou these are the following species: Group IVB, R Ge , R Sn , R Sn , R Pb , R Pb ; Group IIIB, R Ga , R In , R Tl ; Group IIB, RHg ; Group IB, R2Au ; Group VIIIA, R Pt . Several of the methyl derivatives, R = CH , can be produced by the action of methanogenic bacteria or by reaction of methylcobalamin with inorganic compounds of the appropriate metal, but data on methylation under environmental conditions are mainly limited to mercury(II). Most of the information available on the aqueous chemistry pertains to the methyl species since these have the highest s o l u b i l i t y . Characteri s t i c a l l y these ions are sigma-bonded carbanion complexes of the metal in i t s maximum oxidation state. In 1966, the aqueous chemistry of organometallic cations was reviewed (1), but interest in environmental effects of several of these species in recent years has stimulated a good deal of new work. Although the reactions of metal ions in biological systems are exceedingly complex, a knowledge of the hydrolysis constants and s t a b i l i t y constants with a limited number of ligand types will permit a number of predictions about the ionic binding and transport. [In this discussion, unless otherwise indicated, hydrolysis will refer to proton transfer from a coordinated water molecule rather than M-C or M-X bond cleavage in the presence of water.] Thermodynamics will play a large part in governing the reactions of these organometallic species. Without exception, the methyl derivatives are highly labile to substitution at the metal center. In certain cases with bulky alkyl groups, reactions may proceed more slowly because of steric effects. Heterogeneous reactions, e.g. dissolution, are slower with large alkyl groups. Because of their hydrophobic nature, they r e s t r i c t attack at the metal center. 3

2+

+

2

3

+

2+

+

2

3

+

2

2

+

+

2

+

3

3

0-8412-0461-6/78/47-082-130$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

9.

Organometallic Cations

TOBIAS

131

This review w i l l concentrate on the i n t e r a c t i o n of these organometallic c a t i o n s with the solvent water, and a t t e n t i o n w i l l be focused on those ions o f environmental i n t e r e s t , namely the d e r i v a t i v e s o f mercury(II), t i n ( I V ) , and l e a d ( I V ) . The i n t e r a c t i o n with water i s a strong one, i t i s not normally encountered i n the organometallic chemistry o f these elements, and i t has a major influence on r e a c t i o n s a t the metal c e n t e r . Some o f the more a c i d i c species e x h i b i t amphoteric behavior, i . e . the organometallic oxides d i s s o l v e i n a c i d to give c a t i o n i c and i n base to give a n i o n i c s p e c i e s . Strong solvent i n t e r a c t i o n s are responsible f o r the absence from the l i s t above o f organometallic c a t i o n s o f c e r t a i n p e r f e c t l y s t a b l e organometallic m o i e t i e s , e . g . R2Ge(IV) and RSn(IV). These i n t e r a c t so strongly with water that they normally are encountered only as the hydrated o x i d e s . An even more extreme exampl which e x i s t s i n s o l u t i o n only i n the neutral or a n i o n i c form, (CH ) As0 ". U n t i l about a decade ago, i t g e n e r a l l y was f e l t that these metal-carbon bonds were r a t h e r weak and that t h e i r s t a b i l i t y was l a r g e l y k i n e t i c and not thermodynamic (2). Recent s y n t h e t i c work on metal a l k y l s i n d i c a t e s that the metal-carbon sigma bonds o f even h i g h l y r e a c t i v e metal a l k y l s can be quite s t r o n g . For example, the mean bond d i s s o c i a t i o n energy o f the Ta-C bond i n TaiCHjîs has been determined to be 62 ± 2 kcal m o l " ( 3 ) . The observation o f b i o l o g i c a l methylation o f Hg(II) (4,5) showed t h a t the synthesis o f a l e a s t some metal-carbon bonds was p o s s i b l e even in aqueous media. Nevertheless, in s p i t e o f the strength o f the metal-carbon bonds, cleavage r e a c t i o n s i n v o l v i n g water g e n e r a l l y w i l l be thermodynamically f a v o r a b l e , because both metal-oxygen and carbon-hydrogen bonds are formed. 3

2

2

1

Reactions Involving Cleavage o f the Metal-Carbon Bonds Very l i t t l e information i s a v a i l a b l e on the pathways by which the metal-carbon bonds are cleaved i n aqueous systems. For example, most o f these c a t i o n s are s t r o n g l y r e s i s t a n t to concentrated aqueous a c i d s . For a n a l y s i s , CH3Hg(II) compounds have been decomposed by heating with concentrated n i t r i c a c i d i n a bomb a t 150° for an hour (6). Preparative data and mechanistic s t u d i e s with nonaqueous media, some o f which are described elsewhere in t h i s volume ( 7 J , can give some general g u i d e l i n e s to f a c t o r s a f f e c t i n g s t a b i l i t y . From studies on p r o t o n o l y s i s of d i a l k y l m e r c u r y ( I I ) compounds, i t has been found that the rate o f the r e a c t i o n depends upon the e l e c t r o n d e n s i t y i n the Hg-C bond being cleaved and the p o l a r i z a b i l i t y o f the metal center ( 8 ) . With, for example, the very s t a b l e l i n e a r d i a l k y l t i n ( I V ) c a t i o n s , p r o t o n o l y s i s should be slow because the R'Sn(IV) residue i s o f low p o l a r i z a b i l i t y .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

132

R — S n — R '

—**R-H

+

AND

ORGANOMETALLOIDS

— S n — R'

s/ t\

[1]

l\

Η Χ X In a d d i t i o n , there are no strong e l e c t r o n i c e f f e c t s r e l e a s i n g e l e c t r o n density i n the t r a n s i t i o n s t a t e as occurs with c e r t a i n t r a n s i t i o n metal compounds that e x h i b i t strong trans e f f e c t s . For example, strong a c i d s , HX, cleave one a l k y l group r a p i d l y from R3AUL (9), but the product R AuXL i s s t a b l e so long as X i s a reasonable good l i g a n d . The high r e a c t i v i t y o f the t r i a l k y l g o l d ( I I I ) compounds i s due t o high trans e f f e c t o f a l k y l groups which f a c i l i t a t e s e l e c t r o n release to the proton i n the t r a n s i t i o n state i n attack on R3AUL. R Strong trans I e f f e c t ligan 2

R

R ——Air—R

•

R' — Η

+

— A u — R

[2]

H

Χ Χ Most o f the decomposition r e a c t i o n s that have been studied in organic solvents are d i s s o c i a t i v e and involve as the f i r s t step the loss o f one o r more o f the ligands besides the carbanion from the f i r s t c o o r d i n a t i o n sphere. R.ML RML, + L n--m n (m-l) n (m-l)—^Decomposition products R

R

ML

1

X

Γ

M L

3 L

ΐ J

An example i s the p r o t o n o l y s i s o f the R3AUL compounds discussed above which involves d i s s o c i a t i o n o f L i n the f i r s t s t e p . An a l t e r n a t i v e mechanism that has been suggested f o r p r o t o n o l y s i s involves an o x i d a t i v e a d d i t i o n o f HX, i . e . a p r i o r protonation o f an e l e c t r o n - r i c h metal c e n t e r . This i s not a reasonable path f o r o r g a n o - m e r c u r y ( I I ) , - t i n ( I V ) , o r - l e a d ( I V ) compounds, because there i s no stable o x i d a t i o n state two u n i t s higher. Such a mechanism may operate i n the r e a c t i o n o f a l k y l p l a t i n u m ( I I ) compounds with HC1 ( 1 0 ) . CH Pt ciL n

3

+

2

HC1—*>CH (H)Pt Cl L I V

3

Ptnci L 2

2

2

[4]

2

+ CH

4

Another type o f r e a c t i o n t h a t i s observed i n the decomp o s i t i o n o f a l k y l metal complexes i s reductive e l i m i n a t i o n , [ 5 ] . R ML n

*

m

R

n

M L

(m-l)

+

L

L5J n

(m-1 )

^

2

(n-2)

(m-1)

This Intramolecular mechanism requires a r e l a t i v e l y

stable

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

9.

Organometallic Cations

TOBIAS

133

o x i d a t i o n state two units lower than that c h a r a c t e r i s t i c o f the a l k y l complex. For example R2AUL2"*" c a t i o n s decompose r a p i d l y to R2 + AuL-2 when L i s a r e l a t i v e l y weak donor (11 ). In aqueous s o l u t i o n , [ ( C H ^ A u f O ^ ) ? ] * decomposes a t 25° i n hours with the production o f c o l l o i d a l gold and ethane. The low thermodynamic s t a b i l i t y o f t i n ( I I ) r e l a t i v e to t i n ( I V ) makes t h i s decomposition path e n e r g e t i c a l l y unfavorable f o r a l k y l t i n ( I V ) compounds and accounts i n part f o r t h e i r high stability. I t i s p o s s i b l e that coupling occurs with d i a l k y l lead(IV) s o l u t i o n s which are much l e s s stable than t h e i r tin(IV) counterparts. The l e a d ( I I ) i o n i s one o f the observed decomposition products. Most o f the organometallic ions are q u i t e r e s i s t a n t to nucleophilic attack. In s t r o n g l y a l k a l i n e s o l u t i o n , d i m e t h y l t i n ( I V ) has been observed to decompose according to [6] (12). 3(CH ) Sn 3

2+

120H

3(CH ) Sn(0H)

ΊψΓ"

2

3

2

24

[6]

J Slow 2(CH ) SnOH 3

3

+

Sn(0H)g

40H"

2

Reactions i n Which the Metal-Carbon Bonds Remain Intact · Proton Transfer from Coordinated Solvent: Hydrolysis. The aqueous chemistry o f many o f these species i s dominated by the h y d r o l y s i s r e a c t i o n s , i . e . by proton t r a n s f e r from coordinated water molecules, and by subsequent condensation r e a c t i o n s o f the hydroxo complexes to form c l u s t e r s with several organometallic c a t i o n s . + The h y d r o l y s i s r e a c t i o n s o f the RHg , R3Sn , and R2Sn ions were studied i n some d e t a i l over ten years ago, and t h i s and other e a r l y work was reviewed i n 1966. (1) The hydrolyses o f the a l k y l m e r c u r y ( I I ) , - t i n ( I V ) , and-lead^IV) species are the only r e a c t i o n s o f organometallic c a t i o n s included i n the recent monograph on the h y d r o l y s i s o f c a t i o n s by Baes and Mesmer (13). These r e a c t i o n s are somewhat simpler than i s c h a r a c t e r i s t i c o f s t r o n g l y hydrolyzing monatomic metal s p e c i e s , because the a l k y l groups e f f e c t i v e l y block c o o r d i n a t i o n s i t e s a t the metal c e n t e r . Consequently, the c h a r a c t e r i s t i c p o l y condensation r e a c t i o n s tend to give smaller c l u s t e r s with fewer metal atoms. The a l k y l m e r c u r y ( I I ) ions are unusually strong acids f o r u n i v a l e n t c a t i o n s , comparable to H g , r e a c t i o n [ 7 ] . Α

+

+

2

2 +

R

"

H 9 +

(aq)

+

¥ ( 1 )

^=i=

R H

9° (aq) H

+

H

3 (aq) 0 +

^

E q u i l i b r i u m constants f o r R = CH3, C2H5, n-C^Hj, and n-C/jHg are c o l l e c t e d i n Table I. These ions have pK = 5 and are a c i d s comparable i n strength to the c a r b o x y l i c a c i d s . As a a

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

134

ORGANOMETALS

AND

ORGANOMETALLOIDS

consequence, a t pH 7 the r a t i o [C^HgOH]: [Ch^Hg ] very much favors the hydroxide, and the c a t i o n i s a r e l a t i v e l y unimportant species. At pH values i n the v i c i n i t y o f the p K , condensed species a l s o are important, r e a c t i o n [8]. The f r a c t i o n o f the a

C H

3 9 (aq) H

+

+

CF^HgOH ^ H C H g ( 0 H ) H g C H 3

3 ( a q )

log Κ = 2.37 [ 8 ] ( l £ )

+

organometal i n the polycondensed species depends upon both pH and t o t a l organometal c o n c e n t r a t i o n . Very concentrated s o l u t i o n s appear to contain small amounts o f (CH3Hg) 0 , but t h i s i s not s i g n i f i c a n t below 0.2 M (15). In general p o l y nuclear complexes are unimportant below t o t a l metal c o n c e n t r a t i o n s o f ca_. 1 0 * M, so they probably play l i t t l e p a r t i n the r e a c t i o n s of mercurials i n the environment. The d i s t r i b u t i o n o f CH Hg(II) species as a function of pH i s i l l u s t r a t e d i n Figure 1. 3

+

4

3

Table I.

H y d r o l y s i s Constants f o r Univalent Cations at 2 5 °

Organometallic

a

Species CH HgOH (CH Hg) 0H (CH Hg) 0

log * K

-4.59 . CH Hg + CH Hg0H^(CH Hg) 0H log Κ = 2.37 CH HgOH + ( C H H g ) 0 H ^ (CH Hg) 0* + H 0 log Κ = 0 . 3 - 0 . 7 -4.98 -5.12 -5.17 -6.60 -6.81 -9.1

2

3

3

+

7

9

3

2

3

3

3

3

3

5

3

+

3

C H HgOH n-C H Hg0H n-C4H HgOH (CH3) SnOH (C H5) SnOH (CH ) PbOH 2

(14) Q4)

b

3

3

Reference

p q

3

3

+

2

+

2

D

3

3

2

(15) (44) (44) (44.) (16) (16) (17)

a-The symbols used throughout f o r the e q u i l i b r i u m constants are those of the Chemical S o c i e t y Tables o f S t a b i l i t y Constants (37.); b - 20°. Most o f the other u n i v a l e n t organometallic ions are r a t h e r weak aquo a c i d s . T y p i c a l are the t r i a l k y l t i n ( I V ) species which behave as simple monoprotic a c i d s , r e a c t i o n [9]. These have R

3Sn ( +

a q )

+

H 0 2

( 1

j ^

R SnOH 3

( a q )

+

H 0 3

+

( a q )

[9]

Q_6j

pK values between 6 and 7, i . e . a c i d strengths comparable to the weak oxyacids, e . g . HC10. The pK values increase s l i g h t l y with higher a l k y l groups as a l s o i s observed with the RHg ions and as would be expected from i n d u c t i v e e f f e c t s . At neutral pH, the r a t i o [R3SnOH]:[R3Sn ] s t i l l favors the hydroxo complex as i s i l l u s t r a t e d i n the d i s t r i b u t i o n diagram for (CH3)3Sn(IV) i n Figure 1. Since the R3SnOH i s uncharged i t should f a c i l i t a t e a

a

+

+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

9.

TOBIAS

Organometallic Cations

135

Figure 1. Species distributions as a junction of pH for 10~ M solutions of (CH ) Sn\ CH Hg\ and (CH ) Pb\ The fraction of organometal in the binuclear complexes will increase with increasing organometal concentration. Distribution diagrams for more concentrated solutions of CH$Hg* and (CH ) Pb* can be found in Refs. 40 and 117, respectively. 3

s

3

s

s

s

3

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

136

ORGANOMETALS

A N D ORGANOMETALLOIDS

the d i s t r i b u t i o n o f the organotin species into hydrophobic phases. T h i s may be o f importance f o r membrane t r a n s p o r t o f these s p e c i e s . There i s l i t t l e tendency to form polynuclear species. Data on the h y d r o l y s i s constants are c o l l e c t e d i n Table I. As i s to be expected, the t r i a l k y l l e a d ( I V ) c a t i o n s are weaker a c i d s than the t i n analogs and w i l l e x i s t as the aquated c a t i o n s a t neutral pH. For r e a c t i o n [10], the e q u i l i b r i u m (

C H

3)3Pb

+

( a q )

+

constant l o g * K

1 1

H 0 2

( 1

p-(CH ) PbOH 3

i s 9.1 (17).

3

( a q )

+

H 0 3

[10]

+

Some condensation has been

observed with concentrated s o l u t i o n s , r e a c t i o n

[11].

Figure 1 a l s o i l l u s t r a t e s the species d i s t r i b u t i o n f o r a m i l l i molar s o l u t i o n o f (CH3) Pb . The d i p o s i t i v e d i a l k y l t i n ( I V ) ions are much stronger aqup a c i d s than the t r i a l k y l s , and a t concentrations above ç a . 1 0 " M they form s i g n i f i c a n t f r a c t i o n s o f polynuclear h y d r o l y s i s products (1J5,18,19). In g e n e r a l , t h e i r strength as a c i d s i s comparable to that o f S n , and many s o l u t i o n p r o p e r t i e s o f the R2Sn ions are s i m i l a r to those o f Sn^ . The l o g value o f ( C H ) ? S n , £ 3 . 5 , (16), comparable to that f o r n i t r o u s a c i d . This does not t e l l the whole s t o r y , however, because much o f the hydrolyzed organotin i s i n the form o f species such as [ ( ( C H ) S n ) 2 ( 0 H ) 2 ] » [ ( ( C H ) S n ) ( 0 H ) ] , e t c . i n more concentrated s o l u t i o n s . Figure 2 i l l u s t r a t e s the e f f e c t o f c o n c e n t r a t i o n on the species d i s t r i b u t i o n , and Table II l i s t s the h y d r o l y s i s c o n s t a n t s . While these polynuclear complexes should be o f l i t t l e importance i n most environmental or b i o l o g i c a l systems, they w i l l make up a large f r a c t i o n o f the d i a l k y l t i n ( I V ) species i n r e a c t i o n s designed to model these systems a t 3 ^ pH ^ 8 i f the organotin concentration i s as high as m i l l i m o l a r . I t should a l s o be noted t h a t the sets o f e q u i l i b r i u m constants such as those i n Tables I and II normally do not include s o l u b i l i t y product d a t a . While a species d i s t r i b u t i o n can be c a l c u l a t e d with them f o r the e n t i r e pH range, i t w i l l be meaningless a t higher concentrations i f p r e c i p i t a t i o n o c c u r s . (See Figure 15.7 (a), r e f . 13.) This e f f e c t i s i l l u s t r a t e d i n Figure 2 f o r the 10 mM s o l u t i o n . This f i g u r e a l s o c l e a r l y i l l u s t r a t e s the amphoteric behavior o f (CH ) Sn *. Again, the analogous dimethyllead(IV) ions are much weaker a c i d s than the t i n analogs (20), and the e q u i l i b r i u m constants are c o l l e c t e d in Table I I . The p r a c t i c a l consequence o f the magnitude o f these constants i s t h a t very l i t t l e ( C H ) 2 P b e x i s t s i n s o l u t i o n a t pH 7. Approximately one equivalent o f a c i d must be t i t r a t e d to reach pH 7. 3

5

2

2+

2 +

3

3

3

2

1

2 +

2

S

3

2

4

6

2 +

2

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2+

9.

TOBIAS

137

Organometallic Cations

Figure 2.

Species distribution as a function of pH for 10 M and 10' M solutions of (CH ) Sn * 5

2

s

t

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

138

ORGANOMETALS

Table I I .

Summary o f ( C H ) S n 3

Species

3

+

2

2

2

2

3

4

[(CH )|M] (0H) (CH ) M(0H) (CH ) M(0H) 23

3

2

3

2

4

XoÔ -8.29 -4.83

3

2+

0

4

H y d r o l y s i s a t 25°

5-7.4 -15.54 -10.83

-24.31

2

6

2 +

pq

[(CH ) M] (0H) 2 3

2

ORGANOMETALLOIDS

log *K ,M=Pb(20)

pq

2

3

and ( C H ) P b

2 +

log *K ,M=Sn(18.)

(CH ) M(0H) (CH3)2M(0H)o [(CH ) M] (0H) ^ 3

2

AND

-16.17 -20.0 -32.2

-28.52

B. Complexation o Solution. Information on s t a b i l i t y constants of organometallic cations i n aqueous s o l u t i o n makes i t p o s s i b l e to p r e d i c t a number o f t h i n g s . If p a r t i c u l a r l y s t a b l e complexes are formed with a c e r t a i n f u n c t i o n a l group that i s present i n environmental o r b i o l o g i c a l systems, these groups are l i k e l y to be involved i n the t r a n s p o r t and p h y s i o l o g i c a l a c t i v i t y o f the organometal. Often organometals are introduced, as i n the case o f t i n ( I V ) compounds, as the h a l i d e s ; and a knowledge o f the s t a b i l i t y constants f o r complexes with h a l i d e ions w i l l permit a p r e d i c t i o n o f whether the h a l i d e w i l l p e r s i s t o r aquate i n natural waters. With organometallic compounds, syntheses often are c a r r i e d out with non-aqueous s o l v e n t s , a p r a c t i c e t h a t i s l e s s common with simple inorganic s p e c i e s . S t a b i l i t y data can allow p r e d i c t i o n s o f whether model compounds have s u f f i c i e n t s t a b i l i t y to be important species i n d i l u t e aqueous s o l u t i o n . Trends i n S t a b i l i t y : Hard and Soft A c i d Character. The organom e t a l l i c c a t i o n f o r which the most systematic studies on complex s t a b i l i t y have been made i s CH3Hg . It i s a very s o f t a c i d and tends to bind s t r o n g l y to s o f t bases, i . e . to heavier donor atoms ( 2 1 , 2 2 ) . This i s demonstrated by the e q u i l i b r i u m constants for r e a c t i o n [ 1 2 ] with X = halide i o n . These increase markedly +

C H

3 9 H

+

+

X'(aq)

C H

3

H g X

(aq)

[

1

2

]

with heavier h a l i d e s : log K i = 1.50 ( F " ) , 5 . 2 5 ( C I " ) , 6 . 6 2 ( B r " ) , 8 . 6 0 (I") (14). Because o f the high s t a b i l i t y o f the c h l o r i d e , bromide, and iodide complexes, these compounds have quite low aqueous s o l u b i l i t y . The p r i n c i p a l c o o r d i n a t i o n number o f mercury(II) i s two, and the CH3HgX molecules do not i n t e r a c t s t r o n g l y with water. A d d i t i o n o f C I " or B r " can be used to reverse the binding of CH3Hg to n u c l e i c a c i d s , e . g . i n agarose e l e c t r o p h o r e s i s with CH3HgOH as a denaturing agent ( 2 3 ) . +

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

9.

Organometallic Cations

TOBIAS

139

In c o n t r a s t to the aqueous s o l u b i l i t y , the CI^HgX molecules should have reasonable l i p i d s o l u b i l i t y , and chloro complexing may be important i n f a c i l i t a t i n g transport o f methylmercury(II) in b i o l o g i c a l systems. The d i s t r i b u t i o n c o e f f i c i e n t o f CH3HgCl between toluene and an aqueous phase was found to be 1 1 . 1 , r e a c t i o n [13] (24). C H

3 9 H

C 1

(aq)

C H

3 9 H

C 1

(toluene)

™

The a l k y l t i n ( i v ) s p e c i e s behave as hard a c i d s , and i n t h i s respect are very d i f f e r e n t from the alkylmercury(II) ions which are prototype soft acids (21). Experimentally t h i s i s demonstrated by the trend i n the s t a b i l i t y constants o f the h a l i d e ion complexes, r e a c t i o n s [14]: log K] = 2.3 ( F " ) , -0.17 (CI") (25). The Me

!

+ Me

Me

+

X'

(

a

q

)

^=5:

{[(CH ) Sn(0H ) ] -x} 3

!

3

2

2

+

j|

(aq)

llr

-H 0

[14]

2

X i ,Sn

/ 1^ Me

I

%

(aq) Me

Me so small t h a t values have not been determined. I t i s l i k e l y that the complexation i n s o l u t i o n i s mainly o f the outer sphere type, because the formation o f inner sphere (CH3)3SnX requires dehydration and a s t r u c t u r a l change from a planar to a pyramidal skeleton f o r ( O ^ ^ S n * . These data together with the knowledge that s u b s t i t u t i o n a t the t i n center occurs r a p i d l y t e l l us that d i s s o l u t i o n o f ( C ^ ^ S n X , X = C I , B r , I, i n water w i l l y i e l d the same aquated species w i t h i n the time o f mixing. Even i n sea water, mean [Cl~] - 0.5 M o r blood 0.103 M, (CH3)3Sn w i l l be present p r i n c i p a l l y as the aquo c a t i o n a t pH < 5 and (CHj^SnOH at pH 7. The low e q u i l i b r i u m concentration o f (CH3)oSnCi may be important i n processes t h a t involve e x t r a c t i o n into l i p i d phases, e . g . i n membrane t r a n s p o r t , although the hydroxide w i l l a l s o be quite l i p i d s o l u b l e . Studies on the permeability o f mitochondrial membranes show that f^Sn ions mediate the transport o f C I " and OH" across the membrane and provide a means f o r r a p i d e q u i l i b r a t i o n o f pH (26). The d i s c u s s i o n o f the chemistry i n t h i s reference i s somewhat obscured by neglect o f the h y d r o l y s i s o f these ions which was discussed i n 4

+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

140

ORGANOMETALS AND ORGANOMETALLOIDS

the previous s e c t i o n . The R3Pb ions form only very unstable complexes with h a l i d e i o n s : Ki (not log) (CFh^Pb" ^ 6.5 ( F " ) , 2.1 ( C I " ) ; ( C H ) P b = 3.5 ( F " J , 3.7 (CI") (27,28). Also they are not so hard, since K P / K Q I i s only 3.1 for (CH3) Pb , while i t i s 3 χ 1 0 with ( C H ) S n . The R Sn^ ions form somewhat more stable complexes with a n i o n i c 1igands because o f t h e i r d i p o s i t i v e charge, but the h a l i d e complex s t a b i l i t y constants i n d i c a t e that they, too, are very hard a c i d s . For r e a c t i o n [15], the values l o g Ki are 3.70 ( F " l (25), 0.38 (CI") (29), < - 0 . 5 (Br") (29). In the ( C H ) S n - C I " system, Raman spectra demonstrate t h a t the complexing i s mainly o f the outer sphere type, and inner sphere complexing only occurs with very concentrated s o l u t i o n s where the water a c t i v i t y i s reduced to a low value. +

1

2

5

+

3

3

2

3

+

3

2

3

z

2

Me I

2+

'Sn:

+ X"

Ί

^[(CH ) Sn(0H ) ] -X"} 3

(aq)

11

2

Me

2

4

2 +

" ¥

[15]

[(CH ) SnX(0H ) f 3

2

2

n

These data c l e a r l y show the much l e s s favorable displacement o f water by the heavier h a l i d e s in the case o f R S n and R S n compared to the RHg i o n s . A p r a c t i c a l consequence i s t h a t the o r g a n o t i n ( I V ) c a t i o n s w i l l tend to i n t e r a c t r e l a t i v e l y more s t r o n g l y w i t h nitrogen and oxygen donors, p a r t i c u l a r l y n e g a t i v e l y charged ones, compared to s u l f u r donors, while the converse w i l l be true f o r the a l k y l m e r c u r y ( I I ) s p e c i e s . The R Pb* ions form much l e s s s t a b l e complexes than the t i n analogs: (CH ) Pb , 54.0 ( F " ) , 5.8 ( C I " ) ; ( C H ) ? P b 35.0 ( F " ) , 9.2 (CI") (£7,28). Thev a l s o are much l e s s hard than the t i n analogs. For~TCH ) Sn' K P / K Q ] i s C J K 2.1 χ 1 0 , while the r a t i o f o r ( C H ) P b is 9.3. S t a b i l i t y with Biomolecules and Related Ligands. The hard o r s o f t a c i d c h a r a c t e r i s o f use i n p r e d i c t i n g the types o f donors t h a t w i l l give the most s t a b l e complexes. Of a t l e a s t comparable importance i s the i n t r i n s i c b a s i c i t y o f the donor; f o r example, a mereaptide w i l l form much more stable complexes with C H H g than a t h i o e t h e r even though both ligands are s u l f u r donors. With a given type o f donor, reasonably good l i n e a r f r e e energy r e l a t i o n s e x i s t f o r protonation and m e t h y l m e r c u r i a t i o n as observed o r i g i n a l l y by Simpson (30) f o r nitrogen donors and examined more g e n e r a l l y by Erni and Geier (J31_,_32). T h i s i s i l l u s t r a t e d in Figure 3 f o r some oxygen and s u l f u r donors. As expected from the s o f t a c i d c h a r a c t e r o f CH3Hg , the i n t e r c e p t in the l o g K C H v s . log K H L P l o t i s much l a r g e r f o r the s u l f u r than the oxygen donors. S t a b i l i t y con stants f o r a number o f CH3Hg complexes are c o l l e c t e d in Table I I I . +

3

2 +

2

+

2

3

2

2 +

2

3

3

3

2

2

5

2 +

2 +

3

2 +

+

+

H

g

L

+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

9.

TOBIAS

Organometallic Cations

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

141

142

ORGANOMETALS

Table

III.

CHoHg

A N D ORG A N O M E T A L L O IDS

Selected S t a b i l i t y Constants o f Organometallic Cations with Organic Ligands.

H0CH CH S2

2

1 P H 1 6 ^ 6 3 " ' glutathionate C3H6Ô2NS-, c y s t e i n e t e C6H5S-, thiophenolate CCHÎOANOS-, 2,4-dinitrothiof (&2N)2C=S

C

N

S

16.1 15.9 15.7 14.7 10.5 6.9

(14) (45)

5.4 5.5 3.8 3.2 2.7 1.1

(49) (32) (32) (50) (50) (50)

11.8 7.1 8.2 7.6 5.0 7.9 7.2 4.7

(32) (32)

(45) (46) (47) (32)

S(CH?CH C S(CH CH 0H 2

2

2

^ 7 ^ 5 ^ 2 ~ tropolonate C5H5Û"phenolate C6H4O3N" 4 - n i t r o p h e n o l a t e CH C0 " HC0 C1 HC0 " 3

2

2

2

2

3 3 2 ~ imidazolate C H 4 N imidazole H2NCH?CH2NH2 CH3NH2 (Cfl3)3N N H 2 C H C 0 " glycinate 1 2 8 2 1,10-phenanthroline C5H5N p y r i d i n e

C

H

N

3

2

2

C

(CH ) Pb 3

3

+

H

2

N

C-ioHoNo 1,10-phenanthroline C6fl40 N- picolinate C5H70 "acetylacetonate

3.9 5.3 6.0

(35) (35) (35)

CH C0 "

2.6

(54)

2

2+

2

2

2

2

(CH ) Pb 3

2

2+

(52) (53)

1.2 (U) 0.97,0.54(1_7,54) 0.86 (II) 0.52 (U)

2

2

3

(51) (51) (51)

C c H 9 0 2 " pivalate CH C0 " HC0 ~ C1CH C0 " 3

(CH ) Sn

(14)

3

2

(log K

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1.0)

9.

TOBIAS

Organometallie Cations

143

Few data are a v a i l a b l e f o r s t a b i l i t y constants o f other organometallic ions with such l i g a n d s . Recently, some data f o r complexes o f (CH3)3Pb with carboxylates have been reported by Sayer e t a]_. (17). A rough l i n e a r f r e e energy r e l a t i o n i s observed between complexàtion by ( C H j ^ P b * and p r o t o n a t i o n , and t h i s i s i l l u s t r a t e d i n Figure 4. S i m i l a r behavior i s to be expected f o r the R3$n i o n s , although the s t a b i l i t y constants with hard bases should be s l i g h t l y l a r g e r . Consistent with t h i s i s the observation t h a t phosphate b u f f e r s , pH 7 . 4 , decrease the binding o f ^ H c ^ S n * to r a t hemoglobin (33). Phosphate buffers a l s o were observed to decrease the e x t r a c t i o n o f (C2H5h Sn(IV) i n t o a chloroform phase. In a q u a l i t a t i v e study o f complexing o f R3Sn species with a number o f b i o l o g i c a l molecules, no evidence could be found f o r complexes with ATP, g l u t a t h i o n e , a r g i n i n e , o r l y s i n e i n a borate-EDTA buffer a t pH 8.4 (34). The R£Sn and R 2 P b species probably form a much l a r g e r v a r i e t y o f complexes than the t r i a l k y l s p e c i e s , but the extensive h y d r o l y s i s o f the c a t i o n s has made the accurate d e t e r mination o f s t a b i l i t y constants by p o t e n s o m e t r i c t i t r a t i o n s very d i f f i c u l t . While t h i s i s the c l a s s i c a l technique f o r such determinations, i t r e q u i r e s an accurate knowledge o f a l l the h y d r o l y s i s constants as well as the l i g a n d protonation constants. To complicate matters, mixed hydroxide-1igand complexes, e . g . [R2$n(0H) L ], often w i l l be formed g i v i n g a l a r g e number o f p o s s i b l e species and rendering the a n a l y s i s o f t i t r a t i o n data even more d i f f i c u l t . While CF^Hg"*" i s e x t e n s i v e l y hydrolyzed i n s o l u t i o n s with pH > 1, i t s e s s e n t i a l l y monofunctional c h a r a c t e r precludes the formation o f mixed hydroxo-1igand complexes and permits the r e l a t i v e l y s t r a i g h t forward determination o f s t a b i l i t y c o n s t a n t s . A few data have been obtained f o r complexes o f (CH3)2$n with bidentate l i g a n d s , using a computer to analyze the data (35,36). As i s expected from the hard a c i d c h a r a c t e r o f ( C H 3 l ^ S n , the most s t a b l e complex i s formed with the negative bidentate oxygen donor, a c e t y l acetonate, l o g Ki 6 . 0 ; and the l e a s t s t a b l e complex was formed with the neutral bidentate nitrogen donor 1,10 phenanthroline, l o g K] 3 . 9 . The s t a b i l i t y o f the a c e t y l acetonate complex i s s i m i l a r to t h a t o f the N i , complex, l o g Κ ι ^ 6.0 ( 3 7 ) » while the phenanthroline complex i s much l e s s s t a b l e than f o r N i , l o g Κ] ^ 8.6 (37). +

+

4

+

2+

2+

n

m

2+

2+

2 +

2 +

Future Prospects For the organometallic c a t i o n s t h a t are e x t e n s i v e l y hydrolyzed i n s o l u t i o n , s p e c t r o s c o p i c techniques can be used to determine both e q u i l i b r i u m constants and i n many cases the binding s i t e s . While n e i t h e r the organometallic c a t i o n s nor most o f the l i g a n d s o f i n t e r e s t have s u i t a b l e e l e c t r o n i c t r a n s i t i o n s , both Raman and nmr spectroscopy have been used s u c c e s s f u l l y . Resonances o f both the c a t i o n and

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

AND

pivalate

ORGANOMETALLOIDS

Ο

1.0

/ HC0 "

ί

2

Ο

I y

CH3C02"

)

-

acetylgiyc i n a t e - ^

/ /

Ο

0.5 '2.5

°

CICH C0 " 2

3.0

2

3.5

4.0 logK

4.5

50

H L

Figure 4. Stability constants for (CH ) Pb* with carboxylic acids; log K ) PbL vs. log K . Data from Kef. 17. s

(CHs

S

s

HL

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

TOBIAS

9.

Organometallie Cations

145

CH^OH

1201

572'

CH HgOH 3

2

• Ç

'CH^g-N^.H

α 1616 1 ^ 1 5 7 9 ^

Figure 5. Raman perturbation differ ence spectra for the CH Hg(II)-pyridine system at pH 8.4, 6.5, and 4.4. In each set, A is the CH Hg(H) + pyridine vs. CH Hg(II) difference spectrum, while Β is the CH Hg(II) + pyridine vs. pyridine difference. Rehtive ordinate expansions are indicated at the right. s

s

3

1800

1600

1400

1007 1200 1000 800' 600 ' FREQUENCY (CM-1)

s

400

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

146

ORGANOMETALLOIDS

1igand protons have been used to study many r e a c t i o n s o f CH3Hg with amino acids (38) and with the nucleoside i n o s i n e (39). Raman p e r t u r b a t i o n d i f f e r e n c e spectroscopy has been used to study the r e a c t i o n s o f CH^Hg" " with pyrimidine (40,42,43) and purine (39,41,42) n u c l e o t i d e s as well as with c a l f thymus DNA (43). Figure 5 i l l u s t r a t e s the a p p l i c a t i o n o f the Raman technique to the simple C H o H g i l l J - p y r i d i n e system. A t pH 8 . 4 , the CH Hg(II) + p y r i d i n e v s . CH Hg(II) d i f f e r e n c e gives j u s t the spectrum o f p y r i d i n e showing that no r e a c t i o n o f the methylmercury c a t i o n has taken p l a c e . S i m i l a r l y the CH3Hg(II)+ p y r i d i n e ys_. p y r i d i n e d i f f e r e n c e gives j u s t the spectrum o f CH3HgOH. At pH 6.5 and 4.4 both spectra show extensive perturbations. The 1021 c n H band o f the complex i s s u f f i c i e n t l y well resolved from the cm-1 band o f the pyridiniu concentrations o f unreacted 1igand using the Raman i n t e n s i t i e s . While 100% i s unreacted a t pH 8 . 4 , the values are 20% and ç a . 0%, r e s p e c t i v e l y a t pH 6.5 and 4 . 4 . This i s i n good agreement with values c a l c u l a t e d from the known s t a b i l i t y constant. The Raman d i f f e r e n c e technique i s p a r t i c u l a r l y s e n s i t i v e in d e t e c t i n g small amounts o f r e a c t i o r ^ a n d both Raman and nmr can be used to determine the product d i s t r i b u t i o n . These s p e c t r o s c o p i c techniques should be e q u a l l y s u i t a b l e f o r the study o f R Sn and R 2 S n i n t e r a c t i o n s , and a s t a r t a l r e a d y has been made with R3Pb chemistry (17). 1

3

3

2+

3

+

Acknow!edgements. This work has been supported, i n p a r t , by the National Science Foundation Grant CHE 76-18591 and by the P u b l i c Health S e r v i c e , Grant AM-16101 from the National I n s t i t u t e f o r A r t h r i t i s , Metabolism, and D i g e s t i v e Diseases. The author a l s o would l i k e to express h i s a p p r e c i a t i o n to the O f f i c e o f Naval Research, as p a r t o f t h i s material was presented a t a workshop on organotin chemistry i n February, 1978. Thanks are due Mary R. M o l l e r f o r the C H H g ( I I ) - p y r i d i n e spectra. 3

Literature Cited 1. 2. 3.

4. 5.

T o b i a s , R. S., Organometal. Chem. Revs. (1966), 1, 93. Coates, G. E. "Organometallic Compounds," p 72, Methuen, London, 1960. A d e d e j i , F . Α . , Connor, J. Α . , Skinner, Η. Α . , G a l y e r , L . and W i l k i n s o n , G . , J. Chem. Soc. Chem. Commun. (1976), 159. Wood, J. M . , Kennedy, F . S . , and Rosén, C . G . , Nature (London) (1968), 220, 173. Jensen, S. and Jernelöv, Α . , Nature (London) (1969), 223, 753.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

9.

TOBIAS

Organometallic Cations

6.

Β.

147

Schellenberg, M., Ph.D. Thesis, Eidgenössische Technische Hochschule Zürich, 1963. 7. Kochi, J. K., Factors Involved in the Stability of Alkyl— Metal Bonds, this volume. 8. Nugent, W. A. and Kochi, J. K., J. Amer. Chem. Soc. (1976), 98, 273. 9. Komiya S. and Kochi, J. K., J. Amer. Chem. Soc. (1976), 98, 7599. 10. Belluco, U., Giustiniani, M., and Graziani, M., J. Amer. Chem. Soc. (1967), 89, 6494. 11. Kuch, P. L. and Tobias, R. S., J. Organometal. Chem. (1976), 122, 429. 12. Tobias, R. S. and Freidline, C. E., Inorg. Chem. (1965), 4, 215. 13. Baes, C. F., J r . an Cations," Wiley, Ne 14. Schwarzenbach, G. and Schellenberg, M., Helv. Chim. Acta. (1965), 48, 28. 15. Rabenstein, D. L., Evans, C. Α., Tourangeau, M. C., and Fairhurst, M. T., Anal. Chem. (1975), 47, 338. 16. Tobias, R. S., Farrer, H. N., Hughes, M. B., and Nevett, Α., Inorg. Chem. (1966), 5, 2052. 17. Sayer, T. L., Backs, S., Evans, C. Α., M i l l a r , Ε. K., and Rabenstein, D. L., Can. J. Chem. (1977), 55, 3255. 18. Tobias, R. S. and Yasuda, M., J. Phys. Chem. (1964), 68, 1820. 19. Tobias, R. S., Ogrins, I., and Nevett, Β. Α., Inorg. Chem. (1962), 1, 638. 20. Freidline, C. E. and Tobias, R. S., Inorg. Chem. (1966), 5, 354. 21. "Hard and Soft Acids and Bases," R. G. Pearson, E d . , Dowden, Hutchinson, and Ross, Strondsburg, Pa., 1973. 22. Pearson, R. G., J. Chem. Educ. (1968), 45, 581. 23. Bailey, J. M. and Davidson, N., Anal. Biochem. (1976), 70, 75. 24. Gruenwedel, D. W. and Davidson, N., J. Mol. B i o l . (1966), 21, 129. 25. Cassol, A., Magon, L., and Barbieri, R., Inorg. Nuclear. Chem. Lett. (1967), 3, 25. 26. Selwyn, M. J., Dawson, A. P., Stockdale, M., and Gains, Ν., Eur. J. Biochem. (1970), 14, 120. 27. P i l l o n i , G. and Magno, F., Inorg. Chim. Acta. (1970), 4, 105. 28. P i l l o n i , G. and Magno, F., Inorg. Chim. Acta. (1971), 5, 30. 29. Farrer, H. N., McGrady, M. M., and Tobias, R. S., J. Amer. Chem. Soc. (1965), 87, 5019. 30. Simpson, R. B., J. Amer. Chem. Soc. (1964), 86, 2059. 31. Geier, G., Erni, J., and Steiner, R., Helv. Chim. Acta. (1977), 60, 9. American Chemical S o c i e t y Library 16th St. N . Brinckman, W. In Organometals1155 and Organometalloids; F., et al.; ACS Symposium Series; American Chemical Washington, DC, 1979. Washington, D. C. Society: 20036

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32. 33. 34. 35. 36. 37.

38. 39. 40. 41. 42. 43.

44. 45. 46. 47. 48. 49. 50. 51.

52. 53. 54.

ORGANOMETALLOIDS

E r n i , I. W., Ph.D. T h e s i s , Eidgenössische Technische Hochschule Z u r i c h , 1977. Rose, M. S., Biochem. J. (1969), 111, 129. A l d r i d g e , W. N. and S t r e e t , B. W., Biochem. J. (1964), 91, 287. Tobias, R. S. and Yasuda, M., Inorg. Chem. (1963), 2, 1307. Yasuda, M. and Tobias, R. S., Inorg. Chem. (1963), 2 , 207. " S t a b i l i t y Constants o f Metal-Ion Complexes," L. G. S i l l é n and A. E. M a r t e l l , e d s . , Special P u b l i c a t i o n No. 17, 1964, and No. 25, 1971, The Chemical S o c i e t y , London. Rabenstein, D. L., A c c t s . Chem. Res. (1978), 11, 100. Mansy, S. and Tobias, R. S., Biochemistry (1975), 14, 2952. Mansy, S., Wood, T. E., Sprowles, J. C., and Tobias, R. S., J. Amer. Chem. Soc. (1974), 96, 1762. Mansy, S. and Tobias, R. S., J. Amer. Chem. Soc. (1974), 96, 6874. Mansy, S., F r i c k , J. P., and T o b i a s , R. S., Biochim. Biophys. A c t a . (1975), 378, 319. Chrisman, R. W., Mansy, S., P e r e s i e , H. J., Ranade, Α., Berg, Τ. Α., and Tobias, R. S., B i o i n o r g . Chem. (1977) 7, 245. Z a n e l l a , P., Plazzogna, G., and Tagliavini, G., Inorg. Chim. A c t a . (1968), 2, 340. Simpson, R. B., J. Amer. Chem. Soc. (1961), 8 3 , 4711. Schwarzenbach, G. and K a r l e n , U., quoted i n ref. 32. Gross, H., Diplomarbeit, ΕΤΗ Zürich, quoted i n ref. 32. Fehr, R., Diplomarbeit, ΕΤΗ Zürich, quoted i n ref. 32. S t e i n e r , R., quoted i n ref. 32. L i b i c h , S. and Rabenstein, D. L., A n a l . Chem. (1973), 45, 118. Rabenstein, D. L., Ozubko, R., L i b i c h , S., Evans, C. Α., F a i r h u r s t , M. T., and Suvanprakorn, C., J. Coordn. Chem. (1974), 3, 263. Anderegg, G., Helv. Chim. A c t a . (1974), 57, 1340. Hohl, H., Diplomarbeit, ΕΤΗ Zürich, (1968), quoted i n ref. 32. Pilloni, G., M i l a n i , F., Inorg. Chim. A c t a . (1969), 3, 689.

R E C E I V E D August 28,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

10 Organosilanes as A q u a t i c A l k y l a t o r s of M e t a l Ions RICHARD E. DESIMONE Department of Chemistry, Wayne State University, Detroit,MI48202

Much of the chemistr f t thi symposiu ha i recent years received ver has been studied in dept fro variety o perspectives. Ques tions which are now being asked in these areas have become quite detailed and sophisticated, although admittedly much still re mains to be learned. In contrast to this situation, that sur rounding the element silicon, its environmental significance and relevant chemistry, is still in its infancy. Indeed the answer to the simple question "What, if any, is the environmental sig nificance of organosilicon compounds?" is far from clear at this point in time. It is the purpose of what follows to point out some basic and potentially relevant chemistry of silicon and to try to focus to some small degree on i t s environmental import. Silicon:

Occurance and Distribution

It is commonly known that silicon is one of the most abun dant of elements (TABLE I) and also one of the most widely dis tributed (1). The vast majority is tied up in silicate rocks TABLE I.

SILICON - HOW MUCH, AND WHERE? Earth's surface - land, sea and air Oxygen 53.3% Silicon - 15.9% Hydrogen - 15.1% Aluminum - 4.8% Average silicon content 2.77 χ 10 ppm in earth's crust 40 ppm in man 3 ppm in seawater 5

0-8412-0461-6/78/47-082-149$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

150

ORGANOMETALS AND

ORGANOMETALLOIDS

and m i n e r a l s where i t i s r e l a t i v e l y immobile and of l i t t l e concern to us. I n l i v i n g organisms, s i l i c o n p l a y s (and has played) an important r o l e i n n e a r l y a l l stages of e v o l u t i o n a r y development. From s i l i c a t e b a c t e r i a t o protozoa, algae, and the h i g h e r p l a n t and animal organisms, n e a r l y a l l c o n t a i n and use s i l i c o n i n one form or another. I t i s not the purpose of t h i s a r t i c l e to survey the expanding area of b i o - o r g a n o s i l i c o n chemistry (2) nor t o consider the innumerable occurrences of s i l i c o n i n l i v i n g organisms ( 3 ) . I t i s worth mentioning however, t h a t among the myriad of known s i l i c o n compounds i n a wide v a r i e t y of b i o t a , there i s a conspicuous absence of t r u e o r g a n o s i l i c o n molecules. In the higher animal organisms f o r example, s i l i c o n t y p i c a l l y occurs as o r t h o - and o l i g o s i l i c i c a c i d s and s i l i c a t e s , ortho and o l i g o s i l i c i c e s t e r s of carbohydrates, p r o t e i n s , s t e r o i d s , l i p i d s and p h o s p h o l i p i d s , and much has been l e a r n e d i ganisms a great d e a l c e r t a i n l y remains to be d i s c o v e r e d . We know very l i t t l e about the occurrence of n a t u r a l o r g a n o s i l i c o n compounds and we can by no means make the assumption t h a t they do not e x i s t . Much work i s needed i n t h i s area. At t h i s p o i n t i n time and f o r the purposes of t h i s a r t i c l e i t seems t h a t what should be of concern i s not the occurrence of t o x i c o r g a n o s i l i c o n compounds, but the p o s s i b i l i t y t h a t r e a c t i o n s of s i l i c o n compounds w i t h other,more g e n e r a l l y troublesome metals or m e t a l l o i d s , w i l l produce s p e c i e s which are i n f a c t s i g n i f i c a n t l y damaging from an environmental v i e w p o i n t . I n p a r t i c u l a r we w i l l focus on organo group t r a n s f e r r e a c t i o n s i n aqueous media. S i l i c o n as an Organo Group Donor Organo group t r a n s f e r from s i l i c o n has been known f o r some time, the f i r s t r e p o r t e d i n s t a n c e being i n 1896 w i t h the format i o n of an organomercurial, p-dimethylaminophenylmercurie c h l o r i d e ( 4 ) . The r e a c t i v i t y of the c h l o r o s i l a n e i s not s u r p r i s i n g

+

s i n c e these are among the more r e a c t i v e of s i l i c o n s p e c i e s . However, s i m i l a r organo group t r a n s f e r r e a c t i o n s occur i n aqueous media w i t h a l k y l a r y l s i l a n e s , w i t h t r a n s f e r of the a r y l group, and these proceed r e l a t i v e l y q u i c k l y to s u b s t a n t i a l completion (5).

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

10.

DESIMONE

151

Organosihnes

f—\ H

3

EtOH

Si

H

+ SC1

CH

— \0)— < 3>3

C

H C—(Ο)— 8 H

C 1

+

h

(CH ) SiOH

3

/—\ (O/ HCΛ -

2

3

>

Q

+ HCl

3

(2)

HOAc S 1 ( C H

+

3)3

Hg(0Ac)

>

2

7

H

3

+

(CH ) S10H 3

20

+ HOAc

3

H C Such r e a c t i o n s ar limite mercury. A l , P, Ga, F i n both aqueous and non-aqueous media ( 6 ) . examples a r e (7, 8)

(3)

3

SbCl -> ^0)"

Ç((^$1C1 + 2

S i G 1

5

3

A few r e p r e s e n t a t i v e

(^^

+

2

3

+

+ GaCl

+

2

3

HCl <

> (CH ) SiCl

3

3

(CH ) Si - 0 - Si(CH ) 3

k

I

^Q^Sb0(0H)

(CH )i Si

S h C 1

3

+

3

+ GaCl

3

3

(CH ) SiCl 3

3

'

H 0

(4)

2

+ CH GaCl

2

> CH GaCl

2

3

3

+

(5)

((CH ) Si0) 3

2

(6)

n

(6) i s noteworthy i n t h a t the s i l i c o n compound, h e x a m e t h y l d i s i l oxane, i s u s u a l l y considered t o be the s i m p l e s t s i l i c o n e . Thayer has reported t h a t t h i s molecule r e a c t s - w i t h mercuric s a l t s i n a very complex r e a c t i o n y i e l d i n g ^20 products ( 9 ) . The other major c l a s s o f a l k y l a t i n g agents among s i l i c o n compounds i s the o r g a n o f l u o r o s i l i c a t e s . These have been extens i v e l y s t u d i e d by Wuller and co-workers (6, 10). Reaction w i t h H g C l , i n the presence o f NHi+Cl t o i n c r e a s e s o l u b i l i t y , occurs r e a d i l y t o g i v e monomethyl and dimethylmercurie s p e c i e s . 2

20°C HgCl + ( N H ) ( C H S i F ) 2

1+

2

3

5

> Η 0/ΝΗ^01

CH HgCl + (NH ) ( S i F C l ) 3

l+

2

5

2

(

7

)

100°C CH HgCl + ( N H ) ( C H S i F ) - ^ - ^ (CH ) Hg + (NH^) ( S i F C l ) 3

1 +

2

3

5

3

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

5

ORGANOMETALS AND

152

ORGANOMETALLOIDS

S i m i l a r l y , elements such as Sb and B i can be a l k y l a t e d or a r y l a ted w i t h s u b s t a n t i a l y i e l d s (11).

SbF + 3 ( N H ) ( C H S i F ) 3

4

2

3

> H0

5

Sb(CH ) 3

+ 3(ΝΗ ) (SiF )

3

4

2

6

(8)

2

Bi(OH)

/(")V-SiF

+ 3

3

\

(<(θ)^"

Β1 +

+ oNH^F + 3HF

3

^

/

3

H

2°

H0 2

3(^)2

+

(SiF )

(9)

6

I n view of the f a c t t h a "moves" through the biosphere a t a much greater r a t e than occurs n a t u r a l l y , r e a c t i o n s such as (8) are perhaps of more s i g n i f i cance than they might outwardly appear to be. The preceeding would appear to provide ample precedent f o r the a b i l i t y of S i to f u n c t i o n as an organo group donor. Unfor t u n a t e l y much of t h i s work seems not to have r e c e i v e d the recog n i t i o n i t d e s e r v e s , e s p e c i a l l y among persons concerned w i t h en vironmental problems. In 1971, d u r i n g a study of cobalmin-dependent methyl t r a n s f e r to m e r c u r i c s a l t s , i t was observed that the common NMR r e f e r ence compounds sodium 2,2-dimethyl-2-silapentane-5-sulfonate (DSS)(Eqn. 10) and sodium 3 - t r i m e t h y l s i l y l p r o p i o n a t e - d i (TSP) were capable of t r a n s f e r i n g CHj to mercuric s a l t s (12). t

(CH ) Si(CH ) S0 Na 3

3

2

3

3

+

HgX

>

2

(CH ) Si(CH ) S0 Na 3

2

2

3

3

+

CH HgX

(10)

3

X +

Q u a l i t a t i v e l y i t was observed that CH Hg formation occurred w i t h s e v e r a l m e r c u r i c s p e c i e s , i n the order Hg(N0 ) > Hg(0Ac) >> H g C l . Complete demethylation of s i l i c o n was found to occur o n l y w i t h Hg(NO ) . Thayer a l s o f i n d s that t h a l l i u m ( I I I ) ace t a t e and l e a d (IV) a c e t a t e r e a c t to g i v e m e t h y l t h a l l i u m and methy l l e a d compounds ( 9 ) . R e c e n t l y , Βellama (13) and Thayer (9) have s t u d i e d the k i n e t i c s of the r e a c t i o n w i t h v a r i o u s mercuric s a l t s , f i n d i n g second order r a t e constants of 9 χ 10~ M~ s e c " and 5 χ 10" M" s e c - f o r K g C l w i t h TSP and DSS r e s p e c t i v e l y . The r e a c t i o n of Hg(CL0i ) proceeds w i t h k > 10" M" s e c " f o r both DSS TSP, but more r a p i d l y w i t h TSP. For Hg(0Ac) and DSS k=6.6xl0" M" s e c " ( 9 ) . 3

3

2

2

3

2

1

6

1

1

2

1

t

1

1

2

3

2

1

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

10.

DESIMONE

Organosilanes

153

S p e c u l a t i o n on the mechanism has centered on two p o i n t s ; an i n t r a m o l e c u l a r acid-base i n t e r a c t i o n between the s i l i c o n and a t e r m i n a l oxygen of the anion, and the a c i d i t y of the a t t a c k i n g (and q u i t e v a r i a b l e ) mercuric s p e c i e s . The former (12) would be c o n s i s t e n t w i t h the f a c t that TSP always r e a c t s f a s t e r than DSS, which has an e x t r a carbon and would probably not adapt as w e l l to the required- conformation. The second p o i n t , the nature of the a t t a c k i n g mercuric s p e c i e s , i s g e n e r a l l y of great s i g n i f i c a n c e (for any metal). Anion dependent and pH dependent s t u d i e s r e v e a l dramatic e f f e c t s on r a t e f o r these environmental parameters (14). The d e t a i l e d understanding o f any transmethylation r e a c t i o n w i l l r e q u i r e adequate s p e c i a t i o n o f a l l r e a c t a n t s and products under any g i v e n s e t of c o n d i t i o n s . This has g e n e r a l l y been one of the major weaknesses of most s t u d i e s to date. In some work c u r r e n t l the f a c i l e t r a n s f e r of number of 1-organosilatranes i n p r o t i c or a p r o t i c media (15). >p 1 R-Si(OCH CH ) N 2

2

+

3

HgX

+

2

> RHgX

>t 1 X-Si(OCH CH ) N 2

2

(11)

3

I n t e r e s t i n g l y , the parent o r g a n o t r i a l k o x y s i l a n e s a r e i n e r t under s i m i l a r r e a c t i o n c o n d i t i o n s . Presumably the e x t r a e l e c t r o n dens i t y a t the s i l i c o n a c t i v a t e s the Si-C bond t o a t t a c k by H g ( I I ) . Environmental

Considerations

We come now t o the environmental s i g n i f i c a n c e of the chemis t r y j u s t discussed. I n the absence o f s i g n i f i c a n t knowledge of n a t u r a l l y o c c u r r i n g o r g a n o s i l i c o n compounds, i t seems worthw h i l e t o consider the impact of man-made o r g a n o s i l i c o n compounds. By f a r the l a r g e s t group of such substances a r e the s i l i c o n e s , which have found l i t e r a l l y hundreds of uses (Table I I ) , almost a l l i n s p i r e d because o f the chemical i n e r t n e s s of the polymeric m a t e r i a l (16, 17). The estimated s i l i c o n e market i n the United States i n 1973 was 91 m i l l i o n pounds. Most a p p l i c a t i o n s i n v o l v e complete r e l e a s e of the s i l i c o n e i n t o the environment. Most uses, except f o r the proposed use i n e l e c t r i c a l transformers as a replacement f o r PCB s, i n v o l v e very s m a l l q u a n t i t i e s (18). A l e g i t i m a t e question a t t h i s p o i n t seems to be What u l t i m a t e l y happens t o a l l of t h i s m a t e r i a l ? " There appears to be no published work on m i c r o b i a l demethylation of s i l i c o n ( e s ) and i t i s not c l e a r how v a r i o u s environmental f a c t o r s a f f e c t the degradation o f the polymeric m a t e r i a l . Dow-Corning has reported that moist s o i l seems t o be the most d e s t r u c t i v e environment t o f

M

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

154

ORGANOMETALS AND

ORGANOMETALLOIDS

TABLE I I . APPLICATIONS OF SILICONES (16)

1) 2) 3) 4) 5) 6)

Waxes and p o l i s h e s Foaming and antifoaming agents Release agents ( i n molding processes) P r o t e c t i v e coatings Lubricants Cosmetics

n)

Cooling

* a "bulk volume" a p p l i c a t i o n (pending)

the s i l i c o n e molecule (18). i t i s p o s t u l a t e d that the degradation process begins w i t h a d e - p o l y m e r i z a t i o n of the long s i l o x a n e chain to form v o l a t i l e c y c l i c s i l o x a n e s of 4-5 S i - 0 u n i t s , a process w i t h a h a l f l i f e of VLO days. Under the i n f l u e n c e of moisture, oxygen and u.v. l i g h t , the v o l a t i l e c y c l i c s i l o x a n e s are then presumed to degrade i n the atmosphere to SiU2, H2O, and CO2. D e t a i l s on these s t u d i e s are l a c k i n g . One i s c u r i o u s to know f o r example whether the s o i l i n the experiments was s t e r i l e , whether the process could be i n t e r r u p t e d or a l t e r e d by the pre sence of other substances such as methyl acceptors, and whether *C l a b e l i n g s t u d i e s have been used to t r a c e the methyl group carbon to product CO2. H o p e f u l l y these d e t a i l s w i l l be f o r t h coming . I n other experiments, Dow-Corning r e p o r t s that a 15% emul s i o n of s i l i c o n f l u i d subjected to the a c t i o n of a c t i v a t e d sewage sludge f o r a p e r i o d of 70 days showed no evidence of bio-degrada t i o n (18). However Bellama r e p o r t s that r e l a t i v e l y low v i s c o s i t y s i l i c o n e f l u i d s w i l l methylate H g ( I I ) ( 1 9 ) . I n summary, we have b a r e l y scratched the s u r f a c e of some very i n t e r e s t i n g and p o s s i b l y s i g n i f i c a n t chemistry. Much work remains to be done i n areas mentioned and s u r e l y i n others not yet discovered. ll

Literature Cited

1. 2.

Ochiai, Ε., "Bioinorganic Chemistry, An Introduction", 5-12, A l l y n and Bacon, Inc., Boston, 1977. Voronkov, M.G., Chem. Brit.(1973) 9, 411.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

pp.

10.

DESIMONE

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

Organosilanes

155

Voronkov, M.G., Zelchan, G.I., Lukevitz, E.J., " S i l i c o n and L i f e " , Zinatne Publishing House, Riga, 1971. Combes, C., Compt. Rend., (1896), 122, 622. Eaborn, C., "Organosilicon Compounds", Butterworths, London, 1960. Müller, R., Organometal. Chem. Revs., (1966), 1, 359. Jakubowitch, A. J., and Mozarew, G.W., J. Gen. Chem. USSR, (1953), 23, 1414. Schmidbaur, H., Angew. Chem., (1964), 76, 753. Thayer, J.S., personal communication. Müller, R. and Dathe, C., Chem. Ber. (1965), 98, 235. Müller, R. and Dathe, C., Chem. Ber. (1966), 99, 1609. DeSimone, R.E., J.C.S. Chem. Comm. (1972), 780. Bellama, J.M. and Nies, J.D., personal communication. Jewett, K.L., Brinckman paper. Bellama, J.M. and Nies, J.D., J.C.S. Chem. Comm., submitted. Howard, P.H., Durkin, P.R., and Hanchett, A., "Assessment of Liquid Siloxanes", Report # PB 247778, National Technical Information Service, U.S. Dept. of Commerce, 1974. Calandra, J.C., Keplinger, M.L., Hobbs, E.J., and Tyler, L.J. Polymer Preprints, (1976), 17, 1. Pollution Engineering, Aug., 1977, p. 41. Bellama, J.M., personal communication.

Discussion G. E. PARRIS (Food and Drug A d m i n i s t r a t i o n ) : Have there been d i r e c t t o x i c i t y s t u d i e s on s i l i c o n e s from the standpoint of e n v i ronmental impact?. DeSIMONE: There have been many s t u d i e s on d i r e c t t o x i c i t y , i n c l u d i n g intravenous s t u d i e s . Except f o r minor eye i r r i t a t i o n i n c e r t a i n cases, these appear harmless t o j u s t about e v e r y t h i n g . PARRIS: The r e a c t i o n s you showed suggest that s i l i c o n e s may be new m e t h y l a t i n g agents i n the environment. DeSIMONE: I t remains t o be found out whether i n f a c t enough o r g a n o s i l i c o n compounds do e x i s t i n the environment, where they e x i s t , and whether what you j u s t suggested i s t r u e . PARRIS: One of the c r i t i c a l p l a c e s w i l l be i f s i l i c o n e s f i n d more use as d i e l e c t r i c f l u i d s . I doubt that s i l i c o n e s w i l l be the major replacement f o r PCB's. I t h i n k t h a t most people who a r e d e a l i n g w i t h the t o x i c i t y o f s i l i c o n e s and the importance o f e n v i ronmental chemistry of s i l i c o n e s have not considered them as pot e n t i a l m e t h y l a t i n g agents. C. FREY (Dow Corning C o r p o r a t i o n ) :

I would l i k e t o make a

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

156

ORGANOMETALS AND

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couple of comments on the i m p l i c a t i o n s of the paper. The data there showing 91,000,000 l b s . of s i l i c o n e s g a i n i n g entry i n t o the environment could very w e l l be an item f o r some concern, but the great b u l k of t h a t m a t e r i a l , as many people know, i s p o l y d i m e t h y l s i l o x a n e . I t ' s i n t e r e s t i n g to note that the subsequent work of Dr. Thayer [vide i n f r a ] seems to show that mercuric n i t r a t e , which was j u s t about the most potent m e c u r i a l c l e a v i n g agent, i s without e f f e c t on c y c l o d i m e t h y l s i l o x a n e s a f t e r s e v e r a l months of contact. So the n o t i o n t h a t the o r g a n o s i l i c o n compounds, which are not natu r a l l y - o c c u r r i n g but f i n d t h e i r way i n t o the environment, w i l l be cleaved by mercury i s probably d i f f i c u l t to s u s t a i n . De SIMONE : The question i s not whether mercury w i l l cleave these compounds, but r a t h e r during the decomposition ( i n moist s o i l as you suggest i s the most e f f i c i e n t wa to do i t ) what hap pens i f some methyl accepto cleavage products f l o a t i n g FREY: I t h i n k i t ' s important to d i f f e r e n t i a t e between what might be c a l l e d environmental chemistry and the chemistry of s p i l l s ; that i s , what happens i f you have l a r g e concentrations of s i l o x a n e i n contact w i t h l a r g e concentrations of some metal. On an environmental s c a l e , I t h i n k one has to be concerned w i t h the r e a c t i o n of m e t h y l s i l i c o n compounds w i t h n a t u r a l l y - o c c u r r i n g e l e ments or compounds. As f a r as the s o i l i s concerned, w e ' l l present the d e t a i l s t h i s summer at the 5th I n t e r n a t i o n a l O r g a n o s i l i con Symposium i n Karlsruhe [August, 1978]. There i s no unusual chemistry there t h a t i n v o l v e s the c a r b o n - s i l i c o n bonds themselves. J . J . ZUCKERMAN ( U n i v e r s i t y of Oklahoma): The h a l f - l i f e of 10 days, d i d that r e f e r t o the d e p o l y m e r i z a t i o n - c y c l i z a t i o n to the 5- or 4-membered r i n g s ? DeSIMONE: That was the impression I got. ZUCKERMAN: There was another r e a c t i o n you mentioned which i n d i c a t e d the decomposition w i t h respect t o u l t r a - v i o l e t l i g h t g i v i n g C0 2

DeSIMONE: I got t h i s impression from an a r t i c l e i n " P o l l u t ion Engineering" [Reference 18] , an i n t e r v i e w w i t h John Ryan. FREY: I t h i n k the question has something to do w i t h the r a t e s of s o i l - c a t a l y z e d r e a c t i o n , whatever that happens t o be. The d e t a i l s of that r e a c t i o n , l i k e a l l o t h e r s , depend on the circumstances, and w e ' l l be going i n t o that d e t a i l i n a paper t h a t i s i n preparation. J . M. BELLAMA ( U n i v e r s i t y of Maryland): About the nature of water-soluble o r g a n o s i l i c o n chemistry, the TSP and DSS to which you r e f e r r e d are extended chains; s e v e r a l people have proposed a h e a d - t o - t a i l i n t e r a c t i o n where the presence of an e l e c t r o n - r i c h species (an a v a i l a b l e Lewis base moiety somewhere remote i n a molecule from the s i l i c o n ) can bend around and j o i n . We have looked at these k i n d s of i n t e r a c t i o n s [Inorg. Chem. (1965), 14,

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

10.

DESIMONE

Organosifones

157

1618], and we have two f e e l i n g s about them. One i s that these i n t e r a c t i o n s can be important when η (the number of i n t e r v e n i n g methylene groups) i s 1 or 2. Models of these compounds show t h a t the i n t e r a c t i n g atoms are e s s e n t i a l l y i n contact. With longer chains (n = 3-5), there seem to be some i n t e r a c t i o n . When you get t o η = 6, i t looks l i k e no i n t e r a c t i o n remains. Secondly, the nature of the group on the s i l i c o n seems t o be very important. Craig's o r i g i n a l paper J j . Chem. Soc. (1954), 332] p o s t u l a t e s the n e c e s s i t y of inducing a p o s i t i v e charge on s i l i c o n . I t would seem t h a t organic groups such as methyls or phenyls are not going to be p a r t i c u l a r l y good i n t h i s r e s p e c t . I f you have s u b s t i t u e n t s on the s i l i c o n l i k e a c h l o r i n e , or perhaps l i k e a hydrogen, which i s very e l e c t r o n e g a t i v e w i t h respect t o the s i l i c o n , the chances f o r these kinds of i n t e r a c t i o n s are going to be f a r g r e a t e r . So, using water-soluble t r i m e t h y l s i l y l compounds suggests t h a t these kinds of i n t e r a c t i o n s ar ing a s i t e for attack b the case i f other s u b s t i t u e n t s were present on the s i l i c o n . DeSIMONE: The d i f f e r e n c e between the r a t e s of DSS and TSP may be a r e f l e c t i o n of t h a t e x t r a carbon; i t i s a f a c t o r of a couple orders of magnitude. BELLAMA: M u l l e r and Frey [Z. anorg. a l l g . Chem. (1969) 368, 113] p o s t u l a t e d the n e c e s s i t y f o r ammonium f l u o r i d e a d d i t i o n to the m e t h y l t r i c h l o r o s i l a n e p l u s mercuric c h l o r i d e . They c l a i m t h a t i t ' s necessary to have a m e t h y l p e n t a f l u o r o s i l i c a t e species as the intermediate and as the a c t i v e methylating agent. We have done t h i s r e a c t i o n without adding the ammonium f l u o r i d e . We don't know what intermediate i s present, or what i s a c t u a l l y doing the methyl a t i n g , but i t ' s not necessary t o add the ammonium f l u o r i d e i n order t o get t h i s k i n d of r e a c t i o n to occur. J . S. THAYER ( U n i v e r s i t y of C i n c i n n a t i ) : We have found t h a t the DeSimone r e a c t i o n [equation 10] i s not confined t o mercury. One gets s i m i l a r r e a c t i o n s w i t h t h a l l i u m t r i a c e t a t e , w i t h l e a d t e t r a a c e t a t e and, we b e l i e v e , w i t h potassium h e x a c h l o r o p l a t i n a t e . We s t u d i e d the k i n e t i c s of t h i s r e a c t i o n and our f i g u r e s agree moderately w e l l the ones that were quoted here. Secondly, the other r e a c t i o n was the d i r e c t r e a c t i o n between h e x a m e t h y l d i s i l o x ane and mecuric n i t r a t e . The two dozen products a l l u d e d t o are a s e r i e s of l i n e a r and c y c l i c s i l o x a n e s , formed here by a d i s p r o p o r t i o n t i o n r e a c t i o n , p l u s a v a r i e t y of species we have not yet i d e n t i f i e d . Our b e l i e f i s that t h i s r e a c t i o n proceeds by i n i t i a l removal of a methyl group by mercury, from the s i l o x a n e moiety f o l l o w e d by rearrangement. We f i n d t h a t a s i m i l a r r e a c t i o n occurs w i t h the germanium analog, hexamethyldigermoxane. RECEIVED August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11 Influence of E n v i r o n m e n t a l Parameters o n T r a n s m e t h y l a t i o n between A q u a t e d M e t a l Ions K. L. JEWETT and F. E. BRINCKMAN Center for Materials Science, National Bureau of Standards, Washington, DC 20234 J. M. BELLAMA Department of Chemistry, University of Maryland, College Park, MD 20742 While advances hav genic methyl-metals an have relied upon partition coefficients favoring degassing of permethylated species from aqueous media (1,2). Unfortunately, little work has been reported on the basic chemical features of relevant equilibria (z-n)+

(z-n)+

MenM (aq) = MenM (atm), or on determining partition coefficients. Where neutral molecules are involved, e.g., z = n, strong solvation by water is probably not important even though the central atom may be capable of greater than n-fold coordination. For example, in either fresh or salt water, Wasik et al. found that Me Hg partitions nearly equally between solution and atmos phere above (3). Preference for partition into fresh water was noted; presumably more favorable ligation by H O over C1 prevails, the so-called salting-out effect for hydrophobic molecules. Though not yet resolved, there appears to be general agree ment that biomethylation of metals and metalloids follows a step wise process (4,5). A number of very important corollaries o r assessing influences of environmental parameters hinge upon this basic viewpoint: (a) polar, charged (n
-

2

f

0-8412-0461-6/78/47-082-158$07.50/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

j E W E T T E T AL.

Aquated Metal Ions

159 z

n

+

pends on h i g h l y s p e c i f i c c o o r d i n a t i o n o f Me M ( ~ ) by c e r t a i n charged o r n e u t r a l l i g a n d s t o form intermediates not s u f f i c i e n t l y stable f o r further methylation. Aquated Organoelement Ions. Recognition t h a t sigma-bonded organometallic ions e x h i b i t s t a b l e forms i n aqueous s o l u t i o n s was shown many years ago. For example, one fundamental property o f d i s s o l v e d i o n s , that of e l e c t r o l y t i c behavior, was demonstrated by c o n d u c t i v i t y measurements on M e T l ^ (6) and l a t e r polarographic s t u d i e s w i t h MeHg "^ (2). E q u a l l y important c o n s i d e r a t i o n s o f s t r u c t u r e s o f aquated organoelement species have r e c e i v e d cons i d e r a b l e a t t e n t i o n by NMR (8,9) and l a s e r Raman spectrometry (10, 11), p a r t i c u l a r l y w i t h the appearance o f Tobias c l a s s i c review of the f i e l d over a decade ago (12). S i g n i f i c a n t work ha of chemical processes whic h y d r o l y s i s o f water i n c o o r d i n a t i o n spheres o f organometal ions (14). I n t e r e s t i n g l y enough, r e l a t i v e l y scant work has been d i r e c t e d t o k i n e t i c s t u d i e s o f s t a b l e aquated organometal ions as these r e l a t e t o t r a n s a l k y l a t i o n r e a c t i o n s (15,16), though analogous chemistry i n a p r o t i c s o l v e n t s has preoccupied i n o r g a n i c chemi s t s f o r over a century. Nonetheless, a number o f environmental events on a world-wide s c a l e i n recent times has focussed a t t e n t i o n on the need t o d i r e c t research t o t h a t a q u a t i c chemistry which can e l u c i d a t e formation and t r a n s p o r t o f organometal species of b i o l o g i c a l concern ( 4 ) . In t h i s paper we d e a l w i t h s e v e r a l organometal ions demons t r a t e d as b i o g e n i c , but yet which a l s o provide a chemical system amenable t o treatment as c l a s s i c a l aquated i n o r g a n i c i o n s . Thereby, we can assess the i n f l u e n c e of common environmental parameters, such as temperature, pH, s a l i n i t y , and i o n i c s t r e n g t h , both i n terms o f the c o n s t i t u t i o n o f r e a c t i n g organometallic species and t h e i r r a t e s or modes of t r a n s m e t h y l a t i o n . +

2

a

4

1

Experimental Methods P r e p a r a t i o n of S o l u t i o n s and K i n e t i c Runs. S o l u t i o n s o f comm e r c i a l and synthesized (17) t r i m e t h y l t i n compounds and mercury(II) s a l t s were prepared i n d i s t i l l e d water, d i l u t e d , and mixed j u s t p r i o r t o each k i n e t i c run. Precautions f o r e x c l u d i n g a i r from s o l u t i o n s were unnecessary s i n c e r e a c t i o n r a t e s were not measura b l y d i f f e r e n t under anaerobic c o n d i t i o n s . Sodium p e r c h l o r a t e provided gegenions o f choice where h i g h i o n i c strengths were r e q u i r e d because o f reduced l i k e l i h o o d of H g ^ c o o r d i n a t i o n by CIO, (18). Immediately p r i o r to mixing o f r e a c t a n t s , and t h e r e a f t e r , pH measurements were f r e q u e n t l y taken f o r each k i n e t i c run i n NMR tubes o r l a r g e r v e s s e l s w i t h h i g h l y accurate microprobe equipment. For t h i s work, concentrât ions of r e a c t a n t s and i o n i c strengths were d i c t a t e d both by s o l u b i l i t y ( h y d r o l y s i s ) o f +

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

160

ORGANOMETALS AND

ORGANOMETALLOIDS

r e a c t a n t s and r a t e s of r e a c t i o n s amenable t o the NMR measurement scheme employed (17). G e n e r a l l y , r e a c t a n t s were taken at about 0.025 M, p e r m i t t i n g i o n i c strengths from 0.05 to 0.7 f o r observing second order r a t e s between 1 χ 10~* t o 1 χ 10~ M" s" . Proton NMR s p e c t r a provided c o n c e n t r a t i o n data f o r a l l methylated metal s p e c i e s , f o l l o w i n g d i g i t a l i n t e g r a t i o n of peaks and s u i t a b l e weighting of areas (17). These were taken f o r each k i n e t i c run at i n t e r v a l s which i n s u r e d uniform d i s p e r s i o n of input time and c o n c e n t r a t i o n data i n r e g r e s s i o n analyses (19). The r a t e data were f i t t e d by l e a s t squares to the simple second-order law 2

k

bs

2<° >

FC

- TÂ^BT

L N

1

[jffi]

1

·

where A and Β are i n i t i a l r e a c t a n t c o n c e n t r a t i o n s and χ i s extent of r e a c t i o n at any give l y i n g p o i n t s i n f i t t e d dat smoother slopes [ k ( o b s ) values] w i t h i n 95 percent confidence i n t e r v a l s or b e t t e r . 2

E s t i m a t i o n of Reactant and Product Concentrations. A compre hensive computer program, CHEMSPECIES (20), was devised which per m i t t e d c a l c u l a t i o n of e q u i l i b r i u m c o n c e n t r a t i o n s of t i n and mer cury s p e c i e s . Input parameters were a set of formation constants (3) l i s t e d i n Table I s e l e c t e d from l i t e r a t u r e . For s p e c i f i c k i n e t i c runs, observed values f o r [Me^Sn ] , and [Me^Sn ] or [MeHg ] ^ taken from NMR data, along w i t h measured [CI""] - ana pH, provided necessary boundary c o n d i t i o n s f o r com pos i t l 8 n l l a n a l y s i s at any t . Output data computed i n c l u d e d [Hg l and [Cl~" ] , along w i t h r e l a t i v e (mole f r a c t i o n ) or net concentrations or a l l m e t h y I t i n , methylmercury, and mercu ry (II) species present exceeding a s p e c i f i e d value ( u s u a l l y 0.01 mole p e r c e n t ) . t

t

Q

t

a

l

+

t

2 +

f r e e

f

β

β

R e s u l t s and D i s c u s s i o n Choice of K i n e t i c System. Transmethylation between Sn(IV) and Hg(II) i n Water. The u t i l i t y of n e u t r a l t e t r a a l k y l t i n s f o r forming corresponding a l k y l m e r c u r i a l s from HgX s a l t s i n p r o t i c media was shown by Abraham et al. i n a s e r i e s of s t u d i e s (31) con ducted i n methanol-water s o l u t i o n s . S i m i l a r l y , l a t e r work of Dodd and Johnson examined cleavage of sigma-bonded RCH^- groups (R « p y r i d i n e ) on s e v e r a l t r a n s i t i o n metal centers by mercury or t h a l l i u m s a l t s i n aqueous s o l u t i o n s (32). I n both cases, the authors made reasonable assumptions t h a t the methyl donors i n v o l v e d were r e l a t i v e l y i n e r t towards a s s o c i a t i v e s u b s t i t u t i o n , p a r t i c u l a r l y towards p r e - e q u i l i b r i u m d i s t r i b u t i o n of l i g a n d s (anions) i n com p e t i t i o n w i t h the e l e c t r o p h i l i c center. Thereby, e s p e c i a l l y i n the l a t t e r s t u d i e s , the r e l a t i v e r e a c t i v i t i e s of HgCl * " ( o r T1C1 "" ) could be more simply evaluated as a f u n c t i o n of changes 2

2

J

n

n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

j E W E T T ET AL.

Aquated Metal Ions

161

TABLE I Selected Formation Constants f o r T i n ( I V ) and Mercury ( I I ) Species i n Water Formation R e a c t i o n Reactants 2+ Hg~" + C I

log β

References

6.72

21,22

+ 2C1" = HgCl °

13.23

21,22

+ 3C1" = H g C l "

14.23

21,22

2

15.20

21.22

+ 20H* = Hg(0H) °

21.16

22,23

+ 30H" - Hg(0H) "

20.71

22.23

HgCl

Hg

2 +

Hg

2 +

Hg

2 +

+ 4Cl" = HgCl "

Hg

2 +

+ 0H~ - HgOH

Hg

2 +

Hg

2 +

2

3

2

3

+ 40H" = H g ( 0 H ) "

20.26

Hg

2 +

+ OH" + C I " = Hg(0H)Cl°

17.43

22.24

Hg

2 +

+ 20H" + C l "

19.03

24

Hg

2 +

19.60

24

Hg

2 +

16.87

24

Hg

2 +

18.51

24

Hg

2 +

17.07

24

- 0.17

25

- 1.74

25

- 6.77

26

5.25

27

9.51

27

H

g

2 +

2

4

Hg(OH) Cl 2

2

+ 30H" + C l " = H g ( O H ) C l " 3

+ OH" + 2C1" - H g ( 0 H ) C l " 2

2

+ 20H" + 2C1" - H g ( 0 H ) C l " 2

2

2

+ OH" + 3C1" - H g ( 0 H ) C l " 3

+

M e S n + C l " = Me SnCl° 3

3

+

M e S n + 2C1" = M e S n C l " 3

3

2

+

M e S n + OH" = Me Sn0H° 3

3

23

Products: +

MeHg + C l " = MeHgCl

0

+

MeHg + OH" - MeHg0H° +

2MeHg + OH" = (MeHg) 0H

11.74

+

2

Me Sn

2 +

9

9

Me Sn

+ 2Cl" = Me SnCl

2

2

Me Sn

2 +

Me Sn

2 +

2

9

Me Sn 2

+ C l " = Me SnCl

+

2

+ 3Cl" = Me SnCl " 2

+ OH" = Me Sn0H

3

+

?

+ 20H" = Me Sn(0H) 2

2

28

0.37

29

0.14

29

- 1.31

29

- 3.50

30

- 9.00

30

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

162

ORGANOMETALS AND

ORGANOMETALLOIDS

i n the i o n i c p r o p e r t i e s , e.g.> [ C l ~ ] , of the r e a c t i o n medium. As a model system f o r a s s e s s i n g e f f e c t s of environmental parameters on aqueous t r a n s m e t h y l a t i o n , we extended our e a r l i e r work (17) on the r e a c t i o n , +

2 +

2 +

+

Me Sn + Hg « Me Sn + MeHg , 3 aq aq 2 aq aq Q

(1)

0

because of i t s relevance t o the observed b i o m e t h y l a t i o n of Sn(IV) (33) and involvement of a charged methyl donor o f f e r i n g g r e a t e r s i m i l a r i t y t o p o l a r i n t e r m e d i a t e s c u r r e n t l y viewed as important t o b i o g e n e s i s of organometals. As Huber (15) and we (34) have shown, an a t t r a c t i v e a l t e r n a t i v e e x i s t s w i t h the r a p i d t r a n s m e t h y l a t i o n chemistry of aquated methyllead s p e c i e s , but k i n e t i c l i m i t a t i o n s are imposed by the NMR measurement scheme employed. Moreover, though necessary e q u i l i b r i u b u t i o n s of m e t h y l t i n s p e c i e adequate, s u f f i c i e n t formatio constants f o analogous l e a d ions have not. In Tables I I and I I I are c o l l e c t e d , r e s p e c t i v e l y , k i n e t i c parameters obtained f o r r e a c t i o n 1 under c o n d i t i o n s which i s o l a t e e f f e c t s of temperature or i o n i c s t r e n g t h (μ) and s a l i n i t y ( [ C l " ] ) . Over the range of experimental c o n d i t i o n s examined f o r r e a c t i o n 1 i n the present work, a simple b i o m o l e c u l a r r a t e law was obeyed rate - k (obs) W ^ S n ^ 1 4

2

t

o

t

a

1^\^

l

ο

ί

β

1

·

(2)

E x c e l l e n t l i n e a r f i t s of k i n e t i c data were obtained f o r a l l r e a c t i o n s s t u d i e d , each t y p i c a l l y exceeding 75 percent completion. Reaction 1 appears t o be e s s e n t i a l l y i r r e v e r s i b l e : precipitation of Me2Sn2+ or MeHg does not a l t e r the r a t e , nor do these products undergo f u r t h e r t r a n s m e t h y l a t i o n r e a c t i o n s d e t e c t a b l e by NMR. +

E f f e c t s of Temperature. The l o n g - f a m i l i a r A r r h e n i u s equation which r e l a t e s the r e a c t i o n r a t e constant w i t h temperature defines a q u a n t i t y , E*, regarded as the a c t i v a t i o n energy of a component o r o v e r a l l process: E

rate - k - A e ~ *

/ R T

(3a)

and, I n k = -E*/RT + I n A.

(2b)

I n aqueous s o l u t i o n s , e s p e c i a l l y , i t i s apparent (35,36) t h a t the e n e r g e t i c s (or a c t i v a t i o n parameters) of the r e a c t i o n c o o r d i n a t e are profoundly a f f e c t e d by r e o r g a n i z a t i o n of s o l v e n t molecules surrounding the r e a c t a n t molecules, p a r t i c u l a r l y as t h i s m o d i f i e s t h e i r charge d i s t r i b u t i o n . For an i o n i c b i o m o l e c u l a r r e a c t i o n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

JEWETT E T AL.

Aquated Metal Ions

163

TABLE I I E f f e c t s o f Temperature upon Transmethylation +

2 +

3 +

between M e S n and H g or T l 3 aq aq aq 0

RUN*

(a) 1 2 3 4 5

T, ° C

b

k (obs)±S.E. 2

+ 2+ Me Sn + Hg 3

10.511.1 20.110.6 29.010.3 40.010.2 49.810.4

1.7210.06 4.3310.10 9.3310.21 15.5610.32 42.4411.15

r = 0.944 (b) 1 2 3 4 5

6.32 5.50 4.78 3.95 3.26

6.37 5.44 4.67 4.16 3.16 E* - 14.2 1 0.9

20 14 13 14 12

57.4 71.6 79.5 88.9 83.5

17 16 17 13 13

78.5 72.0 81.8 74.0 90.4

In A = 18.9

+ 3+ Me Sn + T 1 J

3

10.010.4 20.110.4 27.810.5 41.310.8 52.610.4

0.7510.03 2.3410.15 9.0610.30 17.2910.71 72.8014.19 r = 0.988

a

&

E* - 19.1 1 1.7

F o r s e r i e s (a) μ = 0.051; f o r (b) μ = 0.17.

deviation f o r Ν observations. of r e a c t i o n , %. Ε

7.12 5.96 5.11 3.75 2.69

7.20 6.06 4.70 4.06 2.62

C

i n k c a l mol

In A = 26.7

b

T 1 standard

k ( o b s ) χ 10 M~ 0

s~ .

Extent

.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979. 4

f

4

2

3

3

2

2 -1 c from NaCIO =1/2 Em ζ i n M~V 0 b t a i n e d at 26 ± 1°; \ . , counterions i c s tersetn ig mt ha t-e dμ upper l i m i t based on maximum NMR R e a c t i o n between Me SnC10 + H g ( C 1;0 ) I,o n 1:1;

3

f

s i g n a l detected a f t e r 23 h r . r u n ; R e a c t i o n between Me SnN0 + H g C l , 1:1.

d

a

0.320 0.353 0.389 0.501 0.768 0.758 0.1023 0.1249 0.1517 0.251 0.594 0.575 0.506 0.387 0.420 0.525 0.788 0.742 0.2565 0.1499 0.1767 0.2761 0.6211 0.550

-1.99 -2.02 -2.11 -2.11 -2.36 -2.34

0.41 0.67 0.58 0.38 0.25 0.19

10.24 9.56 7.80 7.77 4.40 4.61

4.00 5.00 6.07 10.03 22.13 23.03

4 5 6 7 8 9

0.277 0.275 0.275 0.274 0.0767 0.0767 0.0759 0.0753 0.636 0.786 0.420 0.526

0.4041 0.6186 0.1766 0.2764

-2.09 -2.03 -2.02 -2.04

0.53 0.27 0.28 0.24

8.15 9.23 9.45 9.16

3.03 3.06 3,01 3.02

10 11 12 13

1

<-4.4

0.156 0.229 0.224 0.277

—

0.0243 0.0524 0.0504 0.0765

e

0.288 0.322 0.321 0.321

<0.04 0.0828 0.1038 0.1030 0.1028

/[Cl"]

-2.45 -2.11 -2.13 -2.04

[Cl"]

0.35 0.38 0.49 0.36

3.56 7.77 7.45 9.04

1.25 2.00 2.00 2.93

41 0.0

μ

c

0.0

2

log k (obs)

0.288

b

0.0836

3

e

1 2a 2b 3

d

o.o

0

2

Cl/Hg

RUN

k ( o b s ) χ 1 0 ± S.E.

I n f l u e n c e of I o n i c Strength and S a l i n i t y on Reaction Rate'

TABLE I I I

11.

j E W E T T E T AL.

Aquated Metal Ions

A

Z +

Z

+ B " -> [ A - B ]

Z ±

165

(4)

•+ products

d e r i v a t i o n o f AF*, ΔΗ*, and AS* from experimental determinations of equation 3 can provide gross i n s i g h t s i n t o mechanistic pathways accompanying s o l v e n t changes, o r between r e l a t e d r e a c t i o n s systema

TABLE IV Comparison o f A c t i v a t i o n Parameters f o r Transmethylation between Metals i n P r o t i c Media

+

+

Me Sn+HgCl Et Sn+HgCl Me Sn +HgCl M e S n + T l C l 4

Parameter

k (298) 2

E

96% MeOH

M" ^" 3

k c a l mol

2.59

1

1

a AF* k c a l mol" ΔΗ* k c a l m o l "

1

-TAS* k c a l mol"

- 1

0.00602

0.00434

10.42

13.74

14.2

19.1

16.89

20.46

20.5

20.7

9.85

13.15

13.6

18.5

6.97

7.18

1

AS* c a l d e g ^ m o l " -23.4 a

0.00630

-24.1

For comparison S I u n i t s a r e not used.

2.20

6.86

-7.38

-23.0

b e Reference 31. T h i s work..

^References 16 and 37. In Table I J a r e compared E* values f o r demethylation o f Me~Sn by Hg^ and T l (37). Two important general observations can De made. A h i g h degree of l i n e a r i t y p r e v a i l s , i n d i c a t i n g t h a t n e i t h e r does E* d i s p l a y temperature dependence nor do the expected compositional changes i n r e a c t a n t ions and [ A - B ] ~ i m p o r t a n t l y a l t e r a c t i v a t i o n e n e r g e t i c s over the course o f r e a c t i o n 1. Sec ond, the E* v a l u e s determined, p a r t i c u l a r l y w i t h the methyl t i n mercury ( I I ) r e a c t i o n , a r e low, being comparable t o transmethyl a t i o n between n e u t r a l metal species i n non-polar organic media (38) or t e t r a a l k y l t i n s and H g C l i n p r o t i c s o l u t i o n s (31). Table IV provides comparisons f o r these l a s t r e a c t i o n s w i t h a c t i v a t i o n parameters d e r i v e d from the present work. Abraham and Johnston (31) concluded that f o r the n e u t r a l R.Sn r e a c t i o n s , a S 2(open) t r a n s i t i o n s t a t e 5 was more l i k e l y than a f o u r - c e n t e r S Ζ(cyclic) a c t i v a t e d complex 6, z

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

166

ORGANOMETALS AND

ORGANOMETALLOIDS

SnR. R

(S)

AH g C l

R

Cl

HgCl

2

the f o r a e r being more c o n s i s t e n t w i t h v a r i a t i o n s i n AF* and ΔΗ*, or near constancy of AS*, i n s o l v e n t compositions from 100 percent methanol to 30 percent water i n methanol. These authors suggested t h a t the h i g h l y p o l a r [ R ^ S n — R — H g C l ^ * t r a n s i t i o n s t a t e 5 posses ses s a l t - l i k e or i o n - p a i r - l i k e p r o p e r t i e s . In t h i s context i t i s i n t e r e s t i n g to note tha a r a t e measurable by NMR increments of water, measurable r a t e s were observed (16,37). P r e sumably, r e c a l l i n g the a c t i v a t i o n parameters obtained f o r methyla t i o n of H g or T l by t r i m e t h y l t i n s p e c i e s , even l i m i t e d a v a i l a b i l i t y of p o l a r water molecules somehow serves t o support neces sary molecular rearrangements f o r formation of a charge-compensat ed a c t i v a t e d complex which i s e n e r g e t i c a l l y a v a i l a b l e to ground state solutes. In sum, w h i l e we can p r e s e n t l y presume t h a t many a s s o c i a t i v e or i o n - p a i r - l i k e i n t e r a c t i o n s can occur over the course of r e a c t i o n 1 (at a l l temperatures examined) which i n v o l v e a number of p o l a r t r a n s i t i o n s t a t e s composed of Me«SnC]^" and HgCl " s p e c i e s , the low E* values obtained r e q u i r e that s o l v e n t (water) e f f e c t s m i t i gate any c o u l o m b i c a l l y r e p u l s i v e pathways. Water can provide such m i t i g a t i o n e i t h e r by causing formation of new r e a c t a n t s w i t h n e a r l y n e u t r a l charge d i s t r i b u t i o n s , e.g.* [HgCl °] > [ H g C l ] or [HgCl " ] , or by p r o v i d i n g a p p r o p r i a t e a s s i s t a n c e f o r forming lowenergy i o n - p a i r - l i k e t r a n s i t i o n s t a t e s (39). F o r t u n a t e l y , the matter can be put t o s e v e r a l t e s t s based upon c l a s s i c a l theory of kinetic salt effects. E f f e c t s of I o n i c Strength and S a l i n i t y . The k i n e t i c i n f o r mation f o r r e a c t i o n 1 summarized i n Table I I I can be broadly char a c t e r i z e d by three separate r e l a t i o n s h i p s d e p i c t e d g r a p h i c a l l y i n F i g u r e 1. For k i n e t i c runs 1 through 3 ( i n d i c a t e d by φ ) , where i n the i o n i c s t r e n g t h of the r e a c t i o n medium was maintained a t about J\x = 0.3, almost t h r e e - f o l d i n c r e a s e i n the b i m o l e c u l a r r a t e k ( o b s ) r e s u l t e d from increased r e l a t i v e c o n c e n t r a t i o n of c h l o r i d e i o n . S u b s t i t u t i o n of ClO^" (run 2a) by N0 " (run 2b) d i d not s i g n i f i c a n t l y a l t e r the transmethylation r a t e , doubtless i n conse quence of very weak or nonexistent c o o r d i n a t i o n between n i t r a t e i o n and H g (40) comparable to the s i t u a t i o n f o r CIO," (18). We conclude that a v a i l a b l e concentrations of r e a c t i v e HgCl species are not m a t e r i a l l y a f f e c t e d by such non-coordinating anion sub stitutions . E x c l u s i o n of a l l c h l o r i d e by p e r c h l o r a t e i n run 0, however, 2 +

3 +

n

2

m

+

2

2

3

2 +

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

jEWETT

ET AL.

Aquated Metal Ions

167

e f f e c t i v e l y reduced the observed r e a c t i o n r a t e t o a value below NMR d e t e c t i o n . Consistent w i t h t h i s , a very good l i n e a r c o r r e l a t i o n between 41 o r / [ C l " ] and l o g k^iobs) was obtained f o r runs 1-3 ( r = 0.975 and 0.986, r e s p e c t i v e l y ) , making i t very c l e a r t h a t c h l o r i d e i o n e x e r t s a s p e c i f i c i o n e f f e c t (39) on r e a c t i o n 1. Recognizing t h a t we a r e d e a l i n g w i t h metathesis o f c o v a l e n t l y bound l i g a n d s on aquated metal ions i n a h i g h l y p o l a r medium sug gested the expedient o f a p p l y i n g b a s i c p r i n c i p l e s d e r i v e d f o r r e a c t i o n s between simple i n o r g a n i c e l e c t r o l y t e s . According t o the Brrfnsted and Bjerrum a c t i v i t y r a t e theory, i o n i c r e a c t i o n s proceed through formation o f an a c t i v a t e d complex. The r a t e o f r e a c t i o n i s taken as p r o p o r t i o n a l t o the c o n c e n t r a t i o n o f the complex which i s i n e q u i l i b r i u m w i t h medium and r e a c t a n t ions (36), e»g.* equa t i o n 4. The Debye-Huckel l i m i t i n g law f o r a c t i v i t y c o e f f i c i e n t s , γ, permits e v a l u a t i o n o (39) a s s o c i a t e d w i t h th log Y 1 Q

±

- -0.509 z z_viï +

(7)

i n water a t 25° where the i o n i c s t r e n g t h , μ, i s given

μ = 1/2^ο

± Ζ ι

2

.

i Thus, f o r the r e a c t i o n between i o n A of charge z. a t c o n c e n t r a t i o n c. and i o n Β o f charge ζ a t c o n c e n t r a t i o n c_, tne e f f e c t o f i o n i c s t r e n g t h upon the r a t e or r e a c t i o n i s approximately (a i s a con s t a n t o f theory dependent upon u n i t s ) β

(8a)

I n k/k = 2 ζ ζ α/μ, ο À Β Α

Ώ

η

where k becomes the r e a c t i o n r a t e a t i n f i n i t e d i l u t i o n . This primary k i n e t i c s a l t e f f e c t p r e d i c t s g e n e r a l l y that i f z^ and ζ have the same s i g n , k increases w i t h μ i f ζ. and z^ have opposite s i g n , k decreases w i t h μ i f e i t h e r z^ o r z i s z e r o , k i s independent o f μ. U s u a l l y , i t i s assumed here that s p e c i f i c i o n e f f e c t s (viz.j C l above) o r l a r g e ( h i g h l y d e l o c a l i z e d ) ions are not important i n the r e a c t i o n , and μ i s s m a l l (< 0.01). I n p r a c t i c e , a number o f a l t e r n a t e r e l a t i o n s h i p s have been proposed (39), mainly employing e m p i r i c a l constants, t o permit a p p l i c a t i o n t o r e a c t i o n s t r e a t e d a t higher i o n i c s t r e n g t h (μ > 0.1), f o r example (36) β

g

ta k / k

e

- 2 « « A

B

α [fV^

- 0 . 2 μ]

(8b)

A p p l i c a t i o n s o f e i t h e r equation 8a o r 8b t o the two remaining s e t s o f r a t e s l i s t e d i n Table I I I revealed s e v e r a l important p o i n t s . For runs 3 and 10-13 where [ C l " ] was h e l d constant w i t h i n c r e a s i n g μ ( ^ i n Figure 1 ) , reasonable c o r r e l a t i o n s between

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

168

ORGANOMETALS AND

ORGANOMETALLOIDS

l o g k ( o b s ) and /μ are obtained w i t h a s m a l l , s l i g h t l y negative s l o p e , μ = -0.0362 (equation 8a). We regard t h i s r e s u l t as con s i s t e n t w i t h one major t r a n s m e t h y l a t i o n process, or s e v e r a l minor p a r a l l e l r e a c t i o n s , i n v o l v e d i n the rate-determining step wherein r e a c t a n t ions of opposite charge s l i g h t l y c o n t r i b u t e to the over a l l methyl exchange. For the l a s t case ( Q ) shown i n F i g u r e 1, where both [ C l " ] and μ were monotonically i n c r e a s e d , a s u b s t a n t i a l r e d u c t i o n i n k ( o b s ) was measured. Again, c o r r e l a t i o n of runs 3 through 9 l i s t e d i n Table I I I by e i t h e r equation 8a or 8b i n d i c a t e d a s i g n i f i c a n t l i n e a r r e l a t i o n s h i p ( r = 0.888), but the h i g h l y negative slope (m = 0.826) i s now b e l i e v e d t o r e s u l t from two separate e f f e c t s . The f i r s t , suggested by equation 8a, i s t h a t a major pathway, or the sum of s e v e r a l important p a r a l l e l r o u t e s , i n v o l v e s r e a c t i o n of o p p o s i t e l y This c o n c l u s i o n i s c o n s i s t e n of a c t i v a t i o n i s c h a r a c t e r i s t i c f o r the o v e r a l l process at s i m i l a r c o n d i t i o n s of [ C l ] and μ, suggesting such species w i t h minimal coulombic r e p u l s i o n s . A predominant second e f f e c t operates, we b e l i e v e , i n t h i s case as a consequence of e x t e n s i v e l i g a t i o n of Hg by C l (41). K i n e t i c s t u d i e s a l r e a d y noted (32) show t h a t increased concentra t i o n s of HgCl species are r e s p o n s i b l e f o r reducing demethylat i o n r a t e s of a v a r i e t y of methylmetal donors as much as 3 to 150 f o l d as η goes from 2 t o 4 i n the e l e c t r o p h i l e . At constant μ i n the present cases f o r C10,~ and C l " dependence, we found over a 2f o l d d i m i n u t i o n i n k (obs; which must be a t t r i b u t a b l e to [ C l ]. F u r t h e r evidence t h a t i n c r e a s i n g [ C l ] r a t h e r than i n c r e a s i n g μ i s the dominant f a c t o r i n r e t a r d i n g t r a n s m e t h y l a t i o n r a t e r e s u l t e d from our c o r r e l a t i o n of l o g k ( o b s ) w i t h / [ C l ] i n the form of equation 8a. Here, we t r e a t e d [ C l " ] as the dominant c o n t r i b u t o r to i o n i c s t r e n g t h , w i t h the remaining ions behaving as they do i n the [C10^"] dependence case. The problem c o n f r o n t i n g us a t t h i s p o i n t was to devise means by which the r e l a t i v e c o n c e n t r a t i o n s of Me«Sn and H g species could be determined a t v a r i o u s [ C l ] and pH c o n d i t i o n s . Thereby, a k i n e t i c model could be fashioned which f e a t u r e d the p o s s i b l e p a i r - w i s e i n t e r a c t i o n s of a l l r e a c t a n t s . 2

2

n

2

-

2

+

2 +

S p e c i a t i o n of Reactants and Products i n Aqueous Transmethylation between T i n ( I V ) and M e r c u r y ( I I ) . Recent advances (21-30) i n e l e c t r o c h e m i s t r y and spectrometry have spurred new and r e f i n e d d e t e r minations of those e q u i l i b r i a (Table I ) necessary t o con s t r u c t a r e l i a b l e map of compositions f o r methylmetal and metal ions considered i n the present work. We employed an extended v e r s i o n of programs discussed by Dryssen et al. (24) which s i m u l t a n eously considers an a r r a y of formation constants (β . ) within e x p e r i m e n t a l l y observed boundary c o n d i t i o n s of totaî cÊloride, pH, and t o t a l methylmetal i o n s . A r e p r e s e n t a t i v e p l o t of s e v e r a l CHEMSPECIES determinations of mercury and m e t h y l t i n r e a c t a n t P

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

j E W E T T E T AL.

Aquated Metal Ions

169

species a t t = 0 i s d e p i c t e d i n F i g u r e 2. I t i s obvious t h a t sub s t a n t i a l changes i n the composition o f HgCl ' ~ ' occur over about a t e n - f o l d i n c r e a s e i n [ C l ] , w h i l e r e l a t i v e l y s m a l l e r e f f e c t s on Me^Sn species occur. I n s i m i l a r c a l c u l a t i o n s a t lower i o n i c strengths and v a r i a t i o n s i n pH (1-3 u n i t s ) , l i t t l e o v e r a l l change i n the composition diagram was seen. In t h i s f a s h i o n , the CHEMSPECIES program was used t o d e t e r mine both the d i s t r i b u t i o n o f r e a c t a n t s f o r each k i n e t i c run and t o map the d i s t r i b u t i o n o f r e a c t a n t s p l u s products d u r i n g the course o f a r e a c t i o n . R e s u l t s f o r one such r u n a t Cl/Hg = 3 a r e summarized i n g r a p h i c a l form i n F i g u r e 3. Two t r i m e t h y l t i n and t h r e e chloromercury(II) s p e c i e s were found t o account f o r g r e a t e r than 99.9 percent o f r e a c t a n t s (grouped as R i n F i g u r e 3) over the e n t i r e Cl/Hg range o f 3 t o 23 s t u d i e d . Product (P) analyses by the CHEMSPECIES progra i n d i c a t e d t h a t M e S n C l becam s i g n i f i cant only i n l a t e s t a t e h i g h e r [ C l ] . None o employe work generated s i g n i f i c a n t c o n c e n t r a t i o n s (e.g.j < 0.1 mole per cent) o f hydroxy- o r hydroxychloro-species. The pH o f many k i n e t i c runs was monitored as a f u n c t i o n o f time, o r the extent o f r e a c t i o n ( x ) . F i g u r e 4 i l l u s t r a t e s a t y p i c a l v a r i a t i o n o f [ H ] w i t h extent o f r e a c t i o n , corresponding t o the Cl/Hg = 3 r u n above. An acid-forming process was e v i d e n t , j u s t as expected from h y d r o l y s i s o f the metal species i n v o l v e d (14). For example n

+

(9)

+

H g C l + H 0 = Hg(0H)Cl + C l " + H , 2

2

y i e l d s an e q u i l i b r i u m constant, Κ', given by Table I as 3

K

K' - H g ( 0 H ) c r w . P

HgCl

1

5

8

χ

1 0

-10

f

2

-14 where Κ = 10 i s the water d i s s o c i a t i o n constant. f o r procfuet MeHg s p e c i e s , h y d r o l y s i s i s expected by +

Similarly,

+

MeHgCl + H 0 = MeHg (OH) + C l " + H , 2

(10)

f o r which Table I g i v e s K

K" = W 0 H ) - w , 2.09 Ι Ο "

1 0

x

[eHgCl Many such c o m p e t i t i v e h y d r o l y s i s r e a c t i o n s can occur, though i n d i v i d u a l l y l e s s s i g n i f i c a n t . Thus, s i m i l a r treatment o f the analogous Me^SnCl and Me«SnCl h y d r o l y s a t e s i n d i c a t e d t h a t these species c o n t r i b u t e d 1 0 and 1 0 l e s s t o [ H ] than the r e s p e c t i v e Hg species considered i n r e a c t i o n s 9 and 10. A l l o f these r e a c t i o n s , i n sum, w i l l c o n t r i b u t e t o observed pH changes d u r i n g the +

1 1

8

+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

ORGANOMETALLOIDS

-2.3

-2.5-i

-4.1

Figure 1. Plot of log k^obs) vs. V^T shows three classes of behavior for rates of transmethylation between Me Sn* and Hg % depending upon specific availability of [Cl"] (®), high [CIO,'] (9), or high [Cl'] (O). s

2

-0.6 1.0H

•8H

HgCI

2

HgCi " 4

•4H Figure 2. The CHEMSPECIES program cahufotions at constant ionic strength and pH ( ~ 3.0) provide a representative plot of relative abundance (mole fraction) of major reactant species as a function of Cl/Hg

.2

7 c ,

11

'Hg

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

J E W E T T E T AL.

Aquated Metal Ions

171

Figure 3. For a typical NMR kinetic run at Cl/Hg = 3, relative abundances of initial reactants, and subsequent abundances of both reactant and product species are compared as a function of extent of reaction

R X N IV-181 A

Cl:Hg«3 μ - 0.6

—,— 20

40

60 RXN

80

100

Figure 4. Changes in pH for a typical transmethylation reaction are followed as a function of extent of reaction. The [H*] buffering is apparent for 30-70% of the reaction.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

172

ORGANOMETALS AND

ORGANOMETALLOIDS

course of r e a c t i o n 1 but do not d i r e c t l y r e f l e c t the extent of t r a n s m e t h y l a t i o n . CHEMSPECIES c a l c u l a t i o n s w i t h data from Table I can account f o r the l a r g e i n c r e a s e i n H* during r e a c t i o n i n terms of < 500-fold changes i n concentrations of Hg(0H)C1 and MeHgOH, a l l a t < 10" M. Nonetheless, a d d i t i o n a l important (and u n a v a i l able) formation constants i n v o l v i n g hydroxy- or oxo-species are needed f o r f u l l i n t e r p r e t a t i o n of l a t e r e a c t i o n products. NMR s p e c t r a provided no evidence f o r new products, but such s o l u t e s , as w i t h previous examples, could be a t very low concentrations while yet m a n i f e s t i n g l a r g e pH changes, e.g.^ o l i g o m e r i z a t i o n of Me SnOH (12,30). In any case, n e i t h e r p r e c i p i t a t i o n of such acid-forming products was observed, nor d i d s i g n i f i c a n t d e v i a t i o n i n the b i m o l e c u l a r r a t e (equation 2) appear a f t e r s u b s t a n t i a l r e a c t i o n which might i m p l i c a t e oxo-species i n r a t e - d e t e r m i n i n g steps. R e l a t i v e abundance p r i n c i p a l l y c o n t r o l the pH of the r e a c t i o n . In F i g u r e 4, where extent of r e a c t i o n , t h a t i s [ M e H g * ] i/I S ] > versus pH i s compared, t h i s c o n d i t i o n of b u f f e r i n g was apparent. I n the r e g i o n from about 30-70 percent r e a c t i o n , we found t h a t pH v a r i e d l i t t l e more than ±2.7 percent i n e i t h e r the low (Cl/Hg • 3) or h i g h c h l o r i d e (Cl/Hg « 23) s i t u a t i o n s . Over t h i s range, mean pH increased from 2.26 to 2.38 w i t h [ C l " ] , j u s t as expected by s h i f t ing such c o n t r o l l i n g r e a c t i o n s as 9 and 10 to the l e f t . While complex, the g e n e r a l p o i n t s r a i s e d here are t y p i c a l f o r i n o r g a n i c complexes i n n a t u r a l waters, and a number of numerical s o l u t i o n s have been d e s c r i b e d t o t r e a t such e q u i l i b r i a (24,42). I n n a t u r a l waters the types of t r a n s m e t h y l a t i o n r e a c t i o n s of concern to us must occur a t much slower r a t e s , both on account of substan t i a l r e d u c t i o n s i n [ H g 1 _ - and [MeSn l „ -, and r a d i c a l , . ±. r-/total 3 total changes i n [IF] or [ C l ]. _ Based on simulated pH, [ C l ] , and metal concentrations en countered i n n a t u r a l waters, our p r e l i m i n a r y CHEMSPECIES c a l c u l a t i o n s i n d i c a t e that involvement of hydroxy species i n r e a c t i o n 1 would be s u b s t a n t i a l . Nonetheless, i n c o n s i d e r i n g a t r a n s i t i o n from f r e s h water to sea water systems, the e f f e c t s of c h l o r i d e i o n , of the type discussed here, become most important. The con cept of metal i o n b u f f e r i n g by a d d i t i o n of a p p r o p r i a t e l i g a n d s to s o l u t i o n s has been amply discussed (42). In complete analogy to pH c o n t r o l , mixtures of a c i d s and conjugate bases w i l l r e s i s t change i n [metal i o n ] , as 9

2

4

H

t o t a

2+

2 +

t o t a l

+

1

Τττ

Ί

n

z +

r „ - . ,z+ Κ [ML] [metal xon] = — ^ j —

.

ML = metal l i g a n d _ L

U

g

a

n

d

I n g e n e r a l , we must regard such chemistry as b a s i c t o moderating organometal i o n c o n c e n t r a t i o n s i n b i o t a , where a s u b s t a n t i a l v a r i e t y of " a p p r o p r i a t e " l i g a n d s are a v a i l a b l e . Transmethylation r e a c t i o n s w i l l presumably have t h e i r r a t e s s u b s t a n t i a l l y d i c t a t e d by such c h l o r i d e " b u f f e r systems".

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

JEWETT

ET AL.

Aquated Metal Ions

173 2 +

C o n s i d e r a t i o n of Reaction Pathways f o r M e t h y l a t i o n o f H g Species by M e ^ S n * " For the experimentally determined r a t e o f r e a c t i o n 1 we considered a l l p o s s i b l e " i o n p a i r " a s s o c i a t i o n s i m p l i e d by equation 4. We a r e not concerned a t t h i s p o i n t whether these i o n i c a s s o c i a t i o n s possess s u b s t a n t i a l l i f e t i m e s i n s o l u t i o n o r a r e t r a n s i t o r y complexes. I n t u r n , the formation con s t a n t s l i s t e d i n Table I express concentrations o f such p o s s i b l e ion-pair contributions 2

Z

[A "*"] [B *~] ±

association"

*^ATB (

W

[ A B ]

where γ , γ^, and express the usual a c t i v i t y c o e f f i c i e n t s f o r i n v o l v e s ions i n terms o f the Br^nsted-Debye-Huckel equations (36). Consequently, f o r an o v e r a l t i o n 2 i n terms o f the f o r a l l c o n d i t i o n s of [Cl""] employed i n t h i s work: 1

f

+

r a t e = k^tMe^n" "] [HgCl ] + k [ M e S n ] [ H g C l ^ l Y j 2

f

2

+

2

3

2

+ k [ M e S n ] [ H g C l " ] Y + k ' ^ M e ^ n C l ] [HgCl ] 3

3

4

2

2

+ k [ M e S n C l ] [ H g C l ~ ] + k [ M e S n C l ] [ H g C l ^ " ] (12) f

f

5

3

3

6

3

Here, we exclude r e a c t a n t s i n v o l v i n g h y d r o x y - t i n o r -mercury s p e c i e s , a l s o on the b a s i s o f our s p e c i a t i o n r e s u l t s obtained w i t h the CHEMSPECIES program discussed above. We t h e r e f o r e can reason ably presume a l i n e a r c o n t r i b u t i o n t o k«(obs) by a number o f p a i r wise ( i . e . j bimolecular) r e a c t i o n s which proceed c o n c u r r e n t l y (32, 36). In p r i n c i p l e , other b i m o l e c u l a r (or η-order) events could c o n t r i b u t e t o demethylation of M e S n by H g . As described i n the Experimental s e c t i o n , we have constrained pH, p C l , and con centrations of reactants t o insure s u f f i c i e n t reaction rates f o r NMR measurements, w h i l e a v o i d i n g s o l u b i l i t y d i f f i c u l t i e s . By r e ducing excessive h y d r o l y s i s t o i n s o l u b l e hydroxides, involvement of non-bimolecular r e a c t i o n s , p a r t i c u l a r l y w i t h polymeric s p e c i e s , was probably e l i m i n a t e d (30,41). I t i s p o s s i b l e t o experimentally determine the a c t i v i t y co efficients and γ by use o f the Debye-Huckel extensions o f the Br^nsted equation c i t e d before. Normally t h i s i s performed a t i o n i c strengths c o n s i d e r a b l y l e s s than those employed i n the present study. I n h i s elegant e a r l y work, Davis showed procedures by which such i o n - p a i r r e a c t i o n s c o n t r i b u t i n g t o an o v e r a l l b i molecular process could be l i n e a r l y evaluated i n terms of the la and ζ values (43). An a p p l i c a t i o n t o the complex tin-mercury system a l s o seems p o s s i b l e , but i s beyond the scope of the present paper. From equation 12 i t i s seen that q u a n t i t a t i v e e v a l u a t i o n o f +

2 +

3

2

Q

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

174

ORGANOMETALS AND ORGANOMETALLOIDS

s p e c i f i c r a t e constants f o r t h e s i x p a i r - w i s e r e a c t i o n pathways noted r e q u i r e d a m u l t i v a r i a t e a n a l y s i s i n v o l v i n g treatment o f k^iobs) as a v a r i a b l e dependent upon s i x k values and [ C l ] . f

S t a t i s t i c a l A n a l y s i s of the Dependence of k,» (obs) on [ C l ] . In t h e i r treatment of cleavage r a t e s o f sigma-bonded p y r i d i n o methyl d e r i v a t i v e s o f t r a n s i t i o n metals by HgCl or T1C1 , Dodd and Johnston s u c c e s s f u l l y employed (32) an extension of B a v i s l i n e a r sum method f o r concurrent r e a c t i o n p a i r s . B a s i c a l l y , t h i s approach assumes k i n e t i c a l l y independent existence and r e a c t i v i t y f o r each d i s c r e t e e l e c t r o p h i l i c metal s p e c i e s , whether charged or n e u t r a l . Thus, r e l a t i v e concentrations o f HgCl ~ reactants (taken as mole f r a c t i o n s , χ) were used t o weigh? l i n e a r combina t i o n s o f a s s o c i a t e d s p e c i f i c r a t e constants. I t seemed reasonabl a v a i l a b l e data indicate processes i n v o l v i n g c h l o r i d e exchange (44) and aquation (8) probably a l l occur a t r a t e s greater than 10^ times the transmethyl a t i o n r a t e s under study. Consequently, expressing r e a c t i o n 1 i n more general terms by means o f equations 2 and 12, we obtained 1

2

n

n=l m=4 k (obs) - J } ^ . ^

(13)

2

n=0 m=2 i n which k

X

+

02' [Me Sn ][HgCl °] 3

k

, X

2

+

03 [Me Sn ][HgCl ~] 3

k

3

X

+

2

04' [Me Sn ][HgCl ~] 3

k

X

4

0

0

1 2 * [ M e S n C l ] [HgCl,, ] 3

k

X

13' [Me SnCl°][HgCl ~] 3

k

X

3

2

14' [Me SnCl°] [HgC^ ""] 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

j E W E T T E T AL.

Aquated Metal Ions

175

A s e r i e s o f CHEMSPECIES c a l c u l a t i o n s f o r i n i t i a l r e a c t i o n c o n d i t i o n s ( t = 0 seconds) was performed_using s t a r t i n g t o t a l r e actant c o n c e n t r a t i o n s , pH, and t o t a l [ C l " ] . I o n i c strengths (μ = 0.556) were maintained constant f o r a l l Cl/Hg r a t i o s examined. A t a b l e o f i n d i v i d u a l c o n c e n t r a t i o n s f o r each o f the r e a c t i n g spe c i e s was constructed and the cross products o f these v a l u e s , ex pressed as mole f r a c t i o n s , were generated i n accord w i t h i n d i v i d ual rate c o e f f i c i e n t s through k-, above. A necessary and s u f f i c i e n t c o n d i t i o n f o r equation 13 was t h a t the sum of crossproduct mole f r a c t i o n s f o r each s e t o f k s taken f o r each Cl/Hg taken e q u a l l e d u n i t y . F o r each Cl/Hg case k-(obs) was determined by methods given i n the Experimental S e c t i o n . A m u l t i - r e g r e s s i o n a n a l y s i s program was employed which pro v i d e d complete analyses o f v a r i a n c e , from t h e standpoint o f t e s t s for F - r a t i o , multiple c o r r e l a t i o s i o n c o e f f i c i e n t s , and ness, a step-wise r e g r e s s i o n was performed f o r a l l 2 - 1 • 63 com b i n a t i o n s o f the s i x independent v a r i a b l e s , although s e v e r a l s t a t i s t i c a l t e s t s q u i c k l y r e v e a l e d t h a t two s i g n i f i c a n t l i m i t i n g con d i t i o n s were c h a r a c t e r i s t i c t o the data (45). The e v o l u t i o n o f t h e a n a l y t i c a l r e s u l t s a r e summarized i n Table V, where i t i s seen t h a t very s a t i s f a c t o r y f i t s of over 99.5 percent o f the k i n e t i c i n f o r m a t i o n c o u l d be obtained w i t h uniform dispersion of residuals f o r ten (obs) a t v a r i o u s Cl/Hg from 3 t o 23. B a s i c a l l y , we f i n d t h a t t h e s p e c i f i c r a t e c o e f f i c i e n t k ^ f o r the r e a c t i o n p a i r [Me«Sn-Cl°] and [HgCl^ ~] approaches zero ( 1 0 M s ) . I n a d d i t i o n , severe non-orthogonality (conversely, h i g h degree o f c o r r e l a t i o n ) occurred between two p a i r s o f r e a c t a n t s Q3~ 12 04~ 13" c o n d i t i o n was p r e d i c t e d by t h e c o r r e l a t i o n m a t r i x r o r r e g r e s s i o n (19) f

2

_6

k

k

a

k 02 K

k

Q 2

k

03

k

04

k

12

k

13

k

14

n

d

k

k

K

T

k 03

0.013

h

i

s

k

04

k

12

k

13

k

14

-0.987

0.010

-0.988

-0.824

-0.160

1.000

-0.159

-0.546

-0.157

1.000

0.881

-0.156

-0.543 0.881

and the s p e c i a l e q u i l i b r i u m r e l a t i o n s h i p s inherent w i t h formation constants l i s t e d i n Table I . One o f these e q u i l i b r i a can be evaluated f o r the k ^ k ^ case as

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

176

ORGANOMETALS

AND

ORGANOMETALLOIDS

TABLE V Summary of Best L i n e a r F i t f o r k ( o b s ) versus [ C l ~ ] 2

by S i x Independent P a i r - w i s e Rate Constants

Variable

Estimate

nm

k

02

±

S.E.

of t - t e s t

17.37

1.87

< 0.001

03

7.83

0.63

04

9.41

1.25

12

115.8

13

129.8

14

1

9.3 c

<0.01

R e a c t i o n Rate

1.00 0.45

< 0.

J

17.3

<0.01

b

0.54 6.7

< 0.001

7.5

C

* 0.0

a —3 —I — l b c He 10 M s ; Reference 19; Estimated upper v a l u e d e r i v e d from mean sum o f squares d e v i a n t from r e g r e s s i o n . 5

STATISTICAL ANALYSIS* : 3

I n t e r c e p t = -9.25 ± 0.10 χ 1θ" M" Variance

R - 0.998 where R R

2

= 0.995 (100 R

2

Q

Q 1

1

S"

1

= 0.911

= "percent f i t " )

F = 419.0 (df - 6) where F

0

0

0

5

= 12.95

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

J E W E T T E T AL.

Aquated Metal Ions

+

3

[Me Sn ][HgCl,"] r»

ο m u .

[Me SnCl][HgCl ] For the k , k case, the d e r i v e d from 3

Q /

2

+

S

2

B

[Me S n [ [ H g C l ~ ] 4

1

-

0

1

4

·

7

9

(

1

4

)

n

C

1

HgCl

- 10 ' ^Me^nCl 4

-

[Me SnCl][HgCl "] 3

1 7

~

^ f o l l o w i n g numerical r e l a t i o n s h i p can be

1 3

3

HgCl

ι = a

À

177

3

1

1 4

(15)

- 13.80

By s u b s t i t u t i o n of k - 13.80 k and k = 14.79 k , two new independent v a r i a b l e s were generated, e.g., k,^ and k -, r e s p e c t i v e l y , which y i e l d e d a c o r r e l a t i o n m a t r i x showing s a t i s f a c t o r y o r t h o g o n a l i t y (19) three v a r i a b l e s (again provided s t a b l e c o e f f i c i e n t s a s s i g n a b l e as the i n d i v i d u a l o r par t i a l second-order r a t e c o e f f i c i e n t s s i g n i f y i n g the r e l a t i v e con t r i b u t i o n o f each p a i r - w i s e r e a c t i o n path considered. Q 4

3

1 2 3

M e c h a n i s t i c Considérât ions o f S e v e r a l Pathways f o r M e t h y l a t i o n of H g by Me^Sn** i n N a t u r a l Waters. I n c h l o r i d e s o l u t i o n s o f constant i o n i c s t r e n g t h approximating those found i n marine waters (42), where μ * 0.6 and [ C l ~ ] - 0.5M, observed b i m o l e c u l a r t r a n s m e t h y l a t i o n r a t e s were a c c u r a t e l y accounted f o r by a l i n e a r com b i n a t i o n of c e r t a i n t i n and mercury r e a c t i o n p a i r s . Our observed and estimated r a t e s are summarized i n Table V I and compared i n the e r r o r p l o t depicted i n F i g u r e 5. Of c o n s i d e r a b l e i n t e r e s t i s the p o s s i b i l i t y of a p p l y i n g these k i n e t i c r e s u l t s t o estimating rates f o r reaction 1 i n natural a q u a t i c s i t u a t i o n s where l a r g e [ C l " ] and i o n i c s t r e n g t h g r a d i e n t s occur. Such commonplace environmental s e t t i n g s are found i n e s t u a r i n e i n t e r f a c e s w i t h r i v e r f r e s h waters, where i t should a l s o be noted t h a t l i k e l i h o o d o f higher concentrations of b i o a c t i v e metal i o n s i s g r e a t e r from d i s p o s a l o f i n d u s t r i a l e f f l u e n t s (46). F o r our d i s c u s s i o n , we can expect t h a t r e a c t a n t metal species i n r e a c t i o n 1 would be a v a i l a b l e only a t g r e a t l y reduced c o n c e n t r a t i o n s i.e.j < 1 0 " % . On the other hand, we can e n v i s i o n i n t e r - t i d a l water c o n d i t i o n s f a v o r i n g d i s t r i b u t i o n s o f m e t h y I t i n and mercury c h l o r o - s p e c i e s over hydroxy-species, as i m p l i e d by CHEMSPECIES c a l c u l a t i o n s a t pH - 7-8 and p C l - 2. We are thus confronted w i t h a main question of whether reduced, but b u f f e r e d , and [ C l ] , coupled w i t h lowered and v a r i a b l e i o n i c strengths m a t e r i a l l y change the k i n e t i c c o n t r i b u t i o n of r e a c t i o n p a i r s d i s c e r n e d i n the laboratory. We have shown t h a t f o r those r e a c t i o n p a i r s i n v o l v i n g a neu t r a l p a r t n e r i n the a c t i v a t e d complex o r rate-determining s t e p , the Brrfnsted-Debye-Huckel r e l a t i o n s h i p (equations 8a, 8b) p r e d i c t s t h a t I n k = I n k . That i s , k ( o b s ) may become independent o f z +

Q

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

178

AND ORGANOMETALLOIDS

TABLE V I

Based on the Reaction P a i r Model

E s t i m a t i o n of

k (obs)

lun

±

2

0.25

4.40

16

4.49

0.562

22.16 23.03

9

4.61

0.18

4.53

0.550

17

5.85

0.27

5.79

0.382

14.77

7

6.25

0.48

6.39

0.550

11.00

6

6.75

0.23

6.66

0.550

8.97

4

7.11

0.32

7.04

0.550

6.00

3

7.11

0.36

7.19

0.550

4.99 4.01

2

7.40

0.42

7.38

0.550

1

7.63

0.19

7.66

0.550

3.00

8

7.70

0.39

7.67

0.29

8.06

10

0.20

9.12

11

8.II

e

7.69°

0.550

3.00

8.10

d

0.051

2.00

9.06

d

0.051

3.01

d

0.077

4.00

d

0.100

5.00

12

10.24

0.41

7.38° 10.40

13

10.58

0.41

7.20

a

3

1

1

e

11.50

b

k i n 1 0 " M" s" ; G i v e n by k values i n Table V s u b s t i t u t e d i n t o equation 13. C a l c u l a t e d from r e g r e s s i o n equation given i n d

Table V; S e e text and equations 13, 16.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

11.

j E W E T T E T AL.

Aquated Metal Ions

Figure 5. Observed and calculated rate constants (x KPM^s" ) are compared in an error (residual) diagram. Kinetics parameters estimated for various Cl/Hg values in solutions at high ionic strengths accurately predict k (calc) in such conditions (—·—), but fail for rates observed in solutions of low ionic strength (—Ο—). Introduction of a correction factor, based upon changes in ionic strength, into appropriate kinetic parameters per mits fairly accurate extension of original parameters to faster rates in solutions of low ion concentrations (—Ο—). 1

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

179

180

ORGANOMETALS AND

ORGANOMETALLOIDS

i o n i c s t r e n g t h i f s o l u t i o n c o n d i t i o n s favor only formation of n e u t r a l t i n and/or mercury r e a c t a n t s . We have t e s t e d t h i s i d e a i n two ways. F i r s t , by comparing the r e l a t i v e r a t e c o n t r i b u t i o n f o r r e a c t i o n p a i r s i n equation 1 l i s t e d i n Table V. we see the most impor t a n t are M e S n + HgCl °; Me SnCl° + HgCU ; and M e ^ n C l + HgCl". A l l of these pathways are expected to be independent of μ. We now reexamine the e f f e c t s of i n c r e a s i n g μ discussed w i t h Table I I I and F i g u r e 1 employing a mechanistic p i c t u r e : (a) w i t h increased [C10^~], the observed near-zero slope r e s u l t s because v i r t u a l l y no compositional change occurred i n the three p r i n c i p a l r e a c t i o n p a i r s over the range s t u d i e d , hence I n k/k = constant ~ 0; (b) where μ was increased w i t h [ C l ~ ] , s u b s t a n t i a l compositional changes were e f f e c t e d i n favor of H g C l ^ " c o n c e n t r a t i o n s . There by, r e a c t i o n s o c c u r r i n g b " d Me^nCl HgCl^ " e i t h e r y i e l d e d a negativ tarded k^iobs) as k i n e t i c a l l y pathways A second important t e s t i n v o l v e d a f o r t u i t o u s opportunity to experimentally " i s o l a t e " a r e a c t i o n pathway. We determined k ( o b s ) f o r r e a c t i o n 1 where Cl/Hg = 2 and μ = 0.051. Here, at r e a c t a n t concentrations amenable to NMR measurements, CHEMSPECIES c a l c u l a t i o n s showed t h a t M e S n and HgCl ° comprised 99.9 percent of t o t a l r e a c t a n t s . Therefore, equation 13 reduced t o +

0

3

2

3

2

+

2

2

2

+

3

k (obs) = 2

X [ M e

S n

+

] [ R g C 1

2

oj k

Q 2

= 8.06

χ

l O - W

1

-3 This r e s u l t agrees w e l l w i t h the p r e d i c t e d value of 8.11 χ 10 which was based on k i n e t i c parameters obtained f o r r e a c t i o n s conducted at the s i g n i f i c a n t l y higher i o n i c s t r e n g t h of 0.55, Were o p p o s i t e l y charged r e a c t i o n p a i r s t o become c o m p o s i t i o n a l l y important at the lower i o n i c s t r e n g t h , we expect that these could c o n t r i b u t e increased r e l a t i v e r a t e s t o the o v e r a l l k ( o b s ) . Under i d e a l circumstances, where i o n - p a i r a s s o c i a t i o n s and even mecha n i s t i c paths were independent of μ, i n d i v i d u a l l i n e a r c o n t r i b u t i o n s from such z z _ p a i r s should a l t e r by some f a c t o r p r o p o r t i o n a l t o the Δμ s t u d i e d here. We examined t h i s p o s s i b i l i t y f o r r e a c t i o n 1 a t the low i o n i c s t r e n g t h noted. A s t r i k i n g r e v e r s a l i n the r e l a t i o n s h i p of k ( o b s ) w i t h Cl/Hg or [ C l " ] was observed, that of mutual i n c r e a s e , as summarized i n Table V I . P l o t t i n g these k ( o b s ) obtained at low i o n i c s t r e n g t h against k ( c a l c ) obtained w i t h k i n e t i c parameters d e r i v e d a t h i g h i o n i c s t r e n g t h , again as an e r r o r graph i n F i g u r e 5, c l e a r l y demonstrated i n a p p l i c a b i l i t y of c e r t a i n terms i n equa t i o n 13 without a Δμ c o r r e c t i o n f a c t o r f o r charged pathways (39). To account f o r a c c e l e r a t i o n of k ( o b s ) by C l at low i o n i c s t r e n g t h , we can d e r i v e a simple c o r r e c t i o n based upon s e v e r a l important assumptions. For equation 8a or 8b, we take I n k = In k where ζ = 0 and/or μ = 0; i n p r a c t i c e our m u l t i p l e r e g r e s s i o n s o l u t i o n t o equation 13 a l s o produces a c o n c e n t r a t i o n independent term ( i n t e r c e p t ) which probably bears a p h y s i c a l r e l a χ

2

+

2

2

2

2

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t i o n s h i p to k . F u r t h e r , we presume t h a t the concurrent k v a l u e s estimated i n the h i g h i o n i c s t r e n g t h s o l u t i o n s are v a l i d a t low μ. T h i s i s saying that no important mechanistic changes occur i n the t e n - f o l d change o f i o n i c s t r e n g t h examined. With these p o i n t s i n mind, we r e w r i t e equation 8a s o l v i n g f o r k^ correspond ing t o μ^ w i t h e l i m i n a t i o n o f k and Br^nsted's p r o p o r t i o n a l i t y constant α ° I n k^ - 2 z z _ ι/μ^ = I n k^ - 2 z z _ v ^ +

+

2

More c o n v e n i e n t l y , In k ^

= 2 z z_ +

[vH[ -

(16)

We a p p l i e d such a c i t e d i n Table V I . Fo k g f a l l out as p r e v i o u s l y described; f o r runs 11-13, r e a c t i o n p a i r k ^ was e l i m i n a t e d because of i t s s m a l l c o n t r i b u t i o n , hence only r e a c t i o n p a i r s k^^ and k^, r e q u i r e d c o r r e c t i o n w i t h equation 16 u s i n g the two i o n i c strengths employed at μ^ and μ , i.e., 0.550 and 0.051, 0.077, o r 0.100, r e s p e c t i v e l y . F o l l o w i n g t h i s , the c o r r e c t e d terms were summed w i t h appropriate weighting by the cross-product mole f r a c t i o n s as s p e c i f i e d i n equation Id. The new k ( c a l c ) are compared i n Table V I , where i t i s seen t h a t remarkable f i t s (
2

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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c o n s t i t u t i o n or r e l a t i v e c o n t r i b u t i o n s t o k ( o b s ) . I n one sense t h i s i s s u r p r i s i n g , p a r t i c u l a r l y f o r the ion-molecule or i o n - i o n p a r t n e r s , s i n c e i t _ h a s been shown i n r e l a t e d r e a c t i o n s t h a t a 10f o l d change i n [ C l ] can a l t e r k t o a much g r e a t e r extent than that expected from equation 16 wSere Cl/Hg i s l a r g e (32). At much reduced Cl/Hg v a l u e s , formation constants f o r c h l o r o e l e c t r o p h i l e s f a r exceed those f o r i o n - p a i r i n g between C l and methyl donors (8,32), so reducing p o s s i b i l i t i e s f o r a l t e r e d r e a c t i v i t i e s i n the latter. With e i t h e r Me^Sn or Hg , s u b s t a n t i a l evidence i s a v a i l a b l e i n d i c a t i n g t h a t e i t h e r species forms w e l l - d e f i n e d s t r u c t u r e s i n water (8,10,11,12,41,47), f o r which a d i s t i n c t i v e s t e r e o chemical pathway t o t r a n s m e t h y l a t i o n should be reckoned. The three f a s t e s t r e a c t i o n p a i r s measured i n t h i s work a l l i n v o l v e t i n or mercury s p e c i e s whic i c evidence as c o o r d i n a t e l c h l o r o - l i g a n d s do not occupy a l l a v a i l a b l e s i t e s : 6 f o r t i n and four or s i x f o r mercury (11,12,41,47). Therefore, l a b i l e water molecules are a v a i l a b l e f o r a s s o c i a t i v e b r i d g i n g complexes of the type shown w i t h 5 and 6. 2

+

2 +

F i n a l l y , a statement i s i n order, concerning the " t r u e " chemical nature of the e q u i l i b r i u m p a i r s d e f i n e d by equations 14 and 25. These should not be regarded as mathematical devices t o serve requirements of o r t h o g o n a l i t y i n our r e g r e s s i o n a n a l y s i s . T h e i r e x i s t e n c e i s as r e a l as any of the formation constants i n Table I , and the s u b t l e s t r u c t u r a l or e l e c t r o n i c d i f f e r e n c e s which e n e r g e t i c a l l y separate the k ^ p a i r from the k^pair» or k^ from k ^ , should represent bases by which other k i n e t i c p r o p e r t i e s can be d i s t i n g u i s h e d i n a manner s i m i l a r t o the present work. T h e i r r e s p e c t i v e e q u i l i b r i u m constants suggest t h a t we t r e a t them as i o n - p a i r s (46,48). Acknowledgement s The authors thank Mr. R. A. Thompson and Ms. M. Crocker f o r a s s i s t a n c e w i t h NMR s p e c t r a and k i n e t i c runs. D i s c u s s i o n s w i t h Dr. T. D. Coyle concerning k i n e t i c and mechanistic i n t e r p r e t a t i o n s of data were very h e l p f u l . We are e s p e c i a l l y g r a t e f u l t o Mr. M. R. Cordes of the NBS A p p l i e d Mathematics D i v i s i o n f o r h i s t a l e n t e d assembly of c r i t i c a l subroutines r e q u i r e d f o r the CHEMSPECIES program. Continuing encouragement and p a r t i a l f i n a n c i a l support from the NBS O f f i c e of Environmental Measurements and the U.S. Naval Ship Research and Development Center (Annapolis) are g r e a t f u l l y acknowledged by K. L. Jewett and F. E. Brinckman. J . M. Bellama wishes t o express a p p r e c i a t i o n f o r f i n a n c i a l support by the N a t i o n a l Science Foundation Grant OCE-76-23595 and by the U n i v e r s i t y of Maryland Sea Grant Program.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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2.

3. 4. 5.

6. 7. 8. 9.

10.

11.

12. 13. 14. 15. 16. 17.

18. 19. 20.

Brinckman, F.E., Iverson, W.P., and B l a i r , W., In: "Proceed ings of the Third International Biodegradation Symposium," J.M. Sharpley and A.M. Kaplan, Eds., 919, Applied Science Publ., London, 1976. Chau, Y.K. and Wong, P . T . S . , In: "Occurrence and Fate of Organometals and Organometalloids i n the Environment", Amer ican Chemical Society Symposium Series, Washington, D . C . , F . E . Brinckman and J . M . Bellama, Eds., 1978. Wasik, S . P . , Brown, R.L., and Minor, J.I., J. Environ. S c i . Health, (1976) A 11, 99. Ridley, W.P., Dizikes, L.J., and Wood, J.M., Science, (1977) 197, 329. Carty, A.J., In: "Occurrenc Organometalloids i n the Environment", American Chemical Soc iety Symposium Series, Washington, D . C . , F . E . Brinckman and J.M. Bellama, Eds., 1978. Hein, F . and Meininger, Η . , Z. anorg. allgem. Chem., (1925) 145, 95. Benesch, R. and Benesch, R . E . , J. Amer. Chem. Soc., (1951) 73, 3391. F r a t i e l l o , Α . , Prog. Inorg. Chem., (1972) 17 Part II, 57. Including estimation of sp-hybridization of metal-carbon bonds; cf. Holmes, J . R . and Kaesz, H . D . , J. Amer. Chem. Soc. (1961) 83, 3903. H a l l , J . R . , In: "Essays i n Structural Chemistry", A.J. Downs, D.A. Long, and L.A.K. Staveley, Eds., 443, Plenum Press, New York, 1972. Brinckman, F.E., Ρarris, G . E . , B l a i r , W.R., Jewett, K . L . , Iverson, W.P., and Bellama, J . M . , Environ. Health Perspec tives, (1977) 19, 11. Tobias, R . S . , Organometal. Chem. Rev., (1966) 1, 93. Glass, G . E . , Schwabacher, W.B., and Tobias, R . S . , Inorg. Chem., (1968) 7, 2471. Baes, C . F . , J r . and Mesmer, R . E . , "The Hydrolysis of Cations", John Wiley and Sons, New York, 1976. Haupt, H.-J., Huber, F., and Gmehling, J., Z,. anorg. allgem. Chem., (1972) 390, 31. Jewett, K.L., Dissertation, University of Maryland, 1978. Jewett, K.L., Brinckman, F.E., and Bellama, J . M . , In: "Marine Chemistry i n the Coastal Environment", 304, American Chemical Society Symposium Series No. 18, Washington, D . C . , T. Church, E d . , 1975. Johansson, L., Coord. Chem. Rev., (1974) 12, 241 and refer ences cited therein. Chatterjee, S. and Price, Β . , "Regression Analysis by Ex ample", John Wiley and Sons, New York, 1977. A Fortran V l i s t i n g of CHEMSPECIES program i s available from the authors on a limited basis. In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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24.

25. 26. 27. 28. 29. 30. 31. 32. 33.

34. 35. 36. 37.

38. 39. 40. 41. 42. 43. 44. 45.

organometals and organometalloids Ciavatta, I . L . and Grimaldi, Μ., J. Inorg. Nucl. Chem., (1968) 30, 197. Helper, L . G . and Olofsson, G . , Chem. Rev., (1975) 75, 585. S i l l e n , L . G . and Martell, A.E., "Stability Constants of Metal Ion Complexes", The Chemical Society, London, Special Publi cation No. 17, 1964. Dryssen, D . , Jagner, D . , and Wengelin, F., "Computer Calcula tion of Ionic Equilibria and Titration Procedures", Almqvist and Wiksell, Stockholm, 1968. Cassol, Α . , Portanova, R . , and Magon, L., La Ricerca S c i e n t i f i c a , (1966) 36, 1180. Janssen, M . J . and Luijten, J . G . A . , Rec. Trav. Chim., (1963) 82, 1008. Geier, G. and Erni, I.W., Chimia, (1973) 27, 635. Schwarzenbach, G d Schellenberg Μ. Helv Chim A c t . (1965) 48, 28. Cassol, Α . , Magon, L., , , Inorg , (1967) 3, 25. Tobias, R.S. and Yasuda, M . , J. Phys. Chem., (1964) 68, 1820. Abraham, M.H. and Johnston, G . F . , J. Chem. Soc. (A), (1970), 193. Dodd, D . , Johnson, M.D., and Vamplew, D . , J. Chem. Soc. ( Β ) , (1971), 1841. Huey, C.W., Brinckman, F.E., Grim, S . O . , and Iverson, W.P., In: "Proceedings of the International Conference on Trans port of Persistent Chemicals i n Aquatic Ecosystems", II-73, National Research Council, Ottawa, 1974. Jewett, K . L . and Brinckman, F.E., Preprints of Papers (ACS Div. Environ. Chem.), (1974) 14, 218. Blandamer, M . J . and Burgess, J., Chem. Soc. Rev., (1975) 4, 55. Davis, C.W., Progr. Reaction Kinetics, (1961) 1, 161. Jewett, K.L., Brinckman, F.E., and Bellama, J . M . , Abstr. Papers, 172nd National Mtg. ACS, San Francisco, CA, Sept., 1976, INOR 137. Lockhart, J.E., "Redistribution Reactions", Academic Press, New York, 1970. Pethybridge, A.D. and Prue, J.E., Progr. Inorg. Chem., (1972) 17 Part I I , 327. Hester, R . E . and Plane, R . A . , Inorg. Chem., (1964) 3, 769. Sandström, Μ., Acta Chem. Scand., (1977) A 31, 141. Stumm, W. and Morgan, J.J., "Aquatic Chemistry", Wiley-Inter science, New York, 1970. Davies, C.W. and Wyatt, P . A . H . , Trans. Faraday Soc., (1938) 45, 770; 774. For example with HgC1 see: Eigen, M. and Eyring, E . M . , Inorg. Chem., (1963) 2, 636. Davies, O.L. and Goldsmith, P.L., Eds., "Statistical Methods in Research and Production", Hafner Publ. C o . , New York, 1972 n

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185

Purves, D . , "Trace-Element Contamination of the Elsevier Scientific Publ. Co., Amsterdam 1977. see Chapter 7. Deacon, G . B . , Rev. Pure Appl. Chem., (1963) 13, An elegant spectroscopic definition is given by in reference 10.

Environment", Especially 189. Waters, D . N . ,

Discussion J . J . ZUCKERMAN (University of Oklahoma): these reactions occur in homogeneous solution? BELLAMA:

I assume that

Yes.

ZUCKERMAN: In Chesapeak where, in that organic aqueous portion rose, one would get a salting out into the micelle? Micelles perhaps containing or composed of chlorinated hydrocarbons or chlorination agents? Could you comment on it? BELLAMA: These are very complex systems; we and others are just beginning to decipher them. The laboratory situations are complex enough; when you get out into the real world the situation becomes fantastically complex, not only in terms of the chemistry question that you have addressed, but also in terms of the ubiquitous microorganisms. So, yes, that effect is very possible; such effects very l i k e l y do occur. This is the work of the future: to try to discover what the individual pairvise interactions can t e l l us, i f we really can restrict the systems to two separate interacting moieties. F. E . BRINCKMAN (National Bureau of Standards): The real world confronts us and makes what is already a complicated solution to these multicomponent kinetic analyses even more complicated because of phase considerations. In Chesapeake water, the situation is far worse than even in micelles because of abundant microglobules which are of larger size, and in terms of surface activity are very great. These are fecal products, l i p i d s , e t c . , that involve reacting species with partitioning. Unfortunately, we'll not get into i t in this symposium with the exception of papers by Drs. Wasik and Good. We did some work based on the idea of the cybotactic volume [E.M. Kosower, »J. Amer. Chem. Soc., (1958) 80, 3261]. We found that a great number of common bacteria l products, organic materials, which w i l l form homogeneous solutions can be compared as a solvent media for these transmethylation rate studies we showed here. It is the amount of water which is determining the rate. This leads to the idea of Kosower s concept of the cybotactic volume, which is that i n the water or in a strong electrolyte medium, there are long-range structures called micelles i f you l i k e . In a bacterial product 1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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medium such as an acetone, i . e . , acetone-water s o l u t i o n , the acetone w i l l order i t s e l f i n t o a c y b o t a c t i c volume which r e p r e s e n t s , i f you l i k e a "micro-micro m i c e l l e " . I t i s i n those v o l umes that these r e a c t i o n s do not happen. That's about a l l we know. We reported on that i n San F r a n c i s c o [Abstr. Papers, 172nd N a t ' l ACS Mtg., Sept. 1976, IN0R-136]. BELLAMA: One might add here t h a t i n the B a l t i m o r e Harbor, which must be one of the l e a s t - c l e a n areas that we could examine, there i s sewage o u t f l o w , the c o n c e n t r a t i o n of metals i s about enough that you can walk on water wtihout e x t e r n a l a s s i s t a n c e , and you have o r g a n i c s as w e l l ; so the s i t u a t i o n becomes v e r y complex. On the other hand, there are p o r t i o n s of the Bay (some of the s h e l l f i s h i n g areas) that are s t i l l v e r y c l e a n a r e a s , and so one has a c o n t r o l . F. HUBER ( U n i v e r s i t y of Dortmund): In homogeneous s o l u t i o n we measured the r e a c t i o n of d i m e t h y l t h a l l i u m a c e t a t e and mercury a c e t a t e , and we obtained the same order of magnitude f o r the k v a l u e s . We found an a c t i v a t i o n energy of about 18 k i l o c a l o r i e s per mole, and I t h i n k i t ' s about the same as you found w i t h the t i n and t h a l l i u m compounds. In our paper [ t h i s volume], we p o s t u l a t e a mechanism f o r these t r a n s a l k y l a t i o n r e a c t i o n s between d i me thy l t h a l l i u m compounds and mercury compounds. I t ' s about the same as the mechanism f o r the t r a n s a l k y l a t i o n r e a c t i o n we observed between d i m e t h y l t h a l l i u m and t h a l l i u m ( I I I ) a c e t a t e . 2

C. J . SODERQUIST ( U n i v e r s i t y of C a l i f o r n i a , D a v i s ) : Have you t r i e d an experiment where you took Chesapeake Bay water and some sediment and put i n t r i m e t h y l t i n and mercury a t l e v e l s you would encounter t h e r e (0.1 ppm)? Does the r e a c t i o n take place? I f i t does, does i t match what you would p r e d i c t from your data? BELLAMA: We have taken sediment or taken the organisms i s o l a t e d from the Bay by P r o f e s s o r R.R. C o l w e l l ' s group ( U n i v e r s i t y of Maryland) or by Dr. W.P. Iverson ( N a t i o n a l Bureau of Standards) and spiked w i t h one metal o r s e v e r a l metals t o see whether or not the systems would promote m e t h y l a t i o n of a p a r t i c u l a r metal [C.W. Huey, Ph.D. D i s s e r t a t i o n , U n i v e r s i t y of Maryland, 1976]. The r e s u l t s are f a v o r a b l e . BRINCKMAN: Yes, we have done that experiment and t r a n s m e t h y l a t i o n o c c u r s , but t h e r e i s a v e r y s u b s t a n t i a l uptake of the o r g a n o t i n by s u b s t r a t e . T h i s i s t r u e i n the growth medium f o r i n v i t r o experiments dependent upon c o n t a i n e r e f f e c t . E i t h e r a p o l y carbonate P e t r i d i s h e f f e c t , or a sediment e f f e c t o c c u r s , and the uptake of t i n i s v e r y s u b s t a n t i a l . The m e t h y l a t i o n of mercury o c c u r s , but we t h i n k i t i s slower. M. 0. ANDREAE (Scripps I n s t i t u t e of Oceanography):

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

You

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Aquated Metal Ions

187

showed the p r o d u c t i o n of t r i m e t h y l t i n i n sediments. I s that a model experiment, o r i s t h a t a c t u a l l y t r i m e t h y l t i n t h a t you found i n the r e a l sediment? BELLAMA: No, we haven't found i t i n sediment, although some organotins a p p a r e n t l y have been found. [R.S. Braman e t a l . r e p o r t t r a c e m e t h y l t i n s p e c i e s i n f r e s h and marine waters [S.E. R e g i o n a l ACS Meeting, Tampa 1977; submitted, A n a l . Çhem.]. T h e i r p r e c i s e i d e n t i t y i s not r e a l l y q u i t e c l e a r t o us. I t ' s the q u e s t i o n o f s p e c i a t i o n , which i s o b v i o u s l y an extremely important one, and one that a t environmental c o n c e n t r a t i o n s become very d i f f i c u l t t o do by some o f our current a n a l y t i c a l techniques. M e t h y l a t i o n o f metals seems t o occur w i t h v i r t u a l l y every element i n the p e r i o d i c t a b l e . We found that the t r a n s m e t h y l a t i o n r e a c t i o n s seem t o occur much more r e a d i l y than group than a methyl, w i t touched on i n h i s paper [equation 11]. That i s , i n our work on s i l a t r a n e s , we f i n d that t r a n s a l k y l a t i o n r e a c t i o n s a l l seem t o proceed very r e a d i l y ; indeed, many other R groups can be t r a n s f e r r e d a t e s s e n t i a l l y the same r a t e as methyl. With regard t o your q u e s t i o n , a good s t a r t i n g p l a c e f o r t r a n s m e t h y l a t i o n r e a c t i o n i s the t r i m e t h y l t i n c a t i o n , which i s the c l a s s i c a l waters o l u b l e , w a t e r - s t a b l e , methyl-donating species that would be the r e a c t i o n system o f c h o i c e t o most organometal chemists. J . S. THAYER ( U n i v e r s i t y o f C i n c i n n a t i ) : Most o f the r e a c t i o n s t h a t you c i t e had methyl t r a n s f e r r e d t o mercury from some other organometal. Have you observed any r e a c t i o n s where a methyl group i s t r a n s f e r r e d from methylmercury t o some other metal? BELLAMA: In g e n e r a l , mercury seems t o be near the bottom o f the a c t i v i t y s e r i e s ; you can take many methyl donors and t r a n s f e r the methyl group t o mercury, but t h e r e are e x c e p t i o n s . BRINCKMAN: Jewett showed [K.L. Jewett, Ph.D. D i s s e r t a t i o n , U n i v e r s i t y of Maryland (1978)], and i t has been independently shown [N.F. Gol'dshleger e t a l . , D o k l . Acad. Nauk SSSR (1972) 206, 106] that the methyl group can he t r a n s f e r r e d from methylmercury to A u ( I I I ) , P d ( I I ) , and P t ( I I ) w i t h , f o r example, formation o f i n t e r m e d i a t e t r a n s i t o r y methylpalladium s p e c i e s . We found the second order r a t e constant t o be q u i t e slow, about 10 M s , o r less. RECEIVED

August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

12 Demethylation of Methylcobalamin: Some Comparative Rate Studies JOHN S. THAYER Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221 Introduction Various studies have been reported on the kinetics and mechanism of the reaction between inorganic salts and methylcobalamin(1-9). Rate constants have been reported for CH HgX(4,5) and PdC1 (6). Yet there has been no systematic wide-ranging study into the various factors affecting the rate of this reaction. This paper gives a first report on such a study. 2-

3

4

Experimental All reactions were run i n 0.10M acetic acid-0.10M sodium acetate solution (pH=4.55) at 25°C. The rate of disappearance of methylcobalamin was followed by standard spectrophotometric techniques(1,3,10) usually u n t i l 90% or more conversion occurred.Initial reactions followed second-order kinetics (first-order i n each reactant); occasionally the metal substrate was i n great excess, i n which case pseudo-first-order kinetics were observed. Results A.

Metathetical Exchange

Tables I and II list the reaction rate constants for various substrates. Occasionally a metal substrate was only p a r t i a l l y soluble i n the reaction mixture; the listed value i s then the minimum value for the rate constant. For those systems where the reaction had to be studied for many days, controls (methylcobalamin solutions without metal compound) were run

0-8412-0461-6/78/47-082-188$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

12.

THAYER

Methylcobalamin

Table I .

189

Rate Constants f o r M e t a t h e t i c a l Reaction o f Methylcobalamin w i t h Organometals

Compound

Runs

K(s"

1

- )

Mercury CH Hg0Ac C H Hg0Ac 3

6

5

-2

6 3

6. 68 X 1 0 -3 * 3 . 5 X 10

3 3

2. 42 X 1 0 -2 1 . 40 X 1 0

Thallium (CH ) T10Ac CH3TI(OAc)2 2

3

Lead (CH ) Pb0Ac (C H ) Pb0Ac (C H ) Pb0Ac (C H ) PbCl (C H ) Pb(OAc) C H Pb(0Ac) 3

6

3

2

5

3

6

5

3

2

5

6

5

2

5

3

2 4

3 4 6 3

-5 1 . 50 X 1 0 ' - 5 2. 42 X 10" - 4 *5. 0 X 10" - i f 2. 50 X 1 0 '

3 3 3

1 . 95 X 10" 1 . 35 X 10" - i f 1 . 73 X 10"

1

2

2

2. 0 0 *3. 6 2. 32 *1. 0 1 . 08

3 3 2

X X X X X

10 -3 10" -4 10 -if 10" -2 10"

Tin (CH ) Sn0Ac (C H ) Sn0Ac (C H ) Sn0Ac (CH ) SnCl 3

3

2

5

3

6

5

3

3

2

2

Metalloids (CH^As^I (CH ) SbJl (CH ) Te I 3

it

3

3

Table I I .

Rate Constants f o r Reaction o f Methylcobal a m i n w i t h I n o r g a n i c O x y Compounds

Compound

Au 0 2

# Runs

2

3

K(s"M

)

*2.4 X 1 0 "

6

ln 0

1

*7.0 X 10

2

3

* 1 . 3 X 10

QPb(OAc)^

2

*0.40

Na HAsOif

1

Sb 0

1

2

Sn0

3

2

2

5

NaBi0

2

-6

3

6

2.30 Χ

1θ"

*4.2 X 1 0 "

5

5

0.44

•Minimum v a l u e s f o r p a r t i a l l y s o l u b l e c o m p o u n d s . 0Ac= acetate. S)Compound i n t r o d u c e d a s l e a d t e t r a a c e t a t e , b u t h y d r o l y s i s o c c u r s upon c o n t a c t w i t h s o l v e n t .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

190

simultaneously. T h e s e c o n t r o l s s h o w e d no during t h i s time period.

ORGANOMETALLOIDS

reaction

Comparison of r e a c t i o n r a t e s i n d i c a t e t h a t the h e a v i e s t m e t a l s are the most r e a c t i v e . Compounds o f t h e S i x t h Row m e t a l s f r o m P t t h r o u g h B i r e a c t r e a d i l y w i t h m e t h y l c o b a l a m i n , t h o u g h i n many c a s e s t h e i n i t i a l l y f o r m e d m o n o m e t h y l m e t a l compound decomposes. Lighter metals are noticeably less r e a c t i v e , except f o r Pd(6). S u b s t i t u t i o n of o r g a n i c groups onto the metal reduces r e a c t i v i t y very sharply, w i t h the extent of r e d u c t i o n dependin T h u s , i n t h e Pb s e r i e s cobalamin w i l l vary i n the order RPbX

3

>

R PbX 2

2

>

R PbX 3

The n a t u r e o f t h e i n o r g a n i c g r o u p s p r e s e n t o n t h e m e t a l w i l l a l s o change the r a t e o f r e a c t i o n . Table I I I shows t h e e f f e c t o f t h e a n i o n upon t h e r e a c t i v i t y of m e t h y l m e r c u r i c i o n .

T a b l e I I I . E f f e c t o f A n i o n on R e a c t i o n R a t e C o n s t a n t for Methylmercuric Salt-Methylcobalamin Reaction* Anion OAc~ Cl" Br""

Anion 0 1.36 7.55 9.54

i " SCN"

CN"

Cone.

6.57 7.17

X X X X X

S

Ms" ) 1

Ratio

3.60

Χ ΙΟ"**

1.000

3.01

X

10"

0.856

1

10"

2

10"

3

1.37

X

10"

3

Salt

Precipitates

1θ"

3

7.15

X

10"

3

3.44

X

0.381

10" *

10"

5

0.199

10"

5

0.096

* I n a l l c a s e s , t h e c o n c e n t r a t i o n s o f CH HgOAc and m e t h y l c o b a l a m i n w e r e 5.75 X 1 0 " a n d 1.87 X 10 molar r e s p e c t i v e l y . 3

3

4

C o n c e n t r a t i o n o f e x t r a a n i o n added. The c u l a t e d Κ f o r t h i s s y s t e m i s 6.99 X 1 0 ~ 2

cal s^M"" .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1

12.

THAYER

Methylcobalamin

191

A s i m i l a r repressant e f f e c t i s noted f o r inorganic m e r c u r y s a l t s (1,5) a n d a l s o o c c u r s f o r o r g a n o t h a l l i u m compounds, where t h e h a l i d e s a r e l e s s r e a c t i v e t h a n the acetates (10). By c o n t r a s t , o r g a n o t i n c h l o r i d e s seem t o b e s o m e w h a t m o r e r e a c t i v e t h a n t h e c o r r e s p o n ding acetates. B.

Successive

Reactions

The g r e a t d i f f e r e n c e i n t h e r e a c t i o n r a t e c o n s t a n t s f o r H g ( O A c ) a n d CH HgOAc e n a b l e d t h e two m e t h y l a t i o n r e a c t i o n s t o b e s t u d i e d s e p a r a t e l y (.1*3.'^' This c o u l d be extended t o other systems. As Figure 1 shows, K P t C l c l e a r l y undergoes s u c c e s s i v e m e t h y l ations. The r e p o r compound o n l y a c c e p t i n c o r r e c t simply because they d i d not study the system for a s u f f i c i e n t length o f time. Our o b s e r v a t i o n s do support t h e i r c l a i m , however, t h a t t h e r e i s a time l a g between the m i x i n g o f the reagents a n d the s t a r t o f t h e r e a c t i o n (9^) . T a b l e I V l i s t s t h e r a t e c o n s t a n t s f o r a number o f compounds t h a t u n d e r g o p o l y m e t h y l a t i o a 2

2

Table

6

IV.

Rate Constants f o r Successive with Methylcobalamin K,

Compound Tl(OAc) 3

K PtCl 2

*2.0

2

C H Pb(OAc) 5

1

(s"^" )

K (s" 2

1.60

3

CH Tl(OAc) 6

3

X

9.5

3

X

-1 -1 M ) 2

*1.3

χ ίο"

10"

2

*1.3

X

10~

10"

2

1.1

X

10"

3

8.4

X

10~

3

0.965

6

Reactions

k

C a l c u l a t e d on the assumption t h a t m e t h y l t h a l l i u m d i a c e t a t e does n o t decompose i n s o l u t i o n . The f i r s t r a t e c o n s t a n t f o r K P t C l g a g r e e s w e l l w i t h estimated values obtained from the data o f T a y l o r a n d H a n n a (9) . M e t h y l t h a l l i u m d i a c e t a t e h a s b e e n r e p o r t e d t o decompose i n p o l a r s o l v e n t s ( 1 1 ) : 2

CH Tl(OAc) 3

2

+ CH 3OAc + T I O A c

(1)

T h i s d e c o m p o s i t i o n has t o b e t a k e n i n t o a c c o u n t when c a l c u l a t i n g the r a t e constant f o r methylation. By an e l a b o r a t e c a l c u l a t i o n (10) , we f o u n d t h a t t h e r a t e

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

192

ORGANOMETALS AND

ORGANOMETALLOIDS

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

12.

Methylcobalamin

THAYER

193

constant f o r t h er e a c t i o n o f methylthallium d i a c e t a t e w i t h m e t h y l c o b a l a m i n t o b e 5.65 X 1 0 s" ^" . Under these c o n d i t i o n s , methylation and r e d u c t i v e e l i m i n a t i o n a r ecompetitive r e a c t i o n s , and only a f r a c t i o n of methylthallium diacetate i s converted t o the d i m e t h y l compound. 1

1

T h r e e compounds t h a t m i g h t h a v e b e e n e x p e c t e d t o undergo s u c c e s s i v e m e t h y l a t i o n d i d n o t , i n f a c t , do so. T h e s e a r e shown i n T a b l e V. Table

Compound

Kis^M

KAuCl^ Pb(OAc) NaBi0

V

2.08

98.1

*0.40

h

3

Minimum v a l u e

25.0

0.44

25.0

for slightly

s o l u b l e compound

In excess methylcobalamin over an extended time per i o d , KAuCli+ o n l y a c c e p t e d a s i n g l e m e t h y l g r o u p . S i n c e d i m e t h y l g o l d ( I I I ) c o m p o u n d s a r e known a n d s t a b l e , t h e i n a b i l i t y may b e d u e t o t h e f a c i l e d e c o m position

CH3AUCI3

CH3CI

+

AuCl ~

(2)

2

T h i s r e a c t i o n h a s b e e n r e p o r t e d f o r t h e P d a n a l o g (6). No m e t a l l i c A u m i r r o r w a s f o r m e d d u r i n g t h e r e a c t i o n . U n l i k e K P t C l , K A u C l ^ showed no i n i t i a l t i m e l a g ; r e a c t i o n began upon c o n t a c t . 2

6

N e i t h e r P b ( O A c ) ^ n o r N a B i 0 showed s i g n s o f s u c c e s s i v e m e t h y l a t i o n i n t h epresence o f excess methylcobalamin. I n f a c t , o n l y a p o r t i o n o f t h e m e t a l compound a c t u a l l y r e a c t e d . T a y l o r a n d Hanna h a d a s i m i l a r o b s e r v a t i o n f o r Pb(OAc)^(8). MonomethyHead (IV) a n d m o n o m e t h y l b i s m u t h (V) c o m p o u n d s a r e t o t a l l y u n known. I f t h e y f o r m a t a l l , t h e y must decompose s o f a s t t h a t m e t h y l a t i o n cannot proceed t o any e x t e n t . Since t h er a t e constant f o r CH Pb(OAc) would be e x p e c t e d t o b e a b o u t 0.10 s ^ M " , t h e c o n s t a n t f o r the r e d u c t i v e e l i m i n a t i o n r e a c t i o n must be a t l e a s t 3

3

3

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

194

ORGANOMETALS AND

ORGANOMETALLOIDS

comparable i n magnitude. S i n c e b o t h o f t h e s e com pounds a r e s t r o n g o x i d i z i n g a g e n t s , i t i s p o s s i b l e t h a t t h e r e a c t i o n does not i n v o l v e methyl t r a n s f e r but r a t h e r d i r e c t o x i d a t i o n o f the methyl group. C.

R e a c t i o n o f K ^ t C l i * w i t h Me t h y 1 c ob a 1 a m i η

T a y l o r a n d H a n n a r e p o r t e d e s s e n t i a l l y no r e a c t i o n between p o t a s s i u m t e t r a c h l o r o p l a t i n a t e and m e t h y l c o b a l a m i n o v e r a s h o r t p e r i o d o f t i m e (9). Examining t h i s s y s t e m o v e r a l o n g e r t i m e p e r i o d , we f o u n d t h a t a r e a c t i o n does o c c u r . In f a c t , the r e a c t i o n i s autoc a t a l y t i c , a s shown i n T a b l e V I . Table VI.

Data

fo

[cHaB^ Time(ks) 2.22 3.30 12.84 77.64 175.44 287.41

0.01 X 0.02 0.08 0.49 1.32 1.99+

*

10

10

-

ι

-

A

[CH3B1 C a l . a

φ

Reacted

3

12

Κ

Reacted

3.22 4.60 4.94 5.78 10.76 38.06

0.01 X 0.02 0.08 0.49 1.29 2.27

10

1 A

R a t e c o n s t a n t (s M ) c a l c u l a t e d f r o m s e c o n d - o r d e r r a t e law, w i t h i n i t i a l c o n c e n t r a t i o n s K P t C l = 2.00 Χ 1 0 - Μ a n d C H B = 6.51 X 10 M. 2

i +

4

3

1 2

^Concentration of methylcobalamin calculated using a r a t e c o n s t a n t 4.80 X 10 s" M" i n the autoc a t a l y t i c equation (12): l

A χ

+

A

b

, Β 0

=

~

1

+

~ 1 + Β

0

ο

e

-(A

ο

+ Β )kt ο

where χ i s t h e amount o f m e t h y l c o b a l a m i n r e a c t e d a f t e r t i m e t , and A and Β are the i n i t i a l con c e n t r a t i o n s o f K P t C l i and°methy 1 c o b a 1 a m i n r e spectively. 2

f

The a u t o c a t a l y s i s m i g h t h a v e come f r o m t h e p r e s e n c e m e t a l l i c p l a t i n u m , formed by t h e r e a c t i o n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

of

12.

THAYER

Methylcobalamin

PtCl*' CH PtCl 3

195

+

CH B

2

-> C H C 1

3

~

3

-> C H P t C l

1 2

3

+

3

Pt +

2 3

"+

C l ~

(3a)

2C1~

(3b)

We t e s t e d t h i s b y r u n n i n g t h e r e a c t i o n i n t h e p r e s e n c e o f f i n e l y powdered p l a t i n u m m e t a l . The r e a c t i o n shows a marked i n c r e a s e i n r a t e , and f o l l o w e d s t a n d a r d second order k i n e t i c s ( 1 0 ) . D

e

Oxidative

Reaction

with

Methylcobalamin

The r e p o r t t h a t S n ( I I ) s p e c i e s c a n b e c o n v e r t e d t o m e t h y l t i n ( I V ) compounds (13) p r o m p t e d u s t o l o o k at a variety of substrate tive methylation. Tabl with their reaction rate constants. Table VII.

Rate Constants f o r Oxidative Reaction o f M e t h y l c o b a l a m i n w i t h M e t a l Compounds

* Compound

# Runs

—ι —ι Κ (s

M

)

Hg

3

1.0 Χ ΙΟ*"

C5H5TI

2

3.3

CsGeCl (CH ) 3

6

2

3

Sn

2

6

5

3

1.2 X ΙΟ""**

2

3

10~

5.6 Χ ΙΟ""**

2

(C H ) P

Χ

5

4.0 Χ Ι Ο "

4

A l l compounds o n l y p a r t l y s o l u b l e i n r e a c t i o n medium; h e n c e , numbers l i s t e d a r e minimum v a l u e s . I n t h e c a s e o f C s G e C l 3 , one p o s s i b i l i t y i s c h l o r i n e methyl exchange, f o l l o w e d by d i s p r o p o r t i o n a t i o n (Eqn. 4 ) . The o t h e r compounds 2CH GeCl " 3

2

->

(CH ) G e C l 3

2

2

+

Ge

+

2Cl"

(4)

cannot proceed b y t h i s pathway. Investigations are now u n d e r way t o d e t e r m i n e t h e m e c h a n i s m ( s ) b y w h i c h t h e s e compounds r e a c t . Discussion

two

E a r l y workers q u i c k l y recognized that a t l e a s t r e a c t i o n pathways e x i s t e d f o r methylcobalamin r e -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS A N D ORGANOMETALLOIDS

196

a c t i o n s (2) · T h e m e t h y l - c o b a l t b o n d may c l e a v e i n a n y of t h r e e ways: CH

3

-

CO

1 1 1

->

Θ :CH •CH

+

Oco

+

G

1 1 1

(5a)

3

CH CH

3

3

- Co -

CO

1

1

1

1 1 1

-> ->-

(5b)

•Co

3

CH ® 3

:Co

I

(5c)

In t h e l a t t e r two c a s e s , t h e c o b a l t i s b e i n g r e d u c e d , and t h e p r o d u c t s ( B and B ) have q u i t e d i f f e r e n t a b s o r p t i o n s p e c t r a , fiaking t h l m e a s y t o d i s t i n g u i s h , at l e a s t i n p r i n c i p l e . The f i r s t c l e a v a g e o c c u r s without o x i d a t i o n , and t h e product i s aquocobalamin, a l s o w i t h a unique a b s o r p t i o n spectrum. Similar mechanisms c o u l d b R CH3S , t h a t have bee 1 2

1 2

2

A.

Metathetical

Demethylation

T h i s i s t h e m o s t common m e c h a n i s m f o u n d , a n d i s e s s e n t i a l l y a t r a n s f e r o f a methyl carbanion t o a metal, substrate. The s u b s t r a t e i s a l m o s t a l w a y s c a t i o n i c i n n a t u r e ; hence, t h e mechanism o f t h e r e a c t i o n i s a p p a r e n t l y Sg2(14) , p r o c e e d i n g through an i n t e r mediate o f t h e type

By c o r o l l a r y , a n y t h i n g t h a t a f f e c t s t h e e l e c t r o p h i l l i c i t y o f the metal w i l l a f f e c t t h e rate o f reaction. Organic groups, b e i n g good e l e c t r o n donors, s h o u l d lower the e l e c t r o p h i l i c i t y o f a metal; t h i s i s consis tent w i t h t h e observed decrease i n r e a c t i o n rates as t h e number o f o r g a n i c g r o u p s i n c r e a s e s . The r a t e s u p p r e s s i o n by anions (Table I I I ) r e s u l t s from e l e c t r o n - r i c h s p e c i e s c o m p e t i n g f o r t h e same m e t a l c a t i o n . Hence, any s p e c i e s t h a t i s e l e c t r o p h i l i c has t h e p o t e n t i a l o f r e a c t i n g w i t h methylcobalamin by t h i s pathway, even i f t h e i n i t i a l l y formed p r o d u c t subse q u e n t l y decomposes.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

12.

THAYER

197

Methylcobalamin

Workers s t u d y i n g the r e a c t i o n o f m e r c u r i c a c e t a t e w i t h methylcobalamin found t h a t the mercury i n t e r a c t s with the benzimidazole nitrogen o f methylcobalamin t o f o r m t h e " b a s e - o f f " c o m p l e x (.1/3/5) l e a d i n g t o m o r e complex k i n e t i c s . This competing r e a c t i o n , which c a n b e e l i m i n a t e d b y a d d i t i o n o f h a l i d e i o n s (5), w a s a l s o o b s e r v e d f o r P d C l ^ " ( 6 ) . We d i d n o t o b s e r v e i t i n t h e r e a c t i o n s o f organometals with methylcobalamin, perhaps r e f l e c t i n g t h e i r reduced e l e c t r o p h i l i c c h a r a c t e r r e l a t i v e t o Hg(OAc) · 2

2

B.

Redox

Demethylation

The m o s t t h o r o u g h l y s t u d i e d s y s t e m o f t h i s t y p e i s the S n ( I I ) - C H B an o x i d i z i n g a g e n t f o r r e a c t i o n t o o c c u r , a n d the proposed mechanism h a s h o m o l y t i c c l e a v a g e o f the m e t h y l - c o b a l t bond a s i t s c r u c i a l step (13,15). 3

Arsenic, selenium, and t e l l u r i u m are methylated by a d i f f e r e n t pathway, w h i c h i n v o l v e s r e d u c t i o n o f the s u b s t r a t e by removal o f oxygen. The mechanism p r o p o s e d b y C h a l l e n g e r (16) a n d e l a b o r a t e d o n b y C u l l e n e t a l . (17) i n v o l v e s t r a n s f e r o f a m e t h y l c a r bon ium i o n : (HO) A s :

+

3

+

[CH As(OH) ] 3

3

3

(HO) A s : 2

+

->

3

3

2

[ C H A s (OH) ] 3

+ +

2 e" CH

+ 3

+

(

6

a

)

3

-> C H A s O ( O H )

3

CH AsO(OH) CH

CH

+

2

+

H

(6b)

-* C H ( H O ) A s : 3

+

2

2

0 "(6c)

+

[ ( C H ) A s (OH) 3 e t c . (6d) 3

2

2

I n t h e s e s y s t e m s m e t h y l c o b a l a m i n d o e s n o t seem t o b e the m e t h y l a t i n g agent, a t l e a s t not d i r e c t l y ; instead, t h e m e t h y l g r o u p comes f r o m a s u l f o n i u m s a l t ( 1 6 , 1 7 ) . N e v e r t h e l e s s , a s i m i l a r mechanism c o u l d be w r i t t e n for methylcobalamin reactions. The r e a c t i o n b e t w e e n P t ( I V ) o r A u ( I I I ) a n d methylcobalamin h a sbeen a l l e g e d t o r e q u i r e the p r e s ence o f the lower o x i d a t i o n s t a t e o f the metal ( 7 ) . T h i s has been termed a "redox s w i t c h " mechanism, a n d has t h e f o l l o w i n g form (9):

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

198

ORGANOMETALS AND

2

PtCli* " complex

+

+

CH B 3

->

1 2

3

+

(7a)

complex

CH PtCl

PtClg

ORGANOMETALLOIDS

B

+ CI

5

(7b)

1 2

The c o m p l e x , r e p o r t e d b y Wood a n d c o w o r k e r s (115) t o involve i n t e r a c t i o n of P t C l ^ " with a side chain of the c o r r i n r i n g system, i s c h a r a c t e r i z e d by h a v i n g a more l a b i l e m e t h y l - c a r b o n bond t h a n m e t h y l c o b a l a m i n itself. C o n s e q u e n t l y , i t r e a c t s more r e a d i l y . Side c h a i n complexes between m e t a l s and B derivatives h a v e b e e n p r o p o s e d ( 1 8 ) . The m e t a l s f o l l o w i n g t h e "redox s w i t c h " mechanis t e n t i a l for molecula s h o u l d b e n o t e d t h a t t h e P t C l " / P t p o t e n t i a l i s +0.75 ν ( 1 9 ) . Our o b s e r v a t i o n t h a t P t c a t a l y s e s t h a t r e a c t i o n of P t C l i ^ " with methylcobalamin suggests that t h i s couple a l s o f a l l s i n t o the "redox s w i t c h " c a t e gory. Whether the "redox s w i t c h " mechanism i s l i m i t ed s o l e l y t o p l a t i n u m and g o l d o r a p p l i e s t o a w i d e r r a n g e o f m e t a l s r e m a i n s t o be d e t e r m i n e d . 2

1 2

i +

2

C.

In vivo

kinetics

The v a l i d i t y w i t h w h i c h m o s t r e p o r t e d k i n e t i c a n d m e c h a n i s t i c s t u d i e s c a n be e x t e n d e d t o b i o l o g i c a l p r o cesses i s quite uncertain. V e r y few r a t e s t u d i e s have been r e p o r t e d f o r m e t h y l a t i o n by n a t u r a l o r g a n i s m s . _ T r i m e t h y l a r s i n e f o r m e d a t t h e r a t e o f 3.9 X 1 0 " Ms"" when C a n d i d a h u m i c o l a m e t h y l a t e d 5 X 1 0 " M A s 0 s o l u t i o n ( 1 7 ) . When o n e g r a m o f r a t c e c a l c o n t e n t s w e r e t r e a t e d w i t h 2.0 m l 7.4 X 1 0 " M H g C l solution, 17.6 n g CH H g C l w e r e f o r m e d o v e r a p e r i o d o f t w e n t y hours (20)? S i m i l a r slow r e a c t i o n s were found i n t h e b i o l o g i c a l m e t h y l a t i o n o f P b ( I I ) and T l (I) ( 2 1 ) . O b v i o u s l y , r a t e s o f m e t h y l a t i o n under b i o l o g i c a l c o n d i t i o n s a r e g o i n g t o b e much s l o w e r t h a n u n d e r t e s t tube c o n d i t i o n s . One r e a s o n i s t h e much l o w e r c o n centrations involved. A n o t h e r r e a s o n , p r o p o s e d by R o b i n s o n e t a l . (5), i s t h a t m e t h y l c o b a l a m i n i n b i o l o g i c a l systems e x i s t s i n h y d r o p h o b i c e n v i r o n m e n t s , and that surfactants w i l l g r e a t l y i n h i b i t rates of react ions. Much r e m a i n s t o b e d o n e i n t h i s a r e a . χ

1 2

3

2

3

6

2

Acknowledgments We w i s h t o t h a n k D r . J o h n Wood a n d t h e F r e s h w a t e r B i o l o g i c a l Laboratory (Navarre, Minnesota) f o r p r o v i d -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

12.

Thayer

Methylcobalamin

199

i n g the means t o i n a u g u r a t e t h i s p r o j e c t . D r s . M. O r c h i n , J . B . Smart, and R. S. T o b i a s k i n d l y p r o v i d e d some o f the more e x o t i c compounds used i n t h i s s t u d y . D r . E s t e l Sprague p r o v i d e d some v e r y h e l p f u l d i s c u s s i o n on the k i n e t i c s i n v o l v e d i n t h e s e r e a c t i o n s . Literature Cited 1.

DeSimone, R. Ε., P e n l e y , M. W. Charbonneau, L., S m i t h , S. G., Wood, J. Μ . , Hill, H.A.O., Pratt, J. M . , R i d s d a l e , S . , W i l l i a m s , R. J. P., B i o c h i m . B i o p h y s . A c t a (1973), 304, 851.

2.

Bertilsson, 10, 2805.

3.

C h u , V . C . W . , Gruenwedel, (1977), 7, 169.

D. W . , B i o i n o r g . Chem.

4.

C h u , V . C . W . , Gruenwedel, (1976), 31C, 753.

D. W . , Z . N a t u r f o r s c h .

5.

R o b i n s o n , G . C., Amer. Chem. S o c .

6.

Scovell, 3451.

7.

Agnes, G., B e n d l e , S. Hill, H . A . O., W i l l i a m s , F . R . , W i l l i a m s , R. J. P., Chem. Comm. (1971), 850.

8.

T a y l o r , R. T., Hanna, M. (1976), A 1 1 , 201.

L.,

Environ.

9.

T a y l o r , R. 6, 281.

L.,

B i o i n o r g . Chem. (1976),

10.

Thayer,

11.

P o h l , U., Huber, 116, 141.

12.

Capellos, C., Bielski, B . H . J., " K i n e t i c Systems," 59-62, W i l e y - I n t e r s c i e n c e , New Y o r k , 1972.

13.

D i z i k e s , L . J., R i d l e y , W. P., Wood, Amer. Chem. S o c . (1978), 100, 1010.

14.

M a t t e s o n , D . S . , " O r g a n o m e t a l l i c R e a c t i o n Mecha n i s m s , " Academic P r e s s , New Y o r k , 1974.

L.,

N e u j a h r , Η.

Υ.,

Biochem.

Nome, F., F e n d l e r , (1977), 99, 4969.

W. M., J. Amer. Chem. S o c .

J.,

T.,

Hanna, M.

unpublished F.,

J.

J.

(1971),

H.,

J.

(1974),

Sci.

96,

Eng.

results. Organometal. Chem.

J.

(1976),

M.,

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15.

F a n c h i a n g , Y . T., R i d l e y , W. Chapter , t h i s volume.

16.

Challenger,

F.,

C h a p t e r 1,

P.,

this

Wood, J. Μ . ,

volume.

17.

C u l l e n , W. T., F r o e s e , C . L., Lui, Α., M c B r i d e , Β . C . Patmore, D . J., and Reimer, M., J. Organo m e t a l . Chem. (1977), 139, 61.

18.

P r a t t , J. Μ . , I n o r g a n i c C h e m i s t r y o f V i t a m i n 189-190, Academic P r e s s , New Y o r k , 1972.

19.

H a r t l e y , F . R., "The C h e m i s t r y o f P l a t i n u m and P a l l a d i u m , " 13 A p p l i e d S c i e n c e s London 1973

20.

Rowland, I., D a v i e s H e a l t h (1977), 24.

21.

Huber, F., S c h m i d t , this volume.

U.,

B ," 12

Kirchmann, Η . , C h a p t e r

Discussion J . J . ZUCKERMAN (University of Oklahoma): Concerning the l i s t of insoluble species reacting with the methylating agent: Is reaction occurring with soluble species (although the Ksp value for Sn02 is a very small number), or is i t in fact occurring on the surface? If so, are a l l these species in a slurry of similar paricle size? THAYER: In some cases there is a p a r t i a l s o l u b i l i t y , and we expect that many of these are reacting with the species actually in solution, even though we could not get complete s o l u b i l i t y . In some other cases, e.g., lead tetraacetate, which is hydrolyzed to lead dioxide or some sort of oxy-acetato-lead species, there is not appreciable s o l u b i l i t y . There you are probably getting a sur face reaction. This may be true for some other species as well. ZUCKERMAN: Was there some standardization in particle size in the l i s t that you gave? THAYER: I tried to make these solids as finely divided and as homogeneous as I could, but other than that I'm afraid there wasn't any. J . M. WOOD (University of Minnesota): When you are studying these reactions you also must look at problems related to compet ing reactions for the displacement of benzimidazole. You can have

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

12.

THAYER

Methylcobalamin

201

e q u i l i b r i a w i t h the base-on, w i t h base-off or protonated base-off. J u s t r e c e n t l y , we have been able t o show that by making a number of c o r r i n - r i n g d e r i v a t i v e s and comparing complexation w i t h a c o r r i n macro-cycle, one can now form outer-sphere complexes w i t h propionamide s i d e chains. Consequently, the k i n e t i c i n t e r p r e t a t i o n of your r e a c t i o n s can be extremely d i f f i c u l t because you can be l o o k i n g at f o u r or f i v e a l t e r n a t e e q u i l i b r i a i n these systems. THAYER: I agree. Not much can be s a i d yet about mechanisms f o r these r e a c t i o n s . But f o r most organometals I don't t h i n k comp l e x a t i o n e i t h e r w i t h the benzimidazole or the r i n g i s important. With many i n o r g a n i c s p e c i e s , i t i s . ZUCKERMAN: I f the metal species f i n d s i t s e l f i n a complex w i t h the benzimidazole, then i t i s a l s o on the wrong s i d e of the r i n g to e f f e c t m e t h y l a t i o n that? WOOD: I t has a profound e f f e c t on the k i n e t i c s f o r the r e a c t i o n . I f you are l o o k i n g at e l e c t r o p h i l i c a t t a c k on the c o b a l t carbon bond and you d i s p l a c e the benzimidazole, t a k i n g mercury as a simple example, you get about two orders of magnitude d i f f e r e n c e i n the r e a c t i o n r a t e because i t ' s d i f f i c u l t to d i s p l a c e the methyl group as a carbanion. But i f you consider the r e a c t i o n w i t h a s i n g l e - e l e c t r o n oxidant i n t i n ( I I ) , you look at a f r e e r a d i c a l displacement of the methyl group. This seems t o be i n s e n s i t i v e t o c o o r d i n a t i o n by benzimidazole and i s very i n s e n s i t i v e to pH i n these systems. Depending on whether the mechanism i s e l e c t r o p h i l i c a t t a c k or s i n g l e - e l e c t r o n o x i d a t i v e a d d i t i o n , an enormous change i n the r e a c t i o n r a t e s i s seen f o r t h i s r e a c t i o n . However, the chemistry i s not t r i v i a l because the benzimidazole can come o f f , i t can be protonated, or i t can r e a c t w i t h a metal i o n . The formation of a complex w i t h a c o r r i n macrocycle which changes the e l e c t r o n d e n s i t y on the cobalt-carbon bond can g r e a t l y change the r e a c t i v i t y of the methyl group to e i t h e r e l e c t r o p h i l i c a t t a c k or possibly free r a d i c a l attack. ZUCKERMAN: That would change the m o l e c u l a r i t y of the r a t e determining s t e p , i f one metal were t o complex w i t h the benzimida z o l e and a second metal species were t o a t t a c k an a p i c a l s i t e . So that would be revealed i n the data, provided one could i n t e r p r e t those data i n terms of m o l e c u l a r i t y . W. R. CULLEN ( U n i v e r s i t y of B r i t i s h Columbia): We are b r a i n washed by the i d e a that methyl B-^ i s i n v o l v e d i n a l l of these r e a c t i o n s . We f i r m l y b e l i e v e t h a t there i s no B^« i n v o l v e d i n a r s e n i c methylation. P r o f e s s o r Wood pointed out that the nature of the methylating species had to be e s t a b l i s h e d i n nature. Much of our d i s c u s s i o n now i n v o l v e s base-on, base-off d e t a i l s , yet the compound may not i n f a c t be the methylating agent. I suggest t h a t

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

202

AND

ORGANOMETALLOIDS

the most important t h i n g we can do i s t o i n v e s t i g a t e these r e a c t i o n s i n b i o l o g i c a l systems, t o f i n d out what i s going on and what i s doing the methylating. There i s one easy way of g e t t i n g o x i d a t i o n : that i s t o use CH^ as an a t t a c k i n g agent. Use of CH^~ w i t h o x i d a t i o n r e q u i r e s a d d i t i o n a l m a n i p u l a t i o n of e l e c t r o n s . CH~ i s a good methylating agent from nature and i s r e a d i l y a v a i l a b l e . I suggest we should t h i n k more about CH^ ; i t can come from methyl well. +

+

+

a s

WOOD: I agree. The value of t h i s model chemistry i s t o point up p o s s i b l e mechanisms f o r transmethylation r e a c t i o n s i n b i o l o g i c a l systems. But the important t h i n g i s t o e s t a b l i s h p r e c i s e l y which coenzyme intermediate i s i n v o l v e d i n the transmethylation r e a c t i o n . T h a t s why experiments w i t h isotopes are necessary i n complicated systems l i k l a k sediment d mixed m i c r o b i a l n i t i e s . I t ' s important Then you can s t a r t t h i n k i n g terms o mechanism. Fo the m e t a l l o i d s , you are p r i m a r i l y l o o k i n g a t n u c l e o p h i l i c a t t a c k on the carbon-sulfur bond of something l i k e S-adenosylmethionine, or e l s e something l i k e methylated co-enzyme M i n anaerobic systems. You can get methyl t r a n s f e r t o a r s e n i c i n a h i g h o x i d a t i o n s t a t e i f you a c t i v a t e the c o r r i n r i n g by a r e a c t i o n w i t h a platinum complex. That may not have very much s i g n i f i c a n c e t o b i o l o g i c a l systems, but from nmr data you see that platinum complex a c t i v a t e s the s y s tem. I t i s the same s o r t of chemical s h i f t that you see f o r B ^ when i t binds t o the enzymes, where you have t o supply 70 k i l o c a l o r i e s t o break t h a t bond f o r s u b s t r a t e rearrangement r e a c t i o n s i n the enzymes. So, we don't r e a l l y know what i s happening i n the 12 P * 1

B

r o t e i n s

v e t

R. H. FISH ( U n i v e r s i t y of C a l i f o r n i a , B e r k e l e y ) : I don't t h i n k you ever i d e n t i f i e d any compounds i n these r a t e s t u d i e s . that c o r r e c t ? THAYER:

Is

We have not i d e n t i f i e d any products.

FISH: The r e s u l t s seems t o be tenuous unless you i d e n t i f y the compounds. How t r i m e t h y l t i n forms i n the environment i s s t i l l c o n t r o v e r s i a l . P r o f e s s o r Wood shows that t i n ( I I ) goes t o methylt i n ( I V ) , but what happens a f t e r that? We have looked a t methyland d i m e t h y l t i n species r e a c t i n g w i t h methyl B-« and couldn't f i n d any r e a c t i o n o c c u r r i n g . Again, you must i d e n t i f y the products bef o r e you can t a l k about r a t e s of r e a c t i o n p e r t a i n i n g t o methylation* THAYER: Not n e c e s s a r i l y . I n the case of the t i n compounds, i t seems there i s a s u b s t a n t i a l d i f f e r e n c e i n r a t e s of r e a c t i o n depending on what i n o r g a n i c groups are present. With m e t h y l t i n t r i c h l o r i d e , I couldn't see any r e a c t i o n . With m e t h y l t i n t r i a c e t a t e v i r t u a l l y no r e a c t i o n occurred. However, d i m e t h y l t i n d i c h l o -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

12.

THAYER

Methylcobalamin

203

r i d e r e a c t s c o n s i d e r a b l y f a s t e r than d i m e t h y l t i n d i a c e t a t e . I t i s w e l l known that t i n - o x y species w i l l form i n t e r m o l e c u l a r b r i d g i n g bonds r e s u l t i n g i n polymeric species p a r t i c u l a r l y where you have 2 oxy groups per t i n , or even more where you have t h r e e . This may i n f l u e n c e the r e a c t i o n of o r g a n o t i n compounds w i t h whatever methyla t i o n agent there may happen to be. There was one case where we could i d e n t i f y the product, the t r i m e t h y l t e l l u r o n i u m i o n . I found t e l l u r i u m metal and d i m e t h y l t e l l u r i d e . For tetramethylarsonium ion and methylcobalamim a very unpleasant odor which q u i t e proba b l y was t r i m e t h y l a r s i n e was given o f f . F. HUBER ( U n i v e r s i t y of Dortmund): We have p r e l i m i n a r y r e s u l t s on the r e a c t i o n of t i n ( I V ) , not w i t h methylcobalamin, but w i t h me thy lcobaloxime. From nmr measurements we found t h a t we probably get the m e t h y l t i methylcobaloxime. We a l s m e t h y l t i n . We have a problem because the p o s i t i o n s of the nmr s i g n a l s are not very constant. We have to look more at the coordi n a t i o n s i t u a t i o n i n these s o l u t i o n s . We have been l o o k i n g at oxygen systems w i t h these r e a c t i o n s , but we have to consider the n a t u r a l systems which c e r t a i n l y i n v o l v e s u l f u r l i g a n d s . When we make compounds of organolead and o r g a n o t i n compounds w i t h the c a r b o x y l i c a c i d s c o n t a i n i n g SH groups, we f i n d a preference f o r l e a d bonding t o s u l f u r , and not to oxygen. We can make c a r b o x y l a t e s which are bonded through s u l f u r to l e a d , but i t i s d i f f e r e n t w i t h t i n compounds. T h i s i s a very i n t e r e s t i n g f i e l d and we should t r y to i n v e s t i g a t e t h i s f i e l d of s u l f u r c o o r d i n a t i o n to organometal compounds. F. E. BRINCKMAN ( N a t i o n a l Bureau of Standards): This concerns the p r e s s i n g q u e s t i o n of t r a c e metal f l u x ; I'm s t r u c k t h a t there are so many c o r r i n o i d s a v a i l a b l e i n environmental d e t r i t u s , e i t h e r of anthropogenic or n a t u r a l b i o g e n i c o r i g i n , which c o u l d a c t as s o l u b i l i z i n g agents. With Ksp values f o r many of the oxides t h a t you i n d i c a t e d , such s o l u b i l i z a t i o n might be important t o metal f l u x e s . I'm p a r t i c u l a r l y concerned w i t h the t i n case; I'm concerned about i t s b i o a v a i l a b i l i t y . A d m i t t e d l y , methylcobalamin might be the wrong model, but i t i s an attempt to look at i t as a s o l u b i l i z ing agent, not n e c e s s a r i l y as a m e t h y l a t i n g agent, f o r uptake i n t o food webs. Have you looked a t some other t i n m i n e r a l s o l u b i l i t i e s i n your s o l u t i o n s of methylcobalamin? THAYER: No, we haven't. I've confined my t i n ( I V ) s i n c e oxy-metal s p e c i e s seem to undergo r e a d i l y than s p e c i e s w i t h other groups present. of t i n t e t r a a c e t a t e , but under these c o n d i t i o n s mediately hydrolyzed. BRINCKMAN: metal s u l f i d e s ?

a t t e n t i o n to t h i s r e a c t i o n more There i s a r e p o r t I'm sure i t ' s im-

Have you looked at any t i n s u l f i d e s or any other

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

204

ORGANOMETALS AND

ORGANOMETALLOIDS

THAYER: There i s only species w i t h a m e t a l - s u l f u r bond that I have looked a t . This was chloromercury-thiomethyl and - t h i o - t b u t y l . We got a very r a p i d r e a c t i o n w i t h methylcobalamin, but i t was the other group, the c h l o r i d e , that was being removed. In a c i d i c media, w i t h something l i k e bis(methylthio)mercury i n the presence of methylcobalamin, a r e a c t i o n probably would be r a t h e r slow, but I t h i n k you could observe i t . A l i t t l e b i t of b i s - t h i o l d e r i v a t i v e of mercury d i s s o l v e s i n d i l u t e a c i d (~ pH=4) and w i l l react. CULLEN: I want to emphasize that i t ' s very important that we look at s u l f u r involvement i n these compounds, e s p e c i a l l y i n the case of the m e t a l l o i d s , and indeed, i n a l l metals w i t h a h i g h s u l f u r a f f i n i t y . A l s o , nature a c t u a l l y doesn't do a l l these r a t h e r complicated r e a c t i o n s i n one step I t h i n k we ought to look f o r mechanisms that go slower I n other words, we don' a r s e n i c there i s an o x i d a t i o n and then of course a r e d u c t i o n . These are two d i f f e r e n t t h i n g s . WOOD: I n 1953, a f t e r the Minimata (Japan) d i s a s t e r , when people s t a r t e d l o o k i n g f o r the cause, the molecule that was i s o l a t e d from s h e l l f i s h i n Minimata Bay was methylmercurythiomethyl. I t h i n k i t ' s i n t e r e s t i n g that government agencies are s t i l l not a n a l y z i n g f o r i t i n s h e l l f i s h , as f a r as I'm aware. I t took almost four years to persuade the EPA to stop a n a l y z i n g f o r t o t a l mercury and s t a r t a n a l y z i n g f o r methylmercury. RECEIVED August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13 Mechanisms for Alkyl Transfers in Organometals JAY K. KOCHI

Department of Chemistry, Indiana University, Bloomington, IN 47401

The class of vitami one of three major coenzyme transfer in biological systems, being particularly effective with inorganic substrates. Thus methylcobalamin has been i m p l i cated in methyl transfers to a variety of metal ions including mercury, lead, tin, and thallium, as well as platinum, palladium, and gold (1). The mechanism of methyl transfer from cobalt to another metal center, that is, transmetallation, is the subject of extensive study. Two general mechanisms have been proposed for the methylation of metal ions by methylcobalamin (2). In type I reactions, the metal ion acts as an electrophile during the transfer of a methyl anion equivalent. In type II reactions, methyl radicals are transferred between metal centers. Thus type I reactions are considered to involve heterolytic cleavage of the cobalt-carbon bond of methylcobalamin, whereas the homolytic cleavage of the same bond in type II reactions is induced by a reduced member of a redox couple. In a more general sense, type I and type II reactions can be considered as two-equivalent and one-equivalent processes, respectively. The concept of electron transfer relates two-equivalent processes with their one-equivalent counterparts. For example, consider the carbonium ion as the key reactive intermediate in solvolysis reactions, which historically have served as prototypes for numerous ionic processes. Electron transfer by one— equivalent reduction produces alkyl radicals, CH

+ 3

^

w

CH * 3

which are crucial to homolytic processes. The same interchange between ionic and radical species applies to electron transfer processes between carbanions and alkyl radicals. CH " 3

^F=*r CH 3

0-8412-0461-6/78/47-082-205$07.50/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

206

F i n a l l y , an o v e r a l l t w o - e q u i v a l e n t change i n t e r r e l a t e s c a r b o n i u m i o n s and c a r b a n i o n s . ^ 2e CH · CH 3

3

V i e w e d i n t h i s way, t h i s h y p o t h e t i c a l t r a n s f o r m a t i o n i s b e t t e r considered as a two-step p r o c e s s i n v o l v i n g s u c c e s s i v e e l e c t r o n t r a n s f e r s . T h u s , i n e l e c t r o c h e m i c a l p r o c e s s e s , o n l y one e l e c t r o n i s t r a n s f e r r e d i n a s i n g l e a c t s i n c e the s i m u l t a n e o u s t r a n s f e r of two e l e c t r o n s , l i k e a b i p h o t o n i c p r o c e s s , i s a m u c h l e s s p r o b a b l e event. A l t h o u g h the o b s e r v a t i o n of e l e c t r o n t r a n s f e r p r o c e s s e s between a l k y l r a d i c a l s and c a r b o n - c e n t e r e d i o n s a r e as y e t r e l a t i v e l y r a r e , those between m e t a l c o m p l e x e s of c o u r s e r e p r e s e n t a w e l l - e s t a b l i s h e d p a r t of i n o r g a n i c c h e m i s t r y . Outer-sphere and i n n e r - s p h e r e m e c h a n i s m excellent basis for electro m e t a l c o m p l e x e s (3.). T h e p r e s e n c e of a b i m e t a l l i c i n t e r m e d i a t e either as a p r e c u r s o r or successor (postcursor) complex can play an important r o l e i n inner-sphere electron transfer pro c e s s e s . O u t e r - and i n n e r - s p h e r e m e c h a n i s m s h a v e a l s o been a p p l i e d to the o x i d a t i o n - r e d u c t i o n r e a c t i o n s of a l k y l r a d i c a l s w i t h m e t a l c o m p l e x e s (4). H o w e v e r , t h e d e t a i l e d e x a m i n a t i o n of the m e c h a n i s m of o x i d a t i o n - r e d u c t i o n p r o c e s s e s w i t h a l k y l r a d i c a l s i s m a d e d i f f i c u l t b y t h e i r t r a n s i e n t n a t u r e . A s a r e s u l t , the m e c h a n i s m s have been d e r i v e d h e r e t o f o r e f r o m d e d u c t i o n s b a s e d on k i n e t i c o b s e r v a t i o n s and p r o d u c t a n a l y s e s , and a few i n t e r m e d i a t e s have only r e c e n t l y been d e t e c t e d . F o r e x a m p l e , the i n n e r - s p h e r e c o m p l e x between m e t h y l r a d i c a l s and c o p p e r ( l l ) , CH * 3

+

Cu

1

>-

CH3-CU

1

has been o b s e r v e d by flash p h o t o l y t i c t e c h n i q u e s and found to d e c a y w i t h f i r s t - o r d e r k i n e t i c s (k = 7χ 1 0 sec" ) i n aqueous s o l u t i o n s at 25° (.§.). Indeed, the a s s o c i a t i o n of a l k y l r a d i c a l s w i t h m e t a l c o m p l e x e s t h r o u g h i n n e r - s p h e r e c o m p l e x e s m a y be t h e r o u t e b y w h i c h m o s t , i f not a l l , o x i d a t i o n - r e d u c t i o n r e a c t i o n s of a l k y l r a d i c a l s w i t h m e t a l c o m p l e x e s o c c u r , i r r e s p e c t i v e of w h e t h e r they have been p r e v i o u s l y c l a s s i f i e d a s i n n e r - o r o u t e r s p h e r e p r o c e s s e s . In t h i s r e g a r d , the r o o t of the d i f f e r e n c e between w h o l l y i n o r g a n i c s y s t e m s and the h y b r i d a l k y l m e t a l s y s t e m s p r o b a b l y l i e s i n the g r e a t p r o p e n s i t y of the c a r b o n c e n t e r e d i o n s , both c a r b o n i u m i o n s and c a r b a n i o n s , to be h i g h l y s o l v a t e d , e i t h e r a s i o n - p a i r s or i n n e r - s p h e r e c o m p l e x e s . A n i n n e r - s p h e r e a l k y l m e t a l i n t e r m e d i a t e s u c h a s that i n the a b o v e equation m a y be d e r i v e d by an a l t e r n a t i v e r o u t e i n v o l v i n g e i t h e r o x i d a t i o n o r r e d u c t i o n of a s t a b l e a l k y l m e t a l c o m p l e x , e.g., 2

CH -Cu 3

tt

g

" >

CH -Cu

1

m

3

In t h i s i n s t a n c e , the p r e c u r s o r i t s e l f i s u n s t a b l e .

However,

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

207

t h e r e a r e a v a r i e t y of other s t a b l e a l k y l m e t a l c o m p l e x e s extant f r o m which electron transfer is possible. Reversible d i s s o c i a tion of s u c h i n t e r m e d i a t e s then r e l a t e s a l k y l r a d i c a l s to o r g a n o metals derived by conventional two-equivalent processes, i . e . , R

+

M

+

=c=^

^

R-M

^-=^=

R-MÎ"

R-

+

M

+

T h i s d i c h o t o m y i s i n h e r e n t i n a l l of t h e s e p r o c e s s e s , and t h e r e i s a s e v e r e p r o b l e m of r i g o r o u s l y d e m o n s t r a t i n g how e a c h m a y participate i n a particular organometal reaction. S e v e r a l m a j o r q u e s t i o n s a r i s e i n the t r e a t m e n t of a l k y l m e t a l s as i n t e r m e d i a t e s i n t r a n s m e t a l l a t i o n s : (a) the m e c h a n i s t i c d i s t i n c t i o n between e l e c t r o p h i l i c and e l e c t r o n t r a n s f e r m e c h a n i s m s i n the c l e a v a g e of a n a l k y l - m e t a l bond, (b) the s e p a r a t i o n of c o n c e r t e d sive, one-equivalent processes m e t a l s e s p e c i a l l y with r e g a r d to e l e c t r o n t r a n s f e r p r o c e s s e s . B i n a r y a l k y l m e t a l s of m e r c u r y , l e a d and tin a r e u s e f u l m o d e l s for the study of t h e s e q u e s t i o n s s i n c e they a r e s u b s t i t u t i o n - s t a b l e c o m p o u n d s and g e n e r a l l y w e l l b e h a v e d i n s o l u t i o n for k i n e t i c s t u d i e s . In t h i s r e p o r t , we s h a l l d e s c r i b e how v a r i o u s a l k y l d e r i v a t i v e s c a n be e x a m i n e d s y s t e m a t i c a l l y to a l l o w d i r e c t photoe l e c t r o n s p e c t r o s c o p i c study of the b o n d i n g o r b i t a l s i n t h e s e organometals. T w o s e r i e s of w e l l d e l i n e a t e d c l e a v a g e s of a l k y l m e t a l s w i l l then be d i s c u s s e d . T h e s e i n c l u d e : (a) the e l e c t r o p h i l i c p r o t o n o l y s i s of d i a l k y l m e r c u r y compounds, R'HgR and

+

HOAc

RH +

R'HgOAc

(b) the e l e c t r o n t r a n s f e r o x i d a t i o n of the s a m e o r g a n o m e r c u r i a l s with h e x a c h l o r o i r i d a t e ( l V ) . R'HgR

+

IrCl " 6

Rt

H g

2

RÎ

f

a

s

t

^

R'HgR*

>.

R.

+

+

R Hg l

IrCl " 6

+

,

3

etc.

U s i n g t h e s e s y s t e m s , we w i l l c o m p a r e and c o n t r a s t e l e c t r o p h i l i c and e l e c t r o n t r a n s f e r m e c h a n i s m s i n the c l e a v a g e s of a l k y l - m e t a l bonds i n both m a i n g r o u p and t r a n s i t i o n m e t a l c o m p l e x e s . I.

O r g a n o m e t a l s as E l e c t r o n D o n o r s — I o n i z a t i o n P o t e n t i a l s

A. D i a l k y l m e r c u r y C o m p o u n d s . T h e He(l) photoelectron s p e c t r a of d i a l k y l m e r c u r y c o m p o u n d s show two p r i n c i p a l bands of i n t e r e s t ( £ . ) . T h e f i r s t i o n i z a t i o n p o t e n t i a l , Ij> o c c u r r i n g i n a r a n g e between 7.5 7 eV ( d i - t - b u t y l m e r c u r y ) and 9.33 eV ( d i methylmercury) is included i n a fairly broad, u n s y m m e t r i c a l b a n d . A s e c o n d , w e a k e r band o c c u r r i n g between 14.4 and 15.0 eV i s due to i o n i z a t i o n f r o m the m e r c u r y 5 d shell. T h e ionization e n e r g i e s for t h e s e two bands a r e tabulated i n T a b l e I. Repre1 0

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

208

ORGANOMETALS

AND ORGANOMETALLOIDS

T a b l e I. T h e F i r s t and 5 d V e r t i c a l I o n i z a t i o n P o t e n t i a l s (eV) of D i a l k y l m e r c u r y C o m p o u n d s . 1 0

R—Hg—R CH CH C H CH CH CH C H n-C H i-C H C H i-C H n-C H i-C H t—C H i-C H neo-C H 3

2

5

3

5

7

3

7

2

5

3

7

4

9

4

9

4

9

4

9

5

5

3

3

3

5

2

3

2

CH C H C H i-C H i-C H t-C H i-C H n-C H i-C H t—C H t—C n-C i-C H t-C H neo-C H neo-C H 3

3

2

First I

1

n

7

4

9

4

9

3

7

3

7

3

7

4

9

4

9

5

n

5

n

D

5d

1 0

I

9.33 8.84 8.45 8.47 8.75 8.32 8.18 8.29 8.03 8.06

14.93 14.85 14.71 14.86 14.74

8.30 7.57 8.33 8.30

14.47

14.61 14.63 14.46

14.49 14.41

s e n t a t i v e s p e c t r a of only the f i r s t band a r e r e p r o d u c e d i n F i g u r e 1 f o r one s e r i e s of a l k y l m e t h y l m e r c u r y c o m p o u n d s , i . e . , R-HgCH . T h e effect of a l k y l s u b s t i t u t i o n on the f i r s t i o n i z a t i o n p o t e n t i a l of a s e r i e s of a l k y l d e r i v a t i v e s i s a t t r i b u t e d p r i m a r i l y to p o l a r i z a t i o n effects i n the m o l e c u l a r i o n f i n a l state. It has been r e c o g n i z e d that s u c h e l e c t r o n i c effects a r e a d d i t i v e a l o n g the series: M e , E t , i - P r , and t - B u . T h u s , the e n e r g y effect of r e p l a c i n g M e b y E t i s e x p e c t e d to e q u a l that of r e p l a c i n g E t by i-Pr, or of r e p l a c i n g i - P r by t - B u . In e a c h c a s e , α - h y d r o g e n s in C H a r e being sequentially replaced by methyl groups. Addi t i v e e n e r g y effects have been u s e d by T a f t (7) as a c r i t e r i o n for i d e n t i f y i n g p o l a r effects as denoted by the e m p i r i c a l substituent constant σ * : 3

3

(σ*)

M e : Et : i - P r : t - B u

=

0 : 0.10

: 0.19 :

0.30

It has been shown that the T a f t r e l a t i o n s h i p holds for the i o n i z a tion p o t e n t i a l s of a l c o h o l s and other a l k y l c o m p o u n d s . Figure 2 i l l u s t r a t e s the l i n e a r r e l a t i o n s h i p between σ * v a l u e s and the i o n i z a t i o n p o t e n t i a l s of a s e r i e s of a l c o h o l s , a l k y l b r o m i d e s , a l k y l h y d r a z i n e s , and a l d e h y d e s . T h e c o r r e l a t i o n of the i o n i z a t i o n potentials of a s e r i e s of a l k y l m e r c u r i a l s R - H g C H a l s o plotted i n F i g u r e 2 i s d i s t i n c t l y n o n l i n e a r . T h e i n c r e m e n t a l changes i n energies become p r o g r e s s i v e l y s m a l l e r or ' ' s a t u r a t e d " as one p r o c e e d s f r o m m e t h y l to t e r t - b u t y l . M o r e o v e r , the s a m e p a t t e r n of s a t u r a t i o n obtains f o r the a n a l o g o u s s e r i e s of G r i g n a r d r e a g e n t s R - M g X and t r i 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

KOCHi

Alkyl Transfers

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

209

210

ORGANOMETALS AND

ORGANOMETALLOIDS

Or*

0

OJ

0.2

03

No. OF α-METHYL GROUPS Inorganic Chemistry

Figure 2. Correlation of the first ionization po tential of various alkyl-substituted compounds vs. Taft's σ* constant (top scale) and number of α-methyl groups (bottom scale) (6).

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

KOCHi

Alkyl Transfers

211

m e t h y l t i n c o m p o u n d s R S n M e m e a s u r e d i n d e p e n d e n t l y (8,2,). T h e d i f f e r e n c e between e n e r g y effects w h i c h a r e s a t u r a t e d and those that a r e a d d i t i v e m a y be r e l a t e d to the n a t u r e of the highest o c c u p i e d m o l e c u l a r o r b i t a l ( H O M O ) . F o r those s y s t e m s c o n t a i n i n g nonbonding e l e c t r o n s , the i o n i z a t i o n p r o c e e d s f r o m a H O M O w h i c h i s l a r g e l y o r t h o g o n a l to the σ b o n d i n g o r b i t a l s , p a r t i c u l a r l y those a s s o c i a t e d with the bonding of the h e t e r o a t o m to carbon. T h u s , although i n t e r a c t i o n s between the a l k y l g r o u p and the h e t e r o a t o m c a n be o b s e r v e d , i o n i z a t i o n f r o m the H O M O i s only w e a k l y c o u p l e d to the b o n d i n g s y s t e m and a d d i t i v i t y i s o b s e r v e d . In c o n t r a s t , the i o n i z a t i o n p r o c e s s i n o r g a n o m e t a l s such as M e H g p r o c e e d s f r o m a m o l e c u l a r o r b i t a l that has s u b s t a n t i a l m e t a l - c a r b o n bonding c h a r a c t e r . T h i s conclusion is portrayed with a s i m p l e L C B O d i a g r a m as: 3

2

Η 6ρ·0~<:' β

/\ Ης 6s

υ

.--V

H

'

7*=> C £ R , + R 2

Ο —\ y

Inorganic Chemistry

w h e r e the H O M O i s f o r m e d f r o m the b o n d i n g c o m b i n a t i o n of the a n t i s y m m e t r i c c o m b i n a t i o n of the σ type g r o u p o r b i t a l s of the a l k y l f r a g m e n t s with the m e r c u r y 6p a t o m i c o r b i t a l . In fact, i o n i z a t i o n of the H O M O of a l k y l r a d i c a l s ( i . e . , R* — R -f e) s e r v e s as a r e a s o n a b l e m o d e l for the i o n i z a t i o n of the H O M O of organomercurials. S i g n i f i c a n t l y , both the m e a s u r e d i o n i z a t i o n p o t e n t i a l s of a l k y l r a d i c a l s (JJ)) and those obtained f r o m S C F - M O c a l c u l a t i o n s l i s t e d i n T a b l e II (\l ) show the c h a r a c t e r i s t i c s a t u r +

T a b l e II. E x p e r i m e n t a l and C a l c u l a t e d I o n i z a t i o n P o t e n t i a l s of A l k y l R a d i c a l s . A l k y l Radical Methyl Ethyl iso-Propyl tert-Butyl

E x p e r i m e n t a l (eV) 9.84 8.38 7.55 6.93

C a l c u l a t e d (eV) 9-95 8.56 7.60 6.83

a t i o n effect d e s c r i b e d a b o v e , and they c o r r e l a t e w e l l with the f i r s t v e r t i c a l i o n i z a t i o n potentials of the o r g a n o m e r c u r i a l s l i s t e d i n T a b l e I. T h u s , i n t h i s c a s e , i o n i z a t i o n f r o m the H O M O i s s t r o n g l y c o u p l e d to the bonding s y s t e m . In s u c h a s i t u a t i o n , c h a n g e s i n e l e c t r o n r e p u l s i o n m a y w e l l be l a r g e and not e f f e c t i v e l y constant as the a l k y l g r o u p i s s y s t e m a t i c a l l y v a r i e d f r o m M e to t - B u . T h e v a r i a t i o n i n the 5d i o n i z a t i o n p o t e n t i a l t h r o u g h the s e r i e s of d i a l k y l m e r c u r y c o m p o u n d s a r i s e s p r i m a r i l y f r o m c h a n g e s i n the g r o u n d state c h a r g e on the m e r c u r y a t o m . The

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

212

ORGANOMETALS AND ORGANOMETALLOIDS

Ij)(5d) data c a n b e u s e d to c a l c u l a t e the c h a r g e on the m e r c u r y a t o m as p r e s e n t e d i n T a b l e III, together with the c a l c u l a t e d T a b l e III. C a l c u l a t e d C h a r g e s (q) on the M e r c u r y A t o m and A p p r o x i m a t e E l e c t r o n e g a t i v i t i e s of the A l k y l G r o u p s . Dialkylmercury

q

(CH ) Hg (C H } Hg (n-C H ) Hg (i-C H ) Hg (i-C H ) Hg (neo-C H ) Hg

+ 0.0234 - 0.0338 -0.0547 - 0.0990 - 0.0703 - 0.112

3

2

2

5

2

3

7

3

7

4

9

2

2

2

5

n

2

Electronegativity 1.98 1.81 1.75 1.62 1.70 1.58

(CH ) (C H ) (n-C H ) (i-C H ) (i-C H ) (neo-C H ) 3

2

5

3

7

3

7

4

9

5

n

v a l u e s of the e l e c t r o n e g a t i v i t i e 5 d bands c o u l d not be m e a s u r e d with a h i g h d e g r e e of a c c u r a c y . T h e r e f o r e , c a l c u l a t e d c h a r g e s and e l e c t r o n e g a t i v i t i e s of the a l k y l g r o u p s m u s t be r e g a r d e d a s h a v i n g m o r e q u a l i t a t i v e r a t h e r than q u a n t i t a t i v e s i g n i f i c a n c e at this point. N e v e r t h e l e s s , the a p p r o x i m a t e l y e q u a l c h a n g e s i n e l e c t r o n e g a t i v i t y on p r o c e e d i n g f r o m m e t h y l to ethyl (1.98 to 1.81) a n d f r o m ethyl to i s o p r o p y l (1.81 to 1.62) a r e at l e a s t c o n s i s t e n t with the a d d i t i v i t y c i t e d a b o v e . Among binary mercury(ll) derivatives, dialkylmercury c o m p o u n d s p o s s e s s the l o w e s t i o n i z a t i o n p o t e n t i a l s a s shown i n Table IV. 1 0

T a b l e IV. F i r s t V e r t i c a l I o n i z a t i o n P o t e n t i a l s (eV) of B i n a r y M e r c u r y ( l l ) D e r i v a t i v e s . CIHgCl

(11.37)

MeHgCl

(10.88)

BrHgBr

(10.62)

MeHgBr

(10.16)

IHgl

( 9.50)

MeHgl

( 9.25)

MeHgMe

(9.33)

B. T e t r a a l k y l l e a d C o m p o u n d s . T h e vapor phase photoel e c t r ô n ~ ¥ p ë ^ t r â ~ 1 5 I T n ^ ^ i . e . , neopentane, tetramethylsilane, tetramethylgermane, tetramethylstannane and t e t r a m e t h y l p l u m b a n e , have been s c r u t i n i z e d . W i t h the e x c e p t i o n of neopentane, the s p e c t r a a r e a l l s i m i l a r , e a c h s h o w i n g two b r o a d b a n d s . T h e h i g h e r e n e r g y band o c c u r s at about 14 eV, and c o m p a r i s o n w i t h s i m p l e c o m p o u n d s s u g g e s t s that this band i s a s s o c i a t e d with i o n i z a t i o n f r o m the o ( C - H ) b o n d i n g m o l e c u l a r o r b i t a l m a i n l y l o c a l i z e d on the m e t h y l f r a g m e n t . T h e threshold or a d i a b a t i c i o n i z a t i o n e n e r g y of the l o w e r e n e r g y band d e c r e a s e s i n the o r d e r ( C H ^ C > (CH ) Si > (CH ) Ge > (CH ) Sn > ( C H ) P b f r o m 10.25, 9.42, 9.38, 8.85, to 8.38 eV, r e s p e c t i v e l y , i n d i c a t i n g that i o n i z a t i o n i s a s s o c i a t e d with e l e c t r o n s l o c a l i z e d r e l a t i v e l y c l o s e to the m e t a l a t o m . T h e l o w e r b a n d has b e e n a s s i g n e d to i o n i z a t i o n f r o m the 3 t o r b i t a l d e r i v e d p r i n c i p a l l y 3

3

4

3

4

3

4

4

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

213

f r o m t h e a ( M - C ) bonding o r b i t a l s . In t e t r a m e t h y l p l u m b a n e i t i s s p l i t i n t o two w e l l - r e s o l v e d bands. E x a m i n a t i o n of the pes f o r the s e r i e s of m e t h y l / e t h y l l e a d c o m p o u n d s i n T a b l e V r e v e a l s that T a b l e V. Et _ PbMe 4

n

n

I o n i z a t i o n and O x i d a t i o n P o t e n t i a l s of O r g a n o l e a d C o m p o u n d s . O x i d a t i o n P o t e n t i a l (V) I o n i z a t i o n P o t e n t i a l (eV)

Et Pb Et PbMe Et PbMe EtPbMe Me Pb

1.67 1.75 1.84 2.01 2.13

4

3

2

2

3

4

8.13 8.26 8.45 8.65 8.90

the i o n i z a t i o n p o t e n t i a l s u b s t i t u t i o n of e t h y l for m e t h y l g r o u p s a r o u n d the l e a d n u c l e u s . T h e r e g u l a r t r e n d noted o v e r the e n t i r e s e r i e s of m e t h y l / e t h y l l e a d c o m p o u n d s s u g g e s t s that s u b s t i t u t i o n of a n e t h y l g r o u p f o r a m e t h y l g r o u p i s l a r g e l y a n e l e c t r o n i c effect, and that s t e r i c i n t e r a c t i o n s between a l k y l g r o u p s a r o u n d the l e a d a t o m a r e not l a r g e . M o r e o v e r , i t i s i n t e r e s t i n g t o note that the c u m u l a t i v e e f f e c t s of α-methyl g r o u p s a r e s i m i l a r i n a c o m p a r i s o n of the s e r i e s of d i a l k y l m e r c u r y c o m p o u n d s l i s t e d i n T a b l e I w i t h t h o s e t e t r a a l k y l l e a d c o m p o u n d s l i s t e d i n T a b l e V. T h e a n o d i c o x i d a t i o n of the s a m e s e r i e s of m e t h y l / e t h y l l ead c o m p o u n d s has a l s o been e x a m i n e d i n a c e t o n i t r i l e s o l u t i o n s w i t h l i t h i u m f l u o r o b o r a t e a s a s u p p o r t i n g e l e c t r o l y t e (12). The n u m b e r o f e l e c t r o n s i n v o l v e d i n the a n o d i c p r o c e s s was d e t e r m i n e d t o be 1.0 by t h i n l a y e r c h r o n o p o t e n t i o m e t r y u s i n g a p l a t i num electrode for a l l the t e t r a a l k y l l e a d compounds examined. T h e a n o d i c o x i d a t i o n of e a c h of t h e t e t r a a l k y l l e a d c o m p o u n d s w a s found t o be i r r e v e r s i b l e b y c u r r e n t - r e v e r s a l c h r o n o p o t e n t i o m e t r y , s u g g e s t i n g that t h e a l k y l l e a d c a t i o n - r a d i c a l i s u n s t a b l e . E q 1 r e p r e s e n t s i t s m o d e of d e c o m p o s i t i o n . R Pbt 4

•

R Pb 3

+

+

R.

[1]

T h e p o t e n t i a l i n a m a g n e t i c a l l y - s t i r r e d s o l u t i o n of t e t r a a l k y l l e a d depended on the i d e n t i t y of the l e a d compound. S i n c e e a c h of t h e s e o x i d a t i v e p r o c e s s e s i s i r r e v e r s i b l e , the o b s e r v e d poten t i a l s s h i f t e d to m o r e p o s i t i v e v a l u e s a s the c u r r e n t d e n s i t y i n c r e a s e d , and no t h e o r e t i c a l s i g n i f i c a n c e c a n be p l a c e d on the a b s o l u t e v a l u e s of the m e a s u r e d p o t e n t i a l s . A t a g i v e n c u r r e n t d e n s i t y , h o w e v e r , the p o t e n t i a l s r e f l e c t the r e l a t i v e e a s e of r e m o v a l of a s i n g l e e l e c t r o n f r o m the s e r i e s of m e t h y l / e t h y l l e a d c o m p o u n d s e x a m i n e d i n t h i s study. T h e l a t t e r r e s t s on the p r e s u m p t i o n that a n o d i c o x i d a t i o n of t h e s e c l o s e l y r e l a t e d c o m p o u n d s p r o c e e d s v i a a c o m m o n m e c h a n i s m . Indeed, e l e c t r o n detachment f r o m t e t r a a l k y l l e a d m e a s u r e d i n the gas phase b y p h o t o e l e c t r o n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

214

ORGANOMETALS AND ORGANOMETALLOIDS

s p e c t r o s c o p y a l s o shows a s t r i k i n g r e l a t i o n s h i p with the c h e m i c a l oxidation potentials i n a c e t o n i t r i l e solution.

electro

II. E l e c t r o p h i l i c C l e a v a g e of O r g a n o m e t a l s — Q u a n t i t a t i v e E f f e c t s of A l k y l G r o u p s A c e t o l y s i s of d i a l k y l m e r c u r y c o m p o u n d s l i b e r a t e s one e q u i v a l e n t of a l k a n e and of a l k y l m e r c u r y a c e t a t e a c c o r d i n g to eqs 2 and 3 (13). y > E H + R'HgOAc [2] R-Hg-R + HOAc ( Ν ' • R H + RHgOAc [3] k

1

k

!

T h e f u r t h e r c l e a v a g e of a l k y l m e r c u r y a c e t a t e i s too s l o w to i n t e r f e r e w i t h the a c e t o l y s i s study of d i a l k y l m e r c u r y . T h e p s e u d o f i r s t - o r d e r rate constant w e r e d e t e r m i n e d f r o m the r a t e s of l i b e r a t i o n of a l k a n e s R H and R H, respectively. T h e p r o t o n o l y s i s of d i a l k y l m e r c u r y i n a c e t i c a c i d s o l u t i o n s proceeds by a r a t e - l i m i t i n g proton t r a n s f e r . T h e experimental v a l u e s of the k i n e t i c i s o t o p e effect of 9-11 a r e c l o s e to the t h e o r e t i c a l m a x i m u m expected for the t r a n s f e r of d e u t e r i u m r e l a t i v e to p r o t o n i n t h i s s y s t e m . T h e l a r g e v a l u e s of k j j / k £ ) a l s o suggest a r a t h e r l i n e a r t r a n s i t i o n state for p r o t o n t r a n s f e r i n w h i c h the c o n t r i b u t i o n f r o m the s y m m e t r i c s t r e t c h i n g m o d e i s s m a l l . S u c h a t r a n s f e r of a p r o t o n h a l f w a y i n the t r a n s i t i o n state p l a c e s a c o n s i d e r a b l e p o s i t i v e c h a r g e on m e r c u r y . T h e s e r e s u l t s together with the r e t e n t i o n of c o n f i g u r a t i o n d u r i n g p r o t o - d e m e r c u r a t i o n a r e c o n s i s t e n t w i t h a 3 - c e n t e r t r a n s i t i o n state of the type d e picted below. f

: LR

H—OAc

1

T h e m o r e or l e s s t r i a n g u l a r a r r a y of c a r b o n , m e r c u r y and the p r o t o n i n the t r a n s i t i o n state f o r p r o t o n o l y s i s was o r i g i n a l l y p r o p o s e d b y K r e e v o y and H a n s e n (14). T h e extent to w h i c h t h e r e i s n u c l e o p h i l i c a s s i s t a n c e d u r i n g a c e t o l y s i s of d i a l k y l m e r c u r y i s not t r e a t e d e x p l i c i t l y . Instead, f o r the a c e t o l y s i s i n eq 2, the effects of a l k y l g r o u p s on the c l e a v a g e r e a c t i o n c a n be c l a s s i f i e d i n t o two c a t e g o r i e s — n a m e l y , l e a v i n g g r o u p (HgR ) effects and c l e a v e d g r o u p (R) e f f e c t s . S t e r i c e f f e c t s due to the l e a v i n g g r o u p s a r e u n i m p o r t a n t i n a c e t o l y s i s , and i t helps to l i m i t the m e c h a n i s t i c c o n s i d e r a t i o n s to the i m m e d i a t e l o c u s of the r e a c t i o n s i t e . L e a v i n g G r o u p E f f e c t s (HgR ). T h e effect of l e a v i n g g r o u p s H g R on the c l e a v a g e of a p a r t i c u l a r a l k y l - m e r c u r y bond a c c e l e r ates i n the o r d e r : R = M e < Et < i - P r < t - B u . This reactivity s e q u e n c e r e p r e s e n t s the i n c r e a s i n g a b i l i t y of t h e s e a l k y l g r o u p s to a c c o m m o d a t e a p o s i t i v e c h a r g e when they a r e attached to the 1

1

1

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

215 1

d e p a r t i n g c a t i o n i c m e r c u r y (HgR ). E l e c t r o n r e l e a s e b y v a r i o u s a l k y l g r o u p s i n r e s p o n s e to a f i x e d e l e c t r o n d e m a n d i n the ground state of C H H g R i s a l s o r e f l e c t e d i n the m a g n i t u d e s of the m e t h y l proton coupling constants, j ( H g - H ) . M o r e appropriately, e l e c t r o n r e l e a s e b y a l k y l g r o u p s i n the t r a n s i t i o n state f o r a c e t o l y s i s m a y be m o d e l e d b y the c a t i o n - r a d i c a l of d i a l k y l m e r c u r y . T h e l a t t e r i s p r o b e d i n d e p e n d e n t l y b y m e a s u r i n g the e n e r g e t i c s of e l e c t r o n d e t a c h m e n t f r o m a h o m o l o g o u s s e r i e s of RHgR , e.g., f

3

1 9 9

1

CH Hg-R

!

!

>-

3

[CH Hg-R ]

+

+ e

3

as d e s c r i b e d i n the f o r e g o i n g s e c t i o n . Indeed, t h e r e i s a l i n e a r c o r r e l a t i o n of l o g k f o r a c e t o l y s i s a n d the v e r t i c a l i o n i z a t i o n p o t e n t i a l s of a s e r i e s of C H H g - R Sinc photoelectro i o n i z a tion i s a v e r t i c a l process l a r g e l y f r e e of s t e r i c f a c t o r s support c o n c l u s i o n that s t e r i c e f f e c t s of l e a v i n g g r o u p s a r e u n i m p o r t a n t i n a c e t o l y s i s of t h i s s e r i e s of o r g a n o m e r c u r i a l s . T h e c o r r e l a t i o n between r a t e s of c l e a v a g e and i o n i z a t i o n p o t e n t i a l i s not r e s t r i c t e d to o r g a n o m e r c u r i a l s . T h e s a m e r e l a t i o n s h i p i s a l s o obtained i n 4 - c o o r d i n a t e o r g a n o l e a d c o m p o u n d s (15.16). f

k

lv[e

> < )> C H + M e - E t . P b O A c [4] — / v ^ t y > CH3CH3 4- M e E t - P b O A c [5] 4

M e E t . P b + HOAc n

4

n

n

1

4

n

n

3

n

T h u s , the r a t e of a c e t o l y s i s of the M e - P b bond [i.e., l o g k ( M e ) ] d e c r e a s e s l i n e a r l y w i t h the i o n i z a t i o n p o t e n t i a l of M e E t - P b , w h e r e η = 0, 1, 2, 3,4, and a p a r a l l e l r e l a t i o n s h i p i s obtained d u r i n g the c o n c o m i t a n t c l e a v a g e of the E t - P b bond [ l o g k ( E t ) ] . I n c r e a s i n g s t e r i c f a c t o r s i n the l e a v i n g g r o u p ( i . e . , t r i a l k y l l e a d ) p r e v e n t e x t e n s i o n to h i g h e r h o m o l o g s . In the a c e t o l y s i s of d i a l k y l m e r c u r y , the l e a v i n g g r o u p (HgR ) e f f e c t s [under c o n d i t i o n s of a c o n s t a n t c l e a v e d (R) group] can be e x p r e s s e d q u a n t i t a t i v e l y by the l i n e a r f r e e e n e r g y r e l a t i o n s h i p i n eq 6, l o g Κ/Κ = I. [6] n

4

n

1

0

w h e r e K i s the r a t e c o n s t a n t f o r a c e t o l y s i s of R-HgR i n eq 2 when R = M e , and Κ i s that f o r R = E t , i - P r o r t-Bu. I- i s a l e a v i n g g r o u p constant w h i c h has a c h a r a c t e r i s t i c v a l u e f o r e a c h HgR , a n d i t does not depend on the n a t u r e of the c l e a v e d g r o u p (R). N o r m a l i z a t i o n s of I· to I-(Et) = 0.10 a r e l i s t e d i n T a b l e V I as I· to a l l o w d i r e c t c o m p a r i s o n w i t h the T a f t σ* c o n s t a n t s . T h e r e i s a s t r i k i n g d i f f e r e n c e b e t w e e n the v a l u e s of I· and σ*, a l t h o u g h both a r e due to e l e c t r o n i c o r p o l a r e f f e c t s . T h u s , t h e r e i s a " s a t u r a t i o n " i n i n c r e m e n t a l c h a n g e s i n e n e r g y f o r 1» as e a c h h y d r o g e n i n R H g C H i s s e q u e n t i a l l y r e p l a c e d b y m e t h y l g r o u p s i n the s e r i e s ; R H g C H , R H g C H C H , R H g C H ( C H ) , and R H g C ( C H ) . On the other hand, the c o r r e s p o n d i n g changes i n σ* 1

0

1

1

1

1

1

3

3

3

2

3

3

2

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

216

O R G A N O M E T A L S AND

ORGANOMETALLOIDS

Table VI. Leaving Group P a r a m e t e r s i n Acetolysis of D i a l k y l m e r c u r y . C o m p a r i s o n w i t h T a f t σ*. σ* I.* L e a v i n g G r o u p (HgR ) I. 1

HgCH HgCH CH HgCH(CH ) HgC(CH ) 2

3

3

3

2

3

0 0.10 0.19 0.30

0 0.10 0.17 0.19

0 0.76 1.28 1.44

3

11

a r e "additive, i n c r e a s i n g l i n e a r l y f r o m CH , C H C H , ( C H ) C H to ( C H ) C . Indeed, T a f t has e m p l o y e d the a d d i t i v i t y r e q u i r e m e n t for identifying polar effects. T h e d i f f e r e n c e between e n e r g y e f f e c t s w h i c h a r e s a t u r a t e d and t h o s e that a r e a d d i t i v e p r o v i d e s the key to the u n d e r s t a n d i n g of s u b s t i t u e n t e f f e c t s i strong linear correlatio p o t e n t i a l s of a s e r i e s of a l c o h o l s , a l k y l h y d r a z i n e s , a l d e h y d e s and a l k y l h a l i d e s r e p r e s e n t e d by the p r o c e s s : RX — R X ^ " + e. On the other hand, the i o n i z a t i o n p o t e n t i a l s of a s e r i e s of o r g a n o m e r c u r i a l s C H H g R a l s o plotted a g a i n s t σ* show a s a t u r a t i o n effect e q u i v a l e n t to that i n a c e t o l y s i s . T h e s a t u r a t i o n a l s o obtains f o r i o n i z a t i o n f r o m the s a m e s e r i e s of G r i g n a r d r e a g e n t s and a l k y l t r i m e t h y l t i n c o m p o u n d s , ( C H ) S n R . T h e d i f f e r e n c e between s a t u r a t i o n and a d d i t i v i t y e f f e c t s can be e x p l a i n e d by c o n s i d e r i n g the h i g h e s t o c c u p i e d m o l e c u l a r o r b i t a l ( H O M O ) i n e a c h s e r i e s . F o r t h o s e c o m p o u n d s c o n t a i n i n g nonbonding e l e c t r o n s , the i o n i z a t i o n p r o c e e d s f r o m a H O M O w h i c h i s l a r g e l y o r t h o g o n a l to the o r b i t a l i n v o l v e d i n the b o n d i n g of X to c a r b o n i n R-X, and i t s effect on the e l e c t r o n d e n s i t y i n the bond i s m i n i m a l . In c o n t r a s t , the i o n i z a t i o n p r o c e s s i n o r g a n o m e t a l s s u c h as M e H g p r o c e e d s f r o m a b o n d i n g m o l e c u l a r o r b i t a l w i t h a node at m e r c u r y . C o n sequently, the e l e c t r o n d e n s i t y i n the bond to c a r b o n i s d i m i n i s h e d s u b s t a n t i a l l y , and the c a t i o n i c c h a r a c t e r of the α-carbon i s a c c o m p a n i e d by a d e c r e a s e i n e l e c t r o n r e p u l s i o n , w h i c h i s not e f f e c t i v e l y c o n s t a n t as the a l k y l g r o u p i s s y s t e m a t i c a l l y v a r i e d f r o m M e to t-Bu. Indeed, the v a l i d i t y of t h i s d e s c r i p t i o n i s shown by v a l u e s of the i o n i z a t i o n p o t e n t i a l s of a l k y l r a d i c a l s [i.e., R» — • R 4- e], w h i c h a g r e e r e m a r k a b l y w e l l w i t h those obtained f r o m S C F - M O c a l c u l a t i o n s ( l 7.18). S i g n i f i c a n t l y , the i o n i z a t i o n p o t e n t i a l s of a l k y l r a d i c a l s show the c h a r a c t e r i s t i c s a t u r a t i o n effect d e s c r i b e d above, and they a l s o c o r r e l a t e w e l l w i t h l o g k for a c e t o l y s i s and the i o n i z a t i o n p o t e n t i a l s of the o r g a n o m e r c u r i a l s . It i s n o t e w o r t h y that l e a v i n g g r o u p (HgR ) e f f e c t s due to sub s t i t u t i o n of m e t h y l g r o u p s i n the (3-position of the a l k y l c h a i n R a r e h i g h l y attenuated r e l a t i v e to that a c c o m p a n y i n g a - s u b s t i t u t i o n . F o r i n s t a n c e , the p s e u d o f i r s t - o r d e r r a t e c o n s t a n t f o r m e t h a n e e v o l u t i o n f r o m M e H g E t i s 2.35 χ 10" sec** and that f o r M e H g — i - B u i s 2.39 x 10" s e c " . T h u s , l e a v i n g g r o u p e f f e c t s a r e not s i m p l y r e l a t e d to the s i z e of the a l k y l g r o u p (R ). C l e a v e d G r o u p E f f e c t s (R). T h e r a t e s of a c e t o l y s i s of a l k y l 3

3

2

3

3

2

3

f

3

f

3

3

2

+

1

1

6

6

1

1

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

217

Alkyl Transfers

KOCHi

g r o u p s f r o m d i a l k y l m e r c u r y d e c r e a s e i n the o r d e r : R = Et > i - P r > M e > t - B u . T h e c l e a v e d a l k y l g r o u p e f f e c t s [under c o n d i tions i n w h i c h the l e a v i n g g r o u p (HgR ) i s constant] c a n be ex p r e s s e d q u a n t i t a t i v e l y by eq 7, 1

K'A'o

log

=

[7]

C

w h e r e K i s the r a t e constant for a c e t o l y s i s of R - H g R i n eq 2 when R = M e , and K i s that for R = E t or i - P r . C is a cleaved a l k y l g r o u p constant w h i c h has a c h a r a c t e r i s t i c v a l u e for e a c h R, and i t does not depend on the l e a v i n g g r o u p H g R . T h e n o n - s y s t e m a t i c t r e n d i n the v a l u e s of C i n T a b l e VII f

1

0

1

1

Table VII. Cleaved Group P a r a m e t e r s in Acetolysi C l e a v e d A l k y l G r o u p (R)

C

CH CH CH (CH ) CH (CH ) C

0 0.55 0.29 ^-0.9

3

3

2

3

2

3

3

s u g g e s t s that t h e r e a r e at l e a s t two o p p o s i n g effects p r e s e n t i n the a c e t o l y s i s of a n a l k y l - m e r c u r y b o n d . T h e d e c r e a s e o b s e r v e d i n p r o c e e d i n g f r o m E t , i - P r to t - B u f o l l o w s f r o m the i n c r e a s e i n s t e r i c b u l k at the s i t e of p r o t o n a t i o n . O n the other hand, the i n c r e a s e f r o m M e to E t (and to i - P r ) i s i n a c c o r d with e l e c t r o n r e l e a s e f r o m t h e s e R g r o u p s a c c o m p a n y i n g p r o t o n o l y s i s , as described earlier. ( T h e v a l u e of C f o r the t - b u t y l g r o u p i s a p p r o x i m a t e. ) T h e r a t e s of p r o t o n o l y s i s of a l k y l m e r c u r y i o d i d e s (14) i n aqueous p e r c h l o r i c and s u l f u r i c a c i d f o l l o w the o r d e r expected f r o m a d o m i n a n c e of s t e r i c f a c t o r s , v i z . , M e : E t : i - P r : t - B u i n the r e l a t i v e order* 123 : 49 : 16 : 1.0. T h e s m a l l kinetic i s o t o p e effect (kpj/krj)) m e a s u r e d f r o m the p r o t o n o l y s i s of m e t h y l m e r c u r y i o d i d e m a y r e f l e c t e i t h e r a t r a n s i t i o n state i n w h i c h the bond to c a r b o n i s p o o r l y f o r m e d or one i n w h i c h i t i s a l m o s t c o m p l e t e . T h e l a t t e r c o u l d a c c o u n t f o r the r e a c t i v i t y p a t t e r n , but other u n c e r t a i n t i e s i n t h i s s y s t e m d i s c o u r a g e f u r t h e r d i s c u s s i o n . A s i m i l a r effect, h o w e v e r , c a n be o b s e r v e d d u r i n g the a c e t o l y s i s of a s e r i e s of w e l l - b e h a v e d m e t h y l - e t h y l l e a d c o m pounds [ M e E t - P b , when η = 0, 1, 2, 3] ( l 5 , 1 6 ) . If l e a v i n g g r o u p effects a r e taken i n t o account, the c l e a v a g e of M e - P b i s c o n s i s t ently 8.6 t i m e s m o r e f a c i l e than E t - P b c l e a v a g e i n a l l t h r e e i n t r a m o l e c u l a r c o m p e t i t i o n s as w e l l as i n the i n t e r m o l e c u l a r c o m p e t i t i o n u s i n g M e E t « P b (n = 1, 2, 3) and M e P b / E t P b , respectively. It i s n o t e w o r t h y that the M e / E t r e a c t i v i t y i n t e t r a a l k y l l e a d i s r e v e r s e d f r o m that i n d i a l k y l m e r c u r y [ k ( M e ) / k ( E t ) = 0.30], although the k i n e t i c i s o t o p e effect of 9 i n the a c e t o l y s i s of n

4

n

n

4

n

4

4

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

218

ORGANOMETALS

A N D ORGANOMETALLOIDS

t e t r a e t h y l l e a d (]J2) i s c o m p a r a b l e to that o b s e r v e d with d i e t h y l mercury. T h e d i f f e r e n c e i s due to i n c r e a s e d s t e r i c h i n d r a n c e i n the 4 - c o o r d i n a t e o r g a n o l e a d c o m p o u n d s c o m p a r e d to the m o r e accessible 2-coordinate organomercury analogs. The severe s t e r i c r e s t r i c t i o n s i m p o s e d on t e t r a a l k y l l e a d c o m p o u n d s i s a l s o b o r n e out by the f a i l u r e to extend the l i n e a r f r e e e n e r g y r e l a t i o n ships to h i g h e r a l k y l h o m o l o g s i n p r o t o n o l y s i s s t u d i e s . G e n e r a l i z e d E q u a t i o n f o r P r o t o n o l y s i s of D i a l k y l m e r c u r y . T h e l i n e a r f r e e e n e r g y r e l a t i o n s h i p s i n eqs 6 and 7 f o r l e a v i n g g r o u p effects and c l e a v e d g r o u p e f f e c t s , r e s p e c t i v e l y , d u r i n g a c e t o l y s i s of d i a l k y l m e r c u r y suggest that a g e n e r a l i z e d r e l a t i o n s h i p i s p o s s i b l e w h i c h c o r r e l a t e s a l l the r a t e s u s i n g the e m p i r i c a l p a r a m e t e r s i n T a b l e s V I and V I I , i . e . , log k / k

=

[8]

w h e r e ko r e p r e s e n t s the r a t e constant for a c e t o l y s i s of M e H g and k i s that f o r any other R H g R . T h e v a l i d i t y of eq 8 i s shown by c o m p a r i n g the e x p e r i m e n t a l r a t e c o n s t a n t s with t h o s e c a l c u l a t e d f r o m the e q u a t i o n . T h e e m p i r i c a l constant C i n the g e n e r a l i z e d eq 8 f o r a c e t o l y s i s of d i a l k y l m e r c u r y takes into a c c o u n t any s t e r i c i n t e r a c t i o n s due to the c l e a v e d g r o u p (R) at the r e a c t i o n s i t e . In the a b s e n c e of s u c h s t e r i c e f f e c t s , the c l e a v e d g r o u p effect i n e l e c t r o p h i l i c s u b s t i t u t i o n should be i n f l u e n c e d p r i m a r i l y by e l e c t r o n r e l e a s e and thus p a r a l l e l the l e a v i n g g r o u p (HgR ) effects as d e s c r i b e d i n eq 6 and T a b l e V I . S i g n i f i c a n t l y , the r e l a t i v e r e a c t i v i t i e s of the c l e a v e d a l k y l groups i n electron transfer cleavages follow a pattern i n which the i n c r e m e n t a l changes i n e n e r g y f o r R = M e , E t , i - P r and t - B u show a s a t u r a t i o n " effect, w h i c h i s the s a m e as that o b s e r v e d i n the l e a v i n g g r o u p effect (HgR ) denoted b y I* i n T a b l e V I . Indeed, t h e r e i s a l i n e a r c o r r e l a t i o n between the o x i d a t i o n or i o n i z a t i o n potentials and I·· T h u s , the s a t u r a t i o n p a t t e r n f o r a l k y l g r o u p s i s independent of whether they a r e i n v o l v e d as c l e a v e d (R) g r o u p s or as l e a v i n g (HgR ) g r o u p s . It c l e a r l y r e l a t e s to an i n t r i n s i c p r o p e r t y of the a l k y l - m e r c u r y bonds and r e f l e c t s the m a n n e r i n w h i c h an a l k y l g r o u p r e s p o n d s to the p r e s e n c e of a p o s i t i v e c h a r g e on m e r c u r y . T h e s a t u r a t i o n p a t t e r n for a l k y l g r o u p s c a n be u s e d as a d i a g n o s t i c p r o b e f o r the m e c h a n i s m of c l e a v a g e i n organometals. A c e t o l y s i s studies on d i a l k y l m e r c u r y have d e m o n s t r a t e d not only the i m p o r t a n c e of the c l e a v e d g r o u p (R) but a l s o the l e a v i n g g r o u p (HgR ) i n e l e c t r o p h i l i c s u b s t i t u t i o n . A l k y l g r o u p s a r e e x c e l l e n t p r o b e s f o r m e a s u r i n g t h e s e e l e c t r o n i c effects q u a n t i t a t i v e l y , and the c o r r e l a t i o n s of the r a t e s with the i o n i z a t i o n p o t e n t i a l s show that a p o s i t i v e c h a r g e i s d e v e l o p e d on both the l e a v i n g g r o u p (R) and the c l e a v e d g r o u p (HgR ). T h e s e f a c e t s of the r e a c t i v i t y of d i a l k y l m e r c u r i a l s t o w a r d p r o t o n i c e l e c t r o p h i l e s m a y be extended m o r e g e n e r a l l y , s i n c e i t has l o n g b e e n r e c o g 2

1

1

11

1

1

1

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

219

n i z e d that n u c l e o p h i l i c r e a c t i v i t y i s i n f l u e n c e d b y the " p o l a r i z a b i l i t y " of the n u c l e o p h i l e . T h u s , the E d w a r d s o x y b a s e equation c o n t a i n s both a t e r m r e l a t e d to the o x i d a t i o n p o t e n t i a l of the n u c l e o p h i l e as w e l l a s a t e r m r e l a t e d to i t s b a s i c i t y (20,2,2,). T h e m o l e c u l a r o r b i t a l a n a l o g of the E d w a r d s equation has been d e v e l oped by K l o p m a n , i n w h i c h e l e c t r o s t a t i c and c o v a l e n t t e r m s a r e the c o u n t e r p a r t s to b a s i c i t y and p o l a r i z a b i l i t y , r e s p e c t i v e l y (22, 23). O r g a n o m e t a l l i c n u c l e o p h i l e s a r e σ - d o n o r s and have n e g l i g i b l e b a s i c i t y i n the E d w a r d s s e n s e . T h u s , the n u c l e o p h i l i c r e a c t i v i t y of o r g a n o m e t a l s u s i n g e i t h e r the E d w a r d s or K l o p m a n m o d e l s h o u l d r e d u c e to an equation s u c h as eq 8, i n w h i c h e l e c t r o n r e l e a s e by a l k y l g r o u p s i s the i m p o r t a n t c o n s i d e r a t i o n . The l a t t e r , i n e s s e n c e , r e p r e s e n t s a " v i r t u a l ' i o n i z a t i o n of the c a r b o n - m e t a l bond b y the e l e c t r o p h i l e s i n c e it c a n be d i r e c t l y r e l a t e d to the e n e r g e t i c s of e l e c t r o n d e t a c h m e n t . The 3-center t r a n s i t i o n state r e p r e s e n t e juncture. 1

H I . E l e c t r o n T r a n s f e r C l e a v a g e of O r g a n o m e t a l s with H e x a c h l o r o i r i d a t e ( I V ) A. T e t r a a l k y l l e a d Compounds. T e t r a a l k y l l e a d compounds r e a c t r a p i d l y with h e x a c h l o r o i r i d a t e ( I V ) at 2 5 ° C i n a c e t o n i t r i l e or a c e t i c a c i d s o l u t i o n (L2). F o r e x a m p l e , the a d d i t i o n of t e t r a m e t h y l l e a d to a s o l u t i o n of I r C l " " i n a c e t i c a c i d r e s u l t s i n the i m m e d i a t e d i s c h a r g e of the d a r k r e d - b r o w n c o l o r . Methyl c h l o r i d e , t r i m e t h y l l e a d a c e t a t e and the two r e d u c e d i r i d i u m ( l l l ) p r o d u c t s a r e f o r m e d f r o m t e t r a m e t h y l l e a d and h e x a c h l o r o i r i d a t e (IV) i n a c e t i c a c i d s o l u t i o n s a c c o r d i n g to the s t o i c h i o m e t r y : 6

Me Pb+ 2IrCl 4

6

2

"

HOAc

2

>

where S = solvent

M

e

3

P

b

o

A

c

+ CH C1 + 3

IrCl ~+ IrCl (S) " 6

3

[9]

2

5

O n l y one a l k y l g r o u p i s r e a d i l y c l e a v e d f r o m e a c h t e t r a a l k y l l e a d compound. T h e mixed methyl/ethyllead derivatives afford m i x t u r e s of m e t h y l and e t h y l c h l o r i d e s , the y i e l d s of w h i c h depend on the o r g a n o l e a d c o m p o u n d . Me

r—> PbR

Et

2

+ 2IrCl

6

2

Me-Cl

+ EtPbR

2

+

,

etc.

,

etc.

" —(

[10] ν—> Et-Cl

+ MePbR

2

A f t e r n o r m a l i z a t i o n for e a c h type of a l k y l g r o u p i n the r e a c t a n t , the r e l a t i v e y i e l d s of ethyl c h l o r i d e and m e t h y l c h l o r i d e a r e r a t h e r constant at about 25 i n a c e t o n i t r i l e , but v a r y s o m e w h a t i n acetic a c i d . T e t r a a l k y l l e a d c o m p o u n d s r e a c t with h e x a c h l o r o i r i d a t e ( l V ) at d i f f e r i n g r a t e s , w h i c h w e r e f o l l o w e d s p e c t r o p h o t o m e t r i c a l l y by the d i s a p p e a r a n c e of the a b s o r p t i o n b a n d s at 490 and 585 n m . T h e k i n e t i c s showed a f i r s t - o r d e r d e p e n d e n c e on t e t r a a l k y l l e a d

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

220

ORGANOMETALS A N D ORGANOMETALLOIDS

and h e x a c h l o r o i r i d a t e ( l V ) i n both a c e t o n i t r i l e and a c e t i c a c i d solution. T h e s e c o n d - o r d e r rate constants determined i n aceto-d[IrCl "]/dt 6

=

2

2 k[R Pb] [IrCl ~] 4

6

[11]

2

n i t r i l e solutions i n c r e a s e p r o g r e s s i v e l y f r o m M e P b , M e P b E t , M e P b E t , M e P b E t , to E t ^ P b as l i s t e d i n T a b l e VIII. 4

2

2

3

3

T a b l e VIII. T h e C o r r e l a t i o n of S e l e c t i v i t i e s and Rates of O x i d a t i v e C l e a v a g e of T e t r a a l k y l l e a d s b y H e x a c h l o r o i r i d a t e ( l V ) with the E n e r g e t i c s of E l e c t r o n D e t a c h m e n t P r o c e s s e s . PbMe Et . n

4

k

ID

( M " sec )

MeCl

(eV)

(V)

(cm- )

26 11 3.3 0.57 0.02

24 25 24

8.26 8.45 8.65 8.90

1.75 1.80 2.01 2.13

20,400 22,600 23,200 24,300

1

PbEt PbEt Me PbEt Me PbEtMe PbMe 4

3

2

2

3

4

Ε

EtCl

n

l

-

1

T w o i m p o r t a n t c r i t e r i a c a n be u s e d to d i s t i n g u i s h the r e a c tion of t e t r a a l k y l l e a d with h e x a c h l o r o i r i d a t e ( l V ) f r o m the m o r e c o n v e n t i o n a l e l e c t r o p h i l i c p r o c e s s e s , e . g . , those i n v o l v i n g B r o n s t e d a c i d s , s i l v e r ( l ) , c o p p e r ( l ) or c o p p e r ( l l ) c o m p l e x e s , etc. (15,19*24,25). F i r s t , the r a t e of r e a c t i o n of E t » P b M e w i t h h e x a c h l o r o i r i d a t e ( l V ) i n c r e a s e s s u c c e s s i v e l y as m e t h y l i s r e p l a c e d b y ethyl g r o u p s [ s e e η = 4 to 0 i n T a b l e VIII, c o l u m n 2]. S e c o n d , a g i v e n e t h y l g r o u p i s c l e a v e d a p p r o x i m a t e l y 25 t i m e s f a s t e r than a m e t h y l g r o u p [ c o l u m n 3]. Both of t h e s e r e a c t i v i t y t r e n d s a r e d i a m e t r i c a l l y opposed to a n e l e c t r o p h i l i c c l e a v a g e w h i c h o c c u r s d i r e c t l y at the l e s s h i n d e r e d m e t h y l site f a s t e r than at a n ethyl site u n d e r equivalent c o n d i t i o n s . T h e s e r e s u l t s suggest that the r a t e - l i m i t i n g step with h e x a c h l o r o i r i d a t e ( l V ) o c c u r s p r i o r to a l k y l t r a n s f e r . T h e m e c h a n i s m g i v e n i n S c h e m e I i n v o l v e s e l e c t r o n t r a n s f e r i n eq 12 a s the r a t e limiting process. 4

n

n

S c h e m e I; R Pb 4

+ Ir^Cl " 6

2

k

R Pbt

f

a

s

R« + I r ^ C l / "

f

a

s

4

t

t

>

R Pbt

>

R- + R P b

>

RC1 + I i F c i / ' , etc.

4

+ Ir Cl M

3

6

3

"

+

[12] [13]

[14]

Indeed, t h e r e i s a good l i n e a r c o r r e l a t i o n of the r a t e s (log k) with the o n e - e l e c t r o n o x i d a t i o n or i o n i z a t i o n potentials of t e t r a a l k y l l e a d c o m p o u n d s p r e s e n t e d i n T a b l e V . S e l e c t i v i t y i n the c l e a v a g e of a l k y l g r o u p s f r o m o r g a n o l e a d a c c o r d i n g to S c h e m e I o c c u r s d u r i n g f r a g m e n t a t i o n of the c a t i o n - r a d i c a l i n a fast subsequent

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

221

s t e p 13, w h i c h i s c o n s i s t e n t w i t h the m a s s s p e c t r a l study. Thus, a q u a n t i t a t i v e d e t e r m i n a t i o n of the c r a c k i n g p a t t e r n s of the s e r i e s of P b M e E t . showed that s c i s s i o n of the E t - P b bond i s f a v o r e d o v e r the M e - P b bond i n the p a r e n t m o l e c u l a r i o n s , l a r g e l y due to bond e n e r g y d i f f e r e n c e s . n

4

n

Me

Me* + E t P b R >bR

2

2

(

f

Et

[15]

+

. ν—•

Et-

+ MePbR

[16]

2

E x a m i n a t i o n of the e l e c t r o n s p i n r e s o n a n c e s p e c t r u m d u r i n g the r e a c t i o n w i t h h e x a c h l o r o i r i d a t e ( l V ) d i d not r e v e a l the p r e s e n c e of the c a t i o n - r a d i c a l P b E t t , w h i c h m u s t be h i g h l y u n s t a b l e e v e n at t e m p e r a t u r e s a s l o w as - 2 0 ° C . N o n e t h e l e s s , the f o r m a t i o n of ethyl r a d i c a l s i n high y i e l d s was evident f r o m s p i n - t r a p p i n g experiments with nitrosoisobutan w h i c h the w e l l - r e s o l v e obtained. 4

T h e u s e of h e x a c h l o r o i r i d a t e ( l V ) as an e f f i c i e n t s c a v e n g e r f o r a l k y l r a d i c a l s i s i m p l i e d i n S c h e m e I b y the i s o l a t i o n of a l k y l c h l o r i d e s i n h i g h y i e l d s . In s u p p o r t , s e p a r a t e e x p e r i m e n t s do i n d e e d show that e t h y l r a d i c a l s g e n e r a t e d u n a m b i g u o u s l y f r o m the t h e r m o l y s i s of p r o p i o n y l p e r o x i d e a r e q u a n t i t a t i v e l y c o n v e r t e d by h e x a c h l o r o i r i d a t e ( l V ) to e t h y l c h l o r i d e i n eq 14. T h e r e i s an a l t e r n a t i v e p o s s i b i l i t y that a l k y l h a l i d e i s f o r m e d d i r e c t l y f r o m the c a t i o n - r a d i c a l without the i n t e r m e d i a c y of a n a l k y l r a d i c a l . R Pbt + Ir^Cl/' 4

R Pb 3

+

+ R - C l + Ir^Clg " , 2

etc.

T h e d i f f e r e n c e between t h i s f o r m u l a t i o n and that p r e s e n t e d i n eq 13 of S c h e m e I r e s t s on the d e g r e e of m e t a s t a b i l i t y of the c a t i o n r a d i c a l toward fragmentation. T h e f a i l u r e to o b s e r v e the e s r s p e c t r a of R Pb+ and the i r r e v e r s i b i l i t y of the o x i d a t i o n w a v e i n c h r o n o p o t e n t i o m e t r y s u g g e s t s that i t s l i f e t i m e i s s h o r t . 4

B. D i a l k y l m e r c u r y Compounds. Hexachloroiridate(lV) a l s o r e a d i l y c l e a v e s d i a l k y l m e r c u r y c o m p o u n d s by s e c o n d - o r d e r k i n e t i c s s i m i l a r to eq 15 f o r t e t r a a l k y l l e a d (26). M o r e o v e r , the p r o d u c t s , both o r g a n i c and i r i d i u m ( l l l ) , as w e l l as the s t o i c h i o m e t r y of the r e a c t i o n a r e a l s o e q u i v a l e n t to that g i v e n i n eq 9> viz., Me Hg + 2 I r C l " 2

2

MeCl + MeHg

+

+ IrCl " + IrCl (S) " 6

3

5

2

N m r s t u d i e s i n d i c a t e that M e H g i s bound to I r C l ( S ) " i n s o l u t i o n . T h e s a m e s t o i c h i o m e t r y a p p l i e s to the h i g h e r h o m o l o g s ; the only d i f f e r e n c e lies i n the c o m p l e x i o n of the p r o d u c t s , i n c r e a s i n g a m o u n t s of a l k e n e s and a l k y l a c e t a t e s b e i n g f o r m e d at the e x p e n s e of a l k y l c h l o r i d e s on going f r o m e t h y l , i s o p r o p y l to t - b u t y l . T h e c l e a v a g e of d i a l k y l m e r c u r y by h e x a c h l o r o i r i d a t e ( l V ) i s h i g h l y dependent on the s t r u c t u r e of the a l k y l g r o u p s . T h u s , i n +

5

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

222

ORGANOMETALS AND ORGANOMETALLOIDS

the h o m o l o g o u s s e r i e s of R H g C H , the r e l a t i v e r a t e s of c l e a v a g e i n c r e a s e f r o m R = m e t h y l : ethyl : i s o p r o p y l : t e r t - b u t y l , roughly i n the o r d e r of 1 0 ° : 10 · 10 · 1 0 . T h e s e r e s u l t s r u n c o u n t e r to the p a t t e r n o b s e r v e d i n the e l e c t r o p h i l i c c l e a v a g e of the s a m e m e r c u r i a l s d e s c r i b e d i n the f o r e g o i n g s e c t i o n , or to expectations b a s e d on i n c r e a s i n g s t e r i c h i n d r a n c e . Instead, it s u g g e s t s that the r a t e - l i m i t i n g step o c c u r s p r i o r to a l k y l t r a n s f e r . 3

3

5

6

S c h e m e II; R Hg 2

+ Ir^Cl*" R Hgt 2

R. + I r ^ C l " 2

k

f

a

s

f a s t

t

>

R Hgt + Ir Cl

>

RHg

>»

m

2

R

+

6

3

"

[17]

+ R.

[18]

+ Ir ci X " m

o x

5

[19]

n

T h e k i n e t i c s , p r o d u c t s and s e l e c t i v i t y as w e l l as s p i n t r a p p i n g w i t h t - B u N O and 0 a l l a c c o r d w i t h the m e c h a n i s m i n S c h e m e II. T h e o b s e r v a t i o n of p a r a m a g n e t i c i n t e r m e d i a t e s by s p i n t r a p p i n g i n d i c a t e s that a l k y l r a d i c a l s a r e f o r m e d d u r i n g the c l e a v a g e of R H g b y I r C l * " . In fact, the q u a n t i t a t i v e a c c o u n t i n g of the a l k y l f r a g m e n t s as a l k y l p e r o x y p r o d u c t s , when the r e a c t i o n i s c a r r i e d out i n the p r e s e n c e of oxygen, shows that a l l of the a l k y l g r o u p s m u s t d e p a r t f r o m m e r c u r y a s f r e e r a d i c a l s a c c o r d i n g to eq 18. T h e l a t t e r i s s t r o n g l y s u p p o r t e d by the o b s e r v a t i o n that I r C l " d i s a p p e a r s u n d e r t h e s e c o n d i t i o n s at just o n e - h a l f the r a t e o b s e r v e d i n an i n e r t a t m o s p h e r e , as p r e d i c t e d b y S c h e m e II. T h e f a i l u r e to o b s e r v e d i r e c t l y the e l e c t r o n s p i n r e s o n a n c e s p e c t r u m of R H g t s u g g e s t s that i t s l i f e t i m e i s v e r y s h o r t . It i s p r e s e n t as one of the p r i n c i p a l s p e c i e s d u r i n g e l e c t r o n i m p a c t of R H g i n the gas p h a s e , and a m e r c u r y ( l l l ) s p e c i e s has been o b s e r v e d as t r a n s i e n t i n the e l e c t r o c h e m i c a l o x i d a t i o n of H g ( c y c l a m ) +. S e l e c t i v i t y i n the c l e a v a g e of a l k y l g r o u p s f r o m u n s y m m e t r i c a l d i a l k y l m e r c u r y b y I r C l " a c c o r d i n g to S c h e m e II o c c u r s d u r i n g f r a g m e n t a t i o n of R H g t r a d i c a l - c a t i o n subsequent to the r a t e - l i m i t i n g step. T h e u n i m o l e c u l a r d e c o m p o s i t i o n of ( C H ) H g i n the gas phase has been e x a m i n e d b y p h o t o e l e c t r o n photoion c o i n c i d e n c e s p e c t r o s c o p y (27). 2

2

2

6

2

2

2

2

2

2

3

2

+

CH Hg 3

CH HgCH t 3

( \->

3

+

CH Hg3

+ CH 3

[20]

+ CH

3

[21]

T h e t h r e s h o l d e n e r g y f o r f r a g m e n t a t i o n i n eq 20 i s found to be n e a r l y 2.5 v o l t s l o w e r than that f o r eq 21. T h e e x c l u s i v e cleavage of R = t - B u and i - P r and p r e f e r e n t i a l c l e a v a g e of R = E t i n the h o m o l o g o u s s e r i e s of R H g C H i s i n a c c o r d w i t h a w e a k e r a l k y l m e r c u r y c o m p a r e d to a m e t h y l - m e r c u r y b o n d . T h e p r e d o m i n a n t f a c t o r w h i c h d e t e r m i n e s a l k y l v s . m e t h y l c l e a v a g e a r e the s t r e n g t h s of the r e l e v a n t C - H g b o n d s . T h e s e v a l u e s c a n be e v a l uated f r o m the a v e r a g e bond e n e r g i e s f o r M e H g , E t H g , and 3

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

223 1

i - P r H g w h i c h a r e 58, 48, and 42 k c a l m o l " , r e s p e c t i v e l y (28.29)* A c c o r d i n g to S c h e m e II, the i s o l a t i o n of a l k y l c h l o r i d e s i n h i g h y i e l d s i m p l i e s that h e x a c h l o r o i r i d a t e ( l V ) i s an e f f i c i e n t s c a v enger of a l k y l r a d i c a l s i n eq 19 (Rox = RC1, X = S). H o w e v e r , i n a d d i t i o n to the r e d o x t r a n s f e r of c h l o r i n e f r o m h e x a c h l o r o i r i d a t e (IV) i n eq 14, a n a d d i t i o n a l r e d o x step i s r e q u i r e d , e s p e c i a l l y f o r R = i s o p r o p y l and t - b u t y l . T h e o b s e r v a t i o n of i s o b u t y l e n e and t e r t - b u t y l a c e t a t e f r o m t e r t - b u t y l r a d i c a l s and h e x a c h l o r o i r i d a t e (IV) i s a n a l o g o u s to e l e c t r o n t r a n s f e r o x i d a t i o n of a l k y l r a d i c a l s (30). ( C H ) 0 + Ir C l " >- I r C l " + ( C H ) C , etc. 2

2

3

3

3

6

+

6

3

3

The t e r t - b u t y l cation f o r m e d under such c i r c u m s t a n c e s w i l l u n d e r g o s o l v a t i o n , f o r e x a m p l e to t e r t - b u t y l acetate, or l o s s of a β-proton to i s o b u t y l e n e then m a i n t a i n i t s c o o r d i n a t i o the d i s t r i b u t i o n of I r C l ^ " and I r C l ( C H C N ) " a m o n g r e d u c e d i r i d i u m ( l l l ) products formed f r o m various a l k y l m e r c u r i a l s i s p r e c i s e l y i n a c c o r d w i t h t h i s f o r m u l a t i o n . T h u s , the r e s u l t s c l e a r l y i n d i c a t e that m e t h y l and e t h y l r a d i c a l s r e a c t w i t h I r C l ~ i n a c e t o n i t r i l e , e x c l u s i v e l y by c h l o r i n e t r a n s f e r . F o r i s o p r o p y l and t e r t - b u t y l r a d i c a l s , a p p r o x i m a t e l y 85 and 50$, r e s p e c t i v e l y , of the r e a c t i o n p r o c e e d s by c h l o r i n e t r a n s f e r and the r e m a i n d e r by e l e c t r o n t r a n s f e r . T h e l a t t e r b e c o m e s m o r e i m p o r t a n t i n a c e t i c a c i d s o l u t i o n s . T h e d e c r e a s i n g t r e n d of a l k y l r a d i c a l s to r e a c t w i t h I r C l " by e l e c t r o n t r a n s f e r i n the o r d e r : t - B u > i - P r » E t > M e f o l l o w s the e a s e of i o n i z a t i o n of the r a d i c a l i n the o r d e r : t - B u < i - P r < E t < M e as l i s t e d i n T a b l e II. Further m o r e , the opposed t r e n d i n the y i e l d s of a l k y l c h l o r i d e s i s c o n s i s t e n t w i t h the g e n e r a l l y d e c r e a s i n g a l k y l - c h l o r i n e bond energies f r o m M e C l t h r o u g h t - B u C l . W h e t h e r c h l o r i n e t r a n s f e r and c a r b o n i u m i o n f o r m a t i o n r e p r e s e n t i n n e r - and o u t e r - s p h e r e r e d o x p r o c e s s e s , r e s p e c t i v e l y , f o r m s an i n t e r e s t i n g s p e c u l a t i o n . I n n e r - and o u t e r - s p h e r e m e c h a n i s m s m e r i t c o n s i d e r a t i o n f o r the p r o c e s s by w h i c h e l e c t r o n t r a n s f e r o c c u r s f r o m R H g to I r C l " i n the r a t e - l i m i t i n g step i n eq 1 7. A l i n e a r f r e e e n e r g y r e l a t i o n s h i p b e t w e e n l o g k of r e a c t i o n and Ij) of R H g i s e x p e c t e d f o r t h i s s y s t e m i f e l e c t r o n t r a n s f e r o c c u r s by an o u t e r - s p h e r e p r o c e s s . H o w e v e r , the n e g a t i v e d e v i a t i o n of d i - t e r t - b u t y l - , d i i s o p r o p y l - , and d i e t h y l m e r c u r y f r o m the l i n e a r plot s u g g e s t s that s t e r i c f a c t o r s can be i m p o r t a n t i n the e l e c t r o n t r a n s f e r to IrCl ". 5

3

2

6

2

2

2

2

2

6

C. D i a l k y l ( b i s - p h o s p h i n e ) p l a t i n u m ( l I ) C o m p l e x e s . The c l e a v a g e of o r g a n o p l a t i n u m ( I I ) c o m p l e x e s w i t h o u t e r - s p h e r e o x i dants was c a r r i e d out as a c o m p a r i s o n f o r the a l k y l s of the m a i n g r o u p e l e m e n t s , l e a d and m e r c u r y , d e s c r i b e d above. Indeed, cis-dialkyl(bis-phosphine)platinum(ll) complexes are readily oxi d i z e d by h e x a c h l o r o i r i d a t e ( l V ) to a f f o r d two p r i n c i p a l types of p r o d u c t s d e p e n d i n g on the s t r u c t u r e of the a l k y l g r o u p and the

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

224

O R G A N O M E T A L S AND

ORGANOMETALLOIDS

c o o r d i n a t e d p h o s p h i n e (31)· T h u s , the d i e t h y l analog, c i s - E t P t ( L X ) ( P M e P h ) , a f f o r d s E t C l and e t h y l p l a t i n u m ( l l ) s p e c i e s by o x i d a t i v e c l e a v a g e of the E t - P t bond, 2

2

2

2

Et P#L + 2IrCl " 2

2

+

•

6

3

EtP^L S+

EtCl + IrCl "+IrCl

2

6

where L = P M e P h , P P h ; S = 2

2

5

S"

solvent

3

w h e r e a s M e P t ( P M e P h ) u n d e r g o e s o x i d a t i o n to d i m e t h y l platinum(lV) species. 2

2

2

2

Me P
2

2

C

H

3

ç

N

>

3

Me P^(PMe Ph) X + I r C l " + 2

2

2

2

w h e r e X = CI, I r c l ( C H C N ) or C H C N

l r C l

m

5

3

3

*

In the l a t t e r e x a m p l e , th i n d u c e d by r e p l a c e m e n c o m p e t i t i v e l y u n d e r g o e s o x i d a t i o n to d i m e t h y l p l a t i n u m ( l V ) species as w e l l as o x i d a t i v e c l e a v a g e to M e C l and m e t h y l p l a t i n u m ( l l ) species. ι* ά\ M Τ Λ Ρ Ρ Η 1 Z l r C i r / ^ Me P^(PPh ) X [22] Me Pr(PPh ) ( . \ l ?/> MePHPPh ) X+ MeCl [23] Α

m

2

3

2

2

6

2

3

2

( A L d L

π

4 6

3

2

The s t o i c h i o m e t r i c r e q u i r e m e n t of 2 e q u i v a l e n t s of h e x a c h l o r o iridate(lV) r e m a i n s i n v a r i a n t for each dialkylplatinum(ll), inde pendent of the p r o d u c t s of o x i d a t i o n . T h e r a t e s of r e a c t i o n s of d i a l k y l p l a t i n u m ( l l ) c o m p l e x e s w i t h h e x a c h l o r o i r i d a t e ( l V ) i n a c e t o n i t r i l e obeyed s e c o n d - o r d e r k i n e t i c s , b e i n g f i r s t - o r d e r i n e a c h r e a c t a n t a c c o r d i n g to eq 24· 2

-d[IrCl "]/dt 6

=

2

2k[IrCl -][R PtL ] 2

[24]

2

T h e s e c o n d - o r d e r r a t e c o n s t a n t s f o r the o x i d a t i o n of R P t L depend i n an i n t e r e s t i n g m a n n e r on the n a t u r e of the a l k y l g r o u p as w e l l as the p h o s p h i n e l i g a n d as shown i n T a b l e I X . 2

2

T a b l e I X . Rate C o n s t a n t s f o r the O x i d a t i o n of R P t L by H e x a c h l o r o i r i d a t e ( l V ) . R PtL k ( l m o l " sec" ) rel 2

2

1

2

Me Et Me Et

Pt(PMe Ph) Pt(PMe Ph) Pt(PPh ) Pt(PPh )

2 2 2 2

1

2

2

2

2

3

3

2

2

2

4.4 16 2 7.6

χ χ χ χ

2

10 10 10" 10" 2

2

1

k

2.2 χ 10 8 xlO 1.00 38

4 4

T h e e n e r g e t i c s and k i n e t i c s as w e l l as the o b s e r v a t i o n of a l k y l r a d i c a l s by s p i n t r a p p i n g and oxygen s c a v e n g i n g s u p p o r t a m e c h a n i s m i n v o l v i n g the r a t e - l i m i t i n g e l e c t r o n t r a n s f e r f r o m d i a l k y l p l a t i n u m ( I I ) to h e x a c h l o r o i r i d a t e ( l V ) s i m i l a r to S c h e m e s I and

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

225

II f o r t e t r a a l k y l l e a d and d i a l k y l m e r c u r y , r e s p e c t i v e l y . Scheme HI: R PtL 2

+

2

IrCl " 2

RzPtL^ + IrCl "

[25] [26]

6

R PtL^

->

RPtL

R- + I r C l "

-+>

RC1 + I r C l "

->>

R PtL Cl

2

6

R PtL 2

2

+

+

2

IrCl " 2

2

+ R-

+

5

2

3

2

+

[27]

2

+

IrCl " 5

2

A c c o r d i n g to S c h e m e III, the a c t i v a t i o n p r o c e s s i s r e p r e s e n t e d by the e l e c t r o n t r a n s f e r step i n eq 25. T h e g r e a t e r r e a c t i v i t y of ethyl d e r i v a t i v e s c o m p a r e d to the m e t h y l a n a l o g s i n the two series of R P t L i s i n a c c o r d w i t h t h e i r a b i l i t y to a c t a s d o n o r l i g a n d s i n electron transfer reactions the p h o s p h i n e l i g a n d s , P M e P h and P P h , c a n be a t t r i b u t e d to t h e i r v a r y i n g d o n o r p r o p e r t i e s . It i s u n l i k e l y that s t e r i c f a c t o r s a r e d o m i n a n t (or even i m p o r t a n t ) , s i n c e the d i f f e r e n c e i n m e t h y l / ethyl r e a c t i v i t y i n c r e a s e s t e n - f o l d f r o m 3.6 to 38 when the l i g a n d i s changed f r o m P M e P h to the m o r e b u l k y P P h . T h e latter r e f l e c t s a s a t u r a t i o n of e l e c t r o n i c e f f e c t s w h i c h i s a l s o s e e n i n the change i n the r e a c t i v i t y of the m e t h y l d e r i v a t i v e b y a f a c t o r of 22,000 when P M e P h i s r e p l a c e d b y P P h , c o m p a r e d to a c o r r e sponding change of o n l y 2100 o b s e r v e d with the e t h y l d e r i v a t i v e s . T h e f a i l u r e to o b s e r v e the e s r s p e c t r u m of the p a r a m a g n e t i c i n t e r m e d i a t e R P t L ^ i n d i c a t e s that i t s l i f e t i m e i s s h o r t , c o n s i s t e n t w i t h the i r r e v e r s i b i l i t y o b s e r v e d i n the c y c l i c v o l t a m m e t r y of R P t L i . O t h e r e v i d e n c e f o r the f o r m a t i o n of t r a n s i e n t Pt(lII) s p e c i e s have b e e n a d v a n c e d i n the p h o t o l y s i s of P t C l ~ and the p u l s e r a d i o l y s i s of P t C ^ " and P t C l ~ (32,33). T h e r e i s a l s o k i n e t i c e v i d e n c e f o r the e x i s t e n c e of m e t a s t a b l e P t ( l l l ) s p e c i e s i n the o x i d a t i o n of P t C l * " b y h e x a c h l o r o i r i d a t e ( l V ) (34). A c c o r d i n g to S c h e m e III, the p a r a m a g n e t i c R P t L s u f f e r s at l e a s t two p r i n c i p a l fates: c l e a v a g e of a n a l k y l r a d i c a l or f u r t h e r o x i d a t i o n to d i a l k y l p l a t i n u m ( l V ) b y u n i m o l e c u l a r and b i m o l e c u l a r r o u t e s , r e s p e c t i v e l y . T h e c o m p e t i t i o n between t h e s e pathways depends not o n l y on the c o n c e n t r a t i o n of I r C l " , but m o r e i m p o r t a n t l y on the s t a b i l i t y of R P t L ^ as r e f l e c t e d i n the s t r e n g t h of the a l k y l - p l a t i n u m b o n d . A l l e l s e b e i n g the s a m e , ethyl c l e a v a g e i s m o r e f a c i l e than m e t h y l c l e a v a g e , i n g e n e r a l a c c o r d w i t h the t r e n d i n bond s t r e n g t h s . T h e t e n d e n c y f o r methyl c l e a v a g e to o c c u r m o r e r e a d i l y i n the p r e s e n c e of c o o r d i n a t e d d i m e t h y l p h e n y l p h o s p h i n e c o m p a r e d to t r i p h e n y l p h o s p h i n e m a y be a t t r i b u t e d to g r e a t e r e l e c t r o n r e l e a s e b y the f o r m e r . D i f f e r e n c e i n s t e r i c b u l k ( e . g . , c o n e a n g l e s ) of the p h o s p h i n e s m a y a l s o be a factor. T h e f r a g m e n t a t i o n of the a l k y l g r o u p f r o m R P t L ^ a s a f r e e r a d i c a l i n eq 26 d u r i n g o x i d a t i v e c l e a v a g e of E t P t L and M e P t ( P P h ) i s s u p p o r t e d b y s p i n t r a p p i n g a n d oxygen s c a v e n g i n g , a s 2

2

2

3

2

3

2

3

2

2

2

4

2

6

2

2

2

2

2

6

2

2

2

2

3

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2

226

ORGANOMETALS AND ORGANOMETALLOIDS

w e l l as the a b i l i t y of I r C l ~ to c o n v e r t a l k y l r a d i c a l s to a l k y l c h l o r i d e s e f f i c i e n t l y . T h e l a t t e r l e a d s c o n c o m i t a n t l y to the r e d u c t i o n of h e x a c h l o r o i r i d a t e ( l V ) to p e n t a c h l o r o i r i d a t e ( l l l ) a s I r C l ( C H C N ) ~ a c c o r d i n g to eq 27. Indeed, a n a l y s i s of the r e d u c e d i r i d i u m p r o d u c t s shows the p r e s e n c e of e q u i m o l a r a m o u n t s of I r C l ( C H C N ) " and I r C l " , the l a t t e r a r i s i n g f r o m the r a t e - l i m i t i n g e l e c t r o n t r a n s f e r step a c c o r d i n g to S c h e m e III. 6

5

2

2

3

5

3

2

6

3

IV. D e l i n e a t i o n of E l e c t r o p h i l i c and E l e c t r o n Transfer Mechanisms T h e e x a m p l e s c i t e d show that both e l e c t r o p h i l i c and e l e c t r o n t r a n s f e r p r o c e s s e s c a n r e a d i l y p a r t i c i p a t e i n the cleavage of o r g a n o m e t a l s . O f t e n the d i s t i n c t i o n i s not c l e a n l y d e l i n e a t e d . B a s i c a l l y , a n e l e c t r o p h i l i c c l e a v a g e of a c a r b o n - m e t a l bond i s mechanistically distinguishe t r a n s f e r a s outlined i n eqs 28 and 29, r e s p e c t i v e l y .

R-M + E

+

k y———>( Ν ^ >

& [ R*-M f

—

T

[28]

χ

>->. /

k

[R-MÎE-]

R - E + M \ etc. [29]

T h e e l e c t r o p h i l i c c l e a v a g e i n eq 28 i s a o n e - s t e p p r o c e s s w h i c h p r o c e e d s w i t h a s e c o n d - o r d e r r a t e constant k g and i n w h i c h no intermediates are generated. T h e t r a n s i t i o n state d e p i c t e d i n b r a c k e t s r e f l e c t s a bond b r e a k i n g to m e t a l w h i c h o c c u r s s i m u l t a n e o u s l y w i t h bond m a k i n g to e l e c t r o p h i l e d u r i n g the t r a n s f e r of the a l k y l g r o u p . In contrast), the e l e c t r o n t r a n s f e r p r o c e s s i n eq 29 p r o c e e d s by a t w o - s t e p m e c h a n i s m i n w h i c h the i n i t i a l t r a n s f e r of an e l e c t r o n f r o m the o r g a n o m e t a l to the e l e c t r o p h i l e constitutes the r a t e - l i m i t i n g i n t e r a c t i o n with a s e c o n d - o r d e r r a t e constant ^ΕΤ· T h e r a d i c a l i o n p a i r shown i n b r a c k e t s i s an a c t u a l i n t e r m e d i a t e , but i f i t s c o l l a p s e to p r o d u c t s i s m o r e r a p i d than d i f f u s i o n f r o m the s o l v e n t c a g e , no p a r a m a g n e t i c s p e c i e s w i l l be o b s e r v e d . U n d e r t h e s e c i r c u m s t a n c e s , s e l e c t i v i t y studies of the i n t e r m e d i a t e p r o v i d e the only s u i t a b l e a l t e r n a t i v e f o r d i s t i n g u i s h i n g t h e s e m e c h a n i s t i c p a t h w a y s . T h e l a t t e r i s p r e d i c a t e d b y the notion that kj£ and kjr;T show m u c h the s a m e c h a r a c t e r i s t i c s , e s p e c i a l l y w i t h r e g a r d to the s t r u c t u r e of the o r g a n o m e t a l . For e x a m p l e , c o m p a r e the c l e a v a g e of d i a l k y l m e r c u r y ( l l ) c o m p o u n d s b y a c i d s ( e l e c t r o p h i l i c ) and h e x a c h l o r o i r i d a t e ( e l e c t r o n t r a n s f e r ) , presented above: T h e c l e a v a g e of d i a l k y l m e r c u r y ( l l ) b y h e x a c h l o r o i r i d a t e p r o c e e d s f r o m a p r i o r r a t e - l i m i t i n g e l e c t r o n t r a n s f e r step, R'HgR

+

IrCl " 2

>

R'HgR?

+

IrCl " 6

3

but the s e l e c t i v i t y i s d e t e r m i n e d by the f r a g m e n t a t i o n of the r a d i c a l - c a t i o n R'HgR*" i n a fast subsequent r e a c t i o n ,

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

227

Alkyl Transfers

KOCHi

, R'HgRt

r->R. ( \ — R * 1

+

R Hg f

+

+ RHg

A s expected, the r a t e of t h i s c l e a v a g e (log k g ^ ) i s linearlyr e l a t e d to the i o n i z a t i o n p o t e n t i a l of the m e r c u r i a l as shown i n F i g u r e 3. A s i m i l a r c o r r e l a t i o n i s shown by o r g a n o m e t a l s u n d e r g o i n g s u b s t i t u t i o n [ G r i g n a r d r e a g e n t and p e r o x i d e (35)] or i n s e r t i o n [ t e t r a a l k y l l e a d and T C N E (36)] v i a e l e c t r o n t r a n s f e r , and they a r e a l s o i n c l u d e d i n F i g u r e 1 f o r c o m p a r i s o n . T h e r a t e constant k g f o r the e l e c t r o p h i l i c p r o t o n o l y s i s of an a l k y l - m e r c u r y bond, R-HgR

1

+

H

+

k

E

>

R-H +

R»Hg

+

can be d i s s e c t e d i n t o tw the c l e a v e d g r o u p R , and I·, w h i c h depends only on the l e a v i n g g r o u p , R H g , as d e s c r i b e d by eq 8. F i g u r e 4 shows that I· r e s p o n d s l i n e a r l y to the i o n i z a t i o n p o t e n t i a l of the m e r c u r i a l . F u r t h e r m o r e , I· a l s o s t r o n g l y c o r r e l a t e s w i t h the T a f t p o l a r s u b stituent constant, σ*, f o r the a l k y l g r o u p s l i s t e d i n T a b l e X . T h e !

T a b l e X . C o r r e l a t i o n of I· and C P a r a m e t e r s w i t h T a f t P o l a r ( σ * ) and S t e r i c ( E ) C o n s t a n t s . s

σ*

R

0 0.10 0.20 0.30

CH CH3CH2 (CH ) CH (CH ) C 3

3

2

3

3

Leaving Group Effects RHg

+

CH Hg+ CH CH Hg (CH ) CHHg+ (CH )3CHg 3

3

2

3

+

2

+

3

Cleaved Group Effects R CH C H C H2 (CH ) CH (CH ) C 3

3

3

2

3

3

JL( expt.) 0 0.76 1.28 1.44

C (expt.) 0 0.55 0.29 — 1

0 -0.07 -0.47 -1.54 8.1 σ * + 0.65 (cale.)

E

s

0 0.75 1.30 1.45 8.1 σ * + 2.8 (cale.)

E

s

0 0.61 0.30 -1.9

c u r v a t u r e i n F i g u r e 4 f o r the c l e a v e d g r o u p constant, C, on p r o c e e d i n g f r o m m e t h y l to t - b u t y l can be a t t r i b u t e d to an i n c r e a s i n g s t e r i c effect as a r e s u l t of a d d i t i o n a l e n c u m b r a n c e by s u c c è s -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

228

AND

ORGANOMETALLOIDS

3 * Log k

8.5

9.0

Log

Figure 3. Εlectron-transfer processes in electrophilic substitutions. Saturation ef fects followed by alkyl substituents in the cleavage of organometals during the treat ment with various electrophiles: scale left and bottom for ((B) tetraalkyllead with tetracyanoethylene and (Q) dialkylmercury with hexachloroiridate(IV). Scale right (Tafel potential) and top for Grignard reagents and di-tert-butyl peroxide (·).

2

L

Log k

Figure 4. Correlation of cleaved-group constant C and leaving group constant L in acetolysis with the ionization potential of the dialkylmercury compound

C Bii*-HgCH

s

8

9

IONIZATION POTENTIAL,

tV

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

229

s i v e l y m o r e α - m e t h y l groups. T h e latter i s a l s o supported by the s i z e a b l e c o n t r i b u t i o n of the T a f t s t e r i c p a r a m e t e r E to the c o r r e l a t i o n w i t h C, as shown i n T a b l e X . B a r r i n g s t e r i c effects, both I· and C a r e thus s t r o n g l y dependent on the i o n i z a t i o n p o t e n t i a l of the m e r c u r i a l ; that i s , e l e c t r o p h i l i c a t t a c k at a n a l k y l m e t a l bond i s r e s p o n s i v e to e l e c t r o n a v a i l a b i l i t y , n a m e l y the H O M O e n e r g y , i n m u c h the s a m e w a y that the i o n i z a t i o n p o t e n t i a l is. D e s c r i b e d i n an a l t e r n a t i v e way, the t r a n s i t i o n state f o r e l e c t r o p h i l i c c l e a v a g e i n eq 28 c a n be c o n s i d e r e d a s a p e r t u r b a t i o n of the o r g a n o m e t a l b y an e l e c t r o p h i l e , w h i c h i s a k i n to a virtual ionization. T h e s e c o m p a r i s o n s show that e l e c t r o n t r a n s f e r and e l e c t r o p h i l i c a t t a c k both depend h e a v i l y on the e l e c t r o n a v a i l a b i l i t y i n the organometal. It f o l l o w s that a n y c o r r e l a t i o n of the r e a c t i v i t y ( i . e . , r a t e c o n s t a n t s ) w i t h the i o n i z a t i o n or o x i d a t i o n p o t e n t i a l s i s not s u f f i c i e n t to d i f f e r e n t i a t ence between the two i s l a r g e l y due to the v a r i a t i o n s i n the s t e r i c i n t e r a c t i o n s , w h i c h can be l a r g e i n a n i n n e r - s p h e r e , e l e c t r o p h i l i c p r o c e s s ( i . e . , f o r C but not I.) and l e s s i m p o r t a n t i n an o u t e r sphere, electron transfer process. T h i s c o n c l u s i o n s u p p o r t s the g e n e r a l f o r m u l a t i o n that e l e c t r o n t r a n s f e r and e l e c t r o p h i l i c p r o c e s s e s c a n s h a r e a c o m m o n t h e m e of c h a r g e t r a n s f e r i n t e r a c t i o n s . S u c h a c o n c l u s i o n a l s o b e a r s on the m u l t i p l i c i t y of a v a i l a b l e m e c h a n i s m s f o r the c l e a v a g e of o r g a n o m e t a l s . T h e ready a c c e s s i b i l i t y of s u c h c o n c e r t e d and s t e p w i s e p r o c e s s e s f o l l o w s n a t u r a l l y f r o m t h e i r b a s i c s i m i l a r i t y , and i t c a n m a k e the t a s k of differentiation in individual cases difficult. T h e s e s t u d i e s a l s o shed l i g h t on the e f f e c t s of p o l y a l k y l a tion of m e t a l s on t h e i r r e a c t i v i t y to e l e c t r o p h i l i c a n d e l e c t r o n transfer cleavages. T h u s the r a t e s of c l e a v a g e of a s i n g l e a l k y l l i g a n d f r o m G r o u p I V B o r g a n o m e t a l s a l w a y s d e c r e a s e i n the orderR M > R M C 1 > R M C 1 , and f o r the m e r c u r i a l s , R Hg » R H g C l , i n d e p e n d e n t of whether an e l e c t r o p h i l i c o r e l e c tron transfer process pertains. T h i s reactivity sequence natur a l l y f o l l o w s f r o m the a v a i l a b i l i t y of σ - b o n d i n g e l e c t r o n s i n the H O M O as l i s t e d i n T a b l e IV f o r the m e r c u r i a l s . s

4

3

2

2

2

V.

Homolytic Displacements in A l k y l Transfers

O r g a n o c o b a l t ( l I I ) c o m p l e x e s a r e r e a d i l y c l e a v e d by c h r o m o n s i o n i n aqueous p e r c h l o r i c a c i d s o l u t i o n (37). RCo^(DMG)

2

+ Cr + aq 2

• > ZH'

R-Cr*+ + 4 a

Co^DMG^

where D M G = dimethylglyoximate T h e a l k y l g r o u p i s t r a n s f e r r e d to c h r o m i u m ( l l ) e s s e n t i a l l y q u a n t i t a t i v e l y . T h e c l e a v a g e f o r m a l l y r e p r e s e n t s a t r a n s f e r of a n a l k y l r a d i c a l R« to C r + , that i s an o v e r a l l r e d u c t i v e c l e a v a g e of an a l k y l - c o b a l t (III) b o n d . T h e r a t e of t r a n s m e t a l l a t i o n f o l l o w s 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

230

ORGANOMETALS AND ORGANOMETALLOIDS

second-order kinetics, -d[Cr]/dt

+

=

+

k [ R C o ] [ C r ] + k«[RCoH ] [ C r ]

[30]

1

w h e r e k and k r e l a t e to the c l e a v a g e of the n e u t r a l and protonated alkylcobalt(lll) species, respectively. T h e v a r i a t i o n i n k and k w i t h the a l k y l g r o u p s f o l l o w s t h e s a m e o r d e r , a n d d e c r e a s e s i n the o r d e r ; 1

R 1

1

k'fM" s e c " )

=

Me

=

1

10 ·

>

Et >

4

n-Pr >

1

2

ΙΟ" ·*

ΙΟ" ·*

i - P r> i-Bu ΙΟ"

4

4

10" ·

2

A l k y l c o b a l a m i n s a r e a l s o c l e a v e d b y c h r o m o u s i o n (38), +

+

RCo(corrin) + C r

RCr

+ B

[31]

with simple second-orde and i n d e p e n d e n t of p H b e t w e e n 0-2.3. T h e c l e a v a g e s of the m e t h y l [k = 3 . 6 x l 0 M s e c " ] and e t h y l [k = 4.4 M** s e c " ] d e r i v atives proceed with different activation parameters: Δ Η * - 3.8 (Me), 11 (Et) k c a l m o l " ; Δ S* = -34(Me), - 1 8 ( E t ) eu. A l k y l t r a n s f e r s f r o m c o b a l t ( l l l ) t o c h r o m i u m ( l l ) as de s c r i b e d a b o v e a r e a n a l o g o u s t o the r e v e r s i b l e e x c h a n g e b e t w e e n a l k y l c o b a l t ( H I ) and c o b a l t ( l l ) (32,40,41), 2

- 1

1

1

1

1

m

E

R C o ( l ) + Co (2)

C o ( l ) + RCo (2)

=F=*=

[32]

M

w h e r e C o ( l ) and Co(2) r e f e r t o c o b a l t c o m p l e x e s w i t h s l i g h t l y d i f f e r e n t c h e l a t i n g l i g a n d s s u c h a s d i m e t h y l g l y o x i m a t o and c y c l o h e x a n e d i o n e d i o x i m a t o . T h e o v e r a l l p r o c e s s i n eq 32, w h i c h i s e q u i v a l e n t to e l e c t r o n t r a n s f e r , a c t u a l l y o c c u r s b y t r a n s f e r of a n a l k y l g r o u p a s a r a d i c a l a s shown b y l a b e l l i n g t h e c o b a l t a t o m s w i t h d i f f e r e n t c h e l a t i n g l i g a n d s . T h e r a t e of e x c h a n g e f o l l o w s s e c o n d - o r d e r k i n e t i c s , f i r s t - o r d e r i n cobalt(ll) and f i r s t - o r d e r i n a l k y l c o b a l t ( l l l ) . T h e second-order rate constants d e c r e a s e i n the r e l a t i v e o r d e r [ k ( E t ) = 1.1 χ 10" M" s e c " ] : 1

R k

r e l

= =

Me (2>10 ·6) 2

>

Et >

1

1

n-Pr ~ 1

(10°)

2

η-Bu 1

(ΙΟ" · )

4

(ΙΟ" · )

>

i - P r> i-Bu 2

5

(10- · )

(10-3.3)

T h e t r a n s f e r of t h e e r y t h r o - P h C H D C H D - g r o u p o c c u r s w i t h i n v e r s i o n (42). C o u p l e d w i t h the r e a c t i v i t y t r e n d of a l k y l g r o u p s , the c l e a v a g e i s b e s t c o n s i d e r e d a s a h o m o l y t i c d i s p l a c e m e n t on the c a r b o n c e n t e r (43). T h e t r a n s i t i o n state,

τη

E

V

'

η

m

i *

[Co—C—Co J i s s i m i l a r to that i n e l e c t r o p h i l i c c l e a v a g e s o c c u r r i n g w i t h i n v e r s i o n , e x c e p t t h e p r o c e s s i n v o l v e s a o n e - e q u i v a l e n t r a t h e r than a t w o - e q u i v a l e n t change. H o w e v e r , t h e l a t t e r does not a p p e a r to be

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

13.

Alkyl Transfers

KOCHi

231

a d e c i s i v e factor, since a l k y l t r a n s f e r f r o m alkylcobalt(lll) to cobalt(l), i.e., cJfl) + RCo (2)

m

m

R C o ( l ) + Cc?(2)

[33]

o c c u r s w i t h r a t e s and s t e r e o c h e m i s t r y m u c h l i k e that of i t s c o b a l t ( l l ) c o u n t e r p a r t i n eq 32. In p a r t i c u l a r , i n v e r s i o n of c o n f i g u r a t i o n at c a r b o n o c c u r s d u r i n g a l k y l exchange, a n d the s e c o n d - o r d e r r a t e c o n s t a n t s d e c r e a s e i n the r e l a t i v e o r d e r [ k ( E t ) = 1CT M" s e c " ] : 1

R

k

r e l

1

1

=

=

Me 2

> E t > n - P r - η-Bu > i - B u 2

fclO - )

(10°) (ίο- · )

(ίο- · )

1 4

3

(l0- -9)

1 7

A t t e m p t s to m e a s u r e the a l k y l exchange of a l k y l c o b a l t ( i l l ) with cobalt (ill) were unfortunatel and thus s u s c e p t i b l e t l o w r e a c t i v i t y of c o b a l t ( l l l ) i s p r o b a b l y due to i t s s u b s t i t u t i o n s t a b i l i t y , w h i c h l i m i t s the a v a i l a b i l i t y of the a c t i v e 5 - c o o r d i n a t e e l e c t r o p h i l i c s p e c i e s . N o n e t h e l e s s , the t r a n s i t i o n s t a t e s f o r a l k y l e x c h a n g e s i n a l l t h r e e s y s t e m s a r e l i k e l y to b e s i m i l a r , e f f e c t i v e l y i n v o l v i n g a l i n e a r 3-atom c o n f i g u r a t i o n (see above). T h e s i m i l a r i t y i n the r a t e s of the c o b a l t ( l l ) a n d c o b a l t ( l ) r e a c t i o n s s u g g e s t s that the e x t r a 1 a n d 2 e l e c t r o n s , r e s p e c t i v e l y , a r e i n a nonbonding o r b i t a l c e n t e r e d on both c o b a l t a t o m s . T h e c l e a v a g e s of a l k y l - m e t a l bonds b y e a c h of the t h r e e c o b a l t c o m p l e x e s w i t h o x i d a t i o n s t a t e s I, II a n d III a r e r e p r e s e n t a t i v e of what i s c o m m o n l y c o n s i d e r e d t o b e e l e c t r o p h i l i c , h o m o l y t i c a n d n u c l e o p h i l i c p r o c e s s e s , r e s p e c t i v e l y , e.g., C

, °>

R-Co* + M °

LÇsL+. R - C o + M 1

R-M*

1

WïL R-Cc? + M Y e t t h e r e a d y i n t e r c o n v e r s i o n of e a c h c o b a l t s p e c i e s b y onee q u i v a l e n t changes, 1

Co

^ *

Co

^

Co

r a i s e s the i s s u e of w h e t h e r e l e c t r o n t r a n s f e r p r o c e s s e s a r e i n v o l v e d i n a l k y l t r a n s f e r a s d i s c u s s e d i n the p r e v i o u s s e c t i o n s . S u c h p r o c e s s e s a r e e s p e c i a l l y r e l e v a n t i n v i e w of the e a s e w i t h w h i c h the a l k y l c o b a l t c o m p l e x e s t h e m s e l v e s u n d e r g o o x i d a t i o n r e d u c t i o n (44). RCo

111

=

^

RCo^

F o r e x a m p l e , t h e c l e a v a g e i n eq 32 m a y i n v o l v e a t w o - s t e p p r o cess, i n which cobalt(ll) acts as a nucleophile leading to the i n i t i a l r e d u c t i o n of a l k y l c o b a l t ( l l l ) , f o l l o w e d b y e l e c t r o n t r a n s f e r .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

232

ORGANOMETALS

R C o ( l ) + Cc?(2) m

Ccf(l)

+ RdF(2)

^P*=

AND ORGANOMETALLOIDS

Co(l) + R C o ^ ) C
S u c h m e c h a n i s m s a r e not r e a d i l y d i s t i n g u i s h e d f r o m a o n e - s t e p pathway i n v o l v i n g d i r e c t t r a n s f e r of a n a l k y l r a d i c a l , s h o r t of a c t u a l l y detecting the i n t e r m e d i a t e s r e s u l t i n g f r o m e l e c t r o n t r a n s f e r , and q u a n t i t a t i v e l y r e l a t i n g t h e m to the r a t e of r e a c t i o n . T h e r e a r e thermodynamic arguments, however, disfavoring such a formulation (43)· Acknowledgement: I w i s h to thank D r s . H . G a r d n e r , J . Y . C h e n , and W . A . Nugent f o r t h e i r s t i m u l a t i n g c o n t r i b u t i o n s and the National Science Foundation for financial support. Literature Cited 1.

2. 3. 4. 5. 6. 7.

8. 9· 10. 11. 12. 13. 14.

15. 16.

W o o d , J . M., " B i o c h e m i c a l a n d B i o p h y s i c a l P e r s p e c t i v e s i n M a r i n e B i o l o g y , " Vol. 3, D . C. M a l i n s a n d J. R. S a r g e n t , e d s . , A c a d e m i c Press, N e w Y o r k , 1975. R i d l e y , W . P., D i z i k e s , L. J., a n d W o o d , J. M., S c i e n c e (1977), 197, 329. B a s o l o , F . a n d P e a r s o n , R. G., " M e c h a n i s m s of I n o r g a n i c R e a c t i o n s , " 2nd Ed., W i l e y - I n t e rs c i e n c e , N e w Y o r k , 1967. J e n k i n s , C. L. and Kochi, J. K., J. Am. C h e m . S o c . (1972), 94, 842, 845. F e r r a u d i , G., p r i v a t e c o m m u n i c a t i o n . F e h l n e r , T. P., U l m a n , J., Nugent, W. Α., a n d K o c h i , J. K., I n o r g . C h e m . (1976), 15, 2544. T a f t , R. W., Jr., in "Steric E f f e c t s i n O r g a n i c C h e m i s t r y , " M . S. N e w m a n , e d . , W i l e y - I n t e r s c i e n c e , N e w Y o r k , 1956; cf. a l s o S h o r t e r , J., Q u a r t . R e v s . (1970), 24, 433. H o l m , T., A c t a C h e m . S c a n d . (1974), B 2 8 , 809. H o s o m i , A. and Traylor, T. G., J. Am. C h e m . S o c . (1975), 97, 3682. L o s s i n g , F . P . and S e m e l u k , G. P., C a n . J. C h e m . (1970), 48, 955. Streitwieser, Α . , Jr. and Nair, P. M., T e t r a h e d r o n (1959), 5, 149. Gardner, H. C. and Kochi, J. K., J. Am. C h e m . S o c . (1975), 97, 1855. Nugent, W. A. and K o c h i , J . K., J. Am. C h e m . S o c . (1976), 98, 5979. K r e e v o y , M. M. and H a n s e n , R. L., J. Am. C h e m . S o c . (1961), 83, 626 ; K r e e v o y , M. M., J. Am. C h e m . S o c . (1957), 79, 5927. C l i n t o n , Ν . Α., G a r d n e r , H. C., and K o c h i , J. K., J. O r g a n o m e t . C h e m . (1973), 56, 227. G a r d n e r , H. C. and Kochi, J. K., J. Am. C h e m . S o c . (1974), 96, 1982.

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13. KOCHI 17. 18. 19· 20. 21. 22. 23.

24. 25. 26. 27. 28. 29· 30.

31. 32. 33. 34. 35. 36. 37. 38. 39·

Alkyl Transfers

233

S t r e i t w i e s e r , Α . , Jr. a n d Nair, P . M., T e t r a h e d r o n (1959), 5, 149. L o s s i n g , F . P. and S e m e l u k , G . P., C a n . J. C h e m . (1970), 48, 955. Clinton, N . A. and K o c h i , J. K., J. O r g a n o m e t . C h e m . (1972), 42, 229. E d w a r d s , J. O . and P e a r s o n , R. G., J. Am. C h e m . S o c . (1962), 84, 16. D a v i s , R. E. and C o h e n , Α . , J. Am. C h e m . S o c . (1964), 86, 440. K l o p m a n , G., i n Ziegler, K . , Kroll, W . - R . , L a r b i g , W., and Steudel, O . - W . , J . L i e b i g s A n n . C h e m . (1960), 629, 57. A r b e l o t , M., M e t z g e r , J., C h a n o n , M., G u i m o n , C., a n d Pfister-Guillouzo, G., J. Am. C h e m . S o c . (1974), 96, 6217. C l i n t o n , Ν . Α., G a r d n e r O r g a n o m e t . C h e m . (1973), 56, 227. C l i n t o n , N. A. and K o c h i , J. K., J . O r g a n o m e t . C h e m . (1972), 42, 241. C h e n , J. Y., G a r d n e r , H. C., and K o c h i , J. K., J. Am. C h e m . S o c . (1976), 98, 6150. Cant, C . S. T., D a n b y , C. J., and E l a n d , J. H. D., J. C h e m . S o c . , F a r a d a y Trans. II (1975), 71, 1015. G o w e n l o c k , B . G., H a y n e s , R. M., and Majer, J . R., T r a n s . F a r a d a y S o c . (1962), 58, 1905. C a r s o n , A. S. and W i l m s h u r s t , B . R., J. C h e m . T h e r m o d y n . (1971), 3, 251. J e n k i n s , C. L. and K o c h i , J. K., J. Am. C h e m . S o c . (1972), 94, 843 ; K o c h i , J. K., IUPAC, X X I I I r d Int. C o n g r . P u r e A p p l . C h e m . , B o s t o n , P u r e Appl. C h e m . S u p p l . (1972), 4, C h e n , J. Y. and K o c h i , J. K., J. Am. C h e m . S o c . (1977), 99, 1450. W r i g h t , R. C. and L a u r e n c e , G. S., J. C h e m . S o c . , C h e m . C o m m u n . (1972), 132. A d a m s , G. E., B r o s z k i e w i c z , R. B . , and M i c h a e l , B . D., Trans. F a r a d a y S o c . (1968), 64, 1256. H a l p e r n , J. and Pribanic, Μ . , J. Am. C h e m . S o c . (1968), 90, 5942. Nugent, W. Α., B e r t i n i , F., and K o c h i , J. K., J. Am. C h e m . S o c . (1974), 96, 4945. G a r d n e r , H. C. a n d K o c h i , J. K., J. Am. C h e m . S o c . (1976), 98, 2460. Espenson, J . H. a n d S h v e i m a , J . S., J . Am. C h e m . S o c . (1973), 95, 4468. E s p e n s o n , J. H. a n d Sellers, T. D., Jr., J. Am. C h e m . S o c . (1974), 96, 94. V a n D e n B e r g e n , A. and West, Β. O., J. C h e m . S o c . , C h e m . Commun. (1971), p. 52; J. O r g a n o m e t . C h e m . (1974), 64, 125.

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234 40. 41. 42.

43. 44.

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Mestroni, G . , Cocevar, C . and Costa, G . , Gazz. C h i m . Ital. (1973), 103, 273. Dodd, D . and Johnson, M . D . , J. Chem. Soc., Chem. Commun. (1971), 1371. Chrzastowski, J . Z., Cooksey, C . J., Johnson, M . D . , Lockman, B . L. and Steggles, P . N . , J. A m . Chem. Soc. (1975), 97, 932. Dodd, D . , Johnson, M . D . and Lockman, B . L., J. A m . Chem. Soc. (1977), 99, 3664. Halpern, J., Chan, M . S., Hanson, J., Roche, T . S., and Topich, J . Α., J. A m . Chem. Soc. (1975), 97, 1606.

Discussion J . H . ESPENSON (Iow isms, e l e c t r o n t r a n s f e r and systematic decrease i n r a t e the s e r i e s to t - b u t y l , what the k i n e t i c data as a means

the e l e c t r o p h i l i c mechanism, show a constants i n going from methyl down i s the c r i t e r i o n by which you can use o f d i s t i n g u i s h i n g them?

KOCHI: You cannot. The way you must d i s t i n g u i s h between these two mechanisms i s by f o c u s s i n g on the r a d i c a l p a i r t h a t you get i n the e l e c t r o n t r a n s f e r mechanism. The e l e c t r o p h i l i c mechan ism i s e s s e n t i a l l y a one-step mechanism. The r a t e - l i m i t i n g step i n the e l e c t r o n t r a n s f e r process leads t o an intermediate which then goes on t o form product. The way one d i s t i n g u i s h e s between these two i s t o focus on the r a d i c a l p a i r . One can do t h a t by l o o k i n g a t the s e l e c t i v i t y s t u d i e s , that i s , by examining the s e l e c t i v i t y i n the composition of these organometals. The u s u a l c r i t e r i o n o f r e l a t i n g r a t e s t o redox p o t e n t i a l s i s h i g h l y ques tionable. J . J . ZUCKERMAN ( U n i v e r s i t y o f Oklahoma): You have a h i g h c o r r e l a t i o n w i t h i o n i z a t i o n p o t e n t i a l (ground s t a t e , gas phase). Since these are aqueous s t u d i e s , w o u l d n ' t the a p p r o p r i a t e parameter be the e l e c t r o d e p o t e n t i a l , o r i s there a h i g h c o r r e l a t i o n between those two s e t s of data? KOCHI: Y e s , there i s a l i n e a r c o r r e l a t i o n w i t h o x i d a t i o n p o t e n t i a l s o f these organometals w i t h the i o n i z a t i o n p o t e n t i a l s . S o l v a t i o n e f f e c t s do not appear t o be very strong i n t h i s case. RECEIVED August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

14 Pathways for Formation of Transition Metal-Carbon Bonds i n Protic Media JAMES H. ESPENSON Ames Laboratory and Department of Chemistry, Iowa State University, Ames, IA 50011 I plan to review wor concerning the title subject selective, focusing upon only a limited family of compounds and reactions. This main emphasis is on the reactions themselves and the mechanisms by which they occur. R-ML Complexes. The compounds of interest are sigmabonded organometallic complexes, chiefly of cobalt and chromium. This includes a series of tetradentate macrocyclic complexes of cobalt, RCo(chel)B withB=H2O,py, etc., aquochromium complexes, [(H2O) Cr-R ], and chromium complexes containing the macrocyclic ligand [15]ane N . Representative structures are shown in Figure 1. The prototype of the organocobalt structures is that of the vitamin B derivative methylcobalamin. The most successful and abundant family of model compounds are the bis (dimethylglyoximato) complexes developed by Schrauzer (1); these are the compounds R-Co(dmgH) B. Other cobalt chelate structures are also shown in Figure 1 with semi-systematic names as suggested by Busch (2). Detailed reviews of their preparation and chemistry have been published (3,4). A large number of compounds with the general formula (H20)5Cr-R are now known (5-11). Chromium complexes analogous to those of the organocobalts, although known, are much less abundant. West (12) has prepared some perfluoroalkyls Rp-Cr(chel)B, and we have recently prepared an extensive series of the alkyl compounds [R-Cr([15]ane Ν4)Η2θ] + (x") (13). Many other classes and examples of organochromium compounds are of course known (14), but their formation will not be reviewed here. A limited number of related organoiron compounds are also known (15,16,17). Our consideration of synthetic methods for such sigma organometallics, as well as their reaction chemistry, can be systematized by means of somewhat artificial oxidation state 5

2+

5

4

12

2

2+

2

2

0-8412-0461-6/78/47-082-235$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

236

ORGANOMETALS

OÙ Co([14]aneN4)2+

Co(Mo4teteneN4)2+

00

00

Co(meso-Me6[14]aneN4)2+

Co(dpnH) +

AND ORGANOMETALLOIDS

Co(Me6-4,ll-d1eneN4)2+

Co(dr.igH) 2

Journal of the American Chemical Society

Figure 1. Representative structures of cobalt chelates which form organometallic compounds of the form R-Co(chel)B. Chelate abbreviations are based on the suggestions of Busch (2).

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

14.

Transition Metal-Carbon Bonds

ESPENSON

237

assignments. The organic group R i s c u s t o m a r i l y regarded as a carbanion R:~. Thus the f o l l o w i n g s p e c i f i c compounds, c o n s i d e r i n g t h e i r i o n i c charges and those on the other l i g a n d s ( i f any), are a l l d e r i v a t i v e s o f M ( I I I ) : CH CH -Co(dmgH)opy, [(H2O)5Cr-CH CH CH3] +, [CH -Co([14]ane N ) H 0 ] + , and [CH3-Co(dpnH)H20]+. 3

2

2

2

2

3

3

4

2

Survey o f P r e p a r a t i v e Methods. The f o l l o w i n g r e a c t i o n scheme summarizes the modes of r e a c t i v i t y o f R(Co)B and (H 0) Cr-R : Scheme I . R e a c t i v i t y p a t t e r n s : τττ + ο, electrophiles R:~+(Co ) o r Cr [1] 2 +

2

5

>

(

2

or R-Cr + ^

h

u

o

r

1

"

e l n

reagents^

,

11

R +(Co ) or C r

2 +

[2]

nucleophile +

The organic groups shown as R , R°, and R a r e , o f course, combined w i t h other reagents as shown i n these s p e c i f i c r e a c t i o n s : 2

+

R(Co)H 0 + Hg + -> RHg + ( H 0 ) ( C o 2

2

(H 0) Cr-R 2

5

2 +

+ Br2 + RBr + C r ( H 0 )

R(Co)H 0 + Cr^q 2

I I I

2

2

2

)

3 + 6

+

[4]

+ Br"

[5]

1 1

(H 0) Cr-R + + (Co ) 2

5

[6]

I t i s o u t s i d e the scope o f t h i s review t o d i s c u s s t h i s r e a c t i o n chemistry i n d e t a i l , and i t i s mentioned here t o demonstrate that the reverse o f each of the three general r e a c t i v i t y methods can be used to form o r g a n o m e t a l l i c d e r i v a t i v e s . Thus a source of a carbanion such as a Grignard reagent or a l k y l l i t h i u m w i l l r e a c t w i t h a M ( I I I ) d e r i v a t i v e such as a h a l i d e t o form a metal-carbon bond. L i k e w i s e , generation of a carbon-centered f r e e r a d i c a l from a s u i t a b l e source i n the presence of the M(II) complex gives R-M, provided the r a d i c a l capture r a t e i s s u f f i c i e n t l y r a p i d ( i . e . , t h a t M(II) i s s u f f i c i e n t l y l a b i l e to l i g a n d s u b s t i t u t i o n ) , v i a the reverse of r e a c t i o n 2. The n u c l e o p h i l i c process, when permitted by the p r o p e r t i e s o f M ( I ) , o f t e n a f f o r d s the best s y n t h e t i c method. Thus cobaloximes and r e l a t e d compounds are a v a i l a b l e from organic h a l i d e s o r t o s y l a t e s by r e a c t i o n s which are w e l l - c h a r a c t e r i z e d as t y p i c a l S 2 s u b s t i t u t i o n s (18): N

1

m

( C o ) " + RX -> R ( C o ) + X"

[7]

Methods Based on M(II) and Free R a d i c a l s . The accepted scheme by which many reduced metal complexes r e a c t w i t h organic h a l i d e s t o form o r g a n o m e t a l l i c products i s shown i n Scheme I I . The e a r l i e s t examples were reported f o r Co(CN)5^~ (19) and Cr2+ (20,21,22).

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

238

ORGANOMETALLOIDS

Scheme I I . Two-Step R a d i c a l Mechanism: RX + M

11

-> X M

R* + M

11

·> R M

Net:

RX + 2 M

m

+ R*

[8]

111

11

[9] + ΧΜ

1 1 1

+ RM

111

[10]

The requirements f o r t h i s to c o n s t i t u t e a s u c c e s s f u l r o u t e to R - M I H are (1) the reduced metal complex must be a s u f f i c i e n t l y s t r o n g and r e a c t i v e r e d u c i n g agent that the f i r s t step w i l l be f e a s i b l e , and (2) the r a t e of combination of M(II) and R* i n equation 9 must be s u f f i c i e n t l y h i g h t o compete w i t h other processes such as r a d i c a l d i m e r i z a t i o n and d i s p r o p o r t i o n a t i o n The f i r s t requiremen and chromium. Althoug complexe Co(dmgH> r e a c t w i t h such a c t i v a t e d o r g a n i c h a l i d e s as b e n z y l bromide, they remain u n r e a c t i v e toward s a t u r a t e d a l k y l h a l i d e s such as i-C3H7Br and C H 3 I . For systems i n which the M complex i s a s t r o n g e r r e d u c i n g agent, e.g. C r S 0 i n aqueous dimethylformamide (20) or a " C r ^ - e n " complex i n the same s o l v e n t (23), the processes do occur as shown. Recent work by G. J . Samuels (13) has been based on t h i s i d e a . The complex of C r * * and the t e t r a d e n t a t e m a c r o c y c l i c l i g a n d [15]ane N4 forms r e a d i l y , and i t i s a s t r o n g e r r e d u c i n g agent than Cr|+ (E°=-0.58 V v s . -0.41 V f o r C r + ) . I t r e a c t s to form organochromium complexes w i t h a wide v a r i e t y of o r g a n i c h a l i d e s a c c o r d i n g to the s t o i c h i o m e t r y of equation 10. The r a t e s of these r e a c t i o n s f o l l o w t h i s e x p r e s s i o n 11

4

2

II

-d[Cr [15]ane N

2 + 4

11

] / d t = 2k [Cr [15]ane N 8

2 + 4

][RX]

[11]

Values of the second-order r a t e constant kg f o r a s e l e c t e d group of the h a l i d e s are summarized i n Table I . Table I Rate Constants f o r R e a c t i o n of 0 Γ [ 1 5 ] ane N/. w i t h A l k y l H a l i d e s (13) C o n d i t i o n s : 25°C i n 1:1 aq. t e r t - b u t a n o l ι χ

RX

1ko/dnAnol'^s"-*-

RX

kg/dflAnol-^s"!

O

C H Br n-C3H7Br n-C H Br 6-Br-l-hexene (CH3)3CCH2Br i-C3H7Br 2

5

4

Q

0.164 0.167 0.130 0.155 M).05 1.85 5.4

2

5

2

4

n

I •••

0.83 4.93 0.414 1.9xl0 3.2xl0 ^7

4

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

14.

ESPENSON

Transition Metal-Carbon Bonds

239

The f o l l o w i n g f i n d i n g s argue f o r the two-step mechanism of Scheme I I and the involvement o f f r e e r a d i c a l i n t e r m e d i a t e s : (1) The 2:1 s t o i c h i o m e t r y o f r e a c t a n t s and the p r o d u c t i o n o f equimolar c o n c e n t r a t i o n s o f chromium ( I I I ) a l k y l and h a l i d e s ; (2) The second-order r a t e law of equation 11; (3) The r e a c t i v i t y order RI > RBr » RC1; (4) The r e a c t i v i t y order t e r t i a r y > secondary > primary a l k y l h a l i d e ; (5) Production o f methylcyclopentane r e s u l t i n g from a c i d thermolysis of the alkylchromium c a t i o n produced i n the r e a c t i o n of 6-bromo-l-hexene, c o n s i s t e n t w i t h the known c y c l i z a t i o n o f the 6-bromo-l-hexenyl r a d i c a l (24,25). The second requirement p r e v i o u s l y mentioned, a high r a t e of combination o f the carbon-centered r a d i c a l and a second M ( I I ) complex, has been i n f e r r e d from k i n e t i c evidence by v a r i o u s authors (19,23,26). Direc the r a t e o f t h i s r a p i measurements (27,28). The r e a c t i o n o f the vanadium(II) compound VCl2(py)4 w i t h b e n z y l h a l i d e s produces only the c o u p l i n g product RR without d e t e c t i o n o f οrganovanadium(III) (29). The f a i l u r e t o observe the organovanadium even as an unstable intermediate might be due, as suggested, t o the r a p i d i t y o f subsequent a c i d o l y s i s o r e l e c t r o n t r a n s f e r (29), but i t seems e q u a l l y p l a u s i b l e t o t h i s author t h a t i t s formation i s precluded simply by the low r a t e of l i g a n d s u b s t i t u t i o n o f the d^ vanadium(II) complex, l e a v i n g the o r g a n i c r a d i c a l s t o undergo c o u p l i n g r e a c t i o n s . Among other thermal methods o f producing carbon-centered r a d i c a l s are r e a c t i o n s o f organic hydroperoxides, peroxides, peroxo a c i d s , and peroxo e s t e r s . This u s u a l l y uses an e l e c t r o n t r a n s f e r step w i t h the M(II) complex t o general r e a c t i v e i n t e r m e d i a t e s which u l t i m a t e l y y i e l d the carbon-centered r a d i c a l R*. The mechanistic steps shown i n Scheme I I I a r e i l l u s t r a t i v e of the r e a c t i o n s (30,31,32,33); the importance o f the competitive secondary r e a c t i o n s depends upon the p a r t i c u l a r peroxide s t r u c t u r e and the i d e n t i t y o f the M(II) complex. Scheme I I I . t_-Butyl Hydroperoxide and Cr|q: (CH ) COOH + Crf+ 3

Cr|+ + (CH ) C0*

3

3

^(CH ) CO + -CH 3

2

1 Cr2+, H+ ->(CH ) OH + Cr3+ 3

3

I13a]

3

C

(CH ) CO*/ ^

[12]

3

r

2

*Cr-CH +

[13b]

3

[1*1

3

3

KCr-8c(CH ) ] 3

H-CH 0H ?

>

(

C

H

3

)

3

C

O

H

3 +

I"]

3

+ ·0Η 0Η 2

[16a]

Λ

Cr-CH OH

2+

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

[16b]

240

ORGANOMETALS

AND

ORGANOMETALLOIDS

The f i r s t step, r e a c t i o n 12, i s the r a t e - l i m i t i n g process. K i n e t i c data f o r a v a r i e t y of peroxide s t r u c t u r e s f o r C r + (31) and C o ( c h e l a t e s ) (33) have been p u b l i s h e d , and w i l l not be reviewed here. The r a t e s f o r C r , the strongest reducing agent, are c o n s i d e r a b l y higher than those of any of the Co(II) complexes examined. Organic hydrazines have provided u s e f u l routes t o organoc o b a l t and organoiron compounds (34,35), although no mechanistic s t u d i e s have been conducted and the involvement o f f r e e r a d i c a l s i s uncertain. M e t a l ( I I ) complexes may r e a c t with organic h a l i d e s by other mechanisms as w e l l . With s p e c i a l f u n c t i o n a l groups e l e c t r o n t r a n s f e r pathways w i l l be seen (36). An unusual case i s found f o r the c o b a l t ( I I ) complex Vitamin B i (37), and f o r c e r t a i n i r o n ( I I ) porphyrins (38 to be formed). In thes 2

1 1

2 +

2 r

2

-d[M(II)]/dt = k [ M ( I I ) ] [ R X ]

[17]

suggestive perhaps of a dual a t t a c k of the separate metal centers at carbon and halogen. Photochemical Routes via Free R a d i c a l s . The complexes (NH3)5Co02CR + (R=CH3, C2H5) undergo c l e a n photoredox decomposit i o n according to 2

(NH ) Co0 CR 3

5

2

2+

fq^Co

2 +

+ 5NH + + C 0 + *R 4

[18]

2

p r o v i d i n g a source of a carbon-centered f r e e r a d i c a l . When the p h o t o l y s i s i s c a r r i e d out i n the pressence of an a p p r o p r i a t e c o b a l t ( I I ) complex, i t i s p o s s i b l e to o b t a i n reasonable y i e l d s of R(Co)H 0 product (39). A photochemical method has a l s o r e s u l t e d i n the s u c c e s s f u l p r e p a r a t i o n of organocobalt complexes (40). Methylcobaloxime i n s o l u t i o n i s q u i t e p h o t o s e n s i t i v e to v i s i b l e l i g h t , the primary photoreaction c o n s i s t i n g of homolysis to "CH3 and Co(dmgH) (41,42). Although other organocobalt complexes undergo s i m i l a r p h o t o d i s s o c i a t i o n , o f t e n with comparable quantum y i e l d s (35), the lower molar a b s o r p t i v i t i e s a s s o c i a t e d with complexes c o n t a i n i n g m a c r o c y c l i c c h e l a t e l i g a n d s such as Meô[14]ane N4 and Me5[14]4,11-diene N4 render them, i n p r a c t i c e , l e s s p h o t o s e n s i t i v e than methylcobaloxime. A mixture o f a small excess of RCo(dmgH) H 0 and the d e s i r e d c o b a l t ( I I ) complex i n deaerated, d i l u t e , aqueous p e r c h l o r i c a c i d forms the new organocobalt complex upon p h o t o l y s i s with v i s i b l e l i g h t (The a c i d i s u s e f u l i n decomposing Co(dmgH) to Co !" and H dmg, thereby reducing the extent o f recombination or R* and Co(dmgH) ). 2

2

2

2

2

2

2

2

N u c l e o p h i l i c Pathways via C o b a l t ( I ) . T h i s route i s represented by r e a c t i o n [7], and such r e a c t i o n s are w e l l -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

14.

Transition Metal-Carbon Bonds

ESPENSON

241

c h a r a c t e r i z e d Sjg2 processes (18,43); the same i s t r u e of the r e a c t i o n s of s i m i l a r rhodium(I) n u c l e o p h i l i e s (44). I would c a l l a t t e n t i o n t o one i n t e r e s t i n g anomaly i n such r e a c t i o n s w i t h d i h a l i d e s , Br(CH2) Br. The cobaloxime(I) n u c l e o p h i l e r e a c t s c l e a n l y i n two stages: n

1

Br(CH ) Br. + ( C o ) " -> B r ( C H ) ( C o ) + B r " 2

4

2

[19]

4

1

B r ( C H ) ( C o ) + ( C o ) " -> (Co)(CH ) (Co) + B r " 2

4

2

[20]

4

For these processes the r a t e constants (45) a r e not too f a r from s t a t i s t i c a l : ^9/2=4.8 dnAnol~ls~l and k Q=2.04 dnAnol^s"" (and compare n-C HçBr, k=2.13 dnAnol~^s~^) . In c o n t r a s t the c o b a l t ( I ) d e r i v a t i v e o f V i t a m i n B , B , r e a c t s r e a d i l y t o form under f o r c i n g c o n d i t i o n cobalamin (46). T h i s r e s u l t suggests a s u b s t a n t i a ] "neighboring group e f f e c t " f o r B ^ not seen i n the cobaloxime system. R e s u l t s s i m i l a r to B ^ a r e found f o r the r e a c t i o n o f an uncharged rhodium(I) n u c l e o p h i l e w i t h 1,5-dibromopentane (44). The r e s u l t here i s even more dramatic, i n that only the dirhodium product was obtained, even under f o r c i n g c o n d i t i o n s . These p u z z l i n g observations are under c o n t i n u i n g i n v e s t i g a t i o n . 1

2

4

1 2

1 2 s

2 g

2 s

E l e c t r o p h i l i c Pathways. Most o f the e f f o r t i n t h i s area has gone i n t o a study of the metal-carbon bond cleavage process r a t h e r than formation. Many o f the t r a n s - a l k y l a t i o n r e a c t i o n s do a l s o i n v o l v e formation o f a new metal-carbon bond, however, and a b r i e f c o n s i d e r a t i o n i n the context o f the present s u b j e c t i s thus i n order. A number o f s p e c i f i c r e a c t i o n s a r e i l l u s t r a t e d i n Scheme IV. ScJieme^V. H e t e r o l y t i c Reactions ^

• ( C o " I ) + + RHg

m

R(Co )/cHoHg+ J Ρ —

Y

+

[22]

_ 1 r o Q 1 no r e a c t i o n o r very slow r e a c t i o n [23] IV

• O x i d a t i v e cleavage via R ( C o ) +

1

Cr3+ + RHgR (H 0) Cr 2

5

I I i :

[24]

[26]

2 +

-R ^ ^2—y V I B

RBr + C r

3 +

+ Βτ"(not

- — • Br" + C r

3 +

+ RI (not RBr)

2

CrBr +)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

[27]

[28]

242

ORGANOMETALS

Ρ

+4

ORGANOMETALLOIDS

ft-CsH?

CH CI

+ 6

AND

2

Cr-R +Br

2

-

-

y

j£r-R**+

CH Hg* 3

• 2 m/

/

/ ( C o ) - R + H g

2

+

0

-2

-

-4 I -2

Y

1 Ό

1

1

+2

1

+4

+6

Figure 2. Linear free-energy correlations for electrophilic reactions. The rate constants for different reac tion series are plotted on a logarithmic scale against log k for the series (H O) Cr-R + + Hg \ Electrophilic reactivity: KM" -R+EVS. kc - «»++Hg*+g

s

2

2

1

r

nl

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

14.

espenson

Transition Metal-Carbon Bonds

243

The halogen cleavages of organochromium complexes appear to be straightforward electrophilic processes (47) in contrast to the oxidative processes seen for R(Co) systems with bromine. The mercury (II) reactions have been widely studied and have been summarized for cobalt (48) and chromium (11) systems. Reaction [22] proceeds with inversion at the alpha carbon atom, a probably consequence of steric interactions (48). The stereochemistry of these other electrophilic reactions remain unknown, although the kinetic effects are such (11,47) that inversion seems the probable course in each case. An interesting linear-free-energy relationship is found for a l l of these reactions. Figure 2 depicts the rate constant for each reaction plotted (on a logarithmic scale) against that for one series chosen as a standard (Reaction [25] constitutes a good standar largest number of R groups) is high, suggesting a similar Sg2 mechanism (and stereochemical inversion?) in each case. A thorough review of electrophilic cleavage reactions has recently been published (49). Literature Cited 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Schrauzer, G. Ν . , Accounts Chem. Res., (1968) 1, 97. Lovechio, F., V., Gore, E . S., and Busch, D. Η . , J . Am. Chem. Soc., (1974) 96, 3109. Dodd, D. and Johnson, M. D . , J. Organomet. Chem., (1973) 1, 52. Pratt, J. M. and Craig, P. J., Adv. Organomet. Chem., (1977) 99, 5953. Anet, F. A. L., Can. J. Chem., (1959) 37, 58. Dodd, D. and Johnson, M. D . , J. Chem. Soc. Α . , (1968) 34. Schmidt, W., Swinehart, J. Η . , and Taube, H., J. Am. Chem. Soc., (1971) 93, 1117. Ardon, Μ., Woolmington, Κ., and Pernick, A . , Inorg. Chem., (1971) 10, 2812. Kochi, J. K. and Buchanan, D. B . , J. Am. Chem. Soc., (1965) 87, 859. Espenson, J. H. and Williams, D. A . , J. Am. Chem. Soc., (1974) 96, 1008. Leslie, J. P . , II and Espenson, J. H., J. Am. Chem. Soc., (1976) 98, 4839. Van Den Bergen, Α. Μ., Murray, K. S., Sheahan, R. Μ., and West, B. O., J. Organomet. Chem., (1975) 90, 299. Samuels, G. J. and Espenson, J. Η . , unpublished results. Sneeden, R. P. A . , "Organochromium Compounds", Academic Press, New York, 1975. Goedkin, V. L., Peng, S . - M . , and Park, Y . , J. Am. Chem. Soc., (1974) 96, 284. Taube, R., Drevs, H., and Duc-Hiep, T., Ζ. für Chem., (1969) 9, 115.

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ORGANOMETALS AND ORGANOMETALLOIDS F l o r i a n i , C. and Calderazzo, F., J. Chem. Soc. A, (1971) 3665. Schrauzer, G. N. and Deutsch, Ε. Α . , J. Am. Chem. Soc., (1969) 91, 3341. Halpern, J . and Maher, J. P . , J. Am. Chem. Soc., (1965) 87, 5361. Castro, C. E. and Kray, W. C., Jr, J. Am. Chem. Soc., (1963) 85, 2768. Kochi, J. K. and Mocadlo, P. E., J. Am. Chem. Soc., (1966) 88, 4094. Kochi, J. K. and Davis, D. D . , J. Am. Chem. Soc., (1964) 86, 5264. Kochi, J. K. and Powers, J. W., J. Am. Chem. Soc., (1970) 92, 137. Walling, C . , Cooley, J. Η . , Ponaras, A. A., and Racah, E . J., J. Am. Chem. Soc., Carlsson, D. J. an (1968) 90, 7047. Espenson, J. H. and Leslie, J . P . , I I , J. Am. Chem. Soc., (1974) 96, 1954. Cohen, H. and Meyerstein, D . , J. Chem. Soc., Chem. Commun., (1972) 320. Cohen, H. and Meyerstein, D . , Inorg. Chem., (1974) 13, 2434. Cooper, Τ. A., J. Am. Chem. Soc., (1973) 95, 4158. Kochi, J. K. and Mocadlo, P. Ε . , J. Org. Chem., (1965) 30, 1134. Hyde, M. R. and Espenson, J. Η . , J. Am. Chem. Soc., (1976) 98, 4463. Schmidt, W., Swinehart, J. Η . , and Taube, Η . , J. Am. Chem. Soc., (1971) 93, 1117. Espenson, J. H. and Martin, Α. Η . , J. Am. Chem. Soc., (1977) 99, 5953. Geodkin, V. L., Peng, S . - M . , and Park, Y., J. Am. Chem. Soc., (1974) 96, 284. Mok, C. Y. and Endicott, J . F., J. Am. Chem. Soc., (1978) 100, 123. M a r z i l l i , L . G . , M a r z i l l i , P. A., and Halpern, J., J. Am. Chem. Soc., (1970) 92, 5652. Bläser, H. and Halpern, J., unpublished results, as cited by Halpern, J., Ann. N.Y. Acad. Sci., (1974) 239, 2. Castro, C. E., J. Am. Chem. Soc., (1964) 86, 2310. Roche, T. J. and Endicott, J . F., Inorg. Chem., (1974) 13, 1576. Espenson, J. H. and Heckman, R. Α . , unpublished observations. Schrauzer, G. Ν . , Sibert, J. W., and Windgassen, R. J., J . Am. Chem. Soc., (1968) 90, 6681. Golding, J. T., Kemp, T. J., Sellers, P. J., and Nocchi, T., J . Chem. Soc. Dalton, (1977) 1266. Allen, R. J. and Bunton, C. Α . , Bioinorg. Chem., (1976) 3, 241.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

14. 44 45 46 47 48 49

espenson

Transition Metal-Carbon Bonds

245

Collman, J. P. and MacLaury, M. R., J. Am. Chem. Soc., (1974) 96, 3019. Espenson, J. H. and Chao, T - H . , Inorg. Chem., (1977) 16, 2553. Smith, E. L., Merryon, L., Muggleton, P. W., Johnson, A. W., and Shaw, Ν . , Ann. N.Y. Acad. S c i . , (1964) 112, 564. Espenson, J. H. and Samuels, G. J., J. Organomet. Chem., (1976) 113, 143. F r i t z , H. L., Espenson, J. H . , Williams, D. Α . , and Molander, G. Α . , J. Am. Chem. Soc., (1974) 96, 2378. Johnson, M. D . , Accounts Chem. Res., (1978) 11, 57.

Discussion J . M. WOOD (University of Minnesota): Several years ago we synthesized that tetramethylen size the bromide intermediat safrose to use as an affinity column label for purifying enzymes. We were disappointed that we couldn't isolate i t , but Professor R. Abeles iBrandéis University] pointed out that with increased concentration of B^2 in solution, the extinction coefficienct alters; he suggested about 6 years ago that B ^ bas a tendency to dimerize in concentrated solution by forming hydrogen bonds between propionamide groups. That would explain why you principally obtain that product, but i f you work in dilute solution you can isolate some of the tetramethylene bromide intermediate. EPSENSON: Yes, that one can be isolated. Smith did i n fact report that [Ann. Ν. Y. Acad. S c i . , (.1964) 112, 564] although we have not gone back and worked with that particular one. W. P. RIDLEY (University of Minnesota): I'm very interested in the reactivity of sulfur [as RS-] with the alkylcobalt com plexes. This is extremely important biologically. You l i s t e d i t as a nucleophilic attack. The evidence with me thy lcobalamin i s that i t ' s a radical mechanism. ESPENSON: I don't think Schrauzer would agree with that. He gets RSR' products, but not to the extent that you can take as evidence for electrophilic attack. RIDLEY: No, apparently there is a lag period in the reactiv i t y of these thiols with methylcobalamin, and that's taken to be evidence for the generation of a radical species which is the re acting group. ESPENSON: lished?

That's an interesting result; has that been pub

RIDLEY: Yes, i t ' s in Biochem. Biophys. Acta [Frick et a l . (1976) 428, 808].

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

246

ORGANOMETALS

AND

ORGANOMETALLOIDS

WOOD: There i s no change i n the r a t e of t h a t r e a c t i o n over a pH range from 7 to 14, so as you go t o t h i o l a t e anion i n the s y s tem, you don't see any d i f f e r e n c e s i n these r e a c t i o n s . We c o u l d not repeat Schrauzer's experiments. ESPENSON: I have no o r i g i a n l evidence to add c i t e d i n the l i t e r a t u r e . Schrauzer has shown t h a t n e u t r a l s o l u t i o n you get s u b s t i t u t i o n . At h i g h pH t h i o l a t e anion; you get n u c l e o p h i l i c displacement. he has r e t r a c t e d t h a t so you and he are at odds on

t o the RS- case i n low pH or you get the I don't t h i n k this point.

C. P. DUNNE ( C a l i f o r n i a State U n i v e r s i t y , Long Beach): I have to support P r o f e s s o r Wood i n t h i s controversy. I found t h a t i n the system Schrauzer used, a c o n t r o l experiment of the a c e t a t e b u f f e r and c o b a l t comple w i l l generate an enormous amount of so c a l l e d r a d i c a l products Schrauzer has. He's no pounds when you e l i m i n a t e the p o s s i b i l i t y of r a d i c a l r e a c t i o n s . M. KRONSTEIN (Manhattan C o l l e g e , New Y o r k ) : You showed complexes of c o b a l t and chromium w i t h o r g a n i c s , and at the end of a l l your r e a c t i o n s you always got s e p a r a t i o n of R and the metal. How d i d you i d e n t i f y those, and how does t h a t separated R compare w i t h the R you introduced? +

ESPENSON: The R which I showed as R , R-, and R~ i s not f r e e i n t h a t form. R~ would be attached t o the a t t a c k i n g reagent and orgaxioaercurial and organic bromide, and so on, and i t ' s i d e n t i f i e d as such by i s o l a t i n g those compounds c h e m i c a l l y . L i k e w i s e , the metal complex products (chromium(III) or chromium(II), or cob a l t ( I I ) , c o b a l t ( I I I ) , or c o b a l t ( I ) ) are i d e n t i f i e d c h e m i c a l l y e i t h e r by t h e i r a b s o r p t i o n s p e c t r a or by s e p a r a t i o n and chemical i d e n t i f i c a t i o n . Did I c o r r e c t l y understand your question? KRONSTEIN: I have the opposite experience. I f I introduce metal oxides i n t o low organic polymer f r a c t i o n s which continue p o l y m e r i z i n g , the metal doesn't go o f f . Your i d e a i s of importance because there i s a b i g problem t h a t e n v i r o n m e n t a l i s t s f a c e . For example, some a n t i f o u l i n g p a i n t s or p r o t e c t i v e a n t i f o u l i n g m a t e r i a l s i n water can give up t o x i c compounds combining the m e t a l groups and the organic groups. I f the metal and the organic group enter the water s e p a r a t e l y , these would not be as t o x i c . I f metal and R don't separate, the water i s made much more t o x i c . That's why t h a t question would be i n t e r e s t i n g t o study f u r t h e r . [Eds: see chapter by M. L. Good et a l . ] RECEIVED

August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

15 Unstable Organometallic Intermediates i n a Protic M e d i u m 1

JAMES H. WEBER and MARK W. WITMAN University of New Hampshire, Parsons Hall, Durham, NH 03824

For many years (1 of organocobalt compound es are nucleophilic attack, electrophilic attack, and homolytic bond cleavage. Typical examples are given in eqn. 1-3. In the nucleophilic attack (eqn. 1) the RH product occurs because of proton extraction by a carb111

111

RCo (chel) — » NuCo (chel) + RH U) e.g. RS", CN RCo (chel) ël^ » , > Co (chel) + RE (2) e.g. Hg , Pd *, Tl RCo (chel) h ^ R ^ C r ^ S n * R- + Co (chel) (3) anaerobic anionic intermediate. The transient R •product of eqn. 3 is converted to many products depending on the nature of R and the attacking group. Examples are organic products like alkanes, alkenes, dimerized alkanes, and organometallic species such as RCr and RSn . From the environmental point of view, it is important to note that the electrophilic (eqn. 2) and free radical (eqn. 3) reactions occur with methylcobalamin (4, 5). It is possible that methylcobalamin is involved in microbial methylation of lead (6, 7) by the electrophilic attack mechanism (eqn. 2). For these reasons this paper reports the reactions, of the dimethylcobalt complex (8)(CH ) CoL(Structure I) with Zn , Cd and Pb electrophiles. Because we do not know the alkyl donor/alkyl acceptor ratio in the environment, we will discuss a variety of reactant ratios. m

111

2+

2

+

3+

m

3

11

III

IV

2+

3

2+

2+

2

Results and Discussion 2+

2+

2+

Although Zn , Cd and Pb are known to be unreactive toward a variety of RCo(chel) (9,10), they are surprisingly reactive toward the (CHj^CoL carbanionlfonor. Our data based on these reactions supports 1

Current Address: Mobay Chemical Corporation, New Martinsville, W. Virginia 26155 American Chemical )-8412-ft^6/78/V-08^2Ï7$05.00/( © 19^ei*aWeracal Society 1155 16th St. N. W. In Organometals and Organometalloids; Brinckman, F., et al.; Washington, D. C. Society: 20036Washington, DC, 1979. ACS Symposium Series; American Chemical

248

ORGANOMETALS A N D ORGANOMETALLOIDS

Ο

H C

J,

" Ο

^ 3

'

H

CH

Co

I

H C-

CH.

3

( C H

2

V

the formation of intermediate organometallic products of the type C H ^ M and ( C H - ^ M whic solvent employee. In contrast to the reactions of the monoalkyl derivatives RCo(chel) with Hg which demonstrate a simple 1:1 stoichiometry (eqn. 4), the +

+

RCo(chel) + H g

»

2 +

RHg

+

+ Co(chel)

(4)

+

anaerobic reactions of ( C H - L C o L with Z n , C d and P b are quite unique. Preliminary experiments revealed that two very different reactions occurred depending upon whether the metal ion or complex was in excess. In the presence of excess metal ion an instantaneous reaction was observed. With excess complex, however, the instantaneous reaction was followed by a slower reaction which was complete in a matter of minutes. The biphasic nature of this reaction was confirmed using the stopped-flow kinetics technique. These two classes of reactions will be discussed separately beginning with the experiments using excess metal ion. 2 +

2 +

2 +

Reactions with Excess Z n * , C d * and P b ^ . Upaj^reactioj^of ( C H - ^ C o L with an equimolar or an excess of Zn , C d , or Pb * in i j C ^ H ^ O H the ultraviolet-visible spectrum changes instantaneously. These reactions can be monitored most conveniently by observing the disappearance of the visible maximum at 412 nm (ε = 8380 ) which is characteristic of (CH J C o L . The complex product ion C H ^ C o L * was identified by comparison of the spectra of the final solutions with that of a solution made from an analyzed sample of [ C H ^ C o ( L ) H o 1 . From a knowledge of the molar absorptivity of the product ion at 463 nm, ( ε = 2120) it is evident that ( C H j - C o L is quantitatively converted to C H C o L in these reactions. Furthermore, this moiaomethylproduct is indefinitely stable in the presence of excess Zn , C d , or Pb * in accord with the results of Magnuson (10) for the reactions of C H ^ C o L * with the same metal ions in aqueous solution. The stoichiometrics of these fast reactions were determined by spectral titration. This procedure was complicated by the overlapping of the second slower phase of the reaction which was fairly rapid in the early stages. As a consequence a rapid titration technique was devised to 2

2

2

+

+

2

2

+

3

+

+

4

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

+

15.

WEBER

Organometallic Intermediates

wiTMAN

AND

249

minimize any error incurred due to the competing reaction^The method that was found to be most convenient was to deliver the M titrant direc tly into a spectrophotometric cell, which contained an appropriate amount of complex, using a one microliter syringe. In this manner volume cor rections were negligible and the titration could be carried out quite rapidly. The titrations for Zn , C d and Pb yield end points close to a molar ratio (M ^/complex) equal to 1.0 (Figure 1). The fact that the molar ratios are slightly low reflects the contribution due to a competing reaction (see below). An interesting feature of this work is the fate of the liberated methyl group. The fast demethylation reactions described above are followed by relatively slow reactions in which methane is evolved. This is in contrast to the demethylation of ( C H ^ C o L by H ^ O in which the methane is liberated instantaneously ana quantitatively according to eqn. 5. In fact, for the C d an +

+

+

+

+

(CH ) CoL + H 0 * -iasi 3

2

>

3

CH CoL 3

+

+ CH^

(5)

methane was obtained only after ca. 200 hr! The methane could be quantitatively recovered at any time during the course of the reaction, however, by the addition of H 0 * . On the basis of the slow evolution of methane, the sensitivity of the intermediate species to Η - 0 , and the indicated 1:1 staichiometry, we postulate that intermediates o l the type C F k Z n * , C H L C d , and C H P b are formed in these reactions according to eqn. 6. Further support for 3

+

+

3

(CH ) CoL + M 3

2

2

+

—iâ§î

»

CH CoL* 3

+ CH M 3

(6)

+

these species comes from a study of the kinetics of their decomposition. The rate of methane evolution was monitored by G L C for the reactions of ( C H J C o L with the three metal ions. Plots of l n i Q , - C ) versus time were linear over at least four half-lives. The rates were independent of excess metal ion concentration, which precudes the possibility of redistribution equilibria of the type shown in eqn. 7. These results are consistent with a process in which the organometallic inter2

2CH M 3

>

+

(CH ) M 3

+ M

2

2

(7)

+

mediate is decomposed by i - C ^ ^ O H (eqn. 8). Because the solvent is in CH M 3

+

+ i-C H OH 3

>

7

C H ^ + M (i-C H^O) 3

(8)

+

a large excess over the C H J M * species, a pseudo-first-order rate law is followed. A summary of the kinetic data for the methane evolution reactions is presented in Table I. The relative stability C H C d » C H Z n agrees with the known reactivity of saturated organometallic compounds of the Group IIB metals, Zn > C d > Hg (11). In addition the reactivity of organometallic compounds of the type RM" * generally correlates with the ionic character of the carbon-metal bond; both decreasing in the order 4

3

+

3

+

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

AND

ORGANOMETALLOIDS

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

15.

WEBER

251

Organometallic Intermediates

wiTMAN

AND

L i > Mg > Zn > C d > H g (12). Consequently, the stability of C H P b observed here (CH^Pb" " ^ C H T C d > C H - Z n ) agrees with the known covalent character of carbon-lead bonds ( θ ) . 3

+

1

Table I. Summary of Kinetic Data for Methane Evolution During the Reactions of ( C H ^ ) C o L withExcess Zn , C d , and Pb . +

9

Electrophile

l o 6 k

obs

t

( s e c l )

128 3.6 3.2

Zn + Cd£ Pb 2

z +

1/2

(hr)

1.5 52.6 60.1

Additional evidence for the formation of intermediates of the type C H j M comes from the accelerating effect of C H ^ O H on the methane evolution reactions. The reactions of ( C H j J C o L with excess Zn Cd and Pb in solutions containing 20%"tvyv) C h U O H resulted in a considerably faster rate of C H ^ evolution. The fact i h a t the reactions were complete in less than one nour is in agreement with the protonolysis of C H ^ M by the more acidic C H ^ O H (eqn. 9). A similar reaction in which +

CH M 3

+ CH OH

+

>

3

CH^ + M(OCH ) 3

(9)

+

( C H - ^ C o L was reacted with excess C d C l in anhydrous methanol resulted in the rapid formation of a white precipitate together with the simultan eous evolution of C H ^ . This is consistent with a process (eqn. 10) in which 2

(CH ) CoL 3

2

CH Cd 3

+

+ CdCl

+ Cf

»

2

C

H

^

Q

H

CH Cd 3

>

+

+ CH CoL* 3

C H ^ + CdCl(OCH ) 3

(10a) (10b)

unstable C H ^ C d * formed in reaction (10a) reacts with C H O H in the presence of CI" to form solid C d C K O C H j (eqn. 10b). This latter product was filtered from the reaction mixture, washed with C F U O H , and charac terized. The apparent stability of the C H U M * intermediates is somewhat surprising in view of the protic nature of the solvent. Solvation of the C H M species by i - C ^ H y O H presumably contributes to the stabilization of tnese organometallic intermediates, however, since oxygen donors are known to stabilize alkyl zinc and alkyl cadmium bonds (11). The isolation of stable alkyl zinc (14) and alkyl cadmium alkoxides (15Γsire good examples of this effect. Attempts to isolate the C H - M intermediates using stabilizing ligands such as Br", Γ , and bipy Were unsuccessful. Despite this failure, however, the demonstrated 1:1 stoichiometry, the methane evolution data, and other evidence (see below) strongly suggest that C H M * species are indeed intermediates in these reactions. 3

3

+

+

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

252

^Reactions with Excess (CH J G o L . The reactions of excess ( C H J C o L with Zn , C d , ana Fr> I n ~ i - C H O H are markedly different from the reactions using excess metal ion. Instead of a single instantaneous reaction a two-step reaction was observed in which an initial fast step was followed by a relatively slow second reaction. The stoichiometries of these overall biphasic reactions were determined by spectral titration of (CH J - C o L with standard solutions of appropriate metal ions. The same technique employed for the titration of the fast 1/1 reactions was utilized with the exception that the reactions were allowed to proceed l o completion. The results of these titrations for Zn , C d , and Pb are presented in Figure 2. It is readily apparent thpt the end points for all three metal ions are close to a molar ratio (M /complex)equal to 0.5; i.e. one mole of added metal ion reacts with two moles of ( C H L L C o L . This is consistent with a process in which th in the initial fast reaction ?

2

3

+

7

+

+

(CH ) CoL 3

+ M

2

2

—fast

+

>

CH CoL* 3

+ CH M 3

+

(11)

in a subsequent slower reaction ( eqn. 12). The low molar ratio observed (CH ) CoL 3

+ CH M

2

3

slaw

+

>

CH CoL 3

+ (CH^M

+

(12)

2+ for the Zn titration is in agreement with the faster (Table I) protonolysis of C H - Z n by i - C H O H (eqn. 8). Thus the reaction is catalytic in the sense that ~ Zn is continuously regenerated and reacts further with ( C H J C o L (eqn. II). Support for the scheme outlined here comes from experiments conducted by Espenson et^al. (16) on the methyl transfer reactions of (CH^jLCoL and similar complexes with the analogous C H H g species (eqn. D ) . These reactions occur with the indicated 1:1 stoichiometry and +

+

3

7

+

2

3

(CH ) CoL 3

2

+ CH Hg 3

»

+

CH CoL 3

+

+ (CH^Hg

(13)

proceed to completion. Reaction also occurs with C ^ H ^ H g * (and probably with any other mono-organomercury derivative) as the acceptor, and with (C^H J L C o L and ( C ^ H ^ L C o L as alkyl or aryl donor complexes. ine proposed diméthylzinc, dimethylcadmium and dimethyllead products (eqn. 12) are extremely reactive, and are readily decomposed by compounds (including alcohols) which contain active hydrogen (11,13). As a consequence, the rapid formation of methane was anticipatecTînlthese^ reactions. In fact, this was^observed upon reacting ( C H J C o L with C d or Pb in a molar ratio (M ^/complex) equal to 0.5. Tms observation further corroborates the reaction scheme^ The reaction of ( C H ) C o L with C d under these conditions results in the methane evolution profile shown in Figure 3. Two distinct steps are observed. In the first step 50% of the theoretical amount of methane (determined by the acid hydrolysis of ( C H J C o L ) is evolved in a matter of minutes. This is followed by a slow second step which liberates the remaining methane over a period of 150 hr. The methane evolution pattern 2

+

3

2

+

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

WEBER

A N D

Organometallic Intermediates

wiTMAN

l.5|

0.5h-

0.1

0.2

MOLAR

0.3

RATIO,

0.4

[M

2 +

]/

0.5

0.6

[(CH^COL]

Figure 2. Representative spectral titrations for the over all reaction of (CH ) CoL with Zn \ Φ; Cd \ Q- and Fh \ O . s

2

x

2

2

100

L_ Cd

<->

2+

>···

50

• 30

60

3000 TIME,

6000

1

9000

12000

MIN.

Figure 3. Rate of methane evolution for the reac tion of (CH ) CoL with Cd * ([Cd +]/[(CH ) CoL] = 0.5) s

t

2

2

s

x

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS A N D ORGANOMETALLOIDS

254

seen here is consistent with a process in which the ( C H J - C d product formed in eqn. 12 immediately reacts with i - C ^ H j O H to form the wellknown tetramer [CH^Cd ( i - O C H ) ] ^ (15),"ano C H ^ (eqn. 14). The more 3

(CH ) Cd 3

L

2

"^|"7°

>

H

7

lM[CH Cd(i-OC3H )]^ + C H ^ 3

7

(M

stable tetramer is then slowly decomposed by i - C ^ H ^ O H to liberate the remaining methyl group (eqn. 15). This interpretation is in agreement with 1/4 [ C H C d 0 - O C H ) ] 3

3

7

ψ

^~sïffi

Cd 0 - O C H )

y

OH

3

7

+ CH^

2

05)

recent kinetic and N M R studies of the reactions of ( C F U k C d and (C^H j L C d with a variety of alcohols R O H which show fnat the [ Qi-CcI(OR) L products are formed much more rapidly than the C d ( O R ) products (17). * Additional evidence in Figur| 4. In this experiment ( C H - L C o L was titrated with a standardized C d solution in the usual manner while simultaneously monitoring the quantity of methane evolved. The amount of methane liberated after each addition of titrant was determined by G L C , and compared to the theoretical value which was measured by the acid hydrolysis of ( C H . ) C o L . Figure 4 clearly shows the expected 2/1 (complex/Cd ) stoichiomerry (eqn. 16 and 17). In addition it is evident that 50% of the expected amount 9

+

+

2

(CH ) CoL + C d 3

2

(CH ) CoL + C H C d 3

2

>

2 +

3

CH CoL 3

>

+

+

+ CH Cd

CH CoL 3

(16)

+

3

+ (CH ) Cd

+

3

2

(17)

of methane is liberated upon reaching the end point, thus proving the transient existence of ( C H J C d . Perhaps the best evidence for the reaction scheme proposed here comes from the isolation of the well-known tetramer [ C H C d ( i - Q C H ) L as a product of the reaction of excess ( C H J C o L with C d * \ecjn. 16 and 17). The reactions were run using a moiar ratio [ C d + 1 / complex = 0.5 in i - C - H ^ O H . The white isopropoxide compound was recovered by f r e e z ê - d r y m g the reaction mixture and subliming the residue. The tetramer was characterized by its reaction with 1M HCIO^ to yield C H ^ and by comparing its mass spectrum to that of an authentic sample prepared from the reaction of i - C o H O H with ( C H ) C d . The molecular ion peak at m/e 744 confirms tne polymeric nature of this compound. The reaction of ( C H - L C o L with Pb is analogous to the reaction with C d in certain respects. The titration data in Figure 2 is again consistent with a process in which CH-Pb" ", formed in an initial fast reaction (eqn. 18), reacts with a secona mole of ( C H ) C o L to 2

3

3

7

2

7

2

3

+

2

2

+

+

1

3

(CH ) CoL + P b 3

2

2 +

-iôSÎ

form ( C H J P b (eqn. 19). 2

>

CH CoL 3

+

2

+ CH Pb 3

+

Although divalent organolead compounds are

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

(18)

15.

WEBER

AND

(CH ) )CoL + C H P b 3

2

3

255

Organometallic Intermediates

wiTMAN

— ~ — >

+

CH CoL 3

+ (CH^Pb

+

(19)

typically very unstable and frequently disproportionate into organolead(IV) species and lead metal (eqn. 20) 03), this reaction was not observed here. 2R Pb

>

2

R^Pb + Pb°

(20)

Instead, the reaction of ( C F U k C o L with P b (Pb /complex = 0.5) resulted in the methane evolution profile shown in Figure 5, and the simultaneous formation of a light-brown precipitate. The fact that only 50% of the methane is ultimately observed suggests that the precipitate is a stable [CH^Pb ( i - O C ^ H ) ] compound formed by the protonolysis of ( C H ) P b (eqn. 2lX Presumably, the [ C H P b G - O C H ) ] product Iis 2 +

2+

7

3

2

3

(CH ) Pb + i - C H O H 3

2

3

3

7

»

7

polymeric in analogy to [ C H - C d ( i - O C - H j ] ^ since lead alkoxides reportedly exist as polymeric chains liriîcea by oxygen atoms (18). The addition of H 0 to the solution results in immediate evolution of the remaining m é t h a n e and dissolution of the precipitate (eqn. 22), thus +

3

CH Pb G-OC H) + H 0 3

3

3

> CH^ + Pb

+

+ i - C ^ O H

2 +

(22)

lending further support to this interpretation. Unfortunately, elemental analysis of the isolated precipitate did not confirm the presence of C F U P b ( i - O C H ) . The analysis, which indicated that Ν was present, suggested that the product was contaiminated with C H - C o L * . This was confirmed by dissolving the precipitate in H 0 or H 0 and comparing the spectrum of the resulting orange colored solution to that of C H C o L . Cold washing with i - C ^ F U O H did not improve the analysis indicating that C H C o L is tightTy nela. The fact that analogous precipitates were not observed in the reactions of ( C H J ^ C o L with excess Pb , or upon rjixing solutions of C h L C o L * and Pb precludes the presence of Pb adducts as have been isolated from the reactions of Hg with RCo(salen) complexes (19). Despite these negative results, however, the formation of C h L a n c T i - C - H - O H upon dissolution of the precipitate in H 0 suggests that C f L P o ( i - O C H J is at least a minor product of these reactions. 3

7

2

+

3

+

3

3

+

+

+

+

+

2

+

3

Kinetics of the Reactions of ( ) 2 C o L with Excess Zn * Cd \ The kinetic behavior of the 1:1 reaction (eqn. 6) of ( C H ) C o L with Zn and C d was investigated by monitoring the decrease in absorbance due to the complex at 412 nm. These reactions exhibited half-lives on the order of a few milliseconds, and were studied us^ng the stopped-flow technique. The corresponding reaction with Pb * was not studied due to the unexplained extreme sensitivity of the reaction to oxygen, which resulted in the formation of brown precipitate. Plots of the data in the form l n ( A - A ) versus time were invariably linear over at least four half-lives for both metal ions. Since the metal ions were in excess over the complex, the observed kinetics were pseudoC H

3

3

2

+

œ

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

+

ORGANOMETALS

50

AND

ORGANOMETALLOIDS

··· · ·

h 2+

Pb

25

—éïùù

30 TIME,

12(300

M IN.

Figure 5. Rate of methane evolution for the reaction of (CH ) CoL with Pb * ([Pb *]/[(CH ) CoL] = 0.5) s g

2

2

3

t

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

15.

WEBER

A N D

Organometallic Intermediates

wiTMAN

+ "Ό

υ oo

«A CM

(N

ΙΑ Ι^ν

(Ν νθ

Ο «Α

iA

Ό

ε 3

ε

υ + (Ν

Ο

ο

CM C

Ν

•

Ο

ζ*

ο

· · ο

Ο ON

00

2 Ν

+

(Μ fil

«Α (Ν 1^

Ο

ON

•A

c4

NO

CM

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

258

ORGANOMETALS A N D ORGANOMETALLOIDS

first-order. A least squares analysis of the slopes of these lines yielded values for the observed rate constants (k . ) which ranged from 85 to 180 sec" for Zn , and 108 to 231 sec f o r C d . Thejnetal ion depend ence of the reactions was determined by varying [Zn ] and [Cd ] from 7.25 χ 10" to Ζ 2 5 χ 10" M while maintaining the ionic strength constant at 1.8 χ 10" M . The apparent second-order rate constants decreased markedly with increasing metal ion concentration throughout the range studied as can be seen in Table II. A reasonable explanation of this phenomenon is that there is a rapid pre-equilibrium between the reactants and a substitutional^ labile hi adduct that is being saturated as the concentration of the metal ion is increased (eqn. 23). This process is followed by rate-determining +

R CoL

+ M

2

2

+

g

ft

•

M

>

2 + e

+

R CoL

(23)

2

decomposition of the adduc M

2 +

'R CoL

isfeent

2

*

R

M

+

+

RCoLsolv*

(24)

this scheme. If Κ = kx/k^ and k r , k > > k., the rate law (eqn. 25) is derived (20). Plots of the reciprocal of the observed pseudo-first-order rate -d[R CoL] 2

=

^Κ[Μ

dt

2

+

]^ α>υ

(25)

2

1 + Κ [M +] 2

constant versus the reciprocal of the metal ion concentration are linear in agreement with this scheme. The data indicating this linear relation ship are presented in Figure 6. The kinetic and equilibrium parameters were extracted from the slopes (1/k.K) and intercepts (1/k.) of these lines and are summarized in Table III. Table III. Summary of Kinetic and Equilibrium D a | a for the Reaction of ( C H - ^ C o L with Zn and C d . a

Electrophile Zn

2 +

Cd

2 +

a

A t 22.2

C,

10" K(M" ) 3

lO'^feec" )

1

1

lO'^KflVfW" ) 1

3.8

3.8

1.4

10.6

4.0

4.2

μ = 1.8 χ 10" ( L i C l O ^ F ^ O ) in i - C ^ O H . 3

The proposed first-order decomposition of the adduct (eqn. 24) is not easily distinguished from a second-order reaction of metal ion with free R C o L (eqn. 26) since both processes lead to the same kinetics (20). 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

15.

WEBER

A N D

wiTMAN

Organometallic Intermediates

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

259

ORGANOMETALS AND ORGANOMETALLOIDS

260 R CoL 2

+ M

Z

»

+

R M + RCoL*

(26)

+

However, we favor the former reaction (eqr^ 24) in view of the nearly identical k. values observed for both the Zn and C d reactions. If the leaving group R M is loosely held in the adduct similar k. values are expected. The slight difference in k . [ C d ] > k. [ Zn ] may reflect the size difference and thus the lability of the leaving group in the order R C d > R Z n . Presumably, adduct decomposition occurs by way of a five-coordinate intermediate since C H ^ is known to promote the dissociation of trans ligands in octahedral cobait complexes (20). Furthermore, five-coordinate alkyl cobalt intermediates are well known in the anation reactions of [ R C o ( L ) H 0 ] and alkylcobaloximes (21). It is not surprising that adduct formation occurs in these reactions since 1:1 adducts wyere detected in the analogous reactions of the Group IIB metal ion Hg * with several monoalkylcobalt complexe +

+

+

+

+

2

+

Conclusions The reactions of ( C H J C o L with Z n , C d , and P b in i - C H O H show unexpected stability for C H - Z n , C H - C d , and C H ~ P b in a protic medium. The fact that the C H ^ ^ T species are stable enough to react with a second mole of ( C H - L C o L accentuates their unexpected behavior. This chemistry demonstrates that organometallic compounds thought incapable of existing in the aquatic environment might occur-and eventually be found. For example the ( C H - L P b obtained from Pb by microbial processes (6, 7) might arise via tne C H - P b or (CH J P b intermediates observed in this work. 2 +

2

+

2 +

2 +

+

3

7

+

+

+

2

Literature Cited Witman, M. W. and Weber, J. H., Inorg. Chem. (1976), 15, 2375. Witman, M. W. and Weber, J. H., Inorg. Chem. (1977), 16, 2512. Witman, M. W. and Weber, J. H., Inorg. Chim. A c t a (1977), 23, 263. Ridley, W. P., Dizikes, L. J., and Wood, J. M., Science (1977), 197, 329. Dizikes, L . J., Ridley, W. P., and Wood, J. M., J. A m . Chem. Soc. (1978), 100, 1010. 6. Schmidt, U . and Huber, F., Nature (1976), 259, 157. 7. Wong, P. T . S., Chau, Y . K., and Luxon P. L., Nature (1975), 253, 263. 8. Witman, M. W. and Weber, J. H., Synth. React. Inorg. Met.-Org. Chem. (1977), 7, 143. 9. Agnes, G., Bendle, S., H i l l , H . A . O., Williams, F. R . , and Williams, R . J. P., Chem. Commun. (1971), 850. 10. Magnuson, V. E., Ph.D.Dissertation, University of New Hampshire, 1974. 11. Coates, G . E . , Green, M. L., and Wade, K., "Organometallic C o m pounds", Vol. I, pp. 121-147, Methuen and C o . L t d . , London, 1967. 12. Swan, J. M . and Black, D . St. C., "Organometallics in Organic Syn theses", p. 39, Chapman and Hall, London, 1974. 13. Shapiro, H . and Frey, F . W., "The Organic Compounds of Lead", Inter science Publishers, New York, 1968.

1. 2. 3. 4. 5.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

15.

Weber and witman

Organometallic Intermediates

261

14. Herold, R. J., Aggarwal, S. L . , and Neff, V., Can. J. Chem. (1963), 41, 1368. 15. Coates, G. E. and Lauder, Α., J. Chem. Soc. (A) (1966), 264. 16. Espenson, J. H . , Fritz, H. L . , Heckman, R. Α., and Nicolini, C . , Inorg. Chem. (1976), 15, 906. 17. Emptoz, G.andH u e t , F . , J. Organometal. Chem. (1974), 82, 139. 18. Amberger, E. and Grossich, R. H . , Chem. Ber. (1965), 98, 3795. 19. Tauzher, G . , Dreos, R., Costa, G . , and Green, M., J. Organometal Chem. (1974), 81, 107. 20. Wilkins, R. G . , "The Study of Kinetics and Mechanisms of Reactions of Transition Metal Complexes", pp. 26-31, Allyn and Bacon, Inc., Boston, 1974. 21. Costa, G . , Mestroni, G., Tauzher, G., Goodall, D. M., Green, M., and Hill, H. A. O., Chem. Commun. (1970), 34. 22. Adin, Α., and Espenson Discussion T1

D. W. MARGEP M (Purdue University): When you had the metal precursor complex with the dimethylmetal system, did you have d i r ect evidence of that complex? There i s a third kinetic mechanism which could explain the data; that i s , a steady-state, r a t e - l i m i t ing phenomenon rather than a pre-equilibrium. WEBER: Did we get direct evidence for the dimethylcadmium adduct? We didn't. If that mechanism has the same rate law, I'm not sure we could differentiate without direct evidence which mechanism i s correct. Would the mechanism you mention give the same kind of rate constant with different electrophiles? MARGERUM: Yes, i t could give exactly the same type of inter pretation, but you would never be able to spot the intermediate, because i t would never be there in appreciable concentrations. Your equilibrium constant suggests that you ought to be able to see some direct evidence of the complex. WEBER: We do see slight spectral changes during the reac tion; shifts in the absorption which might be indicative of that kind of adduct. MARGERUM: That might be sufficient, and that ought to be adaptable to quantitatively check your proposal. J . J . ZUCKERMAN (University of Oklahoma): I wasn't quite sure of the medium in which those reactions were carried out. Was this isopropanol or was that wet isopropanol? WEBER:

That was dry isopropyl alcohol.

ZUCKERMAN:

I was wondering about the implications for protic

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

262

ORGANOMETALS AND ORGANOMETALLOIDS

media. Would the methylcobalt compound simply act as a h y d r o l y s i s c a t a l y s t f o r the metal ions t o produce oxy-hydroxides o r hydroxi d e s which would then p r e c i p i t a t e w i t h the e v o l u t i o n of methane from the c o b a l t compound? WEBER: media.

You mean i f we were going the r e a c t i o n s i n a q u a t i c

ZUCKERMAN: Yes. Would the products be the hydroxide and methane from t h e c o b a l t ? WEBER: The dimethyl complex does r e a c t w i t h water. The r a t e constant was about 80 M"~^s~l i f you add water t o i s o p r o p y l a l c o h o l . I'm p r e t t y sure i t would r e a c t much more q u i c k l y w i t h these metal i o n e l e c t r o p h i l e s d I predict that k i n d f metal hydroxide would p r e c i p i t a t e ZUCKERMAN: I n the case of your a l k y H e a d compound, i s that a homogeneous system a t that p o i n t o r has that a l k y H e a d a l k o x i d e complex removed i t s e l f from the medium? I s there a w e t t a b i l i t y problem i n t h a t case? WEBER: I n both cases, w i t h the cadmium and w i t h the l e a d , a f t e r you get 50 percent of methane you get a white o r o f f - w h i t e p r e c i p i t a t e . I n the case of cadmium, i t ' s that methylcadmium isopropoxide tetramer. I n the case o f l e a d , there i s a l s o precipitate. F. HUBER ( U n i v e r s i t y o f Dortmund): D i d you f i n d out what happens on t h e o x i d a t i o n of your monome thy H e a d product? I understood t h a t there i s a h i g h s e n s i t i v i t y f o r o x i d a t i o n of the product. WEBER: We had no success i n studying the r e a c t i o n s i f we allowed oxygen i n t o the r e a c t i o n mixture. We got s o l i d products of some k i n d . These might have been l e a d peroxides o r l e a d oxides. We could not i d e n t i f y any of t h e lead p r e c i p i t a t e s by u s i n g x-ray powder p a t t e r n s ; there were, no lead metal o r l e a d o x i d e s , f o r example, as a product. HUBER: D i d you make a normal elemental a n a l y s i s of the product, e.g., C t o Pb r a t i o ? WEBER:

I t d i d not analyze t o anything that we could f i g u r e

out. HUBER: A second question. I s t h i s a s p e c i f i c r e a c t i o n of your c o b a l t compound, o r d i d you t r y other methylcobalt species and r e a c t them w i t h P b ? 2 +

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

15.

WEBER

A N D WITMAN

Organometallic Intermediates

263

WEBER: No, we reacted only t h i s p a r t i c u l a r dimethylcobalt compound. I'm convinced that w i t h a couple o f other l i g a n d s Dr. Espenson c i t e d , you would get the same k i n d o f r e a c t i o n s . HUBER: D i d you f i n d the l a s t 50% o f your methane from the lead compound i f you add acid? WEBER: I n the case o f the cadmium r e a c t i o n , you j u s t w a i t about 100 o r 150 hours t o get the second h a l f o f the methane. I n the l e a d r e a c t i o n , i f you w a i t even 200 hours, you do not get the second h a l f a t a l l . However, any time you put i n a c i d you i n s t a n taneously get the second h a l f . HUBER: I s n ' t i t p o s s i b l e that you have a d i s p r o p o r t i o n a t i o n , and when you add a c i d yo lead? WEBER: We looked f o r v a r i o u s products i n t h i s r e a c t i o n . We considered the p o s s i b i l i t y of d i s p r o p o r t i o n a t i o n ; we found no t e t r a m e t h y l l e a d ; we found no hexamethyldilead, which i s another l o g i c a l product; we found no l e a d metal. So we could f i n d no s i g n of d i s p r o p o r t i o n a t i o n i n t h i s r e a c t i o n . RECEIVED

August 2 2 ,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

16 C h l o r a m i n e E q u i l i b r i a a n d the K i n e t i c s of D i s p r o p o r t i o n a t i o n in A q u e o u s S o l u t i o n 1

2

EDWARD T. GRAY, JR., DALE W. MARGERUM, and RONALD P. HUFFMAN Department of Chemistry, Purdue University, West Lafayette, IN 47907

Introduction The chlorination o ues to enjoy popularity because of the low cost, simplicity, and great effectiveness of the technique. Although the process of disinfection is not well understood, it is known that as chlorine is introduced into waste water, the amines present react rapidly with the chlorine to form chloramines. Chloramines have been shown to be toxic to fish when present at lower than ppb levels (1). However, quantitative analytical procedures sensitive at this level are not available. The high toxicity to aquatic life has prompted investigations in this laboratory aimed at extend ing existing analytical techniques to lower levels of sensitivity. One question which must immediately be addressed in this work is the effect of changing pH upon the distribution, or the very existence, of the chloramines present in a sample taken for analysis. In the case of ammonia, for example, the equilibria of the chloramine species can be expressed by eq 1-3. Equation 1 Κ NH + HOC! ( 3

+

H Y D

> • NHC1 + H0 2

2NHC1 + H JVj?_> 2

(1)

2

NHC1 + NH 2

+

4

(2)

'Current address: Dept. of Chemistry, U. of Hartford, W. Hartford, CT 06117 Current address: Upjohn Co., P.O.B. 685, Laporte, TX 77571

2

0-8412-0461-6/78/47-082-264$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

16.

GRAY

E T

3NHC1 + H 2

Chloramine Equilibria

AL.

+

>

X p T

c

2NC1 + N H 3

might also be expressed, NH

3

+ OCl"

(

» M

Values o f Κ

Η γ ο

4

265

(3)

+

i n basic media, as shown i n eq 4.

NH C1 + OH"

(4)

2

,

K^p, and Kpj have h i s t o r i c a l l y been

c u l t to o b t a i n . C o r b e t t ,

M e t c a l f , and Soper (2j

diffi

reported a value

for K o f 3.6 χ 1 0 M" (15°C, Κ = 4.7 χ 1 0 ' Μ , Κ of πτυ Q w a H0C1 = 2.7 χ 10 M) while Anbar and Yagil (3) o f f e r evidence 9

y v n

1

1 4

2

that v f the number can b greater than 1 0

1 5

M" -8

for H0C1 = 4 χ 10

1

(27.3°C,

M).

Bridging t h i s large gap, Granstrom

c a l c u l a t e d the value for K M"

μ = 1.0 M, c a l c u l a t e d using a Κ (4)

from k i n e t i c data to be 2.4 χ 1 0 ^

u v n

(25°C, μ = 0.45 M, K o f H0C1 = 2.9 χ 10~° M). a The e q u i l i b r i a shown i n eq 2 and 3 have not been evaluated

experimentally because o f the reported l a c k o f s t a b i l i t y o f the p o l y c h l o r i n a t e d species

(2_,

able to estimate values o f 1 0

6_, 7). 6

M"

1

However, J o l l y (8)

and 1 0

rium constants K^p and Kp^, r e s p e c t i v e l y . data o f Chapin (5)

4

M"

1

was

for the e q u i l i b

This was done using

and C o r b e t t , M e t c a l f , and Soper (2)

even

though the l a t t e r authors conclude that t h e i r data do not r e p r e sent an e q u i l i b r i u m c o n d i t i o n . (5J,

Morris (9)

Using the same data o f Chapin

c a l c u l a t e d K^p to be 2.3 χ 1 0

7

M' . 1

Using the

h y d r o l y s i s constant o f C o r b e t t , M e t c a l f , and Soper {2), estimates o f l^p and K p , J o l l y (8) T

electrochemical

and his

was a l s o able to estimate

p o t e n t i a l s for the ammoniacal chloramines.

In the present work, a l l

chloramine s o l u t i o n s are

prepared

with excess amine present and are manipulated with the use o f a double-two-jet in stopped-flow

tangential mixing system, s i m i l a r to those used spectrophotometers.

This assures

rapid and

e f f i c i e n t achievement o f homogeneity ( l e s s than 100

\is).

Chloramine s o l u t i o n s produced in t h i s manner are s i g n i f i c a n t l y

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

266 more s t a b l e

than those produced by hand m i x i n g ; they have e x h i

bited no l i g h t s e n s i t i v i t y ; and experimental consistently duplicated.

r e s u l t s can be

Monochloramine s o l u t i o n s prepared

t h i s manner are s t a b l e at room temperature,

undergo

in

dispropor-

t i o n a t i o n to NHC1 without apparent side reactions at pH <5,

and

2

r e a d i l y form NCI^ i n more a c i d i c s o l u t i o n s . dichloramine are s t a b l e

Monochloramine and

i n the presence o f each other i n a c i d i c

s o l u t i o n for over 24 h but i n the presence o f NCI amines slowly decompose. allowed HYD

K

a

t

These reproducible

the d i r e c t experimental e c

the c h l o r

3

properties

have

determination o f K^p, Κργ, and

l î 1 ibirium. u

Values o f K^p for chloramines prepared

from amines other

than ammonia a l s o have been determined i n t h i s work. determine Κ^ ρ for some o f these other chloramine γ

e q u i l i b r i a o f the type shown i n eq 5 have been NH C1 + RNH 2

2

;

L RNHC1 + NH

In order to

species,

established. (5)

3

These K^p and Κ^ ρ values allow the c a l c u l a t i o n o f e l e c t r o c h e m i γ

cal

potentials

for these

chloramines.

Results and Discussion I.

Equilibria Determination o f l ^ p .

Monochloramines o f ammonia, methyl -

amine, β - a l a n i n e , and g l y c y l g l y c i n e are prepared

i n t h i s work by

r a p i d l y mixing s o l u t i o n s o f these amines with a s o l u t i o n o f hypo c h l o r i t e at pH * 11. and the t r a n s f e r complete.

The amine concentration i s kept i n excess

o f the c h l o r i n e i s observed to be rapid and

Dichloramines are formed upon a c i d i f i c a t i o n .

Figure 1

i s an example o f r e p e t i t i v e spectra o f a s o l u t i o n o f NH C1 2

i t i s adjusted

to pH 3 . 8 .

seen i n the f i r s t spectrum. hour p e r i o d , the absorbance and the absorbance

after

The λ „ o f NH C1 at 243 nm can be max c 0

In subsequent at 294 nm U

at 243 nm decreases

m

a

s p e c t r a , over a onex

o f NHC1 )

accordingly.

2

increases Two c l e a r

i s o s b e s t i c points at 277 nm and 231 nm i n d i c a t e that the t o t a l

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

16.

GRAY

ET

available

267

Chloramine Equilibria

AL.

c h l o r i n e i s constant during the r e a c t i o n .

Equilibrium

mixtures o f monochloramine and dichloramine are observed to be quite stable

for at l e a s t 24 h and have shown no s e n s i t i v i t y to

room l i g h t when prepared in t h i s manner. Values o f the molar a b s o r p t i v i t y o f NH^Cl at various wave lengths are e a s i l y obtained because o f the t o t a l conversion from hypochlorite and NH^ in basic media with excess ammonia.

How

ever, s i m i l a r values of NHC1 presented i n the l i t e r a t u r e vary -1 -1 -1 -1 from 265 M cm (6) to 300 M cm (10) and our present work 9

shows that NHCU i s not f u l l y formed i n s o l u t i o n at e q u i l i b r i u m . I f the molar a b s o r p t i v i t values o f [NH^Cl] and [NHCl D at e q u i l i b r i u m could be determined 2

from eq 6 and 7, where A A

2 9 4

= b(e^

[H0C1]

C 1

[NH Cl]

i s the absorbance

2 g 4

o f the mixture at

+ egJ^CHHC^])

2

(6)

= [ N H C 1 ] + 2[NHC1 ]

T

2

(7)

2

294 nm, b i s the pathlength, e

2 g

|

C 1

and

are the molar

a b s o r p t i v i t i e s o f monochloramine and dichloramine at 294, respectively, [Η001]

refers

γ

to the t o t a l a v a i l a b l e c h l o r i n e i n

terms o f the concentration o f H0C1. Solutions o f NH C1 at constant [NH~]

were brought to NHCl various values o f pH in the range 3 . 5 - 6 . 0 . Since e was not well known, e q u i l i b r i u m concentrations o f NH C1 and NHCl« and NHCl 9

T

2

2 g 4

9

values o f K

M D

were c a l c u l a t e d while varying e

2 2 g 4

by i t e r a t i o n .

The r e l a t i v e standard d e v i a t i o n o f Κ μ reached a minimum when Π

1

ΝΗΠ ε

294

=

cm

2 6 7

(4.3 ± 0.6)

1

χ 10

6

.

Μ~ . Ί

The value o f

for t h i s condition was

The molar a b s o r p t i v i t y i s i n agreement

with that reported by Morris (6)

and K^

ment with the estimate o f J o l l y

(8).

D

i s i n remarkable

S i m i l a r treatment o f methyl ami ne, β-alanine, g l y c i n e give the K^p values absorbance

i n Table I.

agree

and g l y c y l -

Figure 2 shows the

at 304 nm o f e q u i l i b r i u m mixtures o f N - c h l o r o g l y c y l -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

268 Table Summary o f E q u i l i b r i a (μ

I

= 0.50 M (NaC10 ),

25.0°C).

4

Κ NH

+ HOCl «

3

NH C1 + HOCl -< 2

2NH C1 + H 2

1 .5

X

-± NHC1 + H 0

2,.3

X

2CH NHC1 + H 3

„

, ' NHC1

"

+

+ H

+

+ NH

2

3

7

h

+ + Η

2glycylglycine-Cl

2

CH NC1

J

t

23-alanine-Cl

2

2

\

+

NH C1 + HgO

_1

2

4

+

+ CH NH 3

β-alanine-Cl + β-alanineH

3

+

+

2

glycyl g l y c i n e - C l

10 M 8

_ 1

4 .3

X

IOV

3 .5

X

i o V

1

5 .2

X

i o V

1

1

5-1 1.42 χ 10 M

+

g l y c y l glycineH β-alanine +NH C1 ; z = Z Î NH 2

CH NH 3

2

+ NH C1 <

„

2

Ï. NH

β-alanine + HOCl Z=î β-alanine-Cl CH NH 3

2

+ HOCl ;

3

+ β-alanine-Cl

250

3

+ CHgNHCl

830

β-alanine-Cl

+ HOCl ^Σϊ

CH NHC1 + HOCl

3

*

+ H0

2

1.4 χ Ί Ο

2

CH NHC1 + H 0 3

3

M"

1

1.2 χ 1 0 Μ "

]

+ H0

7.5 χ

2

g l y c i n e and Ν,Ν-dichloroglycylglycine v s . - l o g [ H ] . l i n e i s the c a l c u l a t e d f i t o f the resolved e q u i l i b r i u m γ

to a mixture o f NHCl hydrogen

(MO

M) i s

Figure 3 gives

2

2

4

This peak subsequently

efficient

forms a maximum a t

decreases

as the absorb

ance at 336 grows, i n d i c a t i n g the formation o f NCI^. clean i s o s b e s t i c

converted

spectra o f a s o l u t i o n o f

M NH C1 i n 1 M HC10 which f i r s t

294 nm (NHC1 ).

constant.

and NCI^ within 5 minutes by r a i s i n g the

ion concentration to 0.01 M o r higher using

mixing techniques. 2.5 χ 10

2

Monochloramine

i o V

The s o l i d

+

Determination o f Κρ .

11

14

£

2

t J

3,8 χ 10'"M"

2

B-alanine-Cl

' CH NC1

c

+ H0

J3 -l

The two

points at 277 nm and 321 nm again i n d i c a t e no

available

c h l o r i n e i s being reduced i n the t r a n s i t i o n from NHCl

to NCI -J-

The dotted l i n e spectrum, taken a f t e r one hour, shows a

s l i g h t decay o f the e n t i r e spectrum.

Therefore,

the presence

2

of

NCI^ does introduce some i n s t a b i l i t y to the e q u i l i b r i u m mixture.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Chloramine Equilibria

GRAY E T A L .

Figure 1. Spectral changes following a pH jump, from pH 11 to 3.8, of a mono chloramine Solution (kmax = 243) showing the forma tion of dichloramine (k = 294) as equilibrium is approached. max

Isosbestic points are 277 and 231 nm. (Scans taken over a period of 30 min, [NH ] = 9 X I0" M, [HOClJj, = 1.5 X J0" M 1.00-cmpath length, S

T

3

3

230

270

31

Wavelengt

Figure 2. Determination of the disproportionate equilib rium constant of N-chloroglycylglycine. The solid line is the calculated fit using Kj) = 1.42 X 10 for 2RNHCI + H = RNCl, + RNH \ ([Glycylglycine = 1.13 X i 0 M , [HOClJj. = 1.40 X i 0 M , 2.00-cm path length, μ = 0.50M (NaClOJ, 25.0°C). s

I8

+

S

s

-log

+

[H ]

s

Figure 3. Spectral changes following a pH jump, from pH 11 to 1 M HClO of a monochloramine solution showing the loss of NHCl (kmax = 294 nm) and the for mation of NCl (k — 336 nm). it

t

s

max

Isobestic points are at 277 and 321 nm. The dotted line, taken 1 hr after pH jump, shows a slight decay. (Scans taken over a period of 1 hr [NH,] = 10*M, [HOClh = 2.5 X iO-'M, O.50M (NaClOJ, 25.0°C.) T

320

360

Wavelength, nm

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

270

ORGANOMETALS AND ORGANOMETALLOIDS

Since the t o t a l decays s l o w l y , to be s t u d i e d .

available

chlorine in a NHCl /NCl 2

mixture

3

t h i s value must be determined for each e q u i l i b r i u m Therefore,

the molar a b s o r p t i v i t y o f the

NHC^/NClg mixture at 321 nm i n terms o f t o t a l a v a i l a b l e was e s t a b l i s h e d before s i g n i f i c a n t decay had o c c u r r e d . molar a b s o r p t i v i t y was determined to be 54 M"

chlorine This

cm" .

1

1

Solutions o f various hydrogen ion concentrations were prepared and K^j was c a l c u l a t e d i n the same manner as described

for K^p, except that the absorbance was

nm and e~~Î3 was i t e r a t i v e l y v a r i e d .

Jolly's

exhibited

= 272 M

cm"

This molar a b s o r p t i v i t y i s s i i g h t l y higher

than the values o f 260 M" v i o u s l y reported.

fol 1 owed at 336

The value o f K

a minimum r e l a t i v e standard d e v i a t i o n when £ „ 336 and Kp-j. = 130 * 40 M.

previously

1

cm"

1

(12J and 265 M"

The value o f Κρ

γ

1

cm"

1

(6)

pre

i s s i g n i f i c a n t l y lower than

( J J estimate o f 10 M. 4

Confirmation o f Κ^γρ-

The d i s p a r i t y o f reported values

Κ γρ necessitated a réévaluation o f the problem. Η

The c h l o r i n e

atom can be removed from monochloramine v i a two p o s s i b l e both o f which have been observed. NH C1 + H 0

• NH

NH C1 + OH"

• NH 0H + C l "

2

2

2

pathways,

Equation 8 i s the h y d r o l y s i s

+ HOCl

3

of

(8) (9)

2

o f NH^Cl with the c h l o r i n e atom bound to the hydroxide as the product.

Equation 9 involves hydroxide attack on nitrogen to

give hydroxylamine and release c h l o r i d e i o n .

It i s eq 8 which i s

involved in Κ ρ and eq 9 which i s the r e a c t i o n Anbar and Yagil Ηγ

(3)

conclude i n t e r f e r e s

to the extent that Κ^γρ cannot be

measured at e q u i l i b r i u m . s h i f t the e q u i l i b r i a OCT" + H 0) 2

Note that high base concentrations

i n both eq 9 and eq 8 (due

to the r i g h t .

will

to HOCl + O H " — •

However, we f i n d that i n 0.1 M NaOH the

rate o f the r e a c t i o n i n eq 8 i s approximately 100 times that o f eq 9 and that conditions can be chosen to permit the e q u i l i b r i u m

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

16.

GRAY

E T

AL.

Chloramine Equilibria

in eq 8 to be measured without serious Our experimental

value o f K

H y D

271 i n t e r f e r e n c e from eq 9.

i s 1.5 χ Ι Ο * Μ ~ , which i s i n 1

approximate agreement with Granstrom's value

Ί

(4).

The r e s u l t can be expanded to c a l c u l a t e h y d r o l y s i s constants for other monochloramines.

Methylchloramine and N - c h l o r o - β -

a l a n i n e do not decompose r e a d i l y by e i t h e r eq 8 or eq 9» even i n 1 M NaOH.

However, when β-alanine i s mixed with NH^Cl at pH 8

and the absorbance spectrum i s scanned r e p e t i t i v e l y , a set o f spectra s i m i l a r to that shown i n F i g . 4 i s o b t a i n e d .

The s i n g l e ,

sharp i s o s b e s t i c point i n d i c a t e s the establishment o f an e q u i l i b r i u m mixture o f NH^C used with CH^NH^ i n place o f β-alanine and e q u i l i b r i u m constants for the t r a n s f e r o f c h l o r i n e , Κ in Table I.

(eq 5) were determined as shown

γ

Since eq 5 i s the summation o f the h y d r o l y s i s c o n

stants o f two chloramines, K

values were c a l c u l a t e d for

H Y D

N-

c h l o r o - 3 - a l a n i n e and methylchloramine and are given i n Table I f the electrochemical p o t e n t i a l s o f Latimer (11) HOCl, and 0C1" are used as a point o f r e f e r e n c e , potentials

for

Cl

2 >

appropriate

for chloramine species o f NH^, β - a l a n i n e , and CH^NH^

can be c a l c u l a t e d .

These are given i n Table I I .

are c o n s i s t e n t with the previous

These

potentials

reports o f the strong o x i d i z i n g

power o f NH^ chloramines

(8).

CH^NH^ are s i i g h t l y l e s s

but s t i l l

II.

the

I.

The values

for β-alanine and

i n d i c a t e high o x i d i z i n g power.

Kinetics of Disproportionation General

Behavior.

When a monochlorinated primary amine p r e

pared i n basic media i s jumped to high a c i d , a r e a c t i o n occurs and a dichloramine i s

second-order

formed ( i n c e r t a i n cases

other decomposition r e a c t i o n s may occur and, i n the case o f NH^, NCI

3

may form, but these are not part o f the present

discussion).

As the i n i t i a l l y basic monochloramine s o l u t i o n s are jumped to i n c r e a s i n g l y higher a c i d , more and more o f the i n i t i a l l o s t p r i o r to the formation o f the RNC1 s p e c i e s . 2

absorbance i s

This absorbance

loss occurs w i t h i n the mixing time o f the stopped-flow

instrument

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

272

ORGANOMETALS AND ORGANOMETALLOIDS

Table

II

Standard Reduction P o t e n t i a l s Reaction Type

E°'s

(vs.

NHE, 2 5 . 0 ° C ) .

a

( v o l t s ) for the chloramine o f : Ammonia β-alanine Methyl amine

RNHC1 + H 0 + 2e"

Cl" +

2

RNH + OH"

b

2

RNH C1 2

+ H

+

+

+ 2e"

• C l " + RNH^

RNHC1 + 2 H + 2 e " — • C l " + RNH^ +

RNH C1 + H + e ~ - * 1/2 C l +

2

+

RNHC1 + 2 H + e " — • +

2

+

C

c

+ RNH^

1/2 C l

+

+

C

0.75

0.68

0.66

1.40

1.37

1.35

1.44

1.39

1.39

1.45

1.39

1.35

0.79

0.71

0.72

1.34

1.27

1.30

1.33

1.19

1.24

1.24

1.16

1.20

1.29

1.17

1.24

+

2

RNH RNC1

2

+ 2H 0 + 4e" — • 2C1" + RNH 2

+ 20H"

2

b

RNC1

2

+ 3 H + 4e"

• 2C1" + R N H

RNC1

2

+ 3 H + 2e"

• Cl- +

+

+

RNH RNC1 + H 2

RNC1

2

+ 2H

+

+ 2e" — •

2

b

d

Cl" + RNH C1

a

+ C

c

3

+ 2e" — • C l " + RNHCl

+

3

+

d

Referenced to the p o t e n t i a l s for c h l o r i n e species i n r e f . l

M amine and 1 M OH".

c

l M amine H

+

and 1 M H . +

d

(11 ),

1 M

chloramine and 1 M H . +

and i s due to the protonation o f the monochloramine. o f RNC1

2

The amount

formed i s d i r e c t l y dependent on the amount o f RNHC1

i n i t i a l l y present, but i s independent o f the magnitude o f the initial

absorbance

jump.

The rate o f RNC1

formation, however, i s dependent on the

2

amount o f the i n i t i a l

absorbance

observed-second-order

rate constant o f the formation o f NHCl »

N,N-dichloro^-alanine, tion o f a c i d i t y .

jump.

Figure 5 i s a p l o t o f the 2

and Ν , Ν , - d i c h l o r o g l y c y l g l y c i n e

as a func

It i s noteworthy that the k i n e t i c maximum

occurs when 50% o f the i n i t i a l

absorbance o f NH C1 i s l o s t during 9

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

16.

GRAY

the pH jump. is

Chloramine Equilibria

ρτ A L .

273

This implies s t r o n g l y that the r e a c t i o n involved

(using NH as an example): 3

NH C1 + N H C 1 2

3

+

k

p

l

> NHC1 + N H

S

2

4

(10)

+

The rate expression f o r t h i s microscopic r e a c t i o n i s d [ R N C 1

d

2

]

+ = k

2

t

D I S

drRNHPll

[ N H C l ] [ N H C l ] = l/2 ( 2

3

+

d

L g"J)

(11)

R

In terms o f [NH C1] (=[NH C1] + [NH C1 ]) 2

-d[RNHCl] d

t

where

s

2

III.

3

+

D(ΊI S+ HK K

[ H + ] [ N H

NH C1

+

Values o f 2

2

i s the protonation constant for monochloramine (eq 1 3 ) .

NH C1 + H

NH ,

2 k

T

3

(13)

+

and kpj^ were resolved f o r chloramines o f N H , C H 3

3

β - a l a n i n e , g l y c i n e , and g l y c y l g l y c i n e as compared i n Table The values

for g l y c y l g l y c i n e are the r e s u l t o f a c o n s i d e r

able e x t r a p o l a t i o n but are c e r t a i n l y as accurate as they would be if

the 0.5 M i o p i c strength r e s t r i c t i o n had been broken i n order

to achieve the 2-5 M a c i d necessary to obtain data i n the region of

the k i n e t i c maximum. It should be noted that these values o f k p

small and the

I S

are rather

values are higher than expected (12).

protonated monochloramines w i l l

Hence

e x i s t at low pH f o r a s i g n i f i c a n t

time period at low t o t a l concentrations o f RNHC1.

Accordingly,

e q u i l i b r i u m constants and electrochemical p o t e n t i a l s are included for the protonated species i n Tables III.

I and I I .

D i s t r i b u t i o n o f Ammoniacal Chloramines Figure 6 d i s p l a y s the c a l c u l a t e d d i s t r i b u t i o n o f m i l l i m o l a r

c h l o r i n e i n a f i v e - f o l d excess o f ammonia as a function o f pH. This i s analogous to the c o n d i t i o n s used for the preparation o f stock monochloramine i n t h i s work.

Besides the complete forma

t i o n o f monochloramine above pH 9 . 5 , i t i s i n t e r e s t i n g to note

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

274

ORGANOMETALS

AND

ORGANOMETALLOIDS

Figure 4. Approach of a mixture of NH$, β-alanine and their monochloramines toward equilibrium. (1) initial spectrum; (2) equilibrium spec trum, [HOCl] = 1.31 X 10 M, [NH ] = 0.059M, [β-aknineL· = 0.0022M, -log[H+] = 9.08,1-cm path length, μ = 0.50M (NaClO ) 25.0°C; (3)... fully formed N-chloroβ-alanine. S

S

T

h

Figure 5. Dependence of k (M' sec' ) on [H*] for the disproportiona/—d[RNHCl] .2k [RNHCl] ^ tion I dt of monochloramine (Φ), N-chloro-βalanine (A), and N-chloroglycylglycine (O). ([Chloramine] — 1.06 X JO M, μ - 0.50M (NaClOt), 25.0°C).

230

270

310

Wavelength, nm

1

oba

1

ob8

T

s

Figure 6. Distribution of chlor amines in aqueous solution ([NH ] — 10 M, [HOCl]τ — 2.5 X JO M, O.50M (NaCl0 ), 25.0°C.) The decomposition of NHCl, above pH 6is neglected. S

-log

[Hi

2

T

s

4

-tog[H+]

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

16.

GRAY

E T AL.

Chloramine Equilibria

275

Figure 7. Distributions of chloramines in aqueous solutions with [NHS]T — [HOCl] , 25.0°C, 0.50M (NaClOJ. The decomposi tion of NHCl, above pH 6 is neglected: (a) I0" M, (b) 10' M (c) 10- M. T

3

6

9

9

Figure 8. Distributions of chloramines in aqueous solution with a constant ammonia concentration and varying [HOCl] ([NH,] — ΙΟ", 25.0°C, μ — O.50M NaClOJ. T

6

T

The decomposition of NHCl above pH 6 is neglected: (a) [HOCl] = iO M, (b) [HOCl] = I0' M, (c) [HOCl] = I0- M, (d) [HOCl] = 10 M. g e

T

7

logCHl

T

8

T

T

9

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

276

ORGANOMETALS AND ORGANOMETALLOIDS

Table

III

Protonation Constants o f Monochloramines and the Rate Constants for D i s p r o p o r t i o n a t e -d[monochloramine]/dt (μ

from

= k [monochloramine][H-monochloramine DIS

]

= 0.50 M (NaCIO,), 25.0°C)

Amine

K , M" R

k

1

p i s

,

M"

1

Methyl ami ne

36

60

Ammonia

28

980

3-alanine

2.4

Glycine

0.37

Glycylglycine

0.2

sec

330 1200

that the e q u i l i b r i a do not allow f u l l

formation o f dichloramine

or t r i c h l o r a m i n e under these c o n d i t i o n s .

Figure 7 i l l u s t r a t e s

the c a l c u l a t e d d i s t r i b u t i o n s o f chloramines at e q u i l i b r i u m mixing equimolar hypochlorous a c i d and ammonia at concentration l e v e l s .

after

various

These three plots present the changes

which occur upon d i l u t i o n o f chloramines under these concentra t i o n and pH c o n d i t i o n s .

The t r a n s f e r o f c h l o r i n e from nitrogen

to oxygen ( h y d r o l y s i s ) i s the predominant o v e r a l l

process.

Another facet o f the chloramine e q u i l i b r i a i s presented i n Figure 8.

In t h i s figure

the t o t a l ammonia concentration i s held

constant at 10"^ M and the a v a i l a b l e -9 to 10

M.

As the a v a i l a b l e

c h l o r i n e i s varied from 10"^

c h l o r i n e concentration d e c l i n e s ,

c h l o r i n e s i n g l y bound to oxygen or nitrogen becomes preferable to p o l y c h l o r i n a t e d nitrogen m o i e t i e s .

Above pH 6 NHCl2 i s not s t a b l e

r e l a t i v e to s e l f o x i d a t i o n - r e d u c t i o n and therefore

these

distri

butions represent only the maximum p o s s i b l e values o f d i c h l o r amine. Acknowledgment. National

This i n v e s t i g a t i o n was supported by

Science Foundation Grant CHE75-15500.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

16.

gray et

al.

Chloramine Equilibria

277

References and Notes 1. 2.

Merkins, J. C., Water Waste Treatment J., (1958), 7, 150. C o r b e t t , R. E., M e t c a l f , W. S., and Soper, F. G., J. Chem. S o c . , (1953), 1927. 3. Anbar, M. and Yagil, G., J. Am. Chem. S o c . , (1962), 84, 1790. 4. Granstrom, M. L., Ph.D. T h e s i s , Harvard U n i v e r s i t y , 1954. 5. Chapin, R. M . , J. Am. Chem. S o c . , (1929), 5 1 , 2113. 6. M o r r i s , J. C., "Kinetics of Reactions Between Aqueous Chlorine and Nitrogen Compounds" in "Principles and Applications of Water Chemistry," Faust, S . D. and Hunter, J. D . , e d s . , W i l e y , Ν. Υ., 1964, pp 23-53. 7. M e t c a l f , W. S., J. Chem. S o c . (1942), 148. 8. J o l l y , W. L., J. Phys Chem (1956) 60 507 9. W e i l , I. and M o r r i s American Chemical Society 1949. 10. G a l a l - G o r c h e v , H. and M o r r i s , J. C., Inorg. Chem., (1965), 4 , 899. 11. L a t i m e r , W. Μ., "The Oxidation States o f the Elements and T h e i r Potentials in Aqueous Solutions," 2nd e d . , Prentice H a l l , I n c . , New York, 1952, pp 53-55. 12. W e i l , I. and M o r r i s , J. C., J. Am. Chem. S o c . , (1949), 71, 3123. Received August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

17 C h l o r i n a t i o n a n d the F o r m a t i o n of N - C h l o r o C o m p o u n d s in W a t e r T r e a t m e n t 1

2

DALE W. MARGERUM, EDWARD T. GRAY, JR., and RONALD P. HUFFMAN Department of Chemistry, Purdue University, West Lafayette, IN 47907

Chlorine is widel and wastewater. It is used annually for sanitary purposes (1). Chlorine and hypochlorous acid (HOCl) are much more effective than hypochlorite ion (OCl ). Thus, for disinfection four times as much as total chlorine is needed at pH 9 than at pH 7. Below pH 7, a 2 X 10 M concentration of HOCl is sufficient for 99.6% virus inactivation, 99.999% coliform kill, and 99.999% cyst disinfection (2). Ammonia, which is present in waste water and even in many drinking and river waters, will react rapidly with HOCl to form monochloramine (NH Cl). Hence NH Cl becomes the principal chlorine disinfectant in any water containing as much as 0.1 mg/L of NH-N and less than 1.0 mg/L of Cl . Additional chlorine will give dichloramine (NHCl ) and trichloramine (NCl ). Figure 1, the decomposition of residual chlorine is accomplished by the destruction of the chloramines (presumably to N and N0 ) with excess chlorine. A typical breakpoint occurs at 8 mg Cl /L per 1 mg N/L. Beyond the breakpoint additional chlorine dosage introduces more HOCl and often N-chloro-organic compounds as well (2). -

-6

2

2

3

2

2

3

-

2

3

2

'Current address: Dept. of Chemistry, U. of Hartford, W. Hartford, CT 06117 Current address: Upjohn Co., P.O.B. 685, Laporte, TX 77571 2

0-8412-0461-6/78/47-082-278$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

17.

Chloramines are t o x i c to f i s h . c h l o r i n e causes

Thus, 0.08 ppm residual

f i s h k i l l s and long exposure

NH^Cl are l e t h a l

279

Formation of N-Chloro Compounds

MARGERUM ET A L .

to rainbow t r o u t (3).

and combined c h l o r i n e ( j L c

chloramines)

same order o f magnitude

4).

(2»

to ppb l e v e l s o f

The t o x i c i t i e s o f free are considered to be the

Fresh water fishes

suffer

anoxia

due to c h l o r i n e or chloramine o x i d a t i o n o f hemoglobin to methemoglobin

(5J.

I t i s important to know the ease o f formation, the

s t a b i l i t y , and r e a c t i v i t y o f chloramines i n order to understand t h e i r environmental

effects.

The present paper i s concerned with some o f the s o l u t i o n chemistry o f chloramines and d i s s o c i a t i o n o f various N-chloro compounds. Morris and his associates

( £ , 7_ 8, 9^ 10) has f

E a r l i e r work by provided impor-

tant basic information about some o f the properties o f c h l o r amines.

It has been p o s s i b l e

use o f stopped-flow

to expand on t h i s base through the

spectrophotometry and by taking advantage o f

the a b i l i t y to form r e l a t i v e l y s t a b l e species.

s o l u t i o n s o f N-chloro

In the preceding paper we have discussed the determina-

t i o n o f accurate e q u i l i b r i u m constants

for the chloramines and the

k i n e t i c s o f d i s p r o p o r t i o n a t i o n o f monochloramines.

We now con-

s i d e r the k i n e t i c s o f t r a n s f e r o f a c t i v e c h l o r i n e to oxygen and nitrogen as well

as i t s t r a n s f e r

between oxygen and nitrogen

compounds. Reactions o f C l . 2

nitrogen from C l reactions.

2

The t r a n s f e r o f C l

i s r a p i d but measurable

+

to oxygen and to

for several

The k i n e t i c s o f h y d r o l y s i s o f C l HOCl + C l " + H

?

different

(eq 1) have been (1)

+

measured by Eigen and Kustin (11) and by L i f s h i t z and PerlmutterHayman (12).

In the present work we needed to know the e q u i l i b -

rium constant f o r eq 1 i n 0.50 M NaC10

4

at 25.0°C

and i n the

process o f t h i s determination obtained the rate constants which are i n s u b s t a n t i a l

agreement with the e a r l i e r s t u d i e s .

Our values

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

280

are:

ORGANOMETALS AND ORGANOMETALLOIDS

k

= 28.6 s " ,

= 2.8 χ 1 0

1

1

10"^ M .

M"

4

2

s" , 1

and kj/lc^ = 1.0 χ

It can be seen from these r a t e constants that the

2

equilibration of C l

with HOCl and C l " occurs w i t h i n seconds.

2

The rates o f C l

r e a c t i o n with ammonia, alkylamines and

2

amino acids (eq 2) are very f a s t and, i n f a c t , are nearly at the Cl

2

+ RNH

Jl!2—•

2

RNHCl + H

diffusion-controlled

limit.

are not r e a c t i v e with C l constants (Table I)

+ Cl"

(2)

The protonated amine s p e c i e s , RNH^ , +

or with HOCl.

2

We have resolved

rate

for the r e a c t i o n o f these a c t i v e c h l o r i n e

species with the free amine and C l " c o n c e n t r a t i o n s .

Once the monochloramines are formed they

also react r a p i d l y with C l RNHCl k

Cl

2

+ RNHCl J £ h

•

(eq 3).

9

Since protonated monochlor-

ά

RNC1 + H 2

+

+ Cl"

(3)

amine, RNH C1 , forms only at very low pH, the rate o f 2

+

o f RNC12 from C l

2

formation

i s not as e a s i l y suppressed i n a c i d i c s o l u t i o n

as i s the rate o f formation o f RNHCl.

As a r e s u l t dichloramines

may be observed as the products o f the c h l o r i n a t i o n o f amines and the rate-determining step i s eq 2 r a t h e r than eq 3. Table I Second-Order Rate Constants ( M ^ s " ) for the C h l o r i n a t i o n o f 1

Amines and Amino A c i d s , 25.0°C .RNH K

ci

.RNH,>

2

κ 2

0

.RNH H0C1 2

α '

K

2

Ammonia

4.0 χ 1 0

9

2.9 X 1 0

6

Methyl amine

2.8 χ 1 0

9

1.9 X 1 0

8

Glycine

—

1.5 X 1 0

9

5.0 X 10

7

Glycyl g l y c i n e

. . .

2.1 X 1 0

9

5.3 X 1 0

6

α-alanine

—

.

1.0 X 1 0

9

5.4 X 10

7

β-alanine

. . .

1.3 X 1 0

9

8.9 X 1 0

7

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

17.

Formation of N-Chloro Compounds

MARGERUM ET AL.

281

The doubly protonated amino a c i d s , NHgRC00H, are not r e a c +

t i v e with C l

and the concentration o f the completely

2

ed form, Nr^RCOO", i s n e g l i g i b l e Although a monoprotonated

under the a c i d i c conditions

form does react with C l , i t i s

NH^RCOO , but

rather

s p e c i e s , Nr^RCOOH, which i s present as a minor

i s the neutral

species

used.

propos-

2

ed that t h i s i s not the zwi t t e r i o n s p e c i e s ,

component.

unprotonat-

Rate constants c a l c u l a t e d i n terms o f t h i s

i n Table

RNH ° 2

I agree with those found for the free amines and

also are c l o s e to the d i f f u s i o n - l i m i t i n g

values.

Reactions o f HOCl nitrogen i n the r e a c t i o n o f hypochlorous a c i d with ammonia (eq k HOCl + NH

H

3

3 Q )

4)

N H

NH C1 + H 0

C 1

2

(4)

2

i s r a p i d and t h i s i s the main pathway

for monochloramine

t i o n in c h l o r i n a t i o n r e a c t i o n s .

and Morris

taken below pH 6.5 (where NH^

Weil

(6)

formation suppresses

+

used data the rate) and

data taken above pH 12 (where 0C1" formation suppresses to give a rate constant o f 6.2 χ 1 0 our stopped-flow

studies

6

M'^s"

forma

the rate)

for r e a c t i o n 4.

1

In

the r e a c t i o n was measured over the

intermediate pH range as shown i n Figure 2 where ^ ^ j i s a 0

pseudo-first-order

rate constant (eq 5)

using excess

sc

ammonia.

d[NH Cl] ?

" W

- d f —

H

0

C

1

1T

( 5 )

The s o l i d l i n e i n Figure 2 i s c a l c u l a t e d using a value o f 2.8 χ 10

M'V

(0.1 M N a C l O j , 25.0°C) for the second-order rate NH constant, k 3 This value i s based on protonation constants Q *5Q . 1 HOCl 7 ΛΛ -1 6

Kr'^M

1

1

for NH

3

and 1 0

NaClOj at 25.0°C. HOCl and NH

3

are

/ β

^ M

The r e s u l t s

1

for 0C1

a l s o measured i n 0.1 M

confirm the postulate that only

reactants.

The rate constants for HOCl with some a l k y l acids and peptides are summarized i n Table the behavior o f C l , the rate constants 2

of

I.

amines, amino

In c o n t r a s t with

for the HOCl

reactions

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

282

AND ORGANOMETALLOIDS

Water Chlorination

Figure 1. Rehtionship between chlorine dosage and residual chlorine for break point chlorination (2)

CHLORINE DOSAGE

Figure 2. Observed firstorder rate constant for the formation of NH Cl from hypochlorous acid (initially 2.0 X 10 M) with excess ammonia (initially 7.35 X 10' M). The solid line is a calculatedfitusing k oci > — 2.8 X WW s' , K„ for NH — 10 Μ-\ and K„ for OCl- = 10 M-\ 25.0°, = 0.10M (NaClOO. g

5

3

H

1

S

NH

1

939

7A4

μ

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

17.

MARGERUM

Formation of N-Chloro Compounds

E T AL.

283

increase as the b a s i c i t y o f the amines increase as seen i n Figure 3.

A l l the amines except ammonia f a l l

log k 2 with l o g K HOCl " R N H

R N H

2.

along a l i n e c o r r e l a t i n g

This suggests a n u c l e o p h i l i c attack by

the amine on the Cl atom i n HOCl as the rate-determining step i n the r e a c t i o n mechanism. The rate constants for the r e a c t i o n o f monochloramines with HOCl (eq 6) are given i n Table I I . RNHCl + HOCl

•

The smaller rate

constants

RNC1 + H 0 2

(6)

2

agree with the diminished n u c l e o p h i l i c i t y o f the monochloramines. Figure 4 shows the c o r r e l a t i o o f the l o g - l o g

plot is 0.61. Table

II

Protonation Constants and Rate Constants f o r HOCl Reaction with Monochloramines, 0.50 M (NaC10 ), 4

1 0 9

K

H

k

H0Cl

·

M

monochloramine

1.44

150

methylchloramine

1.55

352

N-chloro-3-alanine

0.41

278

N-chloroglycylglycine

-0.67

25.0°C

S

8.7

Below pH 4-5 the a d d i t i o n o f HOCl to RNH s o l u t i o n s 0

results

in RNClp as the observed product rather than RNHCl despite the RNHo fact that the k 2 t e constants are much l a r g e r than the ,RNHCl HOCl HOCl The reason i s that the r a t i o o f RNH /RNH * i s very s m a l l , while the r a t i o o f RNHCl/RNH C1 i s RNHCl DMU ^ large and hence l w - Γ [RNHCl] » k 2[RNH ]. HOCl 2 Reactions o f Monochloramines. The rate o f h y d r o l y s i s o f r a

r

a

t

e

c

o

n

s

t

a

n

t

s

9

0

KNH

H 0 C 1

NH C1 (eq 7) i s r e l a t i v e l y slow. NH Cl ?

k

Η

s ^ for k [ ^ 2 ^ H0

c

2

9

L

J

A rate constant o f 1.9 χ 1 0 "

5

2

NH C1 + H 0 2

+

2θ

a

n

,

NH + HOCl

(7)

3

be c a l c u l a t e d from the formation rate

constant

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND ORGANOMETALLOIDS

284

Figuré 3. Comparison of second-order rate constants (25.0°C) for the chlorination of amines as a function of their base strength. (Φ) RNH and Cl , (A) amino acids (NH,RCOOH form) and Cl , (O) RNHg and HOCl, and (φ) NH and HOCl g

2

2

S

Figure 4. Dependence of the sec ond-order rate constant for HOCl chlorination of amines and mono chloramines with their base strength, 25.0°C, μ — 0.50U (NaClOt)

9

10

log K ™ H *

log

KH

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

17.

Formation of N-Chloro Compounds

MARGERUM ET A L .

285

and the e q u i l i b r i u m constant given i n the preceding paper. NH^Cl forms i t i s slow to release HOCl.

a c t i v e c h l o r i n e i n the form o f

Another h y d r o l y s i s r e a c t i o n to give hydroxylamine NH Cl k

2

(eq 8) i s

2

2ϋ

NH C1 + OH"

Once

•

NH 0H + C l "

(8)

o

a s i g n i f i c a n t pathway only i n strong base. report a value o f 6.3 χ 1 0 " M ^ s " 5

1

Anbar and Yagil

for k ^

2

^·

Rate constants

for the h y d r o l y s i s o f monochloramines and dichloramines ing HOCl) are summarized i n Table

(13)

(releas

III.

Rate Constants f o r the Hydrolysis o f Chloramines, 25.0°C,

0.5 M (NaC10 ) 4

k

s"

1

NH C1

1.9 χ 1 0 "

5

N-Cl-B-alanine

2.1 χ 1 0 "

6

CH NHC1

1.6 χ 1 0 "

6

NHC1

6.5 χ 1 0 "

7

N,N-diCl-e-alanine

1.6 χ 1 0 "

9

CH NC1

4.7 χ 1 0 "

8

2

3

2

3

2

As shown i n the preceding paper monochloramines w i l l proportionate

i n a c i d i n accord with eq 9.

RNHCl + RNH C1 2

+

the value o f k p creases.

k

I S

p

i

S

,

decreases

RNC1

2

+ RNH

3

dis

It i s i n t e r e s t i n g

that

(9)

+

as the base strength o f RNH de 0

The c o n t r a s t with the HOCl c h l o r i n a t i o n dependence i s

s t r i k i n g as shown i n Figure 5.

This suggests a s h i f t

i n the r a t e -

determining step to the breaking o f the N-Cl bond a f t e r

nucleo

p h i l i c attack by RNHCl on the c h l o r i n e o f RNH C1 . 0

Is the d i r e c t t r a n s f e r o f Cl another p o s s i b l e ?

+

from one amine nitrogen to

Yes, recent work by Snyder and Margerum (14)

shows that the rate o f c h l o r i n e t r a n s f e r

i n eq 10 i s f a s t e r

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

than

ORGANOMETALS

8

9

10

AND

ORGANOMETALLOIDS

II

Figure 5. Comparison of the rate constants for monochloramine disproportionation (k ) and the rate constants for the reaction of amines with HOCl (k *) with the basicity of the amines, 25.0°C, μ — 0.50M (NaClOrf. DIS

RNH

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

17.

M A R G E R U M

NH C1 + NH CH C00" £

2

•

2

the rate o f h y d r o l y s i s . from pH 4 to 9.

287

Formation of N-Chloro Compounds

E T AL.

NH^ + C1NHCH C00"

(10)

2

The observed rate constant i s 1.5 M"^s"^

The observed rate constant i s i n v a r i a n t over

t h i s pH range because the r e a c t i v e species are N H ^ C l

+

and NHoCHo-

C00" whereas the predominant species i n s o l u t i o n are Nf-LCl and NH

3

CHoCOO .

Protonated monochloramine, NH^Cl

, i s a very

effec

t i v e c h l o r i n a t i n g agent as seen from the data i n Table I V . The Table IV Rate Constants f o r th NH C1 3

+

to Amino Acids and Peptides

(14_), 25.0°C

k, M"

1

s"

glycyl glycine"

1.3 χ 1 0

7

glycine"

2.5 χ Ί Ο

8

β-alanine"

2.6 χ Ι Ο

8

1

NHgCl* ion reacts considerably f a s t e r than HOCl and i s only about an order o f magnitude slower than C l . On the other hand, the + -1 protonation constant to form NH^Cl from NH C1 i s only 28 Μ , so 9

0

the f r a c t i o n o f protonated species present i n neutral pH i s small and the observed second-order rate constants are not large ( £ . £ . 1.5 M"

1

s"

1

for g l y c i n e ) .

Reactions o f Pichloramines. NHC1 + H 0 2

•

2

The h y d r o l y s i s o f NHCl^ (eq 11)

NH C1 + HOCl

i s slower than the h y d r o l y s i s o f NH^Cl. amines (Table I I I ) reactions.

(11)

2

S i m i l a r l y , other d i c h l o r -

have small rate constants f o r t h e i r h y d r o l y s i s

Obviously the i n s t a b i l i t y o f NHC1 i s not due to 2

simple h y d r o l y s i s r e a c t i o n s . The rate constant and e q u i l i b r i u m constant for the d i s p r o p o r t i o n a t i o n r e a c t i o n o f monochloramine given i n the preceding

-3 paper can be used to c a l c u l a t e a rate constant o f 6.4 χ 10 M -1 -3 s for the r e a c t i o n i n eq 12. Therefore greater than 10 M

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

-1

288

NHC1

ORGANOMETALS AND ORGANOMETALLOIDS

2

+ NH

4

•

+

2NH C1 + H 2

(12)

+

concentrations o f ammonia o r other amines could speed the conver sion o f dichloramines to monochloramines.

The e q u i l i b r i u m p o s i

t i o n o f the r e a c t i o n i n eq 12 also s h i f t s to the r i g h t as the pH becomes greater than 6. Other reactions o f NHC1 must take place i n neutral or

basic

0

solutions

i n order to account for the i n s t a b i l i t y reported

this species,

but as y e t these reactions are not well

Discussion.

for

defined.

The k i n e t i c s data for the t r a n s f e r o f C l

to and

from nitrogen atoms in amine ed r a p i d l y and are slow to release Cl

in a c i d .

Although NHCl

has often been considered an extremely unstable compound i n

2

regard

to s e l f o x i d a t i o n - r e d u c t i o n , t h i s i s not the case i n a c i d i c s o l u t i o n s i n the absence o f a d d i t i o n a l

HOCl.

and other dichloramines i n neutral

and basic s o l u t i o n s need to be

studied.

The reactions o f NHC1

Monochloramines are r e l a t i v e l y s t a b l e in s l i g h t l y

2

basic

and s l i g h t l y a c i d i c s o l u t i o n s and act as a r e s e r v o i r o f a c t i v e chlorine.

The persistence o f residual

c h l o r i n e i n r i v e r water

has been a t t r i b u t e d to the slow decay o f monochloramine The h a l f l i f e o f t h i s r e s i d u a l half l i f e

(15).

c h l o r i n e i s comparable with the

for the h y d r o l y s i s o f NH C1. 0

Table V summarizes some p o s s i b l e forms i n the c h l o r i n a t i o n o f water. namically unfavorable

reactions o f NH^Cl a f t e r Reaction (a)

thermody-12

(the e q u i l i b r i u m constant i s 6.7 χ 10

M*" ) and would occur only i f other processes 1

r e a c t i o n products.

is

Reaction (b)

cern except i n strong base.

were removing the

i s much too slow to be o f c o n

Reaction (c)

is

thermodynamically

favorable only below pH 6 and i t i s second-order

process i n mono

chloramine so t h i s decay would not be a favorable pathway. s e l f redox decomposition o f NHCl

2

Reaction (d)

The

at higher pH could help to

d r i v e the r e a c t i o n but the rate o f r e a c t i o n (c) pH.

it

i s slower at high

depends on the concentration o f other amines,

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

17.

M A R G E R U M

Formation of N-Chloro Compounds

E T AL.

289

Table V Possible C l (a)

NH C1 + H 0 0

t (b)

<

2

Transfer Reactions o f N ^ C l i. HOCl + NH^

= 10 hrs

1 / 2

NH C1 + OH 2

•

7

at pH 8 t ^ (c)

+

2

NH 0H + C l " 2

= 350 y r

2NH C1 + H+

• NHC1 + N H

2

2

4

+

at pH 6 and 1 0 " M NH C1 the f i r s t t 3

(d)

NH C1 + g l y 2

0

• C l - g l y + NH

for 1 0 " M g l y , t 3

]

/

2

= 10 hrs

3

- 0.13 hrs

amino a c i d s , peptides o r proteins and i s one o f the more favorable pathways i f these concentrations are appreciable (!·§.·

m

o

r

e

than 10"^ M ) .

The N-chloroamino a c i d products are

even slower to hydrolyze than i s N H o C l . known about the o x i d a t i o n o f substrates

Relatively 1 i t t l e is by chloramines o r about

species which might c a t a l y z e the s e l f o x i d a t i o n - r e d u c t i o n o f chloramines.

The t r a n s f e r o f C l

+

from one N-compound to another

seems a l i k e l y path to permit the t o x i c chloramines to form i n marine l i f e .

I t i s not y e t c l e a r what redox r e a c t i o n s are

a c t u a l l y responsible f o r the chloramine t o x i c i t y . Acknowledgment. National

This i n v e s t i g a t i o n was supported by

Science Foundation Grant CHE 75-15500.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

290

ORGANOMETALS AND ORGANOMETALLOIDS

L i t e r a t u r e Cited 1. White, G. C . i n "Water C h l o r i n a t i o n " V o l . 1, R. L . Jolley, e d . , Ann Arbor Science Publ., Ann Arbor, Mich., p 2. 2. Johnson, J. D . , ibid., p 41. 3. Merkens, J. C., Water Waste T r e a t . J., (1958), 7, 150. 4. Brungs, W. Α., J. Water P o l l . Control F e d . , (1973), 4 5 , 2180. 5. Grothe, D. R. and Eaton, J. W., T r a n s . Am. Fish., (1975), 104, 800. 6. W e i l , I. and M o r r i s , J. C., J. Am. Chem. Soc., (1949), 71, 1664. 7. Granstrom, M. L., Ph.D. T h e s i s , Harvard U n i v e r s i t y , 1954. 8. F r i e n d , A . G., Ph.D. T h e s i s , Harvard U n i v e r s i t y , 1956. 9. Samples, W. R . , Ph.D. T h e s i s , Harvard U n i v e r s i t y , 1959. 10. M o r r i s , J. C., i n " P r i n c i p l e s and A p p l i c a t i o n s o f Water Chemistry," S . D. York, N . Y . , 1967 11. E i g e n , M. and K u s t i n , Κ . , J. Am. Chem. S o c . , (1962), 84, 1355. 12. Lifshitz, A . and Perlmutter-Hayman, Β . , J. Phys. Chem., (1960), 64, 1663. 13. Anbar, M . , and Yagil, G., J. Am. Chem. Soc., (1962), 84, 1790. 14. Snyder, M. P. and Margerum, D. W. unpublished d a t a . 15. R e f . 2 , p 49. Discussion F. E . BRINCKMAN (National Bureau of Standards): Referring to Table V , you have a l a r g e excess of solvent (water) which i s not reactive with chloramine species. The glycines show a short halfl i f e in terms of reaction with chloramine. What about organometals? I raise this because much f a i t h is being placed in chlor i n a t i o n and/or ozonation processes f o r waste water treatment i n v o l v i n g organometals. Have you done any s t u d i e s i n t h i s direction? MARGERUM: No, I d i d n o t . There i s a vast number of e x p e r i ments, not only with organometals, but a l s o with unsaturated c a r bon compounds, e t c . , that we have not gotten to. Even for simple oxidizable metal ions, the information is not available now. BRINCKMAN: I think we are saying where the action i s . I was quite impressed with the enormous rate differences for these sub s t r a t e s , p a r t i c u l a r l y i n v o l v i n g organonitrogen, or the glycine in this case. J . J . ZUCKERMAN ( U n i v e r s i t y of Oklahoma): I was facinated by the c h l o r i n a t e d amino a c i d s . Are they i s o l a b l e species and do they e x i s t under environmental c o n d i t i o n s i n aqueous media as zwit t e r ions?

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

MARGERUM

17.

E T AL.

Formation of N-Chloro Compounds

291

MARGERUM: F i r s t , you can form these chloroamino a c i d s and keep them i n s o l u t i o n , e i t h e r as the monochloro- o r dichloro-amino a c i d s , and then they are not z w i t t e r i o n s . Both o f these s p e c i e s , as P r o f e s s o r Gray and I have shown, can be kept f o r a long time i n solution. ZUCKERMAN: Can they be taken out of aqueous s o l u t i o n i n t o l i p i d s o r organic media? MARGERUM: The water s o l u b i l i t y changes d r a m a t i c a l l y as you go from monochloramine t o t r i c h l o r a m i n e . Trichloramine i s q u i t e f a t - s o l u b l e , and the same t h i n g i s true as you t o t o the a l k y l amines. The N-chloroalkylamines can be q u i t e f a t s o l u b l e depending on what's on the r e s t of the chain. This i s one of the reasons we were asking th ect t r a n s f e r from one N-chlor i t s q u i t e p o s s i b l e that these could be concentrated i n f a t t y areas. The monochloramine i s h y d r o p h i l i c ; i t has a low s o l u b i l i t y i n organic s o l v e n t s . 1

R. L. JOLLEY (Oak Ridge N a t i o n a l Laboratory): protonated monochloramine was the pH where you determined your 1 0 M~ s~ ? 1

1

You showed the What

1

MARGERUM: We v a r i e d the pH f o r these s t u d i e s from 3 t o 12. From pH 4 t o 9, the observed r a t e was constant. A t those pH l e v e l s , the amount of protonated monochloramine i s very low, so we have t o a s s i g n the proton t o one of the two s p e c i e s , e i t h e r t o the amine o r the monochloramine. We a s s i g n i t t o the monochloramine as the more l o g i c a l r e a c t a n t . This i s how we get that r a t e constant that I gave. JOLLEY: So the h a l f - l i f e of 1.3 hours was over a pH range o f 5 t o 9 which you would expect i n n a t u r a l waters? MARGERUM: R i g h t . By the way, I would l i k e to mention I used Dr. J o l l e y s f i g u r e s w i t h s e v e r a l of these s l i d e s . 1

G. GORDON (Miami U n i v e r s i t y , Ohio): Water treatment i s moving i n the d i r e c t i o n "of combined c h l o r i n e - c h l o r i n e d i o x i d e because of intermediates and the use of some of these intermediates. Have you looked a t any of the o x i d a t i o n r e a c t i o n s of chloramines using C10 t o see what the products might be and what the r a t e s are? 9

1

MARGERUM: We haven't. There i s a tremendous amount of chemi s t r y here which needs t o be done. Much of the e a r l i e r work ran i n t o a l l these problems ( i n s t a b i l i t i e s , e t c . ) . I'm sure that as we i n v e s t i g a t e reasons f o r some of the i n s t a b i l i t i e s , we w i l l see some of the r e a c t i o n s you mention. RECEIVED

August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18 Ozone and

Hydroxyl

Radical-Initiated O x i d a t i o n s of

O r g a n i c a n d Organometallic Trace Impurities in W a t e r JÜRG HOIGNÉ and HEINZ BADER Swiss Federal Institute of Technology Zurich, Institute for Aquatic Sciences and Water Pollution Control, EAWAG, CH-8600 Dubendorf, Switzerland Ozonation is sometime drinking water or wastewate Switzerland, drinking water for a considerable number of communi ties is supplied from lakes. Most of these waters are ozonized in order to improve taste, colour and disinfection. The lakes which are used as water resources for these drinking waters are situated in densely populated areas. They are bordered by many industries. Accidents might occur at any time through which the reservoir might be polluted by toxic or taste forming chemicals. We there fore are interested to learn more about the kinetics by which ozonation can oxidize organic pollutants even in cases when the pollutants are only present as trace impurities. Experience has shown that only very extended ozonation can lead to full mineralization of the solutes - i.e., oxidation to carbonate, nitrate, sulphate and oxidized metal ions. However, because of technical and economic reasons, ozonation processes, applied for water treatment, generally have to be stopped after a reaction time of 10 to 30 minutes and only an ozone concentrat ion below 10 M can be maintained during the ozonation process. The amount of ozone added is generally less than 10 3 mole/L. We therefore are confronted with the question: Which solutes are oxidized to what extent during the time available in a practical ozonation process? -4

-

The Reaction Model Most of the results we found so far on ozonation processes in water fit well into the following model (see Fig. l) : On the one hand, part of the ozone (0^) dissolved in water reacts directly with the solute M. Such direct reactions are highly selective and for many solutes rather slow (time scale of minutes). On the other hand, part of the ozone added to the water decomposes before it reacts with solutes or before it is stripped off. This 0-8412-0461-6/78/47-082-292$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18.

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Ozonation

293

decomposition leads t o f r e e r a d i c a l s . Among these t h e OH* r a d i c a l s "belong t o t h e most r e a c t i v e oxidants known t o occur i n water. Up t o 0.5 mole o f these OH* r a d i c a l s are formed p e r mole o f ozone decomposed (l). OH*radicals can e a s i l y o x i d i z e o r g a n i c , organom e t a l l i c and i n o r g a n i c s o l u t e s . They e x h i b i t l i t t l e s u b s t r a t e s e l e c t i v i t y . Even bicarbonate and carbonate ions a r e o x i d i z e d by OH* r a d i c a l s ; thus OH* r a d i c a l s are consumed q u i c k l y even i n nonp o l l u t e d waters (microsecond time s c a l e ) . The decomposition o f ozone i s c a t a l y s e d by hydroxide ions and proceeds f a s t e r the higher the pH. The decomposition o f ozone i s a d d i t i o n a l l y a c c e l e r a t e d by a r a d i c a l - t y p e c h a i n r e a c t i o n i n which OH"radicals can*act as chain c a r r i e r s . Some types o f s o l u t e s , f o r instance aromatic hydrocarbons, react with OH* r a d i c a l s and form secondary r a d i c a l s (R* Other s o l u t e s , f o r exampl hydroxide only reduce t h e primary r a d i c a l s t o species which do not a c t as chain c a r r i e r s . Such s o l u t e s quench the r a d i c a l - t y p e chain r e a c t i o n . Therefore t h e l i f e t i m e o f 0 i n water depends on the pH as w e l l as on t h e s o l u t e s present. Examples o f l i f e t i m e s are given i n F i g . 2. The o v e r a l l o x i d a t i o n i n i t i a t e d by ozonation i s a superpos i t i o n o f o x i d a t i o n s by t h e ''direct r e a c t i o n " and by t h e "OH* r a d i c a l r e a c t i o n " . The two processes are optimized by d i f f e r e n t process parameters and l e a d t o d i f f e r e n t daughter products. For many systems encountered i n p r a c t i c e these two processes are of comparable importance. Data on t h e d i r e c t r e a c t i o n s can be obtained by studying ozonations performed at low pH v a l u e s , where the ozone decomposition becomes slow, and by adding f r e e r a d i c a l scavengers which i n h i b i t t h e e f f e c t o f t h e " r a d i c a l r e a c t i o n " . Data on t h e " r a d i c a l r e a c t i o n " can be obtained by f o l l o w i n g t h e d e p l e t i o n o f s o l u t e s which only react very slowly i n " d i r e c t r e a c t i o n s " and (or) by l i m i t i n g t h e l i f e t i m e o f t h e ozone f o r instance by i n c r e a s i n g t h e pH. Experimental Experiments performed t o determine r a t e constants w i t h which ammonia or organic s o l u t e s r e a c t with ozone a r e d e s c r i b e d i n references (_3) and (k). A d e s c r i p t i o n o f t h e measurements o f r e l a t i v e r a t e s with which s o l u t e s are e l i m i n a t e d i s g i v e n i n references (1) and ( 3 ) . Methylmercury hydroxide was prepared from CH HgCl (Merck; synthesis grade) by methods described i n r e f . (13;· I t was s t o r e d i n l i g h t p r o t e c t e d b o t t l e s as 0.U5 M s o l u t i o n s , " i t s o x i d a t i o n by ozonation was determined from t h e amount o f methyl mercury mineral i z e d t o inorganic species found a f t e r a l l ozone added had r e a c t e d i n c l o s e d b o t t l e s . Minor m o d i f i c a t i o n s o f t h e Hatch and Ott method

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

294

ORGANOMETALS

AND

ORGANOMETALLOIDS

O3 stripped

Figure 2. Half-life of ozone in different types of water vs. pH. (I) distilled water; (II) distilled water + 2mM carbonate (2(C0 )) (III) distilled water + 0.3mM CH HgOH; (IV) wastewater (70% secondary effluent; DOC = 7 g/m ). 2

;

s

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18.

HOIGNE A N D BADER

Ozonation

295

based on atomic absorption spectroscopy (lU) were a p p l i e d f o r the determination o f the amount of methylmercury m i n e r a l i z e d . The concentration o f the remaining methylmercury was c a l c u l a t e d from the d i f f e r e n c e between the amount of methylmercury a p p l i e d and the amount found as m i n e r a l i z e d . For each s e r i e s the 100$ value was determined from samples i n which a l l the methylmercury was o x i d i z e d at pH 10.5 by adding an excess of ozone. T h i s 100$ value was i n good agreement with values found from d i r e c t c a l i b r a t i o n s with i n o r g a n i c mercury compounds. A l l absorption s i g n a l s were c o r r e c t e d f o r the s i g n a l found on non-oxidized samples (about 2$ of 100$ v a l u e ) . Organotin compounds were l a b o r a t o r y samples s u p p l i e d from the N a t i o n a l Bureau of Standards. The concentrations of the aqueous s o l u t i o n s were measure Hydrogen peroxide wa which contained about 30 mg/l t o t a l organic carbon (measured a f t e r decomposition of H O by MnO^). T h i s value could not be changed by a simple d i s t i l l a t i o n procedure. Hg compounds were not present i n s i g n i f i c a n t amounts. The concentration of the H^O^ was deter mined by iodometric t i t r a t i o n . Results and

Discussion

The d i r e c t r e a c t i o n of ozone with s o l u t e s . Some s o l u t e s become o x i d i z e d d i r e c t l y by molecular ozone:

Vn · 0

+ M

(M)

k — ^

M . «3 oxid. Experiments show t h a t the r a t e s with respect t o ozone and, as a respect t o s o l u t e c o n c e n t r a t i o n which a s o l u t e i s o x i d i z e d , and t e d becomes:

of these r e a c t i o n s are 1st order r u l e , n e a r l y 1st order with (3.,^). Therefore, the r a t e by the r a t e by which ozone i s deple

- d[M]/dt = - η . d[0 ]/dt = η · k · [ O ^ f M ]

(l)

The change of the r e l a t i v e c o n c e n t r a t i o n of M with time i n a batchor plug-type r e a c t o r can be formulated by i n t e g r a t i n g equation ( l ) over r e a c t i o n time t : - In ([Μ] /[Μ] ) = η · k · e ο

[oil

' t

3

where, [Μ] , [M] : i n i t i a l and end concentration o f M ο e η: y i e l d f a c t o r o f M e l i m i n a t e d per ozone used (mole/mole) k r a t e constant of o v e r a l l consumption of ozone by M and i n s t a b l e daughter products.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

(2)

296

ORGANOMETALS AND

[0^]:

ORGANOMETALLOIDS

mean 0^ cone, during r e a c t i o n p e r i o d t .

The r e l a t i v e s o l u t e e l i m i n a t i o n by t h i s " d i r e c t r e a c t i o n " depends only on the mean concentration of ozone (mean over r e a c t i o n t i m e ) , the time the ozonation l a s t s , the r a t e constant k and the y i e l d f a c t o r η ( 3 ) . The y i e l d f a c t o r i s about 1 . 0 i n cases where the s o l u t e i s "an o l e f i n i c compound. I t i s a l s o about 1 . 0 when organom e r c u r i a l s are ozonized i n chloromethylene ( 8 ) . I t i s somewhat lower f o r many other types o f s o l u t e s and assumes a value o f about 0.25 i n the case of ammonia o x i d a t i o n i n water (k). We determined k values f o r many s o l u t e s i n aqueous s o l u t i o n s by measuring the r a t e of ozone consumption i n presence of a s o l u t e concentration which was high enough not t o become changed s i g n i f i c a n t l y by the ozone r e a c t i o n such as f o r pH, t o avoi (_3» h) . For such cases we may w r i t e from equation ( l ) f o r a b a t c h type r e a c t o r : - ln([0

/[0 ]

1

Q

) = k · [Ml

or:

1/T

Where,

[0 ]

,

TQ

: l i f e t i m e of

= k-[M]

q

Q

[0

· t

0

] : i n i t i a l concentration time t

of 0

and cone, at

0^.

The r a t e constants can be c a l c u l a t e d from the l i f e t i m e values o f ozone measured f o r d i f f e r e n t concentrations of a s p e c i f i e d s o l u t e M. The main problem f o r a l l these measurements i n water was t o avoid disturbances by r a d i c a l r e a c t i o n s (compare F i g . l ) . C r i t e r i a f o r the occurrence of pure d i r e c t ozone r e a c t i o n s were: ( i ) the k i n e t i c s stayed f i r s t order i n ozone and s o l u t e concentrations over the e n t i r e concentration range measured; ( i i ) i n the pH range employed, small changes o f pH (one pH u n i t ) had no e f f e c t on the r a t e o f the ozone d e p l e t i o n ; ( i i i ) the a d d i t i o n o f r a d i c a l scaven gers (bicarbonate or propanol) had no e f f e c t on the r e s u l t s . In F i g . 3 are presented a few o f about 60 r a t e constants we have measured so f a r . (3.). The r a t e constants may be read on the l e f t - h a n d s c a l e . A l s o " e l i m i n a t i o n l i n e s " are drawn i n t o t h i s f i g u r e i n d i c a t i n g e l i m i n a t i o n s down t o 21% (by a f a c t o r of e ) , t o 1% or t o 0 . 0 1 % r e s p e c t i v e l y . The r e q u i r e d ozonation time l e a d i n g t o such e l i m i n a t i o n s may be read o f f the h o r i z o n t a l time s c a l e . The s c a l e i n F i g . 3 i s c a l c u l a t e d f o r a p l u g - or batch-type r e a c t o r and f o r a mean ozone concentration o f κΗ+ M (about 5g/m3). T h i s ozone concentration can be considered as a l i m i t i n g value achieved when commercial ozonators are operated w i t h dry a i r . The s c a l e would increase i n v e r s e l y t o the ozone concentration. 9

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18.

HOIGNE

AND

BADER

297

Ozonation

reaction time

t (s)

lurea

ICHC00" 3

•

(<0.04)

{MeSn* JCHHgOH 3

3

f(<0.05)

JCHjHgCl {CHHg+ 3

Figure 3. Examples of direct reactions of ozone with solutes in water. Ordinate values: reaction rate constants (3). Abscissa values: calculated re action time needed to reduce the solute concentra tion to the rehtive value indicated on the elimina tion lines. Assumptions: η = 1.0; [O ] = 10' M (~5g/m*). s

4

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

298

ORGANOMETALS AND

ORGANOMETALLOIDS

The r e l a t i o n "between r e q u i r e d ozonation time and r e a c t i o n r a t e constant given i n t h i s f i g u r e shows t h a t i n a d r i n k i n g water or i n a secondary e f f l u e n t of a domestic wastewater (at pH below 9 ) s o l u t e s may r e a c t s i g n i f i c a n t l y by d i r e c t r e a c t i o n s with ozone only i f t h e i r r a t e constant i s beyond about 5 0 M ^ s . For so l u t e s of lower r e a c t i v i t y and i n case of lower ozone concentrations, o x i d a t i o n s may r a t h e r f o l l o w a p r e l i m i n a r y decomposition of ozone molecules t o OH* r a d i c a l s (to be d i s c u s s e d ) . F i g . 3 does not i n clude data on s o l u t e s which r e a c t so f a s t with ozone that the r a t e of the chemical r e a c t i o n i s beyond the rate-determining step of the o v e r a l l process. For instance n i t r i t e and compounds c h a r a c t e r i z e d by u n s u b s t i t u t e d o l e f i n i c double bonds are above scale. - 1

The compounds l i s t e molecules with s o l u t e s ar cations o f a chemical s t r u c t u r e have l a r g e e f f e c t s on the r a t e constants. Examples: aldehydes, which occur as an ozonation p r o duct i n lakewater (_5 ), need 1 0 0 0 sec of exposure t o lO'^M ozone f o r an e l i m i n a t i o n t o 31% of t h e i r i n i t i a l concentration. A comparable r e a c t i o n time would be r e q u i r e d f o r toluene. However, benzene would r e q u i r e 5 0 0 0 sec. Examination o f the examples quoted i n F i g . 3 i n d i c a t e s t h a t ozone a l s o r e a c t s i n water as an e l e c t r o p h i l e . Substituents which decrease the e l e c t r o n e g a t i v i t y of the r e a c t i o n centers of the molecules render them nonreactive. Extended s t u d i e s on s u b s t i t u t e d benzenes showed t h a t the r e a c t i o n r a t e s of these compounds i n crease with the e l e c t r o n e g a t i v i t y as expected from data known f o r other e l e c t r o p h i l i c r e a c t i o n s . When applying the Stock and Brown l i n e a r energy r e l a t i o n (6) a r e a c t i o n constant ρ = - 2 . 9 was found when σ-values were based on σ -values ( 3 . ) . The simple types of organotin c a t i o n s we t e s t e d d i d not i n t e r a c t with ozone w i t h i n a r e a c t i o n time of p r a c t i c a l i n t e r e s t ^ The r e a c t i o n r a t e constants determined were approximately: Me^Sn (pH 3 . 3 ) 0 . 0 0 6 M ^ s : Bu S n (pH 2 . 3 - H.0) 1.7; B u S n (pH 1 . 9 ) 1 . 5 ( 1 . 2 mM s o l u t i o n o f the c h l o r i d e compound, no b u f f e r added). Approximate r a t e constants are included i n F i g . 3 . These r a t e constants are w i t h i n the range of values expected f o r r e a c t i o n s of ozone with corresponding a l k y l groups such as present i n a l k y l a l c o h o l s ( 3 ) . ( T h e corresponding organotin hydroxides d i d not show enough s o l u b i l i t y f o r performing t h i s type o f measu rements ). - 1

+

+ 2

2

No d i r e c t r e a c t i o n of methylmercury c a t i o n , methylmercury c h l o r i d e or methylmercury hydroxide with ozone could be measured. Such s o l u t e s even s t a b i l i z e d the ozone concentration to some extend by quenching the r a d i c a l induced chain r e a c t i o n which otherwise would a c c e l e r a t e the decomposition of ozone (see F i g . 2 ) . T h e i r r a t e constants f o r the d i r e c t i n t e r a c t i o n with ozone must t h e r e f o r e be lower than the v a l u e s i n d i c a t e d i n F i g . 3 , i.e.k < 10"

2

1

1

M- s~ .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18.

Ozonation

HOIGNE A N D BADER

299

TABLE 1 D i r e c t Reactions o f Ozone with M

k

Organomercurials 1

(M-l-s" )

CH HgCl

0.00T

CH CH HgCl

0.003

(CH ) CHHgCl

0.02

(CH ) CHHgl 2

0.03

(CH ) CH0H

0.0k

3

3

2

3

3

3

2

2

*) measured i n CH C1

Ô

0C

Examples

The organomercurials f o r which we measured the r a t e constants seem not t o represent exceptions. T h i s can he i l l u s t r a t e d bycomparing constants Waters et a l . measured on these and other types of organomercurials i n methylene c h l o r i d e (8) (see examples i n Table l ) . Even though r a t e constants i n water may d i f f e r by orders o f magnitudes from those measured i n non-aqueous systems (3.), such comparisons can g i v e some informations on the general t r e n d s . Waters et a l . a l s o showed that n-alkylmercury h a l i d e s r e a c t with ozone t o produce a l l p o s s i b l e a c i d s and ketones upon chain breakdown. That means, that the r a t e of cleavage o f carbon carbon bonds competes with the r a t e o f cleavage o f the carbon mercury bond and that a l s o f o r t h i s reason the s c i s s i o n o f the carbon - mercury bond must be assumed t o be a r a t h e r slow process. Based on these examples we must expect t h a t organomercurials w i l l g e n e r a l l y have a small chance t o get d i r e c t l y o x i d i z e d by molecular ozone i n a water treatment process except i n cases where the r e a c t i v i t y o f such compounds i s due t o other f u n c t i o n a l groups present i n the organic p a r t of the molecule. Oxidations i n i t i a t e d by OH* r a d i c a l r e a c t i o n s . The amount of the secondary oxidants produced i n an ozonation process i s p r o p o r t i o n a l t o the amount o f ozone decomposed i n water. The o x i d a t i o n s due t o these secondary processes are i n i t i a t e d mainly by OH*radicals. (Decomposition o f ozone can a l s o l e a d t o f u r t h e r secondary oxidants. From k i n e t i c s t u d i e s on systems c o n t a i n i n g d i f f e r e n t types of r a d i c a l scavengers we conclude that only the OH*radicals determine the k i n e t i c s o f the r a d i c a l type r e a c t i o n s ) . The f r a c t i o n o f these OH* r a d i c a l s a v a i l a b l e f o r o x i d a t i o n o f a s p e c i f i e d s o l u t e M i s p r o p o r t i o n a l t o the r a t e with which these oxidants react with M, d i v i d e d by the sum o f a l l the r a t e s by which these are consumed by a l l other s o l u t e s present i n the water:

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

300

ORGANOMETALS

AND

ORGANOMETALLOIDS

reaction^ + M

k

1

[OH*]

[M] M

"3,Δ

η

^

Where,

1

OH*

0

1

3,Δ·

η':

(1+) +

ES. E(k!

[S.])

[0Η·]

0^ decomposed during process y i e l d f o r OH*

formation from 0

.

E(k| [ S ^ ] ) : r a t e o f OH* scavenging by a l l s o l u t e s present i n c l u d i n g by 0^ and M. The r e a c t i v i t y o f OH* r a d i c a l s towards most organic s o l u t e s p r e sent i n a water i s high. Even carbonate i o n s , f r e e ammonia, hydro gen peroxide and ozone i t s e l f may r e a c t with them ( f o r s e l e c t e d k values see F i g . k). T h e r e f o r e , i n n a t u r a l water or i n waste water many s o l u t e s c o n t r i b u t e t o the consumption of t h i s seconda ry oxidant. We can c h a r a c t e r i z e the o x i d a t i o n o f a s p e c i f i e d t r a c e p o l l u t a n t M i n a given water by the f o l l o w i n g expressions which can be derived from formulations given above i n equation k (£) : f

If: we may

k»

[M] «

M

k! i

[S.] l

(5)

write:

(6) or:

e where:

thereby:

thereby:

/Ω

[Μ] /[Μ]

= β"°3,Δ Μ ο

Σ(*,·'[8,·]) "M

"M

Π'.τΓ

(?)

o x i d a t i o n competition value= amount o f ozone which must be de composed per volume t o reduce the s o l u t e c o n c e n t r a t i o n [M] by a f a c t o r o f e ( i . e . t o 37% o f i t s i n i t i a l value [Ml / [ M l = 0,37 f o r 0. e ο 3,a

η" = number o f o x i d a t i o n s i n i t i a t e d per OH* r a d i c a l consumed by s o l u t e M.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

HOIGNE A N D BADER

Ozonation

ozone

decomposed 0 3 , Δ (mmole/L)

0.1

0.4

1

4

10

ι urea I

|(<ΚΓ6)

Figure 4. Examples of oxidations initiated by OH' radical reactions. Ordinate values: reaction rate constants of OH' radical reactions (see Réf. 1). Abscissa: calculated amount of ozone to be decomposed to OH' radicals to achieve a solute oxidation leading to a relative solute concentration indicated on the elimination lines. Assumptions: η - w" = 0.5; rate of radical scavenging = % (kJSj) = 5 · IPs . (Data from Ref. 9 for sec ondary effluents.) 1

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The o x i d a t i o n competition-values, Ω ^ v a l u e s , can e a s i l y be d e t e r mined i n a water f o r s o l u t e s M when c o n d i t i o n s p r e v a i l under which these s o l u t e s M r e a c t only with OH" r a d i c a l s and not with ozone or other oxidants. As long as M represents a t r a c e p o l l u t a n t ( c o n d i t i o n eq. 5 f u l f i l l e d ) Ω ^ values do not depend on s o l u t e c o n c e n t r a t i o n . Experimental examples measured on such types of waters which do not change t h e i r competition v a l u e , ( t h a t means t h e i r scavenging e f f i c i e n c y ) during the ozonation, are given i n F i g . 5 , 6 , 9 , 1 1 . F i g . 5 represents the e f f i c i e n c y with which ozone added t o a model s o l u t i o n , c o n t a i n i n g a small l o a d o f o c t a n o l , m i n e r a l i z e s methylmercury hydroxyde (resp. phosphate). The l i n e a r i t y o f the d e p l e t i o n curve, when p l o t t e d i n a semi-log s c a l e , corresponds f o r m a l l y with equation 6 changed, even when the s o l u t cury i s changed by two orders of magnitudes. In water from the lake o f Z u r i c h comparable d e p l e t i o n r a t e s ( Ω values) f o r toluene were found i n case where the toluene c o n c e n t r a t i o n was i n c r e a s e d from the background l e v e l o f the lakewater ( 2 5 yg/m ) by s p i k i n g t o 2 5 0 mg/m^, i . e . by a f a c t o r o f 1 0 (5.) .However, the Ω values are c h a r a c t e r i z e d by the composition o f the aqueous s o l u t i o n (compare eq.7) R e s u l t s on experiments i n which the Ω values f o r methylmercury or benzene were measured v s . i n c r e a s e d loads o f model scavenger (n-octanol) are shown i n F i g . 7 . Comparable r e l a t i o n s h i p s are found when other i m p u r i t i e s are spiked t o the aqueous s o l u t i o n s . F i g . 8 shows i n case o f benzene how the amount o f ozone used per s o l u t e e l i m i n a t i o n (ΔΟ^/ΔΜ) changes with pH when carbonate i s present. (The expression ΔΟ^/ΔΜ was used i n our e a r l i e r ex periments where we a p p l i e d s o l u t e concentrations which were l a r g e and t h e r e f o r e d i d not f u l f i l c o n d i t i o n o f equation 5 . However, these values g i v e a s e m i - q u a n t i t a t i v e information on the Ω v a l u e s ) . F u r t h e r examples f o r d i f f e r e n t types o f s o l u t i o n s con t a i n i n g carbonates as a hydroxyl r a d i c a l scavenger are given i n r e f e r e n c e ( 2 . ) . A l l the examples quoted on carbonate c o n t a i n i n g s o l u t i o n s demonstrate that at higher pH values a higher amount of ozone i s r e q u i r e d t o achieve a c e r t a i n e l i m i n a t i o n f a c t o r : t h i s i s due t o the d i s s o c i a t i o n o f bicarbonate ions (HCO^ ) t o carbonate ions ( C O ^ ) which scavenge OH*radicals much f a s t e r (see k values given i n Fig.4) . A l s o i n n a t u r a l water part of the pH e f f e c t encountered i s due t o the i n c r e a s e d amount o f carbonate ions present at the higher pH value (2). Such an i n c r e a s e o f Ω values with pH determined f o r a lake water i s e x e m p l i f i e d i n F i g . -

2-

f

9.

In a secondary e f f l u e n t o f a domestic wastewater the Ω values are about ten times higher than i n lakewater (pH 8 ) . T h i s means, t h a t about 1 0 times more ozone i s r e q u i r e d t o achieve a

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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Figure 5. Mineralization of methylmercury hydroxide by the action of ozone decomposed to OH' radicals. The solutions contained 5 g/m octanol added as a model-type impurity; pH 10.5; 0.05M sodium phosphate buffer. [M] : ( · ) , 5 · 10' M CH HgOH; (O), 5 · 10 M CH HgOH; (A), 5 · 10~ M CH HgOH. 3

0

8

s

7

9

s

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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Me/Mo % 100· • spiked toluene (250mq/m 3 ) — | A toluene (25yg/m 3 ) ο 1,4-dichkxobenz. (1ug/m3) • 1,2,4-trimethylbenzene (4/jg/m3}

0.03

0.04

0 3 . Δ (mmole/L) international Symposium on Ozon and Wasser

Figure 6. Elimination of trace impurities in Lake Zurich water upon decomposition of different amounts of ozone. In one experi ment 250 mg/m of toluene was spiked into the water before ozonation. (Measurements performed on samples M from different dates) (5). 3

A i (mmole/L) 0.5

20

15 3

octanol (g/m ) Figure 7. Oxidation competition values (Ω) for the elimination of micropollutants (HgCH OH or benzene) in water vs. the concen tration of octanol which was used as a model type of scavenger: pH 10.5; 0.05M sodium phosphate buffer. H

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18.

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HOIGNÊ A N D BADER

Δθ

305

3

*C H e

6

50 40 /EC02 =17mmot/l

30Η

/

•s

20 /

£C0 =lmmol/l ^ ' 2

m 0

IC0 =0 2

y

^

^

^

^

Vom Wasser Figure 8. Ozone to be decomposed per oxidation of benzene (mol/mol) in waters of specified carbonate concentrations at different pH values. The carbonate ions are more reactive scavengers for OH' radicals than the bicarbonate ions. Therefore the effect of a given amount of total carboate increases with pH (2).

J 0

1

1 004

u \ \ \ l\ Λ 1 1 I 008 012 ozone added (mmole/L)

Figure 9. Elimination of benzene spiked to water of Lac de Bret by decomposition of ozone. DOC — 4 g/m ; 2 [CO,] = 1.6mM. The pH was varied by 0.05M sodium phosphate buffer. 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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306

Figure 10. Effect of added hydrogen peroxide on the oxidation competition value, Ω of a water. Data for the miner alization of methylmercury hydroxide. [CH HgOH] = 5.10 M; pH = 8; 0.05M sodium borate buffer. 8

3

A N D ORGANOMETALLOIDS

2

4

6

mM [H 0 ] 2

2

% M

Figure 11. Elimination of different types of solutes spiked into water of Lac de Bret (DOC = 4 g/m %(C0 ) ~ 1.6mM; ph 8.3; benzene 80 mg/m ; toluene 103 mg/m , tetrachloroethylene 500 mg/m . 3

2

3

3

3

0.06

ozone added (mmole/L)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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comparable e l i m i n a t i o n f a c t o r ( 9 . ) . In a d d i t i o n , some o f the i n i t i a l amount of ozone added t o a wastewater i s used up i n a spontaneous r e a c t i o n and only beyond t h i s the added ozone becomes a v a i l a b l e f o r other o x i d a t i o n s . However, the e f f i c i e n c y w i t h which f u r t h e r ozone a d d i t i o n s o x i d i z e s o l u t e s i s not changed appreciably by f u r t h e r pre-ozonation treatment (see r e f . 9 . ) . F i g . 10 shows the scavenging e f f e c t of hydrogen peroxide on the o x i d i z i n g species formed when ozone decomposes: The Ω value f o r methylmercury hydroxide increases by about 0 . 2 5 mM ozone per mM H^O^ added. An e f f e c t o f t h i s order of magnitude i s expected from eq. 7 and the r e l a t i v e r a t e constants with which OH" r a d i c a l s s e l e c t between H^O^ and methylmercury hydroxide. OH*radicals r e a c t i n g with H 0 become reduced by H O , There by H0 * (0 ) i s formed p

p

2

OH'

+ H 0 2

H

V

2

-> H 0

+

2

Ζ

°2~

+

H0 ' 2

( f o r l i t . see r e f . ( 1 k)

H +

9

)

Now the experiments using H 0 show that the secondary r a d i c a l s formed do not c o n t r i b u t e s i g n i f i c a n t l y t o the o x i d a t i o n o f methyl mercury hydroxide. That means that 0 ~, which i s expected t o be a l s o produced during the docomposition of ozone, does not c o n t r i bute t o the o x i d a t i o n of methylmercury s p e c i e s . In a given water the amount of ozone r e q u i r e d t o e l i m i n a t e a s o l u t e Β by a f a c t o r e, compared with t h a t r e q u i r e d f o r e l i m i n a t i o n of impurity A r e s u l t s from equation 7: 2

2

2

Ω

Α

/ Ω

Β " "V

k ,

B

'

n

Y 'A

'

k

k

'

B

I

k

'

A

The approximation on the r i g h t hand side can be t o l e r a t e d f o r many systems, because the y i e l d f a c t o r η" f o r many s o l u t e s are of comparable magnitudes. That means t h a t the slope of the l o g a r i t h m i c expression of the r e l a t i v e s o l u t e concentration vs. the amount o f ozone decomposed decreases with the r e l a t i v e r e a c t i o n - r a t e con stant with which OH* r a d i c a l s r e a c t with a s o l u t e . An example i s given i n F i g . 11. Because of the importance of OH* r a d i c a l r e a c t i o n s i n r a d i a t i o n chemistry of aqueous systems, l i s t s o f hund reds of r a t e constants f o r OH" r a d i c a l s are p u b l i s h e d ( f o r l i t e r a t u r e see reference (l)). F i g . h represents a few o f such v a l u e s . It shows t h a t most of the organic s o l u t e s have constants i n the order of magnitude of 10 M ^ s " . (The aspect of t h i s f i g u r e i s b i ased somewhat because we a l s o wanted t o emphasize those s o l u t e s which e x h i b i t r a t h e r low c o n s t a n t s ) . F i g . h a l s o shows e l i m i n a t i o n l i n e s . P r o j e c t i n g from these l i n e s v e r t i c a l l y t o the a b s c i s s a , the amount of decomposed ozone r e q u i r e d to y i e l d a c e r t a i n amount o f s o l u t e o x i d a t i o n by t h i s " r a d i c a l - t y p e r e a c t i o n " may be read. The 1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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s c a l e i s based on eq. 6 , assuming a y i e l d f a c t o r η . η " = 0.5 and a sum of the r a t e s of r a d i c a l consumption, E ( k . [ S . ] ) , of 5*10^ s ' . These numerical assumptions give an upper l i m i t f o r the order of magnitude found f o r secondary e f f l u e n t s at pH 8 . I f we compare the o x i d a t i o n competition values Ω, measured f o r d i f f e r e n t s o l u t e s , we f i n d that the Ω value f o r methyl mercury hydroxide i s smaller than t h a t determined f o r benzene (measured i n a 0.05 molar s o l u t i o n of borate/boric a c i d o f pH 8 ) . Because benzene and methylmercury hydroxide e x h i b i t comparable y i e l d f a c t o r s when o x i d i z e d i n pure water ( η . η " ^ Ô.3) t h i s r a t i o i n Ω values r e f l e c t s the r e l a t i v e r a t e constant f o r r e a c t i o n s of the two solutes with OH* r a d i c a l s . In case of methyl mercury compounds these r a t i o s of Ω v a l u e s , however, are s t r o n g l y i n f l u e n c e d by the type when the c h a r a c t e r i s t i c i n respect t o the r a t e of scavenging of 0 H r a d i c a l s . F i g . 12 shows how the Ω values change at given pH with c h l o r i d e i o n concentration. From t h i s i t seems that the methylmercury c h l o r i d e has a higher r a t e constant f o r r e a c t i o n s with OH* r a d i c a l s than the methylmercury hydroxide: In presence o f high concentrations of c h l o r i d e , methylmercury i s o x i d i z e d n e a r l y as f a s t as benzene. At present we, however, cannot e x p l a i n why Ω changes when the pH i s increased from pH 7 Λ t o 8.U and why the c h l o r i d e e f f e c t s the Ω values already at about 3 t o 10 times lower concentrations than those necessary t o convert CHsHgOH s i g n i f i c a n t l y t o CH^HgCl. The range of r e a c t i v i t y however occurs i n the c h l o r i d e - c o n c e n t r a t i o n r e g i o n i n which the f i n a l product i s not Hg(0H) but rather Hg(0H)Cl. (For equilibrium-constants see e.g. reference 10). This enhanced o x i d a t i o n i n presence of small c h l o r i d e concentra t i o n s i s not due t o the formation o f 0C1 by the ozonation: Neither a d i r e c t a d d i t i o n o f 0C1 nor a preozonation o f the c h l o r i d e c o n t a i n i n g water l e a d t o a comparable m i n e r a l i z a t i o n o f methylmercury. A concentration o f only 0.05 M sodiumphosphate/phosphoric a c i d b u f f e r at pH 8 a l s o increased the measured r a t e o f the methylmercury o x i d a t i o n by a f a c t o r o f about 2 when compared with the r a t e found i n a corresponding borate s o l u t i o n . This would mean that the phosphate complex i s a l s o more e a s i l y o x i d i z e d by OH* r a d i c a l s than the methylmercury hydroxide. However, at pH 10.5 the r a t e was the same, whether the pH was adjusted by phosphate (0.05 M) or sodium hydroxide. We assume that t h i s d i f f e r e n c e i s due t o the higher e q u i l i b r i u m concenctration of the methylmer cury hydroxide at t h i s higher pH v a l u e . 1

f

1

1

%

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

HOIGNE AND

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BADER

a

I

I

CHHgX (pH8.4) 3

(mmole/L) 0.20 CH HgX (phÎ7.9) 3

0.16 CH HgX (pH 7.4) 3

0.12

•

k ο

S.

·

0.08 Ben :ene

jp Η 79)

_,

0.04

M {CiFigure 12. Oxidation competition value (Q) for water containing 2.5 g/m octanol as a purity. Ω is measured for the methylmercury tion or benzene oxidation in the presence chloride ion concentrations. CH HgX = 5.10 sodium borate buffer. 3

s

measured model im mineraliza of different M; 0.05M

8

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Conclusions For q u a n t i t a t i v e assessments o f o x i d a t i o n s i n i t i a t e d by ozone i n water the d i r e c t r e a c t i o n of ozone with the s p e c i f i e d s o l u t e s and the OH'radical type mechanism have t o be accounted f o r . The extent of the d i r e c t r e a c t i o n s can be c a l c u l a t e d from - mean ozone c o n c e n t r a t i o n

during r e a c t i o n time,

[5^]

- r e a c t i o n time, t - second order r e a c t i o n - r a t e constant r e a c t i o n s of molecular ozone, k

f o r the

direct

k values can be determined by experiments on model s o l u t i o n s when process parameters are i n t e r a c t i o n s by the f r e ozone. However, many of the organic and organometallic s o l u t e s r e a c t too slowly and are h a r d l y o x i d i z e d by the d i r e c t r e a c t i o n w i t h molecular ozone. But o x i d a t i o n s of a l l types of organic and organometallic s o l u t e s can be i n i t i a t e d by hydoxyl r a d i c a l s which are formed when ozone decomposes t o f r e e r a d i c a l s . The amount of o x i d a t i o n s o f s p e c i f i e d t r a c e p o l l u t a n t s i n i t i a t e d by t h i s mechanisms can be estimated from: - amount of OH'radicals produced from ozone composed during process

de-

- r e a c t i o n - r a t e constant with which OH"radicals t i a t e o x i d a t i o n s o f the s p e c i f i e d s o l u t e M

ini-

- sum o f a l l the r a t e s with which a l l r a d i c a l scavengers present i n the water consume the OH'radicals i n competition t o the s p e c i f i e d s o l u t e s . A water can be c h a r a c t e r i z e d c o n s i d e r i n g the extent o f OH * r a d i c a l consumption by u s i n g a substance such as benzene as a reference s o l u t e . For a few hundred s o l u t e s the r e l a t i v e r a t e constants f o r r e a c t i o n s with OH r a d i c a l s , can be deduced from l i t e r a t u r e data. Therefore, k i n e t i c s t a n d a r d i s a t i o n s based on a k i n e t i c a l l y w e l l known s o l u t e such as benzene are meaningful. From the described ozonation experiments we may conclude that the o x i d a t i o n o f methylmercury compounds i s i n i t i a t e d only by the OH'radical type mechanism. No data on the r a t e o f r e a c t i o n s of organometallics with OH'radicals are however quoted i n the l i t e r a t u r e . Our experiments i n which we i n i t i a t e d the OH'radicals by decomposing ozone show that methylmercury c h l o r i d e or phosphate r e a c t with a r a t e constant comparable t o that of benzene. However, the methylmercury hydroxide r e a c t s i n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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absence o f c h l o r i d e four times slower, and i n absence o f phosphate two times slower. Therefore four o r two times more ozone has

to be decomposed to OH* radicals to achieve a comparable eliminat i o n f a c t o r f o r these m i c r o p o l l u t a n t s i n a given water. More research w i l l be needed to e x p l a i n the phenomena that

even such low concentrations of chloride ions, which are too small to convert a significant part of the methylmercury hydroxide to methylmercury chloride, significantly changed the apparent rates of oxidations of the methylmercury. Acknowledgement s We thank D r . F . E . Brinckman o f the National Bureau o f

Standards for the encouragement t

includ

organometalli

pounds i n our research

with the tinorganic compounds and a description of methylmercury speciation as a function of anion concentration. Their comments on our results are highly appreciated. We also thank Prof. W. Stumm for comments and continous interest and to Dr. H. Hohl for communicating experiences on aquous methylmercury systems. Literature Cited 1. 2. 3. 4. 5.

H o i g n é J. and Bader Η., Water R e s . , 10, 377 (1976). H o i g n é J. and Bader H., Vom Wasser, 48, 283-304 (1977). H o i g n é J. and Bader Η., i n prep. (1978). H o i g n é J. and Bader H., Environm. S c i . Technol., 12, 99 (1978). H o i g n é J., Bader H. and Zürcher F., Internat.Symp.Ozon and Wasser, Berlin, Mai 1977, (Proceedings in P r e s s ) . 6. Exner O., in "Advances in L i n e a r Free Energy R e l a t i o n s h i p s " , J. Shorter e d . (Plenum Press 1972), p . 3 2 .

7. S p i a l t e r L., LeRoy P., Bernstein S t . , Swansinger W.A., Buell G.R. and Michael Ε., in "Advances in Chemistry S e r i e s 112", P . S . B a i l y , e d . (ACS 1972), p p . 65-77. 8. Waters W . L . , Pike P.E. and R i v e r a J.G.,:ibid. pp.78-99. 9. H o i g n é J. and Bader Η., I n t e r n . Assoc. on Water P o l l u t i o n Res., 96th I n t e r n . C o n f . , Stockholm (1978) in: P r o g r . i n Watertechnology, 10, 657-671 (1978). 10. E r n i I . W . , "Relaxationskinetische Untersuchungen von Methyl quecksilberübertragungsreaktionen", D i s s e r t . , Swiss F e d . I n s t . Techn. Zurich (1977).

11. Pike P.E., Marsh P . G . , Erickson R . E . , and Waters W.L. Tetrahedron L e t t . 31, 2679-2682 (1970). 12. Weber P . and Waters W.L., Proc. Montana Academy o f S c i e n c e s , 32, 66-69 (1972).

13. Geier G., Erni I . and Steiner R . , Helv. Chim. Acta 60, 1, 9 - 1 8 (1977). 14. Hatch W.R. and Ott W.L., Anal.Chem. 40, 14, 2085-2087 (1968).

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Discussion J . J . ZUCKERMAN ( U n i v e r s i t y of Oklahoma): The u l t i m a t e o x i d a t i o n products of the organic compounds would be carbon d i o x i d e and water, and of the organometallic compounds would be metal oxi d e s , carbon d i o x i d e and water. Do you know what the products are of the o z o n o l y s i s of n a t u r a l waters c o n t a i n i n g these m a t e r i a l s ? HOIGNE: Where we s t u d i e d methylmercury we measured i n o r g a n i c mercury by atomic a b s o r p t i o n . In water, we measured ozonation products formed from d i f f e r e n t alkylmercury compounds and found d i f f e r e n t carbonic a c i d s , aldehydes, and so f o r t h . That i s , C-C bond s c i s s i o n competed w i t h the alkylmercury s c i s s i o n . That means that the alkylmercury bond r e a c t s so s l o w l y that even the a l k y l group s c i s s i o n s can compet ZUCKERMAN: Did you i s o l a t e any compounds i n the case of l a r g e r a l k y l groups which were hydroxylated on the a l k y l chain? HOIGNE: No. Based on the l i t e r a t u r e , and our analyses, we f i n d mostly a c i d s , ketones, or aldehydes. For i n s t a n c e , when we ozonize water from the l a k e of Z u r i c h , we form a tremendous amount of a l i p h a t i c aldehydes which we see by gas chromatography. ZUCKERMAN: You are u s i n g a chemical oxidant. In the Soviet l i t e r a t u r e there i s a h i n t that e l e c t r o l y s i s of waste water might be an e f f e c t i v e way t o d e a l w i t h organometallic p o l l u t a n t s . Are you aware of t h i s and do you have any comment on that? HOIGNE: Yes. l a t i o n t o my work. system, c o n s i d e r i n g r e a l l y d i f f i c u l t to

However, I do not know where to put i t i n r e You have to be very c a r e f u l to d e f i n e your pH and a l l other f a c t o r s . Otherwise i t i s use t h i s i n f o r m a t i o n .

W. A. PRYOR ( L o u i s i a n a State U n i v e r s i t y ) : I s there evidence f o r epoxides from o l e f i n s or arenes? HOIGNE: I'm not aware t h a t epoxides can be formed i n water, except i n one case. Where you o x i d i z e a l d r i n t o get d i e l d r i n . There have been many s t u d i e s on epoxide formation i n non-aqueous s o l u t i o n s . From these r e s u l t s we may assume you get epoxides, but only when the double bond which i s o x i d i z e d i s i n a very r i g i d framework. That i s a l s o the case f o r the a l d r i n - d i e l d r i n o x i d a t i o n I mentioned. F. GRAY (Colgate-Palmolive): Do you o x i d i z e the c h l o r i d e t o h y p o c h l o r i t e or c h l o r i n e i n these r e a c t i o n s ? HOIGNE: I don't know. They disappear when I look at the gas chromatography a f t e r ozonation. The y i e l d f a c t o r i s about 1.0

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

18.

HOIGNE A N D BADER

Ozonation

313

when compared w i t h ozone u t i l i z e d , and i t i s about 0.5 when com pared w i t h a f r e e r a d i c a l type (·0Η) o f r e a c t i o n . R. L. JOLLEY (Oak Ridge N a t i o n a l L a b o r a t o r y ) : This statement i s r e l a t i v e t o the epoxide question. The only epoxide t o have been reported i n aqueous ozonation was by Dr. C a r l s o n , U n i v e r s i t y of Minnesota. He r e p o r t s t h a t an epoxide was formed on aqueous ozonation of o l e i c a c i d . What h i s concentrations and y i e l d s were, I don't know. RECEIVED

August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

19

P a r t i t i o n of Organoelements in O c t a n o l / W a t e r / A i r Systems STANLEY P. WASIK Chemical Thermodynamics Division, National Bureau of Standards, Washington, DC 20234

Introduction The ability of organic compounds to bioconcentrate in the marine environment was found to be dependent upon the partition behavior of molecules between l i p i d and aqueous phases (1,2). The organic/water partition coefficient is defined as the ratio of the concentration of a chemical in the organic solvent to its concentration in water under equilibrium conditions in an organic solvent/ water system. Neely, Branson, and Blau (1) demonstrated that bioconcentration factors for chlorobenzenes and chlorophenols in trout muscles from water containing low levels of these compounds could be successfully correlated with their partition coefficients in the n-octanol/water system. Dunn and Hansch (3) compiled hydrophobic interactions of a large number of organic compounds and showed that these interactions quantitatively correlated with partition coefficients of organic/water systems. Leo (4) suggested that hydrophobicity, as measured by the noctanol/water partition coefficient, is the most important parameter in bioaccumulation and biotransport. The role of hydrophobicity in non-biological transport may not be dominant but should, nonetheless, be important. Although values for the n-octanol/ water partition coefficient have been reported in the literature for over 10,000 compounds, there is a large number of environmentally significant molecules that are absent. One group of molecules for which the n-octanol/water partition coefficient have not been reported is the organometal compounds.

This chapter not subject to U.S. copyright. Published 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

19.

Partition of Organoelements

WASIK

315

Wasik and coworkers (5,6) reported a method f o r determining the w a t e r / a i r p a r t i t i o n c o e f f i c i e n t from measurements o f the c o n c e n t r a t i o n of the s o l u t e i n the head-space i n e q u i l i b r i u m w i t h the l i q u i d phase. I n t h i s paper, a r e presented, by a s i m i l i a r method, our measurements o f the n-octanol/water p a r t i t i o n c o e f f i c i e n t s of dimethylmercury i n d i s t i l l e d and sea water over a temperature range of 0-25°C. The apparatus i s described and the v a r i o u s f a c t o r s e f f e c t i n g the p r e c i s i o n and accuracy of the p a r t i t i o n c o e f f i c i e n t s a r e discussed. Experimental Methods and C a l c u l a t i o n s Apparatus. A schematic diagram o f the apparatus and the e q u i l i b r a t i o n c e l l used to measure the w a t e r / a i r p a r t i t i o n c o e f f i c i e n t i s shown i F i g u r equilibratio of volume V which contain and a s m a l l volume of the gas phase, V = V - V , i s contained i n a water bath where the temperature i s c o n t r o l l e d t o w i t h i n 0.01°C. The gas c i r c u l a t i n g pump was constructed from a s t a i n l e s s s t e e l bellows (7.6 χ 3 cm) by the NBS shop. The bellows was enclosed i n a s t a i n l e s s s t e e l j a c k e t and was d r i v e n by p u l s a t i n g compressed a i r w i t h a duty c y c l e of 3 seconds. The a i r - s o l u t e mixture was pumped i n t o the apparatus through the 1/16-inch tube connecting the check v a l v e w i t h the 4-port gas v a l v e . The two g l a s s check v a l v e s were made by the NBS g l a s s shop. The pump c i r c u l a t e d the a i r - s o l u t e vapor through a 6-port gas sampling v a l v e . By s w i t c h i n g t h i s v a l v e , a s m a l l sample volume of the gas phase ( V = 0.1 cm ) can be sent t o the gas chromatograph f o r a n a l y s i s without i n t e r r u p t i n g the c i r c u l a t i o n of the a i r s o l u t e mixture. The gas mixture i s then d i r e c t e d t o a 4-port gas v a l v e which i n the c l o s e d - p o s i t i o n passes the gas phase back to the pump, and i n the open p o s i t i o n d i r e c t s the gas mixture through the e q u i l i b r a t i o n c e l l and then back t o the pump. The components of the apparatus a r e connected together w i t h 1/16i n c h s t a i n l e s s s t e e l tubing and commercial tubing connectors. The t o t a l volume o f the pump, v a l v e s , and t u b i n g , V R , i s 85.25 cm . T h i s p a r t of the apparatus i s contained i n an a i r bath a t 100 + 0.05°C. The e q u i l i b r a t i o n c e l l used t o measure the o c t a n o l / a i r p a r t i t i o n c o e f f i c i e n t was constructed i n the form o f a U; the bottom p a r t of the U was a g l a s s r e c t a n g u l a r tube ( 4 x 1 x 1 cm) and the two s i d e arms were g l a s s tubes (1/4-inch 0D χ 3 cm). The c e l l was connected t o the 4-port v a l v e w i t h 1/16-inch tubing and commercial reducing f i t t i n g s . The n-octanol (saturated w i t h water) was weighed i n the c e l l and the volume o f the s o l u t i o n was c a l c u l a t e d from i t s d e n s i t y . The n-octanol was deposited on the bottom of the c e l l and the a i r - s o l u t e mixture c i r c u l a t e d above i t . The volume of the c e l l was 4.821 cm . T

c

t

L

3

s

3

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

AND

ORGANOMETALLOIDS

Figure 1. Schematic showing equilibration cell and apparatus for determination of water/air partition coefficients

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

19.

wAsiK

Partition of Organoelements

317

Before assembly, the s t a i n l e s s s t e e l p o r t i o n s of. the apparatus were cleaned w i t h t r i c h l o r o e t h y l e n e ; the g l a s s p a r t s were washed w i t h 10 percent (by weight) aqueous HF and r i n s e d s e v e r a l times w i t h d i s t i l l e d water. The chromatgraphic column was a Scot column (15 m χ 0.5 mm ID) prepared w i t h f i n e l y ground diatomaceous e a r t h on a fused support and coated w i t h a mixture o f m-bis-(m-phenoxylphenoxyl) benzene and Apiezon L. The e f f l u e n t gas was monitored by a hydrogen flame d e t e c t o r and an e l e c t r o n i c i n t e g r a t o r was used to measure the peak areas. Commercial n-octanol was p u r i f i e d by successive washings w i t h HC1, w i t h d i l u t e sodium b i c a r b o n a t e s o l u t i o n , and f i n a l l y w i t h d i s t i l l e d water. The n-octanol, d r i e d w i t h sodium s u l f a t e , was d i s t i l l e d under reduced pressure. The d i s t i l l e d sample was found by gas chromatograph t b 99.97 mol t n-octanol The water used i n the p r e p a r a t i o over potassium permanganate purity diethylmercury and dimethylmercury was determined by gas chromato graphy t o be 99.4 mole percent. The compound was used without f u r t h e r p u r i f i c a t i o n . The a r t i f i c i a l sea water was prepared a c c o r d i n g to a r e c i p e g i v e n by Sverdrup e t §1 (7) and had a c h l o r i d i t y v a l u e o f 19.0 percent. The c h l o r i d i t y i s the t o t a l amount o f c h l o r i n e , bromine, and i o d i n e ( i n grams) contained i n 1 k g o f sea water where bromine and i o d i n e are replaced by chlorine. n-Octanol/Water P a r t i t i o n C o e f f i c i e n t . Consider a system composed o f two i m m i s c i b l e l i q u i d phases, n-octanol and water, and a gas phase, a i r , i n t o which v o l a t i l e s o l u t e vapor i s i n t r o d u c e d . L e t the e q u i l i b r i u m c o n c e n t r a t i o n o f the s o l u t e i n the a i r be CA» i n the o c t a n o l (saturated w i t h water) be C , and i n the water ( s a t u r a t e d w i t h o c t a n o l ) be C ^ . The octanol/water p a r t i t i o n c o e f f i c i e n t , K(o,w), i s d e f i n e d as the r a t i o 0 /0^ the w a t e r / a i r p a r t i t i o n c o e f f i c i e n t , K(w/a), as <^/0 , and the o c t a n o l / a i r p a r t i t i o n c o e f f i c i e n t , K(o/a) as C /C . A t e q u i l i b r i u m Q

ο

9

3

Q

K(o/w) = C /C = K(o/a)/K(w/a) ο w

a

(1)

p r o v i d i n g the s o l u t e c o n c e n t r a t i o n i s s u f f i c i e n t l y low i n each phase so that there are no i n t e r a c t i o n s between the s o l u t e molecules. For v o l a t i l e s o l u t e s K(o/w) i s d i f f i c u l t t o determine a c c u r a t e l y from i n d i v i d u a l measurements of C and due t o l o s s of s o l u t e by e v a p o r a t i o n d u r i n g sample m a n i p u l a t i o n . K(o/w) may be determined more c o n v e n i e n t l y and a c c u r a t e l y by measuring K(o/a) and K(w/a) i n separate experiments and then c a l c u l a t i n g K(o/w) from t h e i r r a t i o . Water/Air P a r t i t i o n C o e f f i c i e n t . D i s t i l l e d o r sea water was weighed i n the e q u i l i b r a t i o n c e l l and i t s volume was determined from i t s d e n s i t y . The a i r - s o l u t e vapor mixture was introduced i n t o the apparatus w i t h the 4-port v a l v e i n the c l o s e d p o s i t i o n . The gas mixture was then c i r c u l a t e d through the apparatus f o r approximately 10 minutes and a s m a l l volume o f the gas mixture Q

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

318

ORGANOMETALS

AND

ORGANOMETALLOIDS

was i n j e c t e d i n t o the gas chromatograph v i a the 6-port gas sampling v a l v e . The sampling was repeated u n t i l the s o l u t e peak area reached a constant value. The 4-port v a l v e was then switched to the open p o s i t i o n which allowed the gas mixture to bubble through the e q u i l i b r a t i o n c e l l . A f t e r approximately 30 minutes successive p e r i o d i c analyses of the gaseous mixture were made u n t i l the s o l u t e peak area reached a constant v a l u e . From the i d e a l gas law the t o t a l moles of s o l u t e , n, i n the apparatus i s given by

n

t

= PV /RT R

(2)

R

where Ρ i s the p a r t i a l pressure of the s o l u t e before e q u i l i b r i u m with the l i q u i d phase, T i s the temperature of the a i r bath i n k e l v i n s , and R i s the ga the l i q u i d phase R

f

f

P V_ _ n

t

f

PV R

,

P K(w/a)V c

RT_ R

RT

L

RT

c

, ~\ K

'

c

f

where P i s the p a r t i a l pressure of the s o l u t e a f t e r e q u i l i b r a t i o n w i t h the l i q u i d phase, T i s the temperature of the water bath c

i n k e l v i n s and K(w/a) = C /C w

= a

,

where η

i s the moles of

L·

V_ χ

L· s o l u t e i n the l i q u i d phase. Combining equations (3) and (2), s u b s t i t u t i n g A/A = P/P (where A and A are the s o l u t e peak areas before and a f t e r e q u i l i b r a t i o n , r e s p e c t i v e l y ) , and s o l v i n g f o r K(w/a) Τ (A/A - 1)V_ K(w/a) - ^ — & - V /V (4) R L T h i s method f o r determining K(w/a) i s the " s o l u t e absorption method. K(w/a) may be determined by a second method. At e q u i l i b r i u m , with the 4-port v a l v e i n the open p o s i t i o n , η may be expressed as 1

1

1

1

c

L

11

_ n

t

! Λ RT

+

R

!i!ç RT

c

.

p

i

K

(

w

/

RT

a

)

v

L

( 5 ) K

c

'

where P^ i s the p a r t i a l pressure of the s o l u t e a t the f i r s t e q u i l i b r i u m . The 4-port v a l v e i s switched to the c l o s e d p o s i t i o n and the s o l u t e i n V i s purged and replaced with c l e a n a i r . The 4-port v a l v e i s then switched to the open p o s i t i o n and the a i r i s c i r c u l a t e d through the e q u i l i b r a t i o n c e l l u n t i l e q u i l i b r i u m i s e s t a b l i s h e d . Then R

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

19.

Partition of Organoelements

wAsiK

n

!£R RT R

t

!£c RT c

+

?

319

K ( w / a ) V

2

+

L

VR RT_ R

F

+

RT c

,

6

^'

where P i s the p a r t i a l pressure of the s o l u t e a t the second e q u i l i b r i u m . Combining equations (5) and ( 6 ) , s u b s t i t u t i n g A /A f o r P^/I*2» s o l v i n g f o r K(w/a) gives 2

a

1

n

d

2

K

(

W

/

A

T

=

)

J A ' - 1)V C

R ( A

2

-

(7

V*L

>

The procedure may be repeated i number of times g i v i n g the expression

K ( W / A )

=

when i s the s o l u t e peak area a t the itîl e q u i l i b r i u m . l y i t can be shown that

V T R

A

/

l

A

i

"

[

C

±

T (K(w/a)V + V R L c D

+

1

]

_

Similiar-

Λ (

9

)

T

or

log^/A.)

=

[

( i - l)log

I^

V

+

V

+

«

( 1

°> R L c T h i s method f o r determining K(w/a) i s the " s o l u t e e x t r a c t i o n method." P a r t i t i o n C o e f f i c i e n t s a t D i f f e r e n t Temperature. I t i s p o s s i b l e to obtain K(w/a) a t various temperatures i n terms of the values a t some reference temperature, Τ . This can be done simply by measuring the r e l a t i v e s o l u t e p a r t i a l pressure i n the gas phase a t d i f f e r e n t temperatures of the e q u i l i b r a t i o n c e l l . Consider the system i n e q u i l i b r i u m w i t h the l i q u i d phase a t T T( K (

Q

P

V

T

P

R

Ο n

t

.

~RÏ~

=

V

T

P

c

Ο

+

.

K(w/a)V

L

Ο

~R¥~

+

R

T

/ π \

RT

ο

ο

where Ρ i s the p a r t i a l pressure of the s o l u t e and K(w/a) i s known fr8m e i t h e r a s o l u t e absorption or a s o l u t e extraction experiment. When the temperature of the l i q u i d phase i s changed to Τ τ

T

1

P

n

t

=

V

T R

τ Τ

P +

+

P

V

T c

I T

+ +

T

K ( W / A )

RT

V

T L (

1

2

)

R

where P^, i s the p a r t i a l pressure of the s o l u t e a t temperature Τ and K(w/a) i s the water/air p a r t i t i o n c o e f f i c i e n t . Combining T

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

320

ORGANOMETALS

AND

ORGANOMETALLOIDS

equations (11) and (12), s u b s t i t u t i n g Aq> /Ap f o r P /P^ and solving f o r K(w/a) ° ° T

T

V Τ K(w/a)

T

=

V A_ Τ (A^ /A^ - 1) + ^ - ( A /A^ - 1) + ο K(w/a) L R ο L ο T o ° T

τ

A

( χ 3 )

T

In determining K(w/a)x by t h i s method, a s m a l l c o r r e c t i o n should be made f o r V and due to the change i n d e n s i t y of the l i q u i d phase. T h i s method f o r determining K(w/a)m i s the "temperature v a r i a t i o n method." In d e r i v i n g equations ( 4 ) , ( 7 ) , and (13), the example was f o r a s i n g l e s o l u t e system. I n p r a c t i c e many s o l u t e s may be used i n the system as long as they are a t very low c o n c e n t r a t i o n s and can be separated by gas chromatography. N e i t h e r of these c o n d i t i o n s presents a s e r i o u s experimental problem. n-Octanol/Air P a r t i t i o p a r t i t i o n c o e f f i c i e n t , K ( o / a ) , was measured by e i t h e r the s o l u t e a b s o r p t i o n , s o l u t e e x t r a c t i o n , or the temperature v a r i a t i o n method d e s c r i b e d above except t h a t the U-shaped e q u i l i b r a t i o n c e l l was used i n p l a c e of the bubble c e l l . The U-shaped c e l l was designed to keep V s m a l l and to be a b l e to weigh o c t a n o l conveniently. c

c

Results Values f o r K(w/a), K ( o / a ) , and K(o/w) f o r dimethyImercury i n d i s t i l l e d and sea water are given i n t a b l e s I and I I , r e s p e c t i v e l y . Absolute values of K(w/a) and K(o/a) i n d i s t i l l e d water were determined u s i n g the s o l u t e a b s o r p t i o n method a t two tempera t u r e s , 15.42 and 5.38°C. Values of K(w/a) and K(o/a) at other temperatures were obtained u s i n g the temperature v a r i a t i o n method. Absolute values of K(w/a) and K(o/a) i n sea water were determined a t two temperatures 18.42 and 6.42°C. The remaining K(w/a) and K(o/a) were obtained u s i n g the temperature v a r i a t i o n method. The numbers i n parentheses are the standard d e v i a t i o n s of the p a r t i t i o n c o e f f i c i e n t s . No K(o/w) values f o r dimethyImercury are reported i n the l i t e r a t u r e . I n order to compare K(o/w) v a l u e s measured i n t h i s work w i t h l i t e r a t u r e v a l u e s , we determined K(o/w) f o r benzene (132), toluene (482), and ethylbenzene (1420) i n d i s t i l l e d water at 25°C. The values may be compared w i t h those v a l u e s measured Hansch et a l ( 8 ) , e.g., benzene (135), toluene (490), and e t h y l benzene (1413). Discussion The main cause of the spread i n the K(w/a) and K(o/a) v a l u e s a r i s e from d i s p e r s i o n s i n the peak area measurements by the e l e c t r o n i c i n t e g r a t o r . This spread was reduced by t u r n i n g the c i r c u l a t i n g pump o f f before sample i n j e c t i o n i n t o the gas

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

19.

WASIK

Partition of Organoelements

321

TABLE I

Dime thy Imercury P a r t i t i o n C o e f f i c i e n t s i n D i s t i l l e d Water K(w/A) K(o/W) K(o/A)

Temp. (°C)

Number o f Observations

5.38

6

12.41(.050)

1800(6.2)

145.0(.76)

8.02

6

10.5K.041)

1590(5.4)

151.4(.78)

10.40

8

9.11(0.41)

1435(5.4)

157.1(.91)

13.10

7

7.82(.038)

1272(4.8)

162.6(.99)

15.42

6

18.62

6

5.71(.031)

1004(3.9)

175.8(1.1)

20.00

9

5.25(.032)

950(3.6)

180.9(1.2)

24.48

6

4.13(.028)

790(3.4)

191.3(1.3)

TABLE I I

DimethyImercury P a r t i t i o n C o e f f i c i e n t s i n Sea Water Temp. (°C)

Number o f Observations

K(w/A)

6.42

7

8.52(.041)

1720(9.1)

201.9(1.4)

10.02

6

6.82(.034)

1466(6.2)

215.0(1.4)

13.08

7

5.68(.030)

1282(5.2)

225.7(1.5)

15.64

7

4.90(.022)

1151(5.1)

234.9(1.5)

18.42

8

4.15(.021)

1010(5.0)

243.4(1.7)

20.00

6

3.82(.017)

950(4.4)

248.7(1.6)

25.00

6

2.88(.011)

760(3.6)

263.9(1.6)

K(o/W)

K(o/A)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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chromatograph. A group of 30 observations of dimethyImercury peak areas was found to have a c o e f f i c i e n t of v a r i a t i o n of 0.75 percent w i t h the pump on w h i l e the same number of observations gave a v a r i a t i o n of 0.15 percent w i t h the pump o f f . The pump was conveniently turned o f f by stopping the supply of compressed a i r to the pump. I n the methods described above f o r measuring K(o/a) and K(w/a), the term (Α/Αχ - 1) appears i n equations ( 4 ) , ( 7 ) , and (13). The e r r o r , p a r t i c u l a r l y i n the K(w/a) c a l c u l a t i o n s , may be l a r g e f o r s m a l l values of A/A^. This e r r o r may be reduced by choosing the volume of the l i q u i d phase such t h a t A/A^ i s l a r g e . In p r a c t i c e , s e v e r a l e q u i l i b r a t i o n c e l l s of d i f f e r e n t volumes should be a v a i l a b l e f o r t h i s use. T h i s e r r o r may a l s o be reduced by the proper choice of the method used f o r measurin K(w/a) Fo i n s t a n c e th volum f the e q u i l i b r a t i o n c e l l use the l i q u i d volume, V L , equa g a d s o r p t i o n method f o r dimethylmercury i n d i s t i l l e d water a t 16.02°C i t was found that A/A = 10.217 (K(w/a) = 6.00). An e r r o r of 0.50 percent i n A/AJL r e s u l t e d i n a 0.549 percent e r r o r i n K(w/A). Under the same experimental c o n d i t i o n s the s o l u t e e x t r a c t i o n method gave A/A^ = 1.098, r e s u l t i n g i n an e r r o r of 5.31 percent i n K(w/a). I f , under the same experimental con d i t i o n s , a s o l u t e w i t h K(w/a) = 0.10 was measured u s i n g the s o l u t e e x t r a c t i o n method; A/A^ would equal 6.00 r e s u l t i n g i n an e r r o r of 0.7% i n K(w/a) whereas the s o l u t e a b s o r p t i o n method would g i v e A/A^ = 1.20 and an e r r o r of 3.5 percent. I n g e n e r a l , the s o l u t e a b s o r p t i o n method i s p r e f e r r e d f o r K(w/a) values g r e a t e r than u n i t y , w h i l e the s o l u t e e x t r a c t i o n method i s p r e f e r r e d f o r K(w/a) values l e s s than u n i t y . A p o s s i b l e systematic e r r o r i s t h a t a s i g n i f i c a n t f r a c t i o n of the s o l u t e vapor could be adsorbed on the surface of the apparatus r a t h e r than i n the gas phase. To evaluate t h i s e f f e c t , the e x t r a c t i o n f a c t o r (equation 10, where V = 0, V = V ) f o r the dry apparatus was examined f o r dimethylmercury over a 1000f o l d c o n c e n t r a t i o n range by repeatedly e x t r a c t i n g the gas i n VR. V Τ The slope l o g Γ + 1] of the p l o t log(A../A.) versus i - 1 was Τ R l i n e a r and equal to the c a l c u l a t e d v a l u e . Two such experiments a t a i r bath temperature of 100°C and 50°C gave the same r e s u l t s . These experiments i n d i c a t e t h a t surface a d s o r p t i o n was a n e g l i g i b l e f a c t o r i n the K(w/a) and K(o/a) measurements and t h a t the hydrogen flame d e t e c t o r was l i n e a r over the s o l u t e c o n c e n t r a t i o n range measured. The same experiments were repeated w i t h methane as the s o l u t e and gave s i m i l i a r r e s u l t s . In an i d e n t i c a l experiment w i t h diethyImercury as the s o l u t e i t was observed t h a t the s o l u t e peak area d i d not o b t a i n a constant value but decreased w i t h time. Two i m p u r i t y peaks; one i d e n t i f i e d by gas chromatography as η-butane and one as x

L

C

T

c

1

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

19.

WASIK

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323

p o s s i b l y ethane increased i n time. Lowering the a i r - b a t h temperat u r e from 100° to 50°C slowed the thermal decomposition of d i e thy Imercury but d i d not stop i t . These experiments were done i n the absence of l i g h t i n order to r u l e out well-known photodecomposition processes ( 9 ) . The methods described i n t h i s paper f o r measuring K(w/a) and K(o/a) a r e a p p l i c a b l e to compounds having a vapor pressure g r e a t e r than 0.10 T o r r . For compounds w i t h vapor pressures l e s s than 0.1 Torr a d s o r p t i o n of the s o l u t e on the w a l l s of the apparatus would probably lead to erroneous values of K(w/a) and K(o/a). I n any case, f o r compunds having low vapor pressures o r compounds that adsorb s t r o n g l y on s u r f a c e s , the procedure described above should be used to determine the extent of s u r f a c e adsorption. Using Neely jet a l (1) l i n e a r e g r e s s i o equatio t c o r r e l a t the o c t a n o l p a r t i t i o n c o e f f i c i e n chlorohydrocarbons i n t r o u f a c t o r of twenty f o r dimethylmercury i n f r e s h water. T h i s presumes that the l i p o p h i l i c i t i e s of dimethylmercury and the chlorohydrocarbons e i t h e r occur by s i m i l i a r processes o r t h a t the molecular d i f f e r e n c e s are not that important i n r a t e - d e t e r m i n i n g uptake s t e p s . The K(o/w) values f o r dimethylmercury a r e approximately 37 percent g r e a t e r i n sea water than f r e s h water which would i n d i c a t e that the b i o c o n c e n t r a t i o n f a c t o r i s g r e a t e r i n sea water than i n f r e s h water.

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Literature Cited 1. Neeley, W. Β., Branson, D. R., and Blau, G. Ε., Environ. S c i . Technol. 8, 1113 (1974). 2. Branson, D. R., et al., Proceedings of Symposium Structure Activity Correlations in Studies of Toxicity and Bioconcentration with Aquatic Organisms, Canada Center for Inland Waters, Burlington, Ontario, Canada (1975). 3.

Dunn, W., and Hansch, C . , J. Pharm. S c i . 61, 1 (1972).

4. Leo, A. J., Symposium on Nonbiological Transport and Trans formation, National Bureau of Standards, Gaithersburg, MD (1976). 5. Wasik, S. P . , Brown Sci. Health A11(1), 99 (1976). 6. Brown, R. L., and Wasik, S. P . , J. of Res. National Bureau of Standards 78A, 453 (1974). 7. Sverdrup, H. V . , Johnson, M. W., and Fleming, R. Η . , The Oceans Prentice-Hall, Inc., Englewood C l i f f s , New Jersey (1942). 8. Hansch, C . , Quinlan, J. Ε . , and Lawrence, G. L., J. Organic Chem. 33, 347 (1968). 9. Rebbert, R. E., and Steacic, E . W. R., Can. J. Chem. 31, 631 (1953).

Discussion F. E . BRINCKMAN (National Bureau of Standards): By doing the linear free energy relationship as a function of temperature one can generate a thermodynamic property, in this case, the heat of solution. This is a very important concern for organometal chem i s t s who do not have such information for these kinds of species. Experimentally, what kind of v o l a t i l i t y do you need i f you want to do a system as a function of salinity and temperature; for example, one of these organotin species which has ionic properties and strongly solvates in water? WASIK: We have other methods of determining these partition coefficients. This is what we c a l l our volatile solute method. Roughly, i t ' s good for solutes of a boiling point less than 200 . Above 200 we have to use l i q u i d chromatography as a detector. Q

G. E . PARRIS (Food and Drug Administration): People who do partition coefficients, such as octanol-water, where they put the

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

19.

WASIK

Partition of Organoelements

325

two phases i n d i r e c t c o n t a c t , a r e u s u a l l y concerned about there being some water s o l u b i l i t y i n o c t a n o l and some o c t a n o l s o l u b i l i t y i n water. How much d i f f e r e n c e does i t make doing i t i n d i r e c t l y where you a c t u a l l y measure (or can get a c a l c u l a t e d v a l u e ) f o r w a t e r - o c t a n o l , as opposed t o w a t e r - s a t u r a t e d o c t a n o l versus o c t a n o l - s a t u r a t e d water? WASIK: We d i d the experiment where we determined the octano l - a i r p a r t i t i o n c o e f f i c i e n t i n o c t a n o l s a t u r a t e d w i t h water and i n o c t a n o l ; there was about 2% d i f f e r e n c e . The o c t a n o l - a i r p a r t i t i o n c o e f f i c i e n t can a l s o be measured by gas chromatography by measuring the r e t e n t i o n time of the s o l u t e . PARRIS: I s t h i s f i g u r e of 2% t y p i c a l i n view of the heats of s o l v a t i o n f o r d i f f e r e n might v a r y w i d e l y ? WASIK: solute.

Of course

i t would vary w i d e l y a c c o r d i n g t o the

J . S. THAYER ( U n i v e r s i t y of C i n c i n n a t i ) : What a r e the prope r t i e s o f o c t a n o l that make i t a d e s i r a b l e s o l v e n t f o r use i n t h i s p a r t i c u l a r study? WASIK: From the p h y s i c a l chemical s t a n d p o i n t , i t ' s a poor choice. We would have been b e t t e r o f f w i t h something l e s s v o l a t i l e and l e s s s o l u b l e . Water i s f a i r l y s o l u b l e i n o c t a n o l . But I t h i n k people j u s t kept measuring i t and measuring i t , and i t s c o n v e n t i o n a l use grew. Once you measure the octanol-water part i t i o n c o e f f i c i e n t of a parent compound then you can p r e d i c t the octanol-water c o e f f i c i e n t f o r d e r i v a t i v e s . I f you know a coeff i c i e n t f o r benzene, you could p r e d i c t that i t would be f o r x y lenes and butylbenzene because they show a d d i t i v e p r o p e r t i e s . You don't a c t u a l l y have t o measure a l o t of compounds as long as you measure the parent compound. A. J . CANTY ( U n i v e r s i t y of Tasmania): Your comment j u s t then and the p a r t i t i o n c o e f f i c i e n t f o r dimethylmercury r e l a t e t o some work that we have been doing i n v e s t i g a t i n g b o d i l y d i s t r i b u t i o n of phenyl compounds. You would expect a s i m i l a r r e l a t i o n s h i p of p a r t i t i o n c o e f f i c i e n t s f o r diphenyImercury t o dimethylmercury. We f i n d that i n t r a p e r i t o n e a l i n j e c t i o n of diphenyImercury, compared w i t h monophenyImercury, shows a 10 t o 20 times h i g h e r c o n c e n t r a t i o n i n f a t t y t i s s u e which would correspond f a i r l y w e l l w i t h your partition coefficients. M. L. GOOD ( U n i v e r s i t y of New O r l e a n s ) : Are these head-space experiments the same techniques that you use f o r determining the v o l a t i l e m a t e r i a l s from a b a c t e r i a l m e t h y l a t i o n procedure?

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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WASIK:

ORGANOMETALLOIDS

L i k e Dr. Brinckman does?

GOOD: Yes. WASIK: the system.

I b e l i e v e h i s head-spaces a r e i n e q u i l i b r i u m w i t h Do you c i r c u l a t e the v o l a t i l e gases?

BRINCKMAN: We have done both s t a t i c and c i r c u l a t i o n measure ments. Our problem i s d e t e c t o r s e n s i t i v i t y . With some m i c r o organisms, p a r t i c u l a r l y the ρlasmid-altered microorganisms, such as we have acquired from P r o f e s s o r Simon S i l v e r ' s l a b o r a t o r y (Washington U n i v e r s i t y , S t . L o u i s ) , the IS. c o l i which are good methylators of mercury, we might do d i r e c t measurements. You have t o dedicate the apparatus because the experiments r e q u i r e some p e r i o d o f time an s u r f a c e e f f e c t s from th WASIK: One of the most important things about t h i s type of p a r t i t i o n c o e f f i c i e n t measurement i s t h a t these a r e a t i n f i n i t e d i l u t i o n , and from that you can measure a c t i v i t y c o e f f i c i e n t s which g i v e you more freedom t o make new c o r r e l a t i o n s . RECEIVED

November 3,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

20 Aspects of M e r c u r y ( I I ) T h i o l a t e C h e m i s t r y a n d the Biological B e h a v i o r of M e r c u r y C o m p o u n d s ALLAN J. CANTY Chemistry Department, University of Tasmania, Hobart, Tasmania, Australia

Complex formatio cysteine, is believed chemistry of mercury(1). The greater affinity of Hg(II) and MeHg(II) for thiols than other possible biological donor ligands has been well documented by stability constant studies in aqueous solution (2,3). Our interest in mercury(II) thiolates stems from studies of the chemistry of the antidote British anti-Lewisite which indicated that the structure and reactivity of simple thiolate complexes was little understood. In this review our recent work on the interaction of inorganic and organomercury compounds with British anti-Lewisite, simple thiols and sulphur containing amino acids is discussed, followed by an account of animal studies of the distribution and metabolism of phenylmercury compounds. In discussing the implications of chemical results, e.g. reactivity of thiolates, for the biological behaviour of mercury compounds it is assumed here that chemical studies provide only plausible pathways for biological behaviour. In recent years other workers have reported studies of mercury thiolates that are related to the work described here, in particular nuclear magnetic resonance studies of the interaction of MeHg(II) with thiols (4-9) and the preparation (10-16) and X-ray structural analysis of key complexes of Hg(II), MeHg(II), and PhHg(II) with sulphur containing amino acids (10-15). Complexes of British anti-Lewisite and other Thiols British anti-Lewisite [dimercaprol, 2,3-dimercaptopropanol; abbreviated BALH3 to indicate loss of thiol protons on complex formation, e.g. Hg(BALH)] has been used for the treatment of mercury poisoning in humans (17,18) and has been studied extensively in animal experimentsTl8-24). Although it may be eventually replaced by a more satisfactory treatment, e.g. hemodialysis (25,26), it is successful for poisoning by 0-8412-0461-6/78/47-082-327$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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inorganic mercury (17,18) and i s the most s a t i s f a c t o r y a n t i d o t e f o r phenylmercury(II) poisoning [animal experiments only to date ( 1 8 ) ] , but has no therapeutic e f f e c t f o r methylmercury(II) poisoning i n humans or animals (18). For PhHg(II) poisoning BALH3 g r e a t l y increases the amount o f mercury i n the brain compared with the b o d i l y d i s t r i b u t i o n i n the absence of BALH3 treatment Q8,19.,20,2]_), and f o r MeHg(II) i t merely hastens the d i s t r i b u t i o n o f mercury and may increase the amount of mercury i n the b r a i n (18). An increased mercury content i n the b r a i n i s u n d e s i r a b l e , as i t attacks the c e n t r a l nervous system. BALH3 a l s o increases the amount o f mercury i n the b r a i n following i t s a d m i n i s t r a t i o n f o r inorganic mercury poisoning (22,23,24), but t h i s e f f e c t has been explained i n terms o f the timing and dosage of BALH3 (24). I s o l a t i o n o f Hg(BALH) (27,28) and evidence f o r the formation o f [ H g ( B A L H ) (RHg) BALH „ [n = 1 (29), 2 T28); R = CH CH(0MiTCH R'] were reported by several workers soon a f t e r the I n t r o d u c t i o n o f BALH3 as an antidote f o r heavy metal p o i s o n i n g . Mercuric c h l o r i d e reacts immediately with BALH3 i n water to form a white s o l i d i d e n t i f i e d as Hg(BALH) (27,28,30*11)· n

HgCl

3

n

2

2

+ BALH + Hg(BALH) + 2HC1

2

3

C r y s t a l s t r u c t u r e s of simple t h i o l a t e s Hg(SR)2 reveal e i t h e r l i n e a r monomers [R=Me (32), Et (33)] (Figure 1) or a polymeric s t r u c t u r e with t e t r a h e d r a l mercury (R=Bu ) (34) (Figure 2). Infrared and Raman spectra i n d i c a t e t h a t h i g h l y i n s o l u b l e Hg(BALH) has a polymeric s t r u c t u r e based on l i n e a r c o o r d i n a t i o n for mercury (31) (Figure 3 ) , r a t h e r than the c y c l i c s t r u c t u r e u s u a l l y presented (Figure 4 ) . Thus, Hg(BALH) has v c ( S H g S ) 348 and v (SHgS) 298 crrr», s i m i l a r to that o f Hg(SMe)2 (377 and 297 cm-1) and well removed from tetrahedral mercury i n Hg(SBut) (172 and 188 cm-1) (31). Spectroscopic p r o p e r t i e s appropriate f o r i d e n t i f i c a t i o n o f Hg(II) t h i o l a t e s , e . g . i n f r a r e d , Raman, and nuclear magnetic resonance, a r e presented elsewhere ( H , 3 5 , 3 6 , 3 7 , 3 8 , 3 9 ) . The simple t h i o l a t e s HgXSR7 are i n s o l u b l e i n water but s o l u b l e i n organic s o l v e n t s , e . g . Hg(SR) (R=Et,Bu ,Ph) are monomeric i n chloroform. Hg(BALH) i s i n s o l u b l e i n water, even a t concentrations o f c a . 10'^M (40). An impure form of Hg(BALH) can be i s o l a t e d by r e a c t i o n of mercuric acetate with BALH3 i n p y r i d i n e (35). T h i s s o l i d i s s o l u b l e i n p y r i d i n e , and the r e l a t e d complex o f 1,3-dimercaptopropanol, Hg(DMPH), can be i s o l a t e d from water and forms a dimer i n p y r i d i n e (35). The s t r u c t u r e o f Hg(DMPH) i n p y r i d i n e i s unknown but presumably involves p y r i d i n e c o o r d i n a t i o n , [Hg(DMPH)py ] , as i t c r y s t a l l i z e s as Hg(DMPH)py].5 c o n t a i n i n g coordinated p y r i d i n e . The s o l u b i l i t y o f impure Hg(BALH) i n p y r i d i n e i s o f i n t e r e s t as Hg(BALH) i s presumably formed i n many "environments" i n v i v o , t

a

s

2

2

t

2

x

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

CANTY

Mercury Compounds

RS

Hg

SR

Figure 1.

S V

Hg"

" Hg 1

Bu Figure 2.

Hg Figure 3.

Figure 4.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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ORGANOMETALS

AND ORGANOMETALLOIDS

and p y r i d i n e s o l u b i l i t y suggests higher s o l u b i l i t y i n l i p i d t i s s u e than more aqueous r e g i o n s . The neutral complex may be present as a dimer [Hg(BALH)Lv] r e l a t e d to Hg(DMPH) i n p y r i d i n e , or p o s s i b l y as the c y c l i c complex (Figure 4) with a d d i t i o n a l ligands coordinated to mercury. In a l k a l i n e s o l u t i o n Hg(BALH) d i s s o l v e s on a d d i t i o n o f excess BALH3 suggesting (27) formation o f [Hg(BALH)2] ", and a d d i t i o n o f BALH3 to a s o l u t i o n o f impure Hg(BALH) i n p y r i d i n e r e s u l t s i n an increase i n c o n d u c t i v i t y (35). Stability constants f o r formation o f the neutral and i o n i c complexes i n water have r e c e n t l y been determined by potentiometric t i t r a t i o n (40), and the very high values c o n t r i b u t e to the e f f e c t i v e n e s s of B r i t i s h a n t i - L e w i s i t e as an a n t i d o t e . 2

2

Hg

2 +

+ BALH " * ±

Hg(BALH)

2

Hg(BALH) + BALH *

Log Κ = 25.74 ±

[Hg(BALH) ] "

2

2

Log Κ = 8.61 ±

2

.45 0.10

Organomercury d e r i v a t i v e s o f BALH3 may be obtained by r e a c t i o n with phenylmercuric acetate i n water and methyl mercuric acetate i n benzene (35). 2RHg0 CMe + BALH^ + (RHg) BALH + 2MeC0 H 2

2

2

Infrared and Raman spectra o f these complexes and other organomercury t h i o l a t e s i n d i c a t e monomeric s t r u c t u r e s i n the s o l i d s t a t e as v(Hg-S) values (326-388 cm" ) are i n the region expected f o r l i n e a r c o o r d i n a t i o n f o r mercury, and coincidence of i n f r a r e d and Raman values i n d i c a t e absence o f a centre o f symmetry a t mercury (Figure 5,6) (35), thus excluding dimeric s t r u c t u r e s s i m i l a r to t h a t formed by r e l a t e d PhHg(II) alkoxides i n benzene (Figure 7) (41). 1H NMR spectroscopy i s p a r t i c u l a r l y useful f o r c h a r a c t e r i z a t i o n o f organomercury compounds. Thus, (MeHg) BALH has j ( l H - l " H g ) 169 Hz f o r the NeHg(II) group, and PhHg(II) t h i o l a t e s have J(orthOH-199Hg) 144-158 Hz and J(orthOH-meta ) 6-8 Hz (35). The complexes (RHg) BALH (R=Me,Ph) are i n s o l u b l e i n water but d i s s o l v e i n p y r i d i n e and dimethylsulphoxide, and the r e l a t e d t h i o l a t e of lower molecular weight, PhHgSCH CH 0H, i s s o l u b l e and monomeric i n chloroform. However, organomercury t h i o l a t e s formed from n a t u r a l l y o c c u r r i n g t h i o l s i n vivo are l i k e l y to be water s o l u b l e , e . g . the L - c y s t e i n e complexes MeHgSCH2CH(NH3)C0 .H 0 and PhHgSCH CH(NH )C0 contain hydrop h i l i c z w i t t e r i o n i c groups and c r y s t a l l i z e from aqueous ethanol (12,36). Thus, displacement o f b i o l o g i c a l t h i o l ligands with BALH3 i s expected to form more l i p i d s o l u b l e complexes, as suggested by B e r l i n et_aj_. (20), and may account f o r higher concentrations o f mercury i n b r a i n t i s s u e of animals administered BALH3 a f t e r i n j e c t i o n o f organomercury compounds when compared 1

2

H

2

2

2

2

2

3

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

CANTY

Mercury Compounds

R

Hg

SR

Figure 5.

R

Hg

SCH

R

Hg

SCH

2

CH OH 2

Figure 6.

R 0 Ph

Hg

Hg

Ph

0 R Figure 7.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

332

AND

ORGANOMETALLOIDS

with concentrations i n the absence of BALH3 treatment. It was found that (PhHg^BALH decomposes at ambient temperature i n acetone, benzene, and methanol to form Ph2Hg (30,35) (Table I). (PhHg) BALH + Ph Hg + Hg(BALH) 2

2

Table I Decomposition o f Some Phenylmercury (II)

Complex

Solvent

(PhHg)oBALH (PhHg)2BALH PhHg(H3cyst) PhHg(H3pen) (PhHg)2(H cyst)-H20 (PhHg)2H2Pen

aceton benzene benzene benzene benzene benzene

2

Thiolates

Y i e l d o f Ph Hg(%) 2

100 55 81 44 43

From references 35,36. Suspensions a t ambient temperature were s t i r r e d magnetically for seven days. Ph2Hg was i s o l a t e d as a pure s o l i d from the f i l t r a t e . b Y i e l d o f Ph Hg based on ' P h . H 3 c y s t = SCH CH(NH3)C0 ; H c y s t = SCH CH(NH2)C0 ; s i m i l a r l y f o r HSCMe2CH(NH )C0 , DL-pen i ci11 ami ne. 1

2

c

2

3

2

2

2

2

2

I f t h i s r e a c t i o n occurs i n vivo i t may a l s o c o n t r i b u t e to r e d i s t r i b u t i o n of mercury, and to i n d i c a t e whether PI^Hg formation may be a general b i o l o g i c a l r e a c t i o n i n the absence of BALH3 s e r i e s o f PhHg(II) complexes of s u l p h u r - c o n t a i n i n g ami no acids was prepared and t h e i r s t a b i l i t i e s studied (36). The complexes were synthesized by r e a c t i o n of phenylmercuric acetate with the amino acids i n aqueous e t h a n o l , e . g . a

2PhHg0 CMe + ftycyst ·* (PhHg) (H cyst)-H20 + 2MeC02H 2

2

2

The D L - p e n i c i l l a m i n e complexes have been prepared by other workers, but the s t a b i l i t y o f the complexes toward decomposition had not been studied (16). The amino a c i d complexes were found to decompose i n benzene to form Ph2Hg (Table I). The importance of these r e a c t i o n s , and decomposition o f (PhHg)2BALH, i s d i f f i c u l t to assess as they are s o l v e n t dependent and rates o f decomposition v a r y , e . g . (PhHg)2BALH and amino a c i d complexes may be r e a d i l y prepared i n

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

20.

Mercury Compounds

CANTY

333

aqueous s o l u t i o n , they decompose slowly i n benzene, and when PhHgi^CMe and BALH3 ethanol immediate p r e c i p i t a t i o n occurs and PI^Hg may be obtained from the f i l t r a t e on f i l t r a t i o n . I f Ph Hg i s formed i n vivo then the b i o l o g i c a l behaviour o f Ph Hg i s o f i n t e r e s t as phenylmercury compounds, e . g . PhHg0 CMe, are s t i l l widely used i n a g r i c u l t u r e and medicine. I t has been reported t h a t Ph Hg i n " s c a r c e l y d e t e c t a b l e " concentration formed by degradation o f p h e n y l mercuric acetate (formerly contained i n d e r e l i c t s t e e l drums), was s u f f i c i e n t l y t o x i c to k i l l f i s h w i t h i n a few hours i n the Boone R e s e r v o i r , Tennessee V a l l e y (43). a

r

e

r

e

a

c

t

e

d

l

n

2

2

2

2

Biological

Behaviour of

Piphenylmercury

Diphenylmercury has q u i t e d i f f e r e n t p h y s i c a l and chemical p r o p e r t i e s than PhHg(II p o l a r molecule i n s o l u b l e i n water but s o l u b l e i n organic solvents and i s thus expected to be l i p i d s o l u b l e (44), and i n c o n t r a s t to PhHg(II) compounds (45,46,47) i t i n t e r a c t s o n l y weakly with donor molecules (48,49,50). S i m i l a r l y , Me Hg does not form complexes (45) but MeHg(II) forms s t a b l e complexes, e . g . [MeHgL] with p y r i d i n e (51,52), 2 , 2 * - b i p y r i d y l (51,52,53» 54), and 1,10-phenanthroline T52,53). In d i s t r i b u t i o n and metabolism s t u d i e s we have i n j e c t e d ethanol s o l u t i o n s o f mercuric c h l o r i d e , phenylmercuric a c e t a t e , o r Ph Hg i n t r a p e r i t o n e a l l y i n t o r a t s (55,56). The r a t s were s a c r i f i c e d a t i n t e r v a l s ranging from 20 min. to 7 days and samples of b l o o d , b r a i n , l i v e r , kidney, muscle, f a t , and spleen were analysed f o r mercury. In another s e r i e s o f experiments faecal and u r i n a r y e x c r e t i o n was monitored f o r several days after injection. During the f i r s t few days a f t e r i n j e c t i o n , u r i n a r y e x c r e t i o n o f mercury was much higher f o r the diphenylmercury-injected r a t s than f o r the phenylmercuric acetate o r mercuric c h l o r i d e i n j e c t e d r a t s , with mercuric c h l o r i d e having the lowest rate o f excretion. Faecal e x c r e t i o n was s i m i l a r f o r the three compounds, with phenylmercuric acetate being more r a p i d l y excreted (Table II). Analyses o f blood and t i s s u e s f o r t o t a l mercury i n d i c a t e d that a f t e r i n i t i a l marked d i f f e r e n c e s i n b r a i n and f a t t y t i s s u e c o n c e n t r a t i o n s , the d i s t r i b u t i o n o f mercury f o r Ph2Hg resembled those o f the other compounds a f t e r 1 day, but concentrations were g e n e r a l l y lower than f o r the other compounds (55,56). The lower concentrations are explained by the more r a p i d e x c r e t i o n o f mercury from Ph Hg. During the f i r s t hour a f t e r i n j e c t i o n mercury from Ph2Hg accumulated a t a higher c o n c e n t r a t i o n i n the b r a i n than from the other compounds, but a f t e r 6 hours these concentrations had decreased c o n s i d e r a b l y (55_,5(5). The concentration of mercury i n f a t t y t i s s u e was 10-20 times higher f o r diphenylmercury2

+

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

334

ORGANOMETALS

AND

ORGANOMETALLOIDS

Table II Urinary and Faecal E x c r e t i o n o f Mercury from Rats w i t h i n Two Days o f I n j e c t i o n

HgCl

PhHg0 CMe

2

2

Percentage o f dose

2.5 5.2 7.7

Urinary E x c r e t i o n : Faecal E x c r e t i o n : Urinary + Faecal :

2.2 4.5 6.7

4.8 12.2 17.0

8.0 8.4 16.4

Ph Hg 2

excreted

30.5 5.6 36.1

38.3 3.6 41.9

From reference 56. Analyses f o r t o t a l mercury, as described elsewhere (55). Two r a t s were i n j e c t e d i n t r a p e r i t o n e a l l y with each compound, dose 248 mg mercury, a l l r a t s o f weight 160 g.

i n j e c t e d r a t s a t 20 min. a f t e r i n j e c t i o n , but then r a p i d l y dropped to values s i m i l a r to the other mercury compounds (Table III). The much higher c o n c e n t r a t i o n of mercury i n b r a i n and f a t t y t i s s u e immediately a f t e r Ph Hg i n j e c t i o n i s c o n s i s t e n t with d i s t r i b u t i o n o f mercury as, Ph Hg, and t h i s was confirmed by t h i n - l a y e r chromatography. A sample o f f a t t y t i s s u e taken from a diphenylmercury-injected r a t 20 min. a f t e r i n j e c t i o n was blended with benzene using a small Waring blender, and t h i n l a y e r chromatography showed the presence of diphenylmercury ( u l t r a v i o l e t i r r a d i a t i o n ) ; the s i l i c a gel o f the p l a t e a t the Rf value o f Ph Hg contained 5.19 mg. o f Hg/g o f s i l i c a gel compared with 0.15 mg/g f o r s i l i c a gel at lower Rf value on the same p l a t e . It has been e s t a b l i s h e d that phenylmercury i s degraded to inorganic mercury i n a few days i n r a t s (57,58,5£,60,61). Daniel e t a l . (60) represent t h i s breakdown as 2

2

2

C

6 5 H

H g +

+

H +

C

6 6 H

+

H

g

2

+

A s i m i l a r breakdown may occur f o r Ph Hg, presumably v i a PhHg(II), as the i n i t i a l high concentrations o f mercury i n b r a i n and f a t t y t i s s u e f a l l to values s i m i l a r to that obtained with the other compounds a f t e r 6 h r . and 1 h r . , r e s p e c t i v e l y . Thus, i f Ph Hg i s formed i n vivo i t s b i o l o g i c a l e f f e c t s are d i f f i c u l t to evaluate as i t i s more r a p i d l y excreted than PhHg(II) and apparently broken down by the body, but has a q u i t e d i f f e r e n t i n i t i a l d i s t r i b u t i o n . However, i t i s o f i n t e r e s t to note that although mercury vapour i s o x i d i z e d to Hg(II) i n c a . 30 sec. i n blood t h i s i s s u f f i c i e n t time f o r mercury (from vapour) to 2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

20.

CANTY

Mercury Compounds

335

Table III Concentration o f Mercury i n Brain and Fatty T i s s u e s o f Hooded Wistar Rats Injected I n t r a p e r i t o n e a l l y with Mercury Compounds

Time

Brain

Dose o f 6 mg. o f Hg/kg o f r a t . mercuric c h l o r i d e 20 min. (2) 0.16 ± 0.02 1 h r . (2) 0.33 ± 0.07 6 h r . (2) 0.16 ± 0.01 1 day (2) 0.24

Fat

A.

20 min. (2) 1 h r . (2) 6 h r . (2) 1 day (2) 20 min. (2) 1 h r . (2) 6 h r . (2) 1 day (2)

0.14 ± 0.04 0.47 ± 0.03 0.9 ± 0.3 0.65 ± 0.02 diphenyImercury 0.9 ± 0.2 0.7 ± 0.2 0.26 ± 0.01 0.20 ± 0.03

Dose of 1.5 mg. of Hg/kg o f r a t . mercuric c h l o r i d e 20 min. (1) 0.04 phenylmercuric acetate 20 min. (1) 0.01 diphenylmercury 20 min. (1) 0.3

10.5 4.8 3.4 15.7

+ + + +

2.8 2.1 1.3 5

2 5 4.4 + 1.2 4.7 + 0.2 3.5 + 0.3 147 10.4 10.1 3.6

±13 + 3.2 + 3.4 + 0.2

B.

2.34 0.9 27.8

From reference 56_. Recorded as yg o f Hg/g t i s s u e , wet weight, and the range o f values i s i n d i c a t e d . The number o f r a t s i n each category i s given i n parentheses with the time. achieve an c a . t e n - f o l d higher accumulation i n the b r a i n than from i n o r g a n i c mercury poisoning (27,62) leading to higher t o x i c i t y o f mercury vapour. Acknowledgements I thank the National Health and Medical Research Council and the Commonwealth Development Bank f o r f i n a n c i a l support, and my co-workers, R. Kishimoto and R. S. Parsons, f o r t h e i r c o n t r i b u t i o n s to work reviewed here.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

336

organometals and organometalloids

Literature 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

18. 19. 20. 21. 22. 23. 24. 25.

Cited.

See, e.g. Clarkson, T. W., Ann. Rev. Pharmacol. (1972), 12, 375. Simpson, R. B . , J. Am. Chem. Soc. (1961), 83, 4711. Schwarzenbach, G . , and Schellenberg, M . , Helv. Chim. Acta. (1965), 48, 28. Simpson, P. G . , Hopkins, Τ. Ε . , and Haque, R., J. Phys. Chem. (1973), 77, 2282. Rabenstein, D. L., J. Am. Chem. Soc. (1973), 95, 2797. Fuhr, B. J., and Rabenstein, D. L., J. Am. Chem. Soc. (1973), 95, 6944. Rabenstein, D. L., and Fairhurst, M. T., J. Am. Chem. Soc. (1975), 97, 2086. Fairhurst, M. T., (1975), 14, 1413 Sugiura, Y . , Hojo, Y . , Tamai, Y . , and Tanaka, H . , J. Am. Chem. Soc. (1976), 98, 2339. Wong, Y. S., Chieh, P. C., and Carty, A. J., J . C . S . Chem. Comm. (1973), 741. Wong, Y. S . , Taylor, N. J., Chieh, P. C., and Carty, A. J., J . C . S . Chem. Comm. (1974), 625. Taylor, N . J . , Wong, Y. S . , Chieh, P. C., and Carty, A. J., J . C . S . Dalton (1975), 438. Wong, Y. S . , Carty, A. J., and Chieh, P. C., J . C . S . Dalton (1977), 1157. Wong, Y. S . , Carty, A. J., and Chieh, C . , J . C . S . Dalton (1977), 1801. Carty, A. J., and Taylor, N. J., J . C . S . Chem. Comm. (1976), 214. Hojo, Υ . , Sugiura, Υ . , and Tanaka, H . , J. Inorg. Nucl. Chem. (1976), 38, 641. Clarkson, T. W., and DiStefano, V . , in " D r i l l ' s Pharma cology in Medicine", DiPalma, J. R., and Joseph, R . , Eds., Ch. 53, McGraw-Hill, 4th Edn. (1971). Swensson, Α . , and Ulfvarson, U . , Int. Arch. Gewerbepath. Gewerbehyg. (1967), 24, 12. Berlin, Μ., and Ullberg, S., Nature (1963), 197, 84. Berlin, M . , Jerksell, L.-G., and Nordberg, G . , Acta. Pharmacol. Toxicol. (1965), 23, 312. Berlin, Μ., and Rylander, R . , J. Pharmacol. Exptl. Therap. (1964), 146, 236. Fitzsimmons, J. R., and Kozelka, F. L., J. Pharmacol. Exptl. Therap. (1950), 98, 8. Berlin, Μ., and Lewander, T., Acta. Pharmacol. Toxicol. (1965), 22, 1. Magos, L., B r i t . J. Indust. Med. (1968), 24, 152. Kostyniak, P. J., Clarkson, T. W., Cestero, R. V., Freeman, R. B . , and Abbasi, A. H., J. Pharmacol. Exptl. Therap. (1975), 192, 260.

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20. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43.

44. 45. 46. 47. 48. 49. 50. 51. 52. 53.

canty

Mercury Compounds

337

Kostyniak, P. J., Clarkson, T. W., and Abbasi, A. H . , J. Pharmacol. Exptl. Therap. (1977), 203, 253. Gilman, Α . , Allen R. P . , Philips, F. S., and St. John, E., J . C l i n . Invest. (1946), 25, 549. Benesch, R . , and Benesch, R. Ε . , Arch. Biochem. Biophys. (1952), 38, 425. Lehman, J. F., Barrack, L . P . , and Lehman, R. Α., Science (1951), 113, 410. Canty, A. J., and Kishimoto, R., Nature (1975), 253, 123. Canty, A. J., Kishimoto, R., Deacon, G. B . , and Farquharson, G. J., Inorg. Chim. Acta. (1976), 20, 161. Bradley, D. C., and Kunchur, N. R., J. Chem. Phys. (1964), 40, 2258. Bradley, D. C., and Kunchur, N. R . , Can. J. Chem. (1965), 43, 2786. Kunchur, N. R . , Natur Canty, A. J., and Kishimoto, R . , Inorg. Chim. Acta. (1977), 24, 109. Canty, A. J., and Kishimoto, R.,Aust. J . Chem. (1977), 30, 669. Canty, A. J., Kishimoto, R . , and Tyson, R. K . , Aust. J. Chem. (1978), 31, 671. Canty, A. J., and Tyson, R. Κ., Inorg. Chim. Acta. (1977), 24, L77. Canty, A. J., and Tyson, R. Κ., Inorg. Chim. Acta. (1978), in press. Coates, R. L., and Jones, M. M . , J. Inorg. Nucl. Chem. (1977), 39, 677. Bloodworth, A. J., J. Chem. Soc. (C) (1970), 2051. Norseth, T . , Acta. Pharmacol. Toxicol. (1973), 32, 1. Derryberry, Ο.Μ., in "Environmental Mercury Contamination" (Hartung, R . , and Dinman, B. D . , eds.) p.76 Ann Arbor Science, Ann Arbor, Michigan. Neville, G. Α., and Berlin, M . , Environ. Res. (1974), 7, 75. Beletskaya, l. P . , Butin, Κ. P . , Ryabtsev, Α. Ν . , and Reutov, O. Α., J. Organometal. Chem. (1973), 59, 1. Canty, A. J., and Deacon, G. B . , Aust. J. Chem. (1968), 21, 1757. Canty, A. J., Fyfe, Μ., and Gatehouse, Β. M . , Inorg. Chem. (1978), 17, in press. Canty, A. J., and Deacon, G. B., J. Organometal. Chem. (1973), 49, 125. Canty, A. J., and Gatehouse, Β. Μ., Acta. Cryst. (1972), B28, 1872. Puhl, W. F., and Henneike, H. F., J. Phys. Chem. (1973), 77, 558. Coates, G. Ε., and Lauder, Α . , J. Chem. Soc. (1965), 1857. Canty, A. J., and Marker, Α . , Inorg. Chem. (1976), 15., 425. Anderegg. G . , Helv. Chim. Acta. (1974), 57, 1340.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

338 54. 55. 56. 57. 58. 59. 60. 61. 62.

organometals and organometalloids Canty, A. J., and Gatehouse, Β. Μ., J. C. S. Dalton (1976), 2018. Canty, A. J., and Parsons, R. S . , Toxicol. Appl. Pharmacol. (1977), 41, 441. Canty, A. J., and Parsons, R. S., unpublished results. M i l l e r , V. L., Klavano, P. Α., and Csonka, Ε . , Toxicol. Appl. Pharmacol. (1960), 2, 344. Berlin, M . , and Ullberg, S., Arch. Environ. Health (1963), 6, 602. Gage, J. C., B r i t . J. Indust. Med. (1964), 21, 197. Daniel, J. W., Gage, J. C., and Lefevre, P. Α . , Biochem. J. (1972), 129, 961. Takeda, Υ . , Kunugi, T., Hoshino, O., and Ukita, T., Toxicol. Appl. Pharmacol. (1968), 13, 156. Berlin, Μ., J e r k s e l l Environ. Health. (1966)

Received August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

21 M e r c u r y , Lead, a n d C a d m i u m C o m p l e x a t i o n b y S u l f h y d r y l - C o n t a i n i n g A m i n o a c i d s . Implications for H e a v y - M e t a l Synthesis, Transport, a n d T o x i c o l o g y ARTHUR J. CARTY Guelph-Waterloo Centre for Graduate Work in Chemistry, Waterloo Campus, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada According to the A (1) or the Hard and Sof the polarisable heavy metal ions Hg , Cd and Pb should form their strongest complexes with donor atoms from elements i n the second or subsequent periods of the periodic table. It comes as no great surprise therefore that these elements appear i n nature predominantly as their sulfides and that the interaction of sulfur containing molecules and ions with these metals plays a major role in their environmental and bio-chemistry. The advent of man-made heavy metal pollution of natural waters has brought to light significant new aspects of heavy-metal sulfur chemistry and re-emphasised the need for a clear under standing of metal ion behaviour towards sulfur containing ligands. The purpose of this article is to summarise and contrast recent results on the complexation of methylmercury (CH3Hg ) inorganic mercury (Hg(II)),cadmium (Cd(II)) and lead (Pb(II)) as well as methyllead (IV) with small sulfhydryl containing aminoacids and to place these results i n an environmental, biochemical and toxicological context. For mercury there is much evidence pointing to the relevance of mercurial complexes with sulfur aminoacids i n the microbiologi cal transformation of Hg to C^Hg"** and i n the biotransport, metabolism and toxicity of both inorganic and methyl mercury. Thus homocysteine (HSCH CH CH(NH)COO)and cysteine (HSCH CH(NH3) COO)complexes may be implicated i n one mechanism for the methylation of Hg(IT) (as HgCl ) by aerobic cultures of Neurospora Crassa (2) while the synthesis of methylmercury thiomethyl (CH3 Hg SCH3) i n shellfish may involve an L-cysteine complex of methylmercury (Scheme 1) (4). There i s l i t t l e doubt that the simple alkylmercurials (e.g. C^Hg"*", C H Hg ) exert their toxic effects principally by inactivating specific sulfhydryl sites of cysteine residues i n proteins and enzymes. Indeed, the methyl mercury cation C^Hg* has been used for decades by biochemists as a highly selective probe for sulfhydryl groups owing to the specific 1:1 stoichiometry of C^Hg*/sulfhydryl complexation (5). +

2+

2

2

3

2

2

2

0-8412-0461-6/78/47-082-339$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Hg -h C H ,

(Methylcobalamin)

^CHgCHNH^ÎCOO

CH^CHWH^COO

CH^

s

s

(Methylcobalamin)

OOaNH^CHCHgSHg 1 , 4

Scheme I. Environmental synthesis of CH HgSCH

CH 3 HaSCH 3

'(Methyl Cobolomin)

CH^HgSCHjCHjCHd^ycOO

HSCH 2 CH 2 CH(NH^C00

CHj-Hg1,

CKjHgSC^CHiNK^KXK)

HSCH2CH(NiyC00

HSCH 2 CH(NH^COO +

21.

Sulfhydryl-Containing Amino Acids

CARTY

341

As an example, human albumin has been shown to c o n t a i n 0.65 - 0.70 S-H groups per mole as determined by r e a c t i o n s w i t h organic m e r c u r i a l s ( 6 ) . The s t r e n g t h and s t a b i l i t y of mercury-sulfur i n t e r a c t i o n s i n simple t h i o l complexes i s a l s o s i g n i f i c a n t i n the context of c h e l a t i o n therapy treatment f o r " i n o r g a n i c " mercury p o i s o n i n g and development of p o t e n t i a l a n t i d o t e s to Q^Hg**" p o i s o n i n g , s u b j e c t s d e a l t w i t h elsewhere i n t h i s volume (7). Despite the extremely h i g h values of the formation constants f o r CH3Hg /thiol complexes +

H

(log [ c H f f ] [ L ]

^

1 5

*

8

f

°

r

C H

H

3 S

S C H

2

C H ( N H

3

) C 0 0

( 8 )

+

and % 22 f o r the CH^Hg - mercaptalbumin complex (9) there i s evidence t h a t exchange of the methylmercury c a t i o n between s u l f h y d r y l s i t e s may be r a p i d l y exchanges w i t h boun presumably v i a n u c l e o p h i l i c a t t a c k at 2-coordinate mercury generating a pseudo 3-coordinate i n t e r m e d i a t e . Although the r e s i d u a l Lewis a c i d i t y i n CI^HgSR complexes i s low ( v i d e i n f r a ) i t i s c l e a r l y of major s i g n i f i c a n c e i n the context of methylmercury m o b i l i t y i n b i o l o g i c a l systems. Small molecular weight s u l f h y d r y l c o n t a i n i n g molecules such as g l u t a t h i o n e f a c i l i t a t e m e r c u r i a l t r a n s p o r t i n b l o o d ; albumin, which i s present at the 5 gram per cent l e v e l i n mammals may a l s o p l a y a r o l e as a m e r c u r i a l c a r r i e r (11)· Inorganic mercury a l s o forms exceedingly s t r o n g bonds w i t h s u l f u r anions. The s t a b i l i t y constant l o g k f o r the 1:1, H g / L c y s t e i n e complex i s 45.4 a value which can be a p p r e c i a t e d when compared to l o g k =6.74 f o r c h l o r i d e i o n (12). B i s (mercaptides) of mercury are u s u a l l y s t a b l e over the e n t i r e pH range and i t i s evident that the complexation of H g by L - c y s t e i n e residues i n p r o t e i n s and enzymes dominates the biochemistry and t o x i c o l o g y of i n o r g a n i c mercury. " B i s ( c y s t e i n a t o ) mercury" i s a metabolic product of c e r t a i n m e r c u r i a l d i u r e t i c s (13) and mercury may be bound to two (or p o s s i b l y three) c y s t e i n y l s u l f u r atoms i n kidney m e t a l l o t h i o n e i n (14). Considerable evidence e x i s t s f o r b i o l o g i c a l l y and environmentally s i g n i f i c a n t H g complexes of the type RSHgX (X - a n i o n i c or n e u t r a l n o n - t h i o l l i g a n d ) (13,15), and i t i s l i k e l y that s t r u c t u r a l , p h y s i c a l and chemical d i f f e r e n c e s between RHg and H g complexes of L - c y s t e i n e and g l u t a t h i o n e are r e s p o n s i b l e i n l a r g e p a r t f o r d i f f e r e n c e s i n organ d i s t r i b u t i o n , t o x i c i t y and b i o l o g i c a l behaviour f o r these mercurials. I n c o n t r a s t to the b i o c h e m i s t s , i n o r g a n i c chemists showed l i t t l e i n t e r e s t i n the simple aminoacid, peptide or t h i o l complexes of KHg o r Hg u n t i l very r e c e n t l y . A 1972 review (16) of H g / a m i n o a c i d complexes i s almost t o t a l l y devoid of r e l i a b l e s t r u c t u r a l i n f o r m a t i o n e i t h e r i n s o l u t i o n or the s o l i d s t a t e . We thus s e t out to s y n t h e s i z e model compounds w i t h the f o l l o w i n g goals i n mind: (a) to provide q u a n t i t a t i v e i n f o r m a t i o n on the 2+

2 +

2 +

+

2 +

+

2+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

342

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mercury-sulfur interaction, (b) to investigate the importance of secondary mercury-ligand binding, (c) to contrast the structures and properties of C^Hg"*" and Hg complexes with sulfur aminoacids i n a search for features pertinent to mercurial transport and toxicity, and (à) to f u l l y characterise mercury species directly implicated i n environmental synthesis of CH3 Hg and metabolism of CH3Hg+ and H g . +

+

2+

L-Cysteine and PL-Homocysteine Complexes Strange as i t may seem the crystalline compound C^Hg SCH2 ~ CH(NH )C00" H 0 was f i r s t described only i n 1974 (17) although the formation constant for 1:1 C^Hg^/L-cysteine was reported i n 1961 (fi). NMR data have shown that O^Hg " binds to the sulfhydryl site over th structure of CH Hg SCH X-Ray analysis i n our laboratory (19) i l l u s t r a t e s a number of important points : (i) mercury i s linearly 2-coordinate with strong C-Hg (2.09(4) A) and Hg-S (2.35(1) A) bonds, ( i i ) the molecule i s essentially molecular with only weak intermolecular hydrogen bonds between cysteines and water molecules/ and (iil) secondary intramolecular interactiois are weak (Hg-0 (carboxylate) = 2.84(2) Â ) . It i s unlikely that the Hg...0 interaction i s maintained i n solution (18) . This structure illustrates nicely the weak residual Lewis acidity associated with a mercury atom coordinated by one RS~ group and an alkyl group, a key feature of Q^Hg"*" coordination chemistry in biological systems. The molecule CH Hg SCH CH(NH )C00 i s obviously a reasonable model for tissue bound CH3Hg #and displacement of L-cysteine from this complex might well be used as an i n i t i a l test of antidote effectiveness. Finally CH3 Hg SCH CH(NH3)C00 i s a key intermediate en route to CH3 Hg SCH3 (Scheme 1) although,to our knowledge, the experiments to confirm the conversion to me thyImercury thiomethyl via methylcobalamin generated CH^" have not yet been carried out. 3

2

4

3

3

2

3

+

2

+

Although the dominant feature of CH3Hg binding to proteins is the formation of strong Hg-S (cysteine) bonds, the nature of weak secondary interactions from neighbouring sites i s pertinent to the impact of CH Hg on protein structure and conformation. Our single crystal X-Ray diffraction results for the related molecule CH Hg SCMe CH(NH )C00 (Fig. 2) show that intermolecular Hg S (thio-ether type) contacts are barely significant (20). The shortest of these Hg...S distances (Hg.. .S of 3.35(1) &) i s the same as the sum of Van der Waals r a d i i for Hg and S (3.35 &). A recently solved structure of CF Hg SCMe CH(NH )C00-0.5 H 0 (21) (Fig. 3) i l l u s t r a t e s rather dramatically the increase in residual Lewis acidity of mercury which accompanies replacement of an alkyl by a fluoroalkyl group. The arrangement of mercury and sulfur atoms in this structure resembles a distorted cubane +

3

3

2

3

3

2

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

2

21.

CARTY

Sulfhydryl-Containing Amino Acids

343

Figure 1. The structure of CH HgSCH s

t

molecular interaction and 0(3) is the oxy gen atom of the water molecule of crys tallization.

Figure 2. A portion of the crystal struc ture of CH HgSCMe CH(NH )COO · 0.5 H O drawn to show the nature of weak inter- and intramolecular interactions. For clarity only on penicillamine molecule is illustrated. s

2

s

g

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

344

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although only the v e r t i c a l mercury-sulfu r edge bonds are s t r o n g . Secondary Hg...O and Hg....S i n t e r a c t i o n s are both stronger here than i n the D L - p e n i c i l l a m i n e d e r i v a t i v e . Refinement of t h i s s t r u c t u r e ( c u r r e n t R of 0 JLO based on 1462 independent observed r e f l e c t i o n s measured on a GE-XRD-6 Datex automated d i f f r a c t o meter) i s c o n t i n u i n g . Our e f f o r t s to s y n t h e s i s e CHjHg* and HgCl2 d e r i v a t i v e s of DL-homocysteine HSOH CH CH(NH3)C00 were motivated by the o b s e r v a t i o n that t h i s aminoacid s t i m u l a t e s m e t h y l a t i o n of H g i n Neurospora Crassa, a cobalamin independent organism Q ) . Methyl group t r a n s f e r to a homocysteine complex of H g would generate methylmercury homocysteinate i n the proposed mechanism (3). The 1:1 MeHg complex, formed as a p r e c i p i t a t e on adding MeHgOH (0.86 g) i n ethanol (80 ml) to a b a s i c s o l u t i o n of DL-homocysteine (0.5 water 50 m l ) , r e c r y s t a l l i s e e t h a n o l . Microanalyses, i n f r a r e d and Raman s p e c t r a (v(Hg-C) 535 i r , 5 3 8 R cm j v(Hg-S) 334 i r , 3 3 6 R cmT^vtS-H) absent i n Raman) of CH3HgSCH CH2CH(NH3)C00 and the deuterated complex, together w i t h the H nmr i n D 0 which showed a l a r g e downfield s h i f t of the Εγ protons (Δδ - +0.51) and a J H _ Hg ' 2

2

2 +

2 +

+

2

1

2

2

l S 9

C

o f

1 8 6

H z

3

confirmed a s t r u c t u r e e s s e n t i a l l y the same as t h a t of the L - c y s t e i n e d e r i v a t i v e (10., 19) . Under s i m i l a r c o n d i t i o n s but employing 2:1 molar r a t i o s of CH3Hg : homocysteine, a c r y s t a l l i n e 2:1 complex (CH3Hg) S CH CH CH(NH )C00 was obtained. P r e l i m i n a r y X-Ray measurements have e s t a b l i s h e d that t h i s compound i s m o n o c l i n i c , space group C2/c w i t h a = 28.33, b - 11.24, c « 7.31 A; £ - 87° I I and Ζ - 8. From H nmr measurements (22) the two methyl groups appear to be a s s o c i a t e d w i t h one s u l f h y d r y l and one amino s i t e at n e u t r a l pH (Δδ Ηγ= + 0.53 ppm; ΔόΗ =+ 0.37 ppm; J c H - H g = 198 H z ) , as f o r the corresponding DL - p e n i c i l l a m i n e d e r i v a t i v e ( 10»20) . As observed by Rabenstein (10) f o r glutathione/C^Hg^complexation, at a c i d pH < 4 both CH3Hg groups probably become a s s o c i a t e d w i t h the s u l f h y d r y l group. Unfortunately, c r y s t a l l i n e samples of (CH3Hg) SCH CH CH(NH )C00 obtained from a c i d s o l u t i o n are u n s u i t a b l e f o r i n t e n s i t y data c o l l e c t i o n . The " i n o r g a n i c " complexes of homocysteine, prepared from d i l u t e aqueous s o l u t i o n s at n e u t r a l pH are i n t r a c t a b l e powders. Compounds of apparent formulae Hg[SCH CH CH(NH )C00H] CI2 and HgCl[SCH CH CH(MÎ3)C00> % H 0 have been s a t i s f a c t o r i l y analysed from 2:1 and 1:1 mixtures of aminoacid and H g C l . Using HgBr2 and DL-homocysteine under s t r o n g l y a c i d c o n d i t i o n s a complex of unusual s t o i c h i o m e t r y , HgBr2 [SCH2 CH CH(NH )C0] 2HBr was obtained (22) . A f u H 3-dimensional X-Ray study revealed a s t r u c t u r e c o n s i s t i n g of polymeric HgBr|~ ions s h a r i n g two b r i d g i n g bromides packed together w i t h c a t i o n s of homocysteine l a c t o n e SCH CH CH(NH )C0 ( F i g u r e 4 ) . C l e a r l y on a c i d treatment, cleavage of strong Hg-S (homocysteine) bonds occurs to generate the l a c t o n e , i n marked c o n t r a s t to the +

2

2

2

2

e

X

1 9 9

α

3

+

2

2

2

2

2

2

2

2

3

2

2

2

2

2

+

2

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

21.

CARTY

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345

Figure 4. An ORTEP II plot of the molecular structure of [ÉCH CH CH(NH )CO] · HgBr showing the atomic numbering. Bridging bromine atoms are indicated by an additional dashed bond. 2

2

s

2

h

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

346

ORGANOMETALS

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1

L - c y s t e i n e and D L - p e n i c i l l a m i n e complexes of Hg*"*. In view of d i f f i c u l t i e s i n s t r u c t u r a l l y c h a r a c t e r i s i n g the " i n o r g a n i c " complexes of homocysteine p u r p o r t e d l y i n v o l v e d i n CH3Hg s y n t h e s i s we began work on the L - c y s t e i n e and DLpeni c i l l amine d e r i v a t i v e s of HgCl2. Compounds of formulae Hg[SCH CH(NH )C00][SCH CH(NH )C00H] * C l . 0.5 H 0 ( 1 ) , H g C l [SCH CH(NH )C00H](2), Hg[SCH CH(NH )C00](3) [HgCl ] +

2

3

2

2

3

3

2

2

2

2

2

2

[SCMe CH(NH )C00H] 2H 0 ( 4 ) , [Hg{SCMe CH(NH )C00H> C l ] C1.H 0 (£), and HgCl [SCMe CH(NH )C00H](6) have been s y n t h e s i z e d and c h a r a c t e r i z e d by s p e c t r o s c o p i c methods. S y n t h e t i c and s p e c t r o s c o p i c d e t a i l s w i l l be p u b l i s h e d elsewhere ( 2 X 2JÙ but i t i s p e r t i n e n t here to summarise the major s t r u c t u r a l f e a t u r e s of these compounds as r e v e a l e d by s i n g l e c r y s t a l X-Ray d i f f r a c t i o n P i c t o r i a l r e p r e s e n t a t i o n s of 1^ 1^ 4· and 5_ are shown i n F i g u r s t r u c t u r a l f e a t u r e s to the r e l a t i v e l y weak i n t e r a c t i o n s between cEloridê" ions and mercury, the b a s i c s t r u c t u r a l u n i t s present are the c l a s s i c a l two coordinate A^S-Hg- S'VWstereochemistry long thought to represent the bound s t a t e of H g i n p r o t e i n s and dimercaptides. S i g n i f i c a n t l y , l o s s of H and C l " from i would generate "mercury c y s t e i n a t e " , Hg[SCH CH(NH )C00] (13_, 16). The environment of mercuric i o n i n human kidney métallothionein, which binds H g more s t r o n g l y than e i t h e r Z n o r C d , may resemble t h a t i n 1 and w i t h two very s t r o n g Hg-S(cysteine) i n t e r a c t i o n s p r o v i d i n g the main b i n d i n g . I f bond-lengths are used as a rough c r i t e r i o n of bond s t r e n g t h , comparison of Hg-S d i s t a n c e s i n the "2-coo r d i n a t e " H g ^ and C H H g complexes of L - c y s t e i n e and DLpeni c i l l a m i n e , r e v e a l s l i t t l e d i f f e r e n c e between the a f f i n i t i e s of CH Hg and H g f o r deprotonated s u l f h y d r y l groups, ( i i ) Two types of mercapto b r i d g e s , one h i g h l y unsymmetrical i n 4 (Hg(l)S of 2.822(5)1 and Hg(2)-S of 2.356(5)1) ang one almost symmetrical i n £ (Hg-S - 2.490(4), Hg-S = 2.453(4)A) are e v i d e n t . C l e a r l y t h i o l s are q u i t e capable of p r o v i d i n g s i t e s f o r two mercury atoms. This a b i l i t y to b r i d g e mercury atoms may be m e c h a n i s t i c a l l y s i g n i f i c a n t i n s i t e exchange and t r a n s p o r t of i n o r g a n i c m e r c u r i a l s . I t i s noteworthy t h a t sulphur b r i d g i n g i s a l s o a r e c u r r i n g f e a t u r e of simple m e r c u r y - t h i o l chemistry, l e a d i n g to s t r u c t u r e s i n which the degree of p o l y m e r i z a t i o n v a r i e s c o n s i d e r a b l y (25,26). ( i i i ) C h l o r i d e i o n i n t e r a c t i o n s of v a r y i n g s t r e n g t h s are present ( c f H g - C l ( l ) of 2.582(4) i n 2., H g - C l ( l ) of 2.850(5)1 i n 5, H g ( l ) - C l ( 3 ) o f 2.348(5)1 i n 4, and Hg(l) - C l ( 2 ' ) of 3.335(6)1 i n 4) suggesting that c h l o r i d e i o n can compete favourably f o r m e r c u r i a l c o o r d i n a t i o n s i t e s and hence modify the p o l a r i t y and s o l u b i l i t y of the bio-complexes. The d i f f e r e n t d i s t r i b u t i o n r a t i o s of H g and CH Hg between plasma and red blood cells(27,28)may w e l l r e f l e c t the greater C l ~ content i n plasma. T r a n s p o r t a t i o n and membrane p e r m e a b i l i t y of d i f f e r e n t m e r c u r i a l s depend on m e r c u r i a l p o l a r i t y and s o l u b i l i t y , two parameters s e n s i t i v e to h a l i d e i o n i n t e r a c t i o n s . 2

3

2

2

2

2

2

3

2

3

2 +

+

2

3

2

2 +

2 +

2

2 +

+

3

+

2 +

3

f

2 +

+

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

21.

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347 2+

With the complete c h a r a c t e r i z a t i o n of the H g / L - c y s t e i n e d e r i v a t i v e s above,we f e e l c o n f i d e n t that the homocysteine complexes Hg[SCH2CH2CH(NH )C00H]Cl and HgCl[SCH2CH2CH(NH )C00]. 0.5 H2O have c l o s e l y r e l a t e d s t r u c t u r e s based e s s e n t i a l l y on d i g o n a l S-Hg-S or Cl-Hg-S bonds. I n l i n e w i t h our aim to assess the relevance of these c y s t e i n e and homocysteine compounds to environmental mercury methylation, we are c a r r y i n g out m e t h y l a t i o n s t u d i e s u s i n g a c t i v e sediments s p i k e d w i t h the mercury complexes and a l s o w i t h c u l t u r e s of Neurospora Crassa growing i n the presence of these compounds. 3

2

Comparison of B i n d i n g Preferences Cadmium and Lead (11).

3

f o r Inorganic Mercury,

A comparison of s o l u b i l i t and s t a b i l i t y constants gives an i n d i c a t i o n of the r e l a t i v e a f f i n i t i e s one might expect to f i n d f o r mercury, cadmium and l e a d i n t h e i r aminoacid complexes. Mercury c l e a r l y has a very h i g h a f f i n i t y f o r s u l f u r , w i t h cadmium and l e a d having approximately equal but much lower a t t r a c t i o n s . As a converse to t h i s one might expect that i n complexes w i t h s u l f u r aminoacids where Hg-S bonding would predominate, cadmium and l e a d might e x h i b i t c o n s i d e r a b l y more d i v e r s e behavior, b i n d i n g simultaneously to s e v e r a l d i f f e r e n t s i t e s . This i s e x a c t l y the p i c t u r e which has emerged from X-Ray s t u d i e s of mercury^cadmium and l e a d complexation w i t h s u l f u r aminoacids. I n Figure 7 we i l l u s t r a t e s c h e m a t i c a l l y the modes of i n t e r a c t i o n r e c e n t l y found i n a v a r i e t y of complexes. Some r e l a t e d bond d i s t a n c e s are shown i n Table I . Although d i r e c t comparisons between metals are d i f f i c u l t owing to d i f f e r e n t complex s t o i c h i o m e t r i e s and s t a t e s of aminoacid i o n i z a t i o n , the s t r u c t u r e of Cd[SCMe2 CH(NH )C00] H2O ( 3 D i l l u s t r a t e s the a b i l i t y of cadmium to i n t e r a c t w i t h S, Ν and 0 s i t e s of the aminoacid. Comparison of the Cd-S d i s t a n c e s (av 2.565(7)1) w i t h Hg-S bond lengths i n Table I show that the weaker cadmium-sulfur i n t e r a c t i o n s i n the cadmium species are compensated by bonding c a p a c i t y d i r e c t e d to oxygen and n i t r o g e n donors. This tendency of cadmium to p r e f e r a combination of b i n d i n g s i t e s i m p l i e s a much l e s s e r s p e c i f i c i t y than mercury f o r s u l f h y d r y l s i t e s i n p r o t e i n s and i s c o n s i s t e n t w i t h the f a i l u r e o f reagents such as D- p e n i c i l l a m i n e to act as good a n t i d o t e s t o cadmium p o i s o n i n g . These observations a l s o suggest that the stereochemistry of C d i n métallothionein i s l i k e l y to d i f f e r s i g n i f i c a n t l y from that of H g i n the same m e t a l l o p r o t e i n . The l e a d (IT) compound Pb[SCMe CH(NH )COO](29) c l o s e l y resembles Cd[SCMe2CH(NH2)COO] H 0 i n s t o i c h i o m e t r y , and each metal i o n i s pseudooctahedrally coordinated by l i g a n d atoms, w i t h a 3S, 20, Ν donor s e t f o r l e a d and 30, 2S,N f o r cadmium. L i k e cadmium, l e a d seems to favour b i n d i n g to a combination of S, Ν and 0 s i t e s i n aminoacids and thus i t a l s o d i f f e r s from mercury i n t h i s respect. 2

2 +

2 +

2

2

2

American Chemical Society Library 16th st. N. w. In Organometals1155 and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Washington, D. C. Society: 20036Washington, DC, 1979.

348

ORGANOMETALS

A N D ORGANOMETALLOIDS

Cl Cl \ / Hg

~0L Ό-Η- 0 >C-CH-Ch£S-Hg-S-C^CH-c£

'

Hg(L-cystH)(L.cystHJ.CI. ο·5Η 0

(I)

2

Cl Cl \ / Hg^

CH$CH-Cf

HgCL(^.S.L.cystH )

(2)

cr

r

Me

C-CH— C-5—Hg—S-C-CH/ I I I HO NH Me M

HgCKpenH^.CI.HgO

(5)

(HgCI ) U-S.penH ).2H 0 2

2

2

2

(4)

Figure 5. Schematic representations of the crystal structures of Hg[SCH CH(NH )COO][SCH CH(NH )COOH]Cl · 0.5 H 0 (1), HgCl [SCH CH(NH )COOH] (2), [HgCl ] [SCMe CH(NH )COOH] -2H 0 (4), and [Hg—{SCMe CH(NH )COOH) Cl] Cl · H O (5). 2

s

2

s

s

2

2

2

2

2

2

s

s

t

2

2

t

Log Κ so-

\ t t I t

Figure 6. Stabilities of divalent metalligand complexes as indicated by sta bility constants or solubility products. For sulfides and hydroxides log k refers to solubility products; and for ethylenediamine complexes log k refers to sta bility constants. Key: (O) sulfide; (A) nitrogen; (X) oxygen.

Mn 1% Co Ni Cu Zn

Ag Cd

Hg

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Pb

21.

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349

CH,

I œ

ry ο Pb(p-pen)

(Ref. 29) 0

Ι

Br

Cd--

/

0

H

2 . C — CH

Ο

C d " ^

C H ^

^ C H ,

0 Cl:H,

Jb

Cd Cd

Cd(loL-penH)Br.H 0).2H 0 (Ref. 30) 2

2

Cd(o-pen). H 0 (Ref. 31) 2

Figure 7. Pictorial representations of metal-ligand interactions in lead and cadmium-penicillamine complexes. For comparison with mercury complexes, see Figure 5.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

350

ORGANOMETALS

A N D ORGANOMETALLOIDS

Table I M-X Bond Lengths i n Amino A c i d Complexes Compound

M-S

M-N

M-0

Ref.

C H H g ( S C H C H (NH ) C O O ^ 3

HgCl

2

2

3

[SCH CH ( N H ) 2

3

M

2.490(4)

C00H]

2.453(4) H g [ S C H C H ( N H ) C O O ] H C 1 *0.5 2

3

24

2.355(3)

H 0

2

2

2.329(5) (HgCl ) [SC(CH ) CH(NH )C00H]2H 0 2

2

3

2

3

2

23

2.822(5) 2.356(5)

CdBr [SC(CH ) CH(NH ) COO] 3H 0

2.444(2)

Cd[SC(CH ) CH(NH )COO]H 0

2.563(7)

3

2

3

2

2.262(5) 30 2.715(5) 2.490(6) 31

2.567(7)

2.38(2) 2.57(2) 2.51(2) 2.40(2)

Pb[SC(CH ) CH(NH )COO]

2.716

2.444

29

Me Pb[SCH CH(NH )C00]

2.50(1)

2.46(3) 2.55(4)

3

2

3

2

2

2

2

2

2

2

2.444 2.768

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

39

21.

351

Sulfhydryl-Containing Amino Acids

CARTY

METHYLATION AND DEMETHYLATION OF LEAD Recently there has been a major upsurge i n i n t e r e s t i n environmental l e a d chemistry w i t h r e p o r t s t h a t t r i m e t h y H e a d ( I V ) (32) and lead(TT) n i t r a t e (33) can be b i o l o g i c a l l y methylated to t e t r a m e t h y l l e a d contrary t o e a r l i e r p r e d i c t i o n s . The m e t h y l a t i o n o f environmental l e a d t o t o x i c Me^Pb would pose a p o t e n t i a l h e a l t h t h r e a t i f proven^since l e a d , p a r t i c u l a r l y i n the form o f l e a d ( I I ) , continues t o accumulate i n the environment as a product of i n t e r n a l combustion engines. Although an i n i t i a l controversy (34) arose concerning the chemical ( i . e . d i s p r o p o r t i o nation) o r b i o l o g i c a l nature o f processes e f f e c t i n g the Me3Pb(IV) Me4Pb conversion, recent experiments appear to have c o n c l u s i v e l y proven the e x i s t e n c e o f a b i o l o g i c a l m e t h y l a t i o n sequence (35). For Pb(TT) s a l t s ther r e j e c t i n g the p o s s i b i l i t With the e x c e p t i o n o f a few a i r and moisture s e n s i t i v e compounds w i t h bulky groups (36)r l e a d ( X I ) a l k y l s are unknown. Even monomethyllead(IV) species are unstable i n the absence o f s t a b i l i s i n g l i g a n d s . Furthermore, the o x i d a t i o n r e d u c t i o n p o t e n t i a l f o r Pb(XI)/Pb(IV) d i s f a v o u r s e l e c t r o p h i l i c mechanisms f o r Pb (ΤΙ) , p e r t i n e n t i n b i o l o g i c a l m e t h y l a t i o n o f other metals (e.g., H g ( l l ) , P d ( I l ) ) (37).Thus t r a n s f e r o f a methyl group as Οΐβ" (say frcm methylcobalamin) would y i e l d a h i g h l y unstable M e - P b ( I l ) s p e c i e s from which MePb(lV) could o n l y be generated by an unfavourable 2 - e l e c t r o n o x i d a t i o n o r v i a d i s p r o p o r t i o n a t i o n . I n our view a much more l i k e l y mechanism i s what can e s s e n t i a l l y be d e s c r i b e d as o x i d a t i v e a d d i t i o n o f CH3"** t o an uncharged ( o r a n i o n i c ) l e a d ( I X ) complex : +

CH

3

+ 3

+

[ r P b " L ]< - > - [ C H 3 2

n

n

+

+

- Pb

I V

L ] n

( 3

-

n ) +

(L = uninegative l i g a n d ) A v a r i e t y o f b i o l o g i c a l m e t h y l a t i n g agents (compare f o r example the recent paper o f McBride and C u l l e n on a r s e n i c m e t h y l a t i o n (38)) capable o f t r a n s f e r r i n g carbonium ions a r e p o t e n t i a l l y capable of s y n t h e s i s i n g CH3Pb(JV)in t h i s way. The P b ( I I ) - p e n i c i l l a m i n e complex ( F i g u r e 7) i s a p o t e n t i a l model f o r the l e a d ( I X ) c h e l a t e . However, i t would c l e a r l y be advantageous i f the lead(XT) lone p a i r was s t e r e o c h e m i c a l l y a v a i l a b l e f o r f a c i l e m e t h y l a t i o n , as i n J7 where X simply represents the backbone o f a t r i p o d - l i k e t r i d e n t a t e l i g a n d . -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

352

A N D ORGANOMETALLOIDS

Figure 8. A perspective view of the molecular structure of (CH ) Pb[SCH CH(NH )COO] · H0 s

2

g

8

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

21.

CARTY

Sulfhydryl-Containing Amino Acids

353

Experiments designed to e s t a b l i s h the best choice of l i g a n d and methylation c o n d i t i o n s f o r the Pb(IT) -> Me^Pb i n t e r c o n v e r s i o n are c u r r e n t l y i n progress i n our l a b o r a t o r y i n c o l l a b o r a t i o n w i t h Drs. Y.K. Chau and P.T.S. Wong at CCIW B u r l i n g t o n . Although l e a d ( I I ) s a l t s are the major l e a d p o l l u t a n t s i n the environment, o c c a s i o n a l l y high concentrations of tetramethyHead or t r i m e t h y l l e a d species accumulate from g a s o l i n e s p i l l s , improperly burnt f u e l , e t c . I n such cases, the i n f l u e n c e of n a t u r a l l i g a n d s on the r a t e of environmental degradation to l e s s t o x i c lead(IT) s a l t s i s p e r t i n e n t . There i s evidence that s u l f u r l i g a n d s may f a c i l i t a t e the cleavage of l e a d ( I V ) - a l k y l bonds. Thus (CH3)3 PbOAc r e a c t s s l o w l y w i t h L - c y s t e i n e or DLp e n i c i l l a m i n e i n aqueous s o l u t i o n to g i v e dimethyllead(IV) c y s t e i n a t e ( F i g . 8) or p e n i c i l l a m i n a t e (39). By c o n t r a s t , trimethyllead i n acidic shows very l i t t l e decompositio of s e v e r a l months (40). The dimethyllead(IV) c y s t e i n a t e i s polymeric w i t h each c y s t e i n a t e coordinated to one l e a d atom v i a S and Ν s i t e s and to a second l e a d atom v i a a carboxylate oxygen. This conversion of ( O ^ ^ P b l V to (CH3) Pb(cyst) under m i l d c o n d i t i o n s may have b i o l o g i c a l i m p l i c a t i o n s ; a l k y l l e a d s are potent neurotoxins, and may exert t h e i r e f f e c t s v i a b i n d i n g to a c t i v e s u l f h y d r y l s i t e s i n t i s s u e s (cf F i g . 8 ) . 2

Acknowledgements I would very much l i k e to acknowledge the major c o n t r i b u t i o n s which Dr. Nicholas J . T a y l o r a research a s s o c i a t e at Waterloo, has made to t h i s work. Most of the s y n t h e t i c and X-Ray s t r u c t u r a l work quoted i n t h i s a r t i c l e has been c a r r i e d out by Dr. T a y l o r . I n i t i a l s t u d i e s of methylmercury complexation were undertaken by a graduate student (now Dr) Y.S. Wong and the homocysteine work i n progress i s due to L.F. Book. I would a l s o thank my colleague Dr. P.C. Chieh who has c o l l a b o r a t e d w i t h me i n some of t h i s work. F i n a n c i a l support has been provided by Environment Canada, p r i n c i p a l l y through the Water Resources Support Program.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

354

organometals and organometalloids

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Pearson R . G . , J. Amer. Chem. Soc., (1963), 85, 3533.

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Landner L., Nature, (1971), 230, 452.

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Wood J . M . , Adv. Environmental S c i . Technol. (1971), 2, 39.

5. Hoch F.L., and Vallee B . L . , Arch. Biochem. Biophys., 91, 1. 6.

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7. Canty, A.J., "Chemical Problems i n the Environment: Occurrence and Fate of Organoelements" ACS Advances i n Chemistry Series, F . E . Brinckman and J . M . Bellama, Eds., (1978) 8.

Simpson R . B . , J. Amer. Chem. Soc., (1961), 83, 4711.

9. Hughes W.L. Jr., Cold Spring Harbour Symposium on Quantitative Biology, (1950), 14, 79. 10. Rabenstein D.L. and Fairhurst M . T . , J. Amer. Chem. Soc., (1975), 97, 2086. 11. Webb J.L., "Enzyme and Metabolic Inhibition", V o l . 2, Academic Press, New York (1969). 12. Schwarzenbach G. and Schellenberg Μ., Helv. Chim. A c t a . , (1965), 48, 28. 13. Weiner I . M . , Levy R . I . and Mudge G . H . , J. Pharmacol. Exp. Ther. (1962) 138, 96. 14. Kagi J.H.R. and Vallee B.L., J. B i o l . Chem., (1961), 236, 2435. 15. Hilton B . D . , Man Η . , Hsi Ε., and Bryant R . G . , J. Inorg. Nucl. Chem., (1975), 37, 1073. 16. McAuliffe C . A . , and Murray S . G . , Inorg. Chim. Acta Rev., (1972) 6, 103. 17. Wong Y.S., Taylor N.J., Chieh P.C. and Carty A.J. J. Chem. Soc. Chem. Commun., (1974), 625. 18. Rabenstein D . L . , Accounts Chem. Res., (1978), 11, 100.

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19. Taylor N.J., Wong Y.S., Chieh P . C . and Carty J. Chem. Soc. Dalton Trans., (1975), 438.

A.J.,

20. Wong Y.S., Carty A.J. and Chieh C . , J. Chem. Soc. Dalton Trans., (1977), 1801. 21. Carty A.J. and Taylor N.J., unpublished 22. Book L.F., Chieh C . , and Carty

A.J.,

results.

unpublished

results.

23. Taylor N.J., Carty A.J. and Wong Y.S., J. Chem. Soc. Dalton Trans., to be published. See also Taylor N.J. and Carty A.J., J. Chem. Soc. Chem. Commun., (1976) 214. 24. Carty A.J. and Taylo preliminary account se Chem. Soc., (1977), 99, 6143. 25. Canty 24, 109.

A.J.

and Kishimoto R . , Inorg. Chim. A c t a . , (1977)

26. Canty A.J. and Tyson

R.K.,

Inorg. Chim. A c t a . , (1977) 24, L77.

27. Aberg B., Ekman L., Falk R . , Grietz U., Pearson G . , and Snihs J.O., Arch. E n v i r . H e a l t h . , (1969) 19, 478. 28. Lundgren K.D., Swensson A . and Ulfvarson, U . Lab. I n v e s t . , (1967), 20, 164. 29. Freeman H.C., Stevens G . N . , and Taylor Chem. Commun., (1974), 366. 30. Taylor N.J. and Carty

A.J.,

I.F.

Scand J. Chim. Jr.,

J.

Chem. S o c . ,

Inorg. Chem., (1977), 16, 177.

31. Freeman H.C., Huq F., and Stevens G . N . , J. Chem. Soc. Chem. Commun., (1976), 90. 32. Wong P.T.S., 253, 263.

Chau, Y . K . and Luxon, P.L., Nature (1975),

33. Schmidt U., and Huber Η . , Nature, (1976) 259, 177. 34. Jarvie A . W . P . , Markall R . N . and Potter H . R . , Nature (1975), 225, 217. 35. Chau Y . K . and Wong P.T.S., "Chemical Problems in the Environment: Occurrence and Fate of Organoelements" ACS Advances in Chemistry S e r i e s , F . E . Brinckman and J . M . Bellama, Eds., (1978)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

356 36. Davidson P.J. and Lappert M.F., (1973), 317. 37. R i d l e y W.P., 183, 1049. 38. C u l l e n W.R., and Reimer M.,

ORGANOMETALLOIDS

J . Chem. Soc., Chem. Commun.,

D i z i k e s L . J . and Wood J.M.,

Science

(1977),

Froese C.L., L u i Α., McBride B.C., Patmore J . Organometal. Chem., (1977), 139, 61.

39. Carty A . J . and T a y l o r , N.J., 40. S a y e r T.L., R a b e n s t e i n D.L.,

AND

unpublished

D.J.,

results.

B a c k s S., E v a n s C.A., Millar E.K. Can. J . Chem., (1977) 55, 3255.

and

Discussion F. E. BRINCKMAN ( N a t i o n a l Bureau of Standards): To emphasize your l a s t p o i n t concerning the appropriate c o o r d i n a t i o n of l e a d , the J a r v i e mechanism [Nature, (1975) 255, 217] , i n v o l v e s an a b i o t i c r e d i s t r i b u t i o n , presumably to form tetramethyllead. We reported t h a t i n Chesapeake Bay anoxic sediments w i t h h i g h biogen i c s u l f u r content, not only d i d gaseous elemental mercury form from b i o l o g i c a l a c t i v i t y , but mercury a l s o p a r t i t i o n e d i n t o the l i p i d or o i l phases i n the sediment body. The mercury was p r i n c i p a l l y i n s o l u b l e form; about 2% or so as the element and/or methylm e r c u r i a l s but p r i n c i p a l l y i n much l a r g e r molecules not yet char a c t e r i z e d by us or anybody e l s e . But the p o i n t here i s b i o a v a i l a b i l i t y . I t h i n k we w i l l f i n d a number of c o o r d i n a t i o n s i t e s which w i l l h o l d the metal a v a i l a b l e f o r other a c t i v i t y besides simple m i n e r a l i z a t i o n as the s u l f i d e . S u l f u r doesn't seem to be the only key element i n understanding t h i s c o o r d i n a t i o n chemistry and the b i o a v a i l a b i l i t y i n these systems.

ever

R. H. FISH ( U n i v e r s i t y of C a l i f o r n i a , B e r k e l e y ) : looked at t h i o e t h e r s ?

Have you

CARTY: We looked at both the methylmercury and the i n o r g a n i c complexes i n methionine, and the c r y s t a l l i n e methylmercury complex contains the methionine bound t o mercury by the n i t r o g e n . In s o l u t i o n i t i s l i n e a r . I t ' s w i t h t h i s z w i t t e r i o n i c complex w i t h a p o s i t i v e charge on mercury and a negative charge on the c a r b o x y l ate. FISH:

What about H g C l ? 2

2+ CARTY: In Hg , the p e r c h l o r a t e contains the methionine bound through two t h i o e t h e r s and two carboxylates . FISH: Yes, because we looked at a p y r i d y l e t h y l - c y s t e i n e molecule. We found a nine-numbered r i n g w i t h the p y r i d y l - n i t r o g e n and the amino f u n c t i o n . The s u l f u r never i n t e r a c t e d .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

21.

CARTY

Sulfhydryl-Containing Amino Acids

357

CARTY: I t h i n k the t h i o e t h e r i n t e r a c t i o n s are much l e s s s t r o n g . In f a c t , i n s o l u t i o n s of methionine w i t h CH«Hg , the t h i o e t h e r c o o r d i n a t i o n o n l y occurred at pH of l e s s than 2, o t h e r wise i t i s NH or c a r b o x y l a t e t h a t i n t e r a c t s . +

2

F. HUBER ( U n i v e r s i t y of Dortmund): We examined compounds of organolead and organotin mercaptocarboxylic a c i d s . We observed that the l e a d species can coordinate to the s u l f u r , or t o oxygen, or to even both. We d i d experiments w i t h mercaptopropionic a c i d as a model compound f o r c y s t e i n e , without an NH group, and observed that i n many cases there i s c o o r d i n a t i o n between l e a d and s u l f u r . The c a r b o x y l i c a c i d d i d n ' t r e a c t . With t r i m e t h y l l e a d ( I V ) and dimethyHead(IV) compounds, e s p e c i a l l y w i t h the t r i m e t h y l l e a d compounds, there was an a c i d o l y s i s r e a c t i o n g i v i n g methane and dimethyllead(IV). 2

CARTY: I n s o l u t i o n trimethyllea L-cysteine, i f you look by nmr techniques at the r e a c t i o n w i t h a pH of 6 or 5, you f i n d only weak c o o r d i n a t i o n of the s u l f h y d r y l group. At a l k a l i n e pH, d i m e t h y l a t i o n occurs. HUBER: We t r y t o work i n n e u t r a l s o l u t i o n s . W. P. RIDLEY ( U n i v e r s i t y of Minnesota): Your suggestion t h a t we should not ignore the p o s s i b i l i t y t h a t l e a d ( I I ) c o u l d accept a carbonium methyl group from some b i o l o g i c a l methyl donor should c e r t a i n l y be i n v e s t i g a t e d . T h a l l i u m ( I ) could be methylated i n the same f a s h i o n , assuming a proper complex c o u l d be formed, i . e . , the t r a n s f e r of CH to T1(I) t o g i v e m o n o m e t h y l t h a l l i u m ( I I I ) . The standard r e d u c t i o n p o t e n t i a l s of the l e a d ( I I ) t o l e a d ( I V ) and t h a l l i u m ( I ) t o t h a l l i u m ( I I I ) couples are very s i m i l a r , suggesting t h a t they may proceed i n a s i m i l a r f a s h i o n . 3

HUBER: On the p o s s i b i l i t y of m e t h y l a t i o n of P b ( I I ) , i n many complexes we do not see an a v a i l a b l e lone p a i r ; the P b ( I I ) adopts o c t a h e d r a l c o o r d i n a t i o n . Nonetheless, I t h i n k the p o s s i b i l i t y exists for this reaction. W. R. CULLEN ( U n i v e r s i t y of B r i t i s h Columbia): I f the s u l f u r was a l r e a d y coordinated t o the l e a d , then m e t h y l a t i o n of the s u l f u r could o f f e r means f o r t r a n s f e r of methyl onto the l e a d or onto the t h a l l i u m . This might be a v i a b l e route by which o x i d a t i v e a d d i t i o n might take p l a c e . HUBER: When s u l f u r i s coordinated to l e a d , there might be a p o s s i b i l i t y t h a t the lone p a i r could be s t e r e o c h e m i c a l l y d i r e c t e d . H a l i d e complexes u s u a l l y have an o c t a h e d r a l geometry, but there are some complexes, e s p e c i a l l y w i t h thiophosphates, where the lone p a i r i s a c t i v e .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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AND

ORGANOMETALLOIDS

CARTY: C e r t a i n l y , w i t h the a b i l i t y that i n o r g a n i c chemists have these days t o tailor-make l i g a n d s , one would not be s u r p r i s e d to f i n d that you can make a l i g a n d which would a c t u a l l y t i e the bonds back and l e t the lone p a i r be f r e e f o r m e t h y l a t i o n . G. E. PARRIS (Food and Drug A d m i n i s t r a t i o n ) : Potassium antimony t a r t r a t e has a s t r u c t u r e i n which one s i d e of the a n t i mony i s open, and i t i s o f the few s o l u b l e compounds of i n o r g a n i c antimony. The p o s s i b i l i t y of t r a n s f e r r i n g CH^ t o t h i s p o t e n t i a l n u c l e o p h i l e i s i n t e r e s t i n g . However, s i n c e antimony Mossbauer has shown t h a t the lone p a i r i s probably more i n a S-type o r b i t a l , as i t i s i n t r i m e t h y l s t i b i n e , there i s some question whether o r not these are good n u c l e o p h i l e s f o r accepting CH^*. M. L. GOOD ( U n i v e r s i t the Mossbauer i s d e f i n i t i v CARTY: There are some a l k y l compounds of l e a d ( I I ) , c o n t a i n i n g bulky a l k y l groups, which have been prepared by P r o f e s s o r M.F. Lappert ( U n i v e r s i t y of Sussex). I n those compounds the P b ( I I ) behaves as a donor t o t r a n s i t i o n metals, so the lone p a i r i s available. RECEIVED

August 22,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

22 Release Mechanisms of O r g a n o t i n Toxicants from Coating Surfaces: A L e a c h i n g M o d e l for A n t i f o u l i n g Coatings CHARLES P. MONAGHAN, VASANT H. KULKARNI, and MARY L. GOOD Department of Chemistry, University of New Orleans, Lakefront, New Orleans, LA 70122 Fouling of ship hull d marin installation b vegetabl and/or animal organism results in significant economic loss due to structural damage or fuel requirements (1,2,3). Thus any program for fuel economy and preservation of marine structures by the Navy, the shipping industry, or the fishing fleet must contain the development of effective antifoulant procedures as a high priority. The only practical solution to the fouling problem through the years has been the utilization of paints and coatings having antifoulant activity. Most of the successful coatings have been paint formulations containing a toxic component. The most widely used toxicant has been cuprous oxide although various organometallic compounds of arsenic, mercury, lead and tin have been used. Studies have indicated that the organotin antifoulants show particular promise, since they exhibit control over a variety of fouling organisms for relatively long periods of time and they do not promote corrosion when applied over conductive substrates (4,5). However, if these organotin containing coatings find widespread application in the marine industry and in naval operations, their long term environmental impact on harbors and shipyards w i l l become most important. In addition, the need for laboratory testing techniques for coating evaluation and comparison w i l l be c r i t i c a l . Thus the development of laboratory procedures for the chemical speciation of the toxicant released to the environment and methods for evaluating the leaching parameters becomes an area of fertile research. This paper will report our initial efforts to develop in detail a leaching model for the loss of organotin toxicants from conventional antifouling coatings. Work on the speciation of the released toxicant moieties w i l l be presented in a subsequent paper. For an antifouling paint to be effective, the toxicant must leach from the coating at a rate high enough to repel or k i l l organisms at the coating surface but not so high as to cause rapid depletion and early failure of the coating. De l a Court and de Vries (6,7) and Marson (8,9) have outlined those parameters 0-8412-0461-6/78/47-082-359$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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which are necessary to d e s c r i b e the l e a c h i n g of t o x i c a n t from an i n s o l u b l e matrix c o n t a i n i n g cuprous oxide (Cu«0). The models developed by these authors show considerable i n s i g h t i n t o the l e a c h i n g process. Coatings i n which the t o x i c a n t p a r t i c l e s and s o l u b l e pigment p a r t i c l e s are dispersed throughout the c o a t i n g m a t r i x i n such a manner that the p a r t i c l e s are always i n contact are c a l l e d "continuous contact c o a t i n g s " . In these c o a t i n g s , i t i s assumed t h a t when the p a r t i c l e s d i s s o l v e , pores are developed through which the t o x i c a n t d i f f u s e s to the surface of the c o a t i n g and the porous exhausted m a t r i x remains i n t a c t a f t e r the p a r t i c l e s have d i s s o l v e d . S e v e r a l steps are r e q u i r e d to d e s c r i b e the l e a c h i n g process. The s o l v e n t d i f f u s e s through the exhausted m a t r i x to the l e a c h i n g zone where i t d i s s o l v e s the t o x i c a n t or s o l u b l e pigment, l e a v i n g a pore. The s o l v a t e the exhausted m a t r i x t quiescent l a y e r i n t o the b u l k of the s o l u t i o n (sea or harbor water). Cuprous oxide d i s s o l v e s i n sea water to e s t a b l i s h a r e a c t i o n e q u i l i b r i u m as f o l l o w s : 1/2

Cu 0 + H 2

+

+ 2Cl" ^

CuCl" + 1/2

H0 2

The r a t e determining steps f o r t o x i c a n t l e a c h i n g are considered to be the d i f f u s i o n of CuCl through the exhausted matrix and the subsequent d i f f u s i o n of CuCl" through the quiescent l a y e r . I f these assumptions are c o r r e c t , a c o n c e n t r a t i o n approaching s a t u r a t i o n w i l l develop i n the l e a c h i n g zone. A s t a t i o n a r y s t a t e w i l l be e s t a b l i s h e d where the c o n c e n t r a t i o n of the t o x i c a n t i s constant throughout any cross s e c t i o n of the exhausted m a t r i x and throughout the quiescent l a y e r . Under these c o n d i t i o n s the f l u x of t o x i c a n t through a u n i t cross s e c t i o n i s the same i n both the exhausted m a t r i x and the quiescent l a y e r . I t i s evident from the f o r m u l a t i o n of t h i s model that a d e t a i l e d study of the m a t r i x i s necessary to c h a r a c t e r i z e the l e a c h i n g process. There are s e v e r a l p o i n t s where coatings c o n t a i n i n g o r g a n o t i n compounds d i f f e r from those c o n t a i n i n g cuprous oxide. These d i f f e r e n c e s complicate the study of the l e a c h r a t e s and makes examination of the surface mandatory. The most e f f e c t i v e organo t i n t o x i c a n t s , of general formula R SnX, e x i s t e i t h e r as s o l i d s or as l i q u i d s . For conventional coatings where the t o x i c a n t i s p h y s i c a l l y mixed w i t h the p a i n t m a t r i x i n a common s o l v e n t , the l i q u i d organotins would be expected to d i s p e r s e homogeneously throughout the c o a t i n g ; whereas, the s o l i d m a t e r i a l s may d i s p e r s e as f i n e p a r t i c l e s forming a heterogenous mixture. The u s u a l p i g ments, carbon, f e r r i c oxide and t i t a n i u m d i o x i d e , are i n s o l u b l e i n most c o a t i n g formulations and are a l s o dispersed as f i n e p a r t i c l e s . In s u c c e s s f u l organotin c o n t a i n i n g c o a t i n g s , the percentage of t o x i c a n t i s about ten percent or l e s s as contrasted to the f o r t y to f i f t y percent t o x i c a n t composition commonly used i n cuprous oxide c o a t i n g s . Thus the "continuous contact" l e a c h i n g

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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E T AL.

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models are not appropriate f o r these m a t e r i a l s . I t has been proposed (10, 11, 12, 13) that some o f the m a t r i x must d i s s o l v e f o r l e a c h i n g t o occur i n a c o a t i n g c o n t a i n i n g organometalli c t o x i cants. To evaluate t h i s p r o p o s i t i o n the c o a t i n g surface must be examined i n d e t a i l t o c h a r a c t e r i z e the aging mechanisma ( d i s s o l u t i o n o f c o a t i n g m a t r i x , c r a c k i n g , sloughing o f f o f exhausted m a t r i x , etc.) and/or the l e a c h s o l u t i o n must be analyzed f o r d i s solved m a t r i x . I t has a l s o been proposed (10) t h a t the leachate species f o r a l l o f the coatings c o n t a i n i n g R^SnX i s the same molecule, namely R^SnOH, and that the l e a c h i n g r a t e depends n o t only on the m a t r i x , but a l s o on the p h y s i c a l s t a t e o f the t o x i cant i n the c o a t i n g . The model developed below has been designed w i t h the view that a p r a c t i c a l goal o f any l e a c h i n g model i s t o p r e d i c t the usef u l l i f e t i m e o f an a n t i f o u l i n l a b o r a t o r y and f i e l d t e s t i n g general e m p i r i c a l approach t o the l e a c h i n g problem w i t h l i t t l e emphasis on microscopic d e t a i l . Laboratory t e s t s can be performed and the model can be used t o determine the amount o f organotin remaining i n the m a t r i x f o r a given s e t o f experimental c o n d i t i o n s . A reasonable extension of the model i s the p r e d i c t i o n o f minimum c o a t i n g l i f e t i m e s by d e f i n i n g the extreme c o n d i t i o n s t h a t a c o a t i n g i s l i k e l y t o encounter and then designing l a b o r a t o r y t e s t i n g procedures which simulate those c o n d i t i o n s . D e t a i l s Of The Leaching Model At any time during the l i f e t i m e o f the a n t i f o u l i n g c o a t i n g , t o x i c a n t molecules d i f f u s e out o f the c o a t i n g i n a d i r e c t i o n normal t o the c o a t i n g plane. The molecules d i f f u s e through a t h i n quiescent l a y e r o f s o l u t i o n adhering t o the s u r f a c e and i n t o a well-mixed t u r b u l a n t l a y e r o f s o l u t i o n (the environment). This d i f f u s i o n process i s described by F i c k ' s F i r s t Law o f D i f f u s i o n . According t o t h i s Law (14) J

= MP)

m

\6x/y,z (1) where D i s the d i f f u s i o n c o e f f i c i e n t and J , the f l u x , i s the q u a n t i t y o f substance d i f f u s i n g per u n i t time through a u n i t area. Thus, A dt Therefore,

to

_ _ /|cX \ôx/y,z DA

dt

( 3 )

Let δχ/

y,ζ

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

(4)

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where c i s the c o n c e n t r a t i o n i n the bulk s o l u t i o n , c i s the o r g a n o t i n c o n c e n t r a t i o n at the c o a t i n g s u r f a c e , and χ i s the thickness of the quiescent l a y e r which i s a f u n c t i o n of the water v e l o c i t y moving pass the s u r f a c e . See Figure 1 f o r a p i c t o r i a l r e p r e s e n t a t i o n of the l e a c h i n g process. Thus, dm DA, » dF " - ϊ - ί ^ β )

(5)

For an experimental c o n t a i n e r of volume v, one o b t a i n s dc dt

_

DA, (c-c ) xvv s'

(6)

I f an o r g a n o t i n compound i s a l i q u i d i t w i l l mix thoroughly w i t h i t s m a t r i x formin compound i s a s o l i d , i s o l v e n t forming a low polymers of a s s o c i a t e d t o x i c a n t molecules, or i t may remain as s o l i d p a r t i c l e s d i s p e r s e d throughout the m a t r i x (15,16). The regions of s u r f a c e that are a c t i v e i n the l e a c h i n g process w i l l depend on the development of pores and channels through the m a t r i x as the o r g a n o t i n compound and/or m a t r i x d i s s o l v e and l e a c h i n t o the environment. I f the area of the s u r f a c e plane i s A and i f f i s the f r a c t i o n of the plane that i s a c t i v e , then ° A - f A and

(7) ο DfA

, dc dt

ο

C

C

( " s)

(8)

I n t e g r a t i n g , one o b t a i n s DfA c - c s

expf s

\

Q

t) XV

/

/QX (9)

The c h a r a c t e r i z a t i o n of a c o a t i n g i n v o l v e s determining c and Df/x by measuring the b u l k c o n c e n t r a t i o n s at v a r i o u s t i m l s and u s i n g the l e a s t squares technique to f i t the t h e o r e t i c a l equation to the experimental data. The general form of the equation i s A c = c - c exp(- α - f t ) s

s

( 1 Q )

where α i s Df/x and i s c h a r a c t e r i s t i c of the c o a t i n g f o r a g i v e n temperature and flow c o n d i t i o n . Now consider o b t a i n i n g an expression f o r the l i f e t i m e of the c o a t i n g knowing c and a: s

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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dm dt

s

" χ

o_ , . ( ^ ) C

C

S

(

n

)

In a l a r g e body o f water (ocean o r h a r b o r ) , c i s always n e g l i b l e and A i s the s u r f a c e area o f the s h i p continuously exposed t o the water. Then dm dt "

α

. o s

(12)

I n t e g r a t i n g , one obtains

where m i s the mass o f organotin leached out o f the c o a t i n g . Define a c r i t i c a l d e n s i t y , ρ , which i s achieved a t the time τ where f o u l i n g becomes a p p r e c i a b l e (say 50%). The mass o f organo t i n l o s t from the c o a t i n g i s given by m = α A c τ, τ o s

(14)

ρ = ρ -ac τ τ ο s

(15)

and

where ρ i s the o r i g i n a l mass o f o r g a n o t i n per u n i t area. The minimum u s e f u l l i f e t i m e o f the c o a t i n g i s then given by = — ( ρ ac ο s ν κ

κ

- ρ ) τ'

(16)

Experimental S e c t i o n S t a t i c leach t e s t s were performed on aluminum panels coated w i t h Alum-A-Tox (a commerical c o a t i n g obtained from Standard P a i n t and V a r n i s h Company o f New Orleans) c o n t a i n i n g an o r g a n o t i n compound as t o x i c a n t . Alum-A-Tox i s a v i n y l - t y p e c o a t i n g con t a i n i n g t i t a n i u m d i o x i d e as pigment. E i t h e r b i s ( t r i b u t y l t i n ) ox ide, t r i b u t y l t i n chloride, t r i b u t y l t i n acetate, t r i p h e n y l t i n a c e t a t e , o r t r i p h e n y l t i n c h l o r i d e was mixed i n t o the c o a t i n g so that a c o a t i n g composition o f 3.6% Sn by weight was obtained. The aluminum panels ( 3 " χ 4" χ 1/16") were sanded and cleaned w i t h carbon t e t r a c h l o r i d e . They were sprayed w i t h the p a i n t on one s i d e and were allowed t o a i r - d r y f o r a t l e a s t three weeks. Each panel was then immersed i n 550 mL a r t i f i c i a l sea water (17) i n a beaker and maintained a t 21±2°C f o r the d u r a t i o n o f the e x p e r i ment. S o l u t i o n s were r e p l a c e d a t the time o f sampling (about every two weeks). The leachates were analyzed f o r t i n u s i n g c o l o r i m e t r i c methods. The organotin c o n c e n t r a t i o n i n the leachate was determined

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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a f t e r e x t r a c t i n g the o r g a n o t i n compounds from the aqueous phase. The 550 ml of leachate from a given sample were d i l u t e d t o 1000 ml. w i t h d i s t i l l e d water, and 100 ml* was then p i p e t t e d i n t o a separatory f u n n e l . A f t e r adding 10 mL of chloroform to the separatory funnel and shaking v i g o r o u s l y f o r one minute, the contents were allowed to separate i n t o two l a y e r s . The c h l o r o form l a y e r was removed, the e x t r a c t i o n procedure was repeated three to four times to achieve complete e x t r a c t i o n of the organo t i n compounds, and a l l of the chloroform p o r t i o n s were combined. T i n present i n the chloroform was determined by the d i t h i z o n e c o l o r i m e t r i c method (18). Any t i n species remaining i n the aqueous phase were s u b j e c t ed to an o x i d a t i o n procedure before measuring the t i n concentra t i o n . The aqueous phase was a c i d i f i e d w i t h 16M HNO- and evaporated c a u t i o u s l y t s m a l l volume A f t e addin 5-6 L f 18M H S0^, the s o l u t i o SO . The residue was d i s s o l v e r e s u l t i n g s o l u t i o n was d i l u t e d to 100 mL. The t i n present i n t h i s s o l u t i o n was determined u s i n g the phenylfluorone c o l o r i m e t r i c method (19). No t i n above background was found i n the aqueous phase f o r any sample. This suggests t h a t the t i n i n the leachate i s s o l e l y i n the o r g a n o t i n form and not i n the i n o r g a n i c form. I t was assumed that the l e a c h i n g would be slow enough t h a t 2

Ac ^ d c At ~ d t where Ac i s the measured o r g a n o t i n c o n c e n t r a t i o n and At i s the time of accumulation. The l e a c h r a t e - time data were f i t t e d w i t h a q u a d r a t i c equation, and t h i s e m p i r i c a l equation was i n t e g r a t e d to o b t a i n concentration-time data. I n i t i a l guesses f o r c and α were obtained a f t e r comparing the concent r a t ion-time data w i t h simulated data generated f o r t r i a l v a l u e s of c and α by a program c a l l e d LEACH2. The best values o f c and α r e s u l t i n g from the previous procedure were f u r t h e r r e f i n e d by a l e a s t squares program c a l l e d LEACH1. As the concentration-time data were obtained from smoothed d a t a , u n c e r t a i n t i e s i n c and α have not been c a l c u l a t e d . To determine the s o l u b i l i t i e s of the o r g a n o t i n compounds used i n t h i s study, 50 mg of each compound were mixed w i t h 100 mL of a r t i f i c i a l sea water. The s o l u t i o n s were maintained at 21±2°C f o r two days w i t h o c c a s i o n a l s t i r r i n g . The amount o f o r g a n o t i n d i s s o l v e d i n the sea water was determined by the d i t h i z o n e c o l o r i m e t r i c method (18). g

s

R e s u l t s and D i s c u s s i o n The l e a c h i n g r e s u l t s f o r the t r i b u t y l t i n compounds and t r i p h e n y l t i n compounds are shown i n F i g u r e 2 and F i g u r e 3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

the

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Quiescent Layer

Figure 1. Pictorial representation of the leaching of toxicant molecules from an antifouling coating

time

(days) Proceedings of the 4th Annual Controlled Release Pesticide Symposium: Anti-Fouling Section

Figure 2. Leaching of tributyltin compounds from Alum-A-Tox coatings: ( Q ) — (CHo^SnOAc, (A) — [(C H ) Sn] 0, and (O) — (C H ) SnCl. Each solid line represents the least squares fit to Equation 10. 4

9

3

2

k

9

s

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

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AND ORGANOMETALLOIDS

4.0

Proceedings of the 4th Annual Controlled Release Pesticide Symposium: Anti-Fouling Section

2.0

Figure 3. Leaching of triphenyltin compounds from Alum-A-Tox coatings: (Q) = SnOAc and (O) = <£ SnCL Each solid 0 . 0 line represents the least squares fit to Equation 10. s

3

20

40 time (days)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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r e s p e c t i v e l y . The parameters g i v i n g the best f i t t o the concen t r a t i o n - t i m e data and the s o l u b i l i t i e s are given i n the Table. TABLE I Parameters f o r Alum-A-Tox Coatings Containing Organotin Compounds α (cm day "*")

Toxicant

c (ppm)

<|>SnOAc

772

57T5

<|>SnCl

2.2

0.18

4.22

12.8

0.19

1.88

3.3

0.45

1.57

3

3

(C.H ).Sn0Ac 4 93 (C.HJ SnCl 4 93 [(C H ) Sn] 0 o

4

9

3

2

S o l u b i l i t y (ppm) J7&

9.

As t goes t o l a r g e v a l u e s , c approaches c (see equation 10). The maximum c o n c e n t r a t i o n o f organotin i n sea water i s i t s s o l u b i l i t y . From t h i s argument c , the c o n c e n t r a t i o n o f organo t i n a t the s u r f a c e , would have the s o l u b i l i t y as i t s maximum v a l u e . From the t a b l e i t can be seen t h a t c i s o f the same order g

of magnitude as the s o l u b i l i t y but the values o f c are l a r g e r than the s o l u b i l i t y i n many cases. The parameter α must be considered t o be e m p i r i c a l . There are no d i f f u s i o n constants a v a i l a b l e f o r organotin compounds, and i t i s impossible to measure the t h i c k n e s s o f the quiesent l a y e r . However, s i n c e the s o l v a t e d o r g a n o t i n species are expected to be the same ( f o r R^SnX where R i s constant) i n a l l cases (10), the same d i f f u s i o n constant would be a p p l i c a b l e . Under constant flow c o n d i t i o n s , the t h i c k n e s s o f the quiescent l a y e r would be the same f o r a l l the c o a t i n g s . Values o f α would t h e r e f o r e provide a r e l a t i v e measure t o rank o r order the f r a c t i o n of the a c t i v e surface between the v a r i o u s c o a t i n g s . This f r a c t i o n of the surface that i s a c t i v e i n the d i f f u s i o n process i s expect ed to be dependent on the p h y s i c a l s t a t e o f the organotin com pound i n the c o a t i n g as w e l l as the p o r o s i t y o f the m a t r i x . However, s i n c e only one matrix and a few s e l e c t e d t o x i c a n t com pounds were s t u d i e d , any f u r t h e r d i s c u s s i o n based on the magni tude o f c and α would be e n t i r e l y s p e c u l a t i v e . These p r e l i m i n a r y r e s u l t s are promising i n t h a t an e m p i r i c a l d i f f u s i o n model has been developed which appears t o be g e n e r a l l y a p p l i c a b l e f o r d e s c r i b i n g the l e a c h i n g process a s s o c i a t e d w i t h a s e r i e s o f organotin t o x i c a n t s contained i n a commercial c o a t i n g v e h i c l e . The r e s u l t s do i n d i c a t e t h a t i t should be f e a s i b l e t o design l a b o r a t o r y t e s t i n g procedures f o r making r e l a t i v e compari sons o f the p r o p e r t i e s o f a s e r i e s o f coatings o f d i f f e r e n t f o r mulations. However, f u r t h e r s t u d i e s must be c a r r i e d out before the optimum range o f c and α f o r s a t i s f a c t o r y a n t i f o u l i n g per formance can be a s c e r t a i n e d . I n a d d i t i o n , f u r t h e r t e s t i n g i s s

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necessary before additional refinements to the model can be made. The experimental design for this i n i t i a l study was not optimum in that the leaching rates were faster than anticipated. This makes suspect the assumption that the leach rate can be approximated by the measured organotin concentration divided by the accumulation time. The second iteration of this experiment w i l l include other types of coating matrices and a new sampling procedure which w i l l allow c o n c e n t r â t i o n - t i m e data to be acquired directly. After these static tests have been completed, the effect of the depth of the quiescent layer and the possibility of accelerated leaching w i l l be evaluated by carrying out a l l of the measurements on coatings mounted on rotating drums designed for a variety of speeds. Acknowled gemen t s This work is a result of research sponsored by the Office of Naval Research and the NOAA Office of Sea Grant, Department of Commerce, under Grant No. R/MTR-1. The Alum-A-Tox coating base was supplied by Standard Paint and Varnish Company of New Orleans. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

11. 12. 13. 14. 15.

Starbird, E . A. and Sisson, R. F., National Geographic (1973) November, 623. Starbird, E . A., The Readers Digest (1974) March , 123. Murray, C . , Chemical and Engineering News (1975) January 6, 18. Evans, C. J., J. Paint Tech. (1970) 34, 17. Vizgirda, R. J., Paint and Varnish Prod. (1972) 62, 25. de l a Court, F. H. and De Vries, H. J., Prog. Org. Coat. (1973) 1, 375. de l a Court, F. H. and De Vries, H. J., J. O i l Colour Chem. Assoc. (1973) 56, 388. Marson, F., J. Appl. Chem. (1969) 19, 93. Marson, F., J. Appl. Chem. Biotechnol. (1974) 24, 515. Monaghan, C. P. Hoffman, J. F., O'Brien, E . J., Jr., Frenzel, L. M. and Good, Mary L., "Proceedings of the 4th Annual Controlled Release Pesticide Symposium: Antifouling Section", R. L . Goulding, E d . , Corvallis, Oregon, August, 1977. Kronstein, Μ., Mod. Paint and Coat. (1977) 67 (8) 57. Carr, D. S. and Kronstein, Μ., Mod. Paint and Coat. (1977) 67 (11) 41. Kronstein, M., Am. Chem. Soc., Div. Org. Coat. Plast. Chem. Pap. (1978) 38, 705. Crank, J., "The Mathematics of Diffusion," Oxford at the Clarendon Press, 1956. Hoffman, J . F. Kappel, K. C . , Frenzel, L . M. and Good, M. L., "Organometallic Polymers, " C. E . Carraher, Jr., J. E . Sheats, and C. U. Pittman, Jr., Eds., p. 195, Academic Press, New

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

22.

M O N A G H A N ET A L .

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369

York, 1978. 16. O'Brien, E. J., Monaghan, C. P. and Good, M. L., "Organometallic Polymers," C. E. Carraher, Jr., J. E. Sheats, and C. U. Pittman, Jr., Eds., p. 207, Academic P r e s s , New York, 1978. 17. LaQue, F. L., "Marine C o r r o s i o n : Causes and P r e v e n t i o n , " p.98, John Wiley and Sons, New York, 1975. 18. K u l k a r n i , V. H. and Good,M. L., under p r e p a r a t i o n . 19. K u l k a r n i , V. H. and Good, M. L., A n a l . Chem., in press. Discussion C. MATHEWS (Naval C i v i l Engineering Laboratory, Port Hueneme, C a l i f o r n i a ) : You s a i d that you didn't f i n d any i n o r g a n i c t i n after a stated length o that i t was r a t h e r n i c e i c compound. D i d I get that r i g h t ? GOOD: Yes, you d i d . I t ' s not a c o n f l i c t . What he i s saying i s that i t breaks down i n the atmosphere. These a r e not atmosp h e r i c t e s t s ; these a r e t e s t s done i n a l a b o r a t o r y where I don't have a l o t o f u l t r a v i o l e t l i g h t . The question of p e s t i c i d e s i s one t h i n g , but boat coatings i s another. The p e s t i c i d e s a c t u a l l y s i t out on the ground, where they get q u i t e a l o t o f s u n l i g h t ; the organotin leachates a r e not going t o have such UV exposure when they come o f f . I'm saying nothing here about the u l t i m a t e species that may o r may not be i n the environment. I'm simply t e l l i n g you what comes o f f t h e s u r f a c e . M. KRONSTEIN (Manhattan C o l l e g e , New Y o r k ) : I f you use r e a l c o a t i n g m a t e r i a l s the r e a c t i o n mechanism i s complete d i f f e r e n t . The organotin i n t e r a c t s w i t h v e h i c l e o f the p a i n t , i n p a r t i c u l a r w i t h the low polymer f r a c t i o n o f the v e h i c l e , even i n the case of v i n y l polymers. This can e a s i l y be determined by e x t r a c t i n g leachate water w i t h e t h y l e t h e r , then d i s s o l v i n g the r e s i d u e i n carbon t e t r a c h l o r i d e . With an i n f r a r e d spectrum and w i t h an atomic a b s o r p t i o n spectrum you w i l l see the amount of organic moiety and t i n that a r e i n the water. Now they l e a c h out bound and not separate. I f the water i s exposed t o sunshine o r t o r a d i a t i o n i n the l a b o r a t o r y , the r e l e a s e d r e a c t i o n product cont i n u e s t o polymerize, turns i n s o l u b l e , then p r e c i p i t a t e s out. I f you analyze the p r e c i p i t a t e you observe organic m a t e r i a l and t i n (or the copper o r the l e a d i f they were used i n the p a i n t ) . The important p o i n t i s t h a t the organotin may come out as t i n hydroxide o r t i n oxide and may not be as t o x i c . I f i t i s s t i l l p a r t o f the polymer, i t may be as t o x i c as i t was i n the p a i n t . I w i l l g i v e a paper on the l e a d case tomorrow [ c f . A b s t r . Papers, 175th N a t ' l Meeting ACS, Anaheim, CA., ORPL-135]. GOOD: I s p e c i f i c a l l y chose a commercial p a i n t which i s s o l d

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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ORGANOMETALLOIDS

and used i n South L o u i s i a n a . The m a t e r i a l which comes o f f i n t h i s p a r t i c u l a r case i s not p a r t of the polymer; i t i s j u s t the t o x i c a n t . I t i s t r u e that i n some m a t e r i a l s the organotin coating can r e a c t w i t h the polymer. I can t e l l you which ones do; i t i s very c l e a r from the Mossbauer and the i n f r a r e d s p e c t r a . I n t h i s p a r t i c u l a r case they do n o t . The model may a c t u a l l y work f o r those kinds of m a t e r i a l s i n v o l v e d i n e i t h e r case, provided we determine what the a c t u a l bond-breaking mechanism i s . F r a n k l y , we don't q u i t e know the mechanism f o r a l l those polymeric ones y e t . F. E. BRINCKMAN ( N a t i o n a l Bureau o f Standards): I'm i n t r i g u e d by your extension over the many models we have seen i n the past i n v o l v i n g d i f f u s i o n o r c o n t r o l l e d r e l e a s e w i t h near z e r o t h order k i n e t i c s . I t i s your conception t h a t the t i m e - t o - f a i l u r e w i l l depend on some c o n c e n t r a t i o a c t i v i t y . I s that wha so, we a r e t a l k i n g about a p o t e n t i a l standard. GOOD: That i s what one assumes. There i s a d i f f e r e n c e be tween assumption i n t h i s case and knowing that f o r c e r t a i n because the problem i s that the k i l l mechanism o r the c o n t r o l mechanism i s not t o t a l l y understood. BRINCKMAN: That's r i g h t , because the most c r i t i c a l p a r t o f the a n a l y t i c a l expression i s the s i z e o f x. The i s s u e i s that d i f f u s i o n g r a d i e n t , o r that c o n c e n t r a t i o n g r a d i e n t , immediately above the surface a t instantaneous time when that microorganism comes i n . GOOD: This p a r t i c u l a r experiment has another p o s s i b l e aspect, a b i o l o g i c a l one. You can determine χ g r a p h i c a l l y and get a reasonable value f o r i t . You ought t o be a b l e t o do that i f you can determine the d i f f u s i o n c o e f f i c i e n t s by some other method. Then, i f you could determine χ f o r a s t a t i c experiment o r a r o t a t i n g experiment, then we might be a b l e t o answer the question how c l o s e the organism has t o get t o the t o x i c a n t before i t ' s e f f e c t i v e . You remember, we don't know what the depth o f the t o x i c a n t l a y e r has t o be before you get c o n t r o l . G. E. PARRIS (Food and Drug A d m i n i s t r a t i o n ) : With regard t o the l e a c h r a t e and t o x i c i t y t o organisms, I t h i n k t h i s i s an a p p r o p r i a t e approach i n terms o f d i f f u s i o n through a quiescent l a y e r . However, i n terms o f t i m e - t o - f a i l u r e , t h i s reminds me o f the system which r e c e n t l y r e c e i v e d a t t e n t i o n , the l e a c h i n g o f tris(2,3-dibromopropyl)phosphate from p o l y e s t e r f i b e r s . There, i s n ' t t h e l i m i t i n g c h a r a c t e r i s t i c the d i f f u s i o n w i t h i n the s o l i d phase r a t h e r than the l i q u i d phase? I n the " t r i s " case, you can wash the f i b e r s e v e r a l times t o get r i d o f a s u r f a c e l o a d i n g and e s t a b l i s h some s o r t of a steady-state l e a c h i n g c o n d i t i o n . I f you take the f i b e r out o f s o l u t i o n and l e t i t s i t , the t o x i c a n t m i -

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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371

grates very s l o w l y t o the surface by completely d i f f e r e n t k i n e t i c a GOOD: This model a t t h i s moment does not i n c l u d e t h a t . I t looks only a t what i s coming o f f a t the surface i n v o l v i n g t o x i c a n t i s l a n d s . As I discussed, t h i s model may be a l l r i g h t because you are not t a l k i n g about l e a c h i n g through cracks and c r e v i c e s i n b i g polymers. PARRIS: You used a c o r r e c t i o n f a c t o r t o account f o r the f a c t that you do have i s l a n d s and not a continuous s u r f a c e . What conc e n t r a t i o n do you use, the c o n c e n t r a t i o n i n the i s l a n d o r some average concentration? GOOD: I t ' s an average c o n c e n t r a t i o n . PARRIS: I s n ' t tha but then you are assuming t h a t the c o n c e n t r a t i o n i s continuous. GOOD: You mean that the c o n c e n t r a t i o n i s continuous a t the surface? You can't do much about t h a t unless you make a much more completed model. We can check that very e a s i l y e x p e r i m e n t a l l y by going t o l e s s and l e s s concentrated systems. That i s , make the i s l a n d s f u r t h e r apart. PARRIS: I t i s then a question o f how you i n t e r p r e t the diffusion coefficient? GOOD: That's t r u e . What we would see on t h i s model i s an e f f e c t i v e d i f f u s i o n c o e f f i c i e n t which i s not p r e c i s e l y the same as a d i f f u s i o n c o e f f i c i e n t i n v o l v i n g the t o t a l s o l i d and an i n t e r face. R E C E I V E D August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

23 Metal-Ion Transport Mediated b y H u m i c and Fulvic Acids GORDON K. PAGENKOPF Department of Chemistry, Montana State University, Bozeman, MT 59717 The movement of trac involves a large numbe waters one particular type of reaction will be dominant whereas in others a balance will be established. This report presents a brief look at the interactions between trace metals and two commonly encounted natural chelating agents. Humic and Fulvic Acid In many cases most of the organic material found in natural waters is derived from natural sources. The leaching of soil and decaying plants accounts for most of this material making the number of possible organic compounds virtually limitless. One group, the humates, appears to play a role in metal transport and has been widely studied (1). These materials are dark colored and in many cases comprise a majority of the organic material found in natural waters. The substances have been divided into two general classes on the basis of solubility. The first class, which is designated as humic acid, is that material soluble in base but insoluble in acid and/or alcohol. Fulvic acid, the second class, is soluble in both base and acid. The isolation of these materials from natural waters can be tedious since the normal concentration range is 1-5 mg/l. There are reports of higher values however (2,3). Both of these acids may be precipitated from solution with excess barium. A selected group of elemental analyses for humic (HA) and fulvic acid (FA) is shown in TABLE I. It should be noticed that the oxygen content of fulvic acid is significantly greater than the values observed for humic acid and the carbon content of humic acid is greater than that of fulvic acid. The oxygen functionality includes carboxyl, phenolic, alcoholic , carbonyl, and methoxyl groups. The total acidity is considered equal to the sum of the carboxyl and phenolic acidity. These groups also appear to play a major role in the binding of metal ions. TABLE II summarizes some representative acidity 0-8412-0461-6/78/47-082-372$05.00/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

23.

PAGENKOPF

Metal-Ion Transport

TABLE I Elemental A n a l y s i s o f Humic and F u l v i c Acids ( 1 ) . S o i l HA %G

%H

%0

%S

%N

56.4 53.8 60.4

5.5 5.8 3.7

32.9 36.8 33.6

1.1 0.4 0.4

4.1 3.2 1.9

64.8

4.1

28.7

1.2

1.2

42.5 47.6

5. 4.

50.9

3.3

44 .8

0.3

0.7

5.9

45.3

—

Coal HA

S o i l FA

Water FA 46.2 a)

3

2.6

n o t determined

TABLE I I A c i d i t y Values f o r Humic and F u l v i c A c i d s Total Acidity meq/g g/eq

Ref

Carboxyl meq/g

Phenolic meq/g

151 114 175 98 122

4.5 3.0 1.5 4.7 4.7

2.1 5.7 4.2 5.5 3.6

137 135

4.4 3.4

2.9 4.0

1 1

8.5 9.1 9.1 7.0

5.7 3.3 2.7 3.2

1 Î 1

HA 6.6 8.7 5.7 10.2 8.2

1 I

1 1 Γ

C o a l HA 7.3 7.4 FA 14.2 12.4 11.8 10.2

70.4 80.7 84.7 97.9

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

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ORGANOMETALLOIDS

v a l u e s . The data i s presented as meq/g and g/eq. These n a t u r a l complexing agents e x h i b i t c o n s i d e r a b l e v a r i a t i o n i n n i t r o g e n content. Studies w i t h humic a c i d and f u l v i c a c i d , which c o n t a i n 4% n i t r o g e n , i n d i c a t e t h a t approximately onef o u r t h of the t o t a l n i t r o g e n i s present as amino a c i d n i t r o g e n and a comparable amount i s present as ammonia n i t r o g e n ( 6 ) . This amount of n i t r o g e n could provide a d d i t i o n a l c o o r d i n a t i o n s i t e s . A v a r i e t y of techniques have been u t i l i z e d t o o b t a i n the average gram formula weight of these a c i d s . The values range from a few hundred t o s e v e r a l m i l l i o n . In g e n e r a l , the molecular weights of f u l v i c a c i d are l e s s than humic a c i d , w i t h values l y ing i n the range of a few hundred t o a few thousand. Complexom e t r i c s t u d i e s u t i l i z i n g i o n s e l e c t i v e e l e c t r o d e s have provided FA a c i d values of 600, 1200, 1750, 2000, and 2775 daltons (5.,^). Similar studies with coa 6761 daltons ( 4 ) . In a d d i t i o n the HA i n F l o r i d a r i v e r waters l i e s w i t h i n the 1000-5000 range (£). Many of the problems a s s o c i a t e d w i t h o b t a i n i n g values by more c o n v e n t i o n a l methods l i e w i t h the obtainment and u t i l i z a t i o n of a p p r o p r i a t e standards. The i o n s e l e c t i v e e l e c t r o d e t e c h n i q u e , u s i n g cadmium, may prove t o be a r e l i a b l e method f o r obt a i n i n g these d a t a . P o t e n t i o m e t r i e t i t r a t i o n s of HA and FA w i t h s t r o n g base suggests t h a t a l a r g e f r a c t i o n o f the i o n i z a b l e protons are t i t r a t e d by pH 7 (4 ,_5,9,10,11). A combination of the g/eq data t h a t i s summarized i n TABLE I I and the observed average gram formula weights provides a l a r g e number of i o n i z a b l e protons per molecule. For example, the FA c h a r a c t e r i z e d by Brady (S) which has an a v e r age gram formula weights of 2775 and a t o t a l a c i d i t y of 10.2 meq/g w i l l have approximately 28 i o n i z a b l e protons, and i f more than h a l f of these are t i t r a t e d by pH 7, t h i s molecule w i l l have a h i g h net negative charge which w i l l f a c i l i t a t e complexation. The exact d e s c r i p t i o n o f these l i g a n d s has not as y e t been assigned but a reasonable q u a l i t a t i v e p i c t u r e of the molecules would be a polymeric p o l y e l e c t r o l y t e . There are many a c i d i c groups capable of complexing metals and probably a few n i t r o g e n donor s i t e s . The s p a t i a l o r i e n t a t i o n of the complexation s i t e s i s not known; however, i t i s presumed t h a t s e v e r a l donors are a v a i l a b l e f o r simultaneous c o o r d i n a t i o n of metal i o n s . Charge n e u t r a l i z a t i o n i s important i n determining the s o l u b i l i t y o f these molecules as evidenced by the f a c t t h a t HA i s i n s o l u b l e i n s t r o n g a c i d and t h a t FA can be p r e c i p i t a t e d by excess barium. Complexation A v a r i e t y of techniques have been u t i l i z e d t o evaluate the c o n d i t i o n a l s t a b i l i t y constants f o r the complexation of t r a c e metals by humic and f u l v i c a c i d s . These i n c l u d e p o t e n t i o m e t r i c t i t r a t i o n s , i o n exchange, spectrophotometry, e l e c t r o c h e m i c a l measurements, m e t a l - i o n s p e c i f i c e l e c t r o d e s , n u c l e a r magnetic

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

23.

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Metal-Ion Transport

resonance, and o t h e r s . A s e l e c t e d sample o f the c o n d i t i o n a l s t a b i l i t y constants i s l i s t e d i n TABLE I I I . This l i s t i n g i s by no means complete, b u t i t does provide a summary o f the s t a b i l i t y constant v a r i a t i o n w i t h pH and metal i o n . One of the f i r s t proposed models f o r the complexation o f metal ions by HA and FA i s s i m i l a r t o b i d e n t a t e c o o r d i n a t i o n by s a l i c y l i c a c i d (9,20). The l i g a n d s c e r t a i n l y c o n t a i n s u f f i c i e n t f u n c t i o n a l i t y t o accommodate t h i s mode o f complexation. The pH p r o f i l e data i n d i c a t e t h a t protons are d i s p l a c e d by metal ions

(21). Since the pKa value g r e a t e r than c a r b o x y l i c groups, there i s some question as t o the extent o f phenolic oxygen p a r t i c i p a t i o n i n b i n d i n g r e a c t i o n (4,J5} Another mode o f complexation (22) would i n v o l v e bidentate c a r b o x y l i c a c i d groupings. This grouping would a l s o e x h i b i t hydrogen i o n dependence. \

^

\

^°°2

C

+M= C0 H o

+

2

C^

^

H

+

H

C — 0 0

A comparison t o model compounds such as o x a l i c and malonic a c i d p r e d i c t s s i z a b l e complex s t a b i l i t y . This type o f c o o r d i n a t i o n has been u t i l i z e d t o r a t i o n a l i z e the increase i n average gram formula weight o f the l i g a n d s t h a t occurs c o i n c i d e n t w i t h metal i o n f a c i l i t a t e d p r e c i p i t a t i o n (22). I n t h i s case, the metal i s thought t o b r i d g e two o r more polymeric chains together. The complexation o f more than one metal i o n per l i g a n d , each w i t h comparable s t a b i l i t y , r e q u i r e s the presence o f repeating u n i t s w i t h i n the l a r g e polymeric molecule. The magnitude o f the s t a b i l i t y constants i s s i m i l a r t o t h a t expected f o r d i c a r b o x y l a t e c o o r d i n a t i o n , and the i n f l u e n c e o f changing pH i n the near neut r a l r e g i o n may be assigned t o a n e t negative charge increase i n the l i g a n d as the pH i n c r e a s e s . The formation o f these m u l t i metal complexes suggests many i n t e r e s t i n g phenomenon regarding t r a c e metal c a r r y i n g c a p a c i t y and d i v e r s e metal i o n competition f o r donor s i t e s . The s t a b i l i t y constants obtained a t low pH a r e not l a r g e , most l y i n g between 100 and 1000, and i t i s probable t h a t i o n p a i r i n g or monodentate c o o r d i n a t i o n i s o p e r a t i v e . Recent nmr s t u d i e s (23) w i t h M n ( I l ) and f u l v i c a c i d may be interprétated by the formation o f e l e c t r o s t a t i c outer sphere complex. The s t a b i l i t y o f the complex i s n o t t o o much l a r g e r than a comparable one w i t h Κ . S i m i l a r s t u d i e s w i t h F e ( I I l ) s u b s t a n t i a t e an inner

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

ORGANOMETALLOIDS

TABLE I I I Selected C o n d i t i o n a l S t a b i l i t y Constants Complex

£H

CuFA 3.0 CuFA 5.0 4.0 CuHA 4.0 CuHA 4.0 CuFA 3.0 CuFA 4.0 CuFA 5.0 CuFA 3.0 CuFA CuFA CuFA CdFA CdFA 5.7 CdFA 6.7 CdFA 7.7 CdFA 5.7 Cd FA 6.7 Cd FA 7.7 CdfjA 5. Cd FA 6. CdilFA Cd^FA 7. ZnFA 3. ZnHA 5. ZnHA 6. ZnHA 3, ZnHA 5. ZnHA 7. ZnHA 4. ZnHA 5.8 MnFA 3.0 MnFA 5.0 Fe(IIl)FA Fe(II)FA Fe(II)FA Fe(IIl)HA Fe(III)HA 9

9

z

Log Κ

ref

Complex

3.3 4.2 9 5 4 2 a 0 8 0

10 1Û 12

a

6

a

12 12 13 13 13

11 7

£H

Log Κ

re£

CdHA CdHA CdHA CdHA Cd HA Cd HA Cd HA Cd^HA Cd^HA Cd^HA

5.5 6.0 7.0 7.5 6.0 7.0 7.5 6.0 7.0 7.5

4.9 5.3 5.9 6.3 9.2 10.6 11.7 13.7 15.7 16.5

4 4

Co(Il)FA Co(Il)FA Co(Il)HA Co(Il)HA Co(II)HA Co(ll)HA NiFA NiFA ZnFA ZnFA Fe(IIl)FA Fe(IIl)FA Fe(IIl)FA Fe(IIl)FA Hg(Il)FA Hg(Il)FA PbFA PbFA PbFA PbFA CaFA CaFA MgFA A1FA

4.0 4.5 6.0 6.6 4.5 6.0 6.0 8.3 4.7 4.6 5.8 5.5 3.0 3.2 4.2 5.0 3.0 2.2 5.0 3.6 1.0 4.45 1.5 4.18 4.18 2.5 3.5 5.1 3.0 4.9 4.0 5.1 3.0 2.7 5.0 4.0 6.8 5.5 6.8 10.4 3.0 2.7 3.3 5.0 2.1 1.9 2.35 3.7

9 z

9

I4 4 4

9

9

Z

Z

a)

3.0 3.4 5.3 5.6 6.0 9.8 10.6 10.7 14.0 15.5 15.4 1.7

a

13 5 5 5 5 5 5

I5 14 17

12 18

4.2 5.3 2.2 3.7 6.1 5.4 5.6 6.8 7.2

18 18 16

la

m 10 10

15 15 13 12.

9

a

a

Values estimated from F i g u r e 1 i n reference 13.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

15 15

M 16 16 10 10

12 10 10

12 19 19

11 13 13 10 10 7 7

10 10 10 10

23.

PAGENKOPF

377

Metal-Ion Transport

sphere mode o f complexation. As the pH increases from near 2 t o 8, the c o n d i t i o n a l constants f o r i n n e r sphere complexation w i l l become more f a v o r a b l e and i t i s expected t h a t i n n e r sphere comp l e x a t i o n w i l l predominate a t the higher pH v a l u e s . E l e c t r o n paramagnetic resonance s t u d i e s o f a Cu-HA complexes suggest t h a t copper i s bound, i n a porphyrin type o f donor network (23). These complexes should be more s t a b l e than those p r e v i o u s l y presented and i n a d d i t i o n the metal ions may not be l a b i l e . The b i n d i n g o f copper by a c o a l humic a c i d e x h i b i t s two major types o f i n t e r a c t i o n (25) i n the pH 1-3 r e g i o n . One i n volves hydrogen exchange comparable t o those previous presented and the other i s nonexchange. The l a t t e r i s most important a t low pH and does n o t f i t b a s i c a d s o r p t i o n t h e o r y . A t these pH values the l i g a n d may be aggregated by a metal o r hydrogen i o n which u l t i m a t e l y provide molecular bridges i s b e l i e v e The c o a g u l a t i o n o f peat humic a c i d s through the a d d i t i o n o f metal ions i s presumed due t o the formation o f a c o i l e d hydrophobic conformation and concurrent e x p u l s i o n o f water from the organic matrix ( 2 6 ) . At low pH the i n t e r a c t i o n s a r e dominated by a d s o r p t i o n and i o n exchange t h a t may or may n o t i n v o l v e inner sphere c o o r d i n a t i o n . As the pH i s i n c r e a s e d , the more c o n v e n t i o n a l mode o f complexation i n v o l v i n g t h e i n n e r sphere o f the metals and oxygen and n i t r o g e n donors takes over. The observed s t a b i l i t i e s a r e comparable t o m u l t i d e n t a t e c o o r d i n a t i o n . Rate o f Complex Formation and D i s s o c i a t i o n I t i s sometimes r e p o r t e d t h a t complexation o f t r a c e metals by humic and f u l v i c a c i d r e s u l t s i n i n e r t complexes which render the t r a c e metals u n a v a i l a b l e f o r t r a n s p o r t . There i s l i m i t e d experimental evidence t o support t h i s concept and i n f a c t many of the i n t e r a c t i o n s should be l a b i l e . The only d e t a i l e d study i n v o l v e s the complexation o f F e ( I I I ) w i t h f u l v i c a c i d (19). This r e a c t i o n was s t u d i e d over the pH range o f 1 t o 2.5. The r a t e o f f o r m a t i o n o f the complex i s f i r s t order i n each r e a c t a n t and the observed r a t e constant i s 196M~-*-sec~ . This r a t e constant i s a f a c t o r o f t h i r t y l e s s than the r a t e constant f o r the r e a c t i o n Fe

+ SO^

- FeS0

4

1

which i s 6370 sec"" ( 2 7 ) . This l a t e r v a l u e i s i n agreement w i t h the p r e d i c t e d value u t i l i z i n g the r a t e o f water l o s s from F e ( I I l ) and the outer sphere a s s o c i a t i o n constant ( 2 8 ) . I t i s d i f f i c u l t t o p r e d i c t t h e outer sphere a s s o c i a t i o n constant f o r FA, b u t from these r e s u l t s i t appears t h a t the v a l u e i s approximately 0.1 a t low pH. I t i s b e l i e v e d (19) t h a t c o o r d i n a t i o n o f the f i r s t FA b i n d i n g s i t e i s a s s o c i a t e d w i t h t h e r a t e determining

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

378

ORGANOMETALS

AND

ORGANOMETALLOIDS

s t e p . I f t h i s i s s o , and i f i t holds f o r other s i m i l a r complexes, one can make a reasonable estimate f o r the r a t e of formation o f a l l metal-FA complexes. The r a t e constant f o r the d i s s o c i a t i o n o f F e ( I I l ) - F A i s c a l c u l a t e d t o be 0.007 s e c " . The h a I f - l i f e f o r d i s s o c i a t i o n i s i n excess o f 10 seconds, which i s a f a i r l y slow r a t e by some standards ; however, i t i s f a s t when compared t o geochemical life-time. I t should be emphasized t h a t these a r e homogeneous phase r e a c t i o n s . I f s o l i d p a r t i c l e s a r e present where other processes are r e q u i r e d t o l i b e r a t e the metal from the complexation s i t e , the r e a c t i o n s may be much slower. The r a t e constants f o r the formation o f a v a r i e t y o f metal complexes may be estimated from the r e l a t i o n s h i p (29) 1

f

os m-H 0 2

where k~ i s the r a t e constant f o r the formation of the complex, K i s the outer sphere a s s o c i a t i o n constant (28) and ^ ^ is Q g

the r a t e constant f o r l o s s o f water from the p a r t i c u l a r metal i o n . Water l o s s values f o r s e l e c t e d metals are l i s t e d i n TABLE IV ( 3 0 ) . With e x c e p t i o n of A l ( I I I ) a l l metal ions should r e a c t more r a p i d l y than F e ( I I l ) . As the pH increases the s t a b i l i t y con s t a n t s i n c r e a s e which i s a s s o c i a t e d w i t h an increased forward r a t e constant due t o a favored e l e c t r o s t a t i c a t t r a c t i o n between the metal i o n and the p r o g r e s s i v e l y deprotonated l i g a n d . The deprotonation of the l i g a n d should a l s o decrease the r a t e con s t a n t f o r l i g a n d d i s s o c i a t i o n . Since Κ = k - Z k both of these eq f r &

TABLE IV C h a r a c t e r i s t i c Water Loss Metal Cu(Il) Cd(Il) Co(Il) Ni(Il) Zn(Il) Mg(Il) AI(III)

Log k, s e c " 8.5 8.3 5.5 4.2 7.5 5.1 0.5

1

Values Metal Mn(Il) Fe(IIl) Fe(II) Hg(II) Pb(Il) Ca(II)

Log k, sec 6.6 2.0-3.3 6.1 9.3 7.7 8.5

changes tend t o increase the values o f the e q u i l i b r i u m c o n s t a n t s . As was mentioned p r e v i o u s l y f o r i r o n ( I I l ) , the c o n s i d e r a t i o n s only apply f o r homogeneous phase r e a c t i o n s . These r e a c t i o n s should be of major importance i n waters o f near n e u t r a l pH w i t h

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

23.

PAGENKOPF

Metal-Ion Transport

379

HA and FA a c t i n g t o b u f f e r the t r a c e metal concentrations i n s o l u t i o n . I f the mode of complexation i s not dominated by c a r boxy l a t e donors, as i n the porphyrin complexes, the r a t e of metal exchange may be s i g n i f i c a n t l y l e s s . This could lead t o the i d e n t i f i c a t i o n of " l a b i l e " and " i n e r t " types of complexation w i t h i n a given l i g a n d . Heterogeneous Phase I n t e r a c t i o n s The mode and extent of t r a c e metal exchange between the s o l u t i o n and s o l i d phases i s c r i t i c a l t o the i n t e r p r e t a t i o n of t r a c e metal t r a n s p o r t . There are a v a r i e t y of c o n t r o l l i n g processes that have been i d e n t i f i e d . These include ion exchange, p r e c i p i t a t i o n , and absorption onto the surfaces of c l a y s , hydrous oxides (31), and s o l i d organi remove t r a c e metals fro p l e x a t i o n tend t o s o l u b i l i z e the metals and r e t u r n them t o the s o l u t i o n phase. These exchange i n t e r a c t i o n s are of course comp l i c a t e d by the d i v e r s i t y of the systems; however, s e v e r a l l a b oratory studies have provided i n s i g h t i n t o what may be expected i n a n a t u r a l system. A l a b o r a t o r y model (32) t h a t simulates many of the c o n t r o l ing processes included three s o l i d phases; potassium b e n t o n i t e , hydrous Mn0 , and s o l i d humic a c i d . Carbonate, bicarbonate, tannic a c i d , and s o l u b l e humic a c i d were the s o l u b i l i z i n g l i g a n d a The observed d i s t r i b u t i o n of C u ( I l ) , C d ( I l ) , and Z n ( I l ) i s pH dependent with f i f t y percent of the t o t a l copper being absorbed at pH 6.5. The copper i n s o l u t i o n was completely complexed as determined by anodic s t r i p p i n g voltammetry. The t o t a l concent r a t i o n s of the metals were higher by a f a c t o r of 10-100 than those commonly observed i n n a t u r a l waters. A v a r i e t y of s t u d i e s have focused on the i n t e r a c t i o n of FA with c l a y s (33, 34). I t i s observed t h a t FA can r e a d i l y s o l u b i l i z e C u ( I l ) âFsorFed onto montmorillonite (35). Over the pH range of 2.5 to 6.5 the amount copper s o l u b i l i z e d by 50mg of FA doubled, i n c r e a s i n g from .12 t o .26 mg. At the higher pH v a l u e , v i r t u a l l y a l l of the s o l u b l e copper was complexed by FA. The amount s o l u b i l i z e d a t pH 6.5 represented 49% of the o r i g i n a l C u ( I l ) absorbed onto the c l a y . The absorption of Pb-FA by three s o i l s has been studied (36) and the r e s u l t s are presented i n Table V. The s o i l s include a montmorillonite c l a y , a loam, and a f i n e s i l t y san^. The con-_g centrâtion of the lead complex v a r i e d from 1 χ 10~ M t o 1 χ 10 M, and the amount of the complex absorbed was determined by measuring both lead and f u l v i c a c i d concentrations i n the s o l u t i o n phase. C o r r e c t i o n f o r absorption t o the r e a c t i o n f l a s k s has been made. The loam and the f i n e - s i l t do not e x h i b i t the absorption c a p a c i t y demonstrated by montmorillonite f o r Pb; however, they do absorb a s i z a b l e f r a c t i o n of the lead complex. The montmorillonite ab sorbs more and i s capable of reducing the concentration of the 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

380

ORGANOMETALLOIDS

complex t o l e s s than 10" M which corresponds t o l e s s than 20jug/l Pb. The f u l v i c a c i d data i n d i c a t e t h a t there i s p a r t i a l d i s s o c i a t i o n of the complex w i t h the f r e e Pb being p r e f e r e n t i a l l y absorbed. S i m i l a r Pb absorption s t u d i e s without any f u l v i c a c i d r e s u l t e d i n much lower c o n c e n t r a t i o n of lead i n s o l u t i o n . From t h i s study i t appears t h a t f u l v i c a c i d i s capable o f e l e v a t i n g the concentration of lead i n s o l u t i o n ; however, the amount i n s o l u t i o n i s very dependent upon the p h y s i c a l charac t e r i s t i c s of the heterogeneous phase. For c l a y s t h a t demonstrate a s i z a b l e a b s o r p t i o n c a p a c i t y f o r organic compounds, the amount of f u l v i c a c i d i n s o l u t i o n w i l l be s m a l l , l e s s than 1 mg/l. For other s o i l s the i n t e r a c t i o n i s l e s s . As a consequence, more o f the complexing l i g a n d w i l l remain i n s o l u t i o n and be a v a i l a b l e f o r the m o b i l i z a t i o n and t r a n s p o r t of t r a c e metals.

Absorption of Lead-Fulvic Acid Complex (36)

Pb-FA M

T

Percent Absorbed (As Per Pb A n a l y s i s ) Amsterdam Holloway Marias Fine-Silt Loam Montmorillonite a

a

7

62

7

82

84

88

6

77

84

85

6

97

53

86

5

98

45

81

1.0 x 10"

3.0 χ 10~

1.0 χ 10" 3.0 χ 10"

1.0 χ 10"

Percent Absorbed (As Per FA A n a l y s i s ) 5

1.0 χ 10"

75

21

44

pH of s o l u t i o n s

7.6

6.5

8.3

a) Not determined. Chemical S p e c i a t i o n Many of the t r a c e metals t h a t are found i n n a t u r a l waters are e x t e n s i v e l y complexed. With pH values near or above n e u t r a l and bicarbonate concentrations of 1.5 χ 10" M, the hydroxide and carbonate complexes may dominate the s p e c i a t i o n . In waters w i t h high s u l f a t e and c h l o r i d e ion c o n c e n t r a t i o n s , these complexes may a l s o represent a s i z a b l e p o r t i o n of the t o t a l s o l u b l e metal. One method of p r e d i c t i n g the concentrations of t r a c e metals i n s o l u t i o n i s t o assume t h a t the c o n c e n t r a t i o n of the f r e e metal

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

23.

PAGENKOPF

381

Metal-Ion Transport

i o n i s r e g u l a t e d by the s o l u b i l i t y of an i n s o l u b l e carbonate or hydroxide s a l t . By s p e c i f y i n g the pH and a l k a l i n i t y the t o t a l metal i n s o l u t i o n i s r e a d i l y p r e d i c t e d u t i l i z i n g the a p p r o p r i a t e e q u i l i b r i u m c o n s t a n t s . The r e s u l t s o f such c a l c u l a t i o n s f o r cop per, l e a d , cadmium and z i n c i s shown i n TABLE V I . TABLE V I P r e d i c t e d T o t a l Trace Metal Concentrations' 2+

Copper Cadmium Lead Zinc

a)

T o t a l Metal Ug/1

Free M «8/1 .06 6.00 0.7 65.00

Metal

Observed Cone. Range (37) jig/1

11

9.5

190

64.0

S o l i d phases are CuO, CdC0 , P b ( 0 H ) , pH = 8.3, 3

THCO"] = 1.5 χ 1 0 "

2

3

For copper the c o n c e n t r a t i o n o f the f r e e metal i o n represents a s m a l l f r a c t i o n o f the t o t a l . The other metals are not as e x t e n s i v e l y complexed. The c o n c e n t r a t i o n o f organic m a t e r i a l i n n a t u r a l water o f t e n ranges from 1-5 mg/l. I f an average gram formula weight per com p l e x i n g s i t e i s assumed t o be 1,000, one would p r e d i c t an e f f e c t i v e complexation c o n c e n t r a t i o n o f 1-5 χ 10~°M. A survey of the e f f e c t i v e s t a b i l i t y constants l i s t e d i n TABLE I I I i n d i c a t e s t h a t the values are t o o s m a l l a t low pH t o make a s i g n i f i c a n t c o n t r i b u t i o n t o the t o t a l complexation. As the pH i s increased the c o n d i t i o n a l s t a b i l i t y constants i n c r e a s e , and by pH 7 the values have reached 10 . Constants o f t h i s magnitude a r e probably a minimum f o r any s i g n i f i c a n t c o n t r i b u t i o n t o the s p e c i a t i o n s i n c e 10 o f f r e e complexation s i t e s would be r e q u i r e d t o achieve a 1 t o 1 d i s t r i b u t i o n of M t o the complexed form. At present, the a v a i l a b l e data f o r the metals t h a t form the most s t a b l e complexes (copper, n i c k e l , i r o n ( I I I ) , and l e a d ) sug g e s t c o n d i t i o n a l s t a b i l i t y constants g r e a t e r than 10^ a t n e u t r a l pH. I f these values a r e as h i g h as 10**, the r a t i o o f f r e e metal t o organic complexed metal could be as high as 100. This i s com parable t o the r a t i o observed f o r some o f the hydroxo and carbo nate complexes (see TABLE V I ) . With s t a b i l i t y constants as l a r g e as 10**, the complexing c a p a c i t y o f the HA and FA would be equal t o the e f f e c t i v e complexation s i t e c o n c e n t r a t i o n . 2 +

Transport Some o f the f a c t o r s t h a t i n f l u e n c e the t r a n s p o r t of t r a c e

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

382

ORGANOMETALS AND ORGANOMETALLOIDS

metals by humic and f u l v i c a c i d have been d i s c u s s e d . Past and c u r r e n t s t u d i e s i n d i c a t e t h a t HA and FA form complexes w i t h s u f f i c i e n t s t a b i l i t y t o complex s i z a b l e f r a c t i o n s o f the t r a c e metals a t c one e n t r a t i ons commonly found i n n a t u r a l waters. The r a t e s o f formation and d i s s o c i a t i o n a r e p r e d i c t e d t o be r a p i d on the geochemical time s c a l e and thus the systems may, i n many cases, approach dynamic e q u i l i b r i u m . The i n t e r a c t i o n s between the s o l u t i o n and s o l i d phases a r e p r i m a r i l y r e s p o n s i b l e f o r the r e g u l a t i o n o f the s o l u t i o n c o n c e n t r a t i o n s . These i n t e r a c t i o n s not only provide a source o f m a t e r i a l t o be desorbed but a l s o c o n t r o l the maximum concentrations t h a t w i l l occur i n s o l u t i o n . The system can be thought o f as a l a r g e dynamic metal-ion b u f f e r . Since there i s a c o n t i n u a l i n p u t o f organic m a t e r i a l , i t s conc e n t r a t i o n remains f a i r l y constant and a v a i l a b l e t o m o b i l i z e or r e l e a s e t r a c e metals. Bot pending upon the p a r t i c u l a The mean l i f e time of a metal complex i n the system i s regu l a t e d by the r a t e of complex f o r m a t i o n , d i s s o c i a t i o n , and exchange w i t h the s o l i d phase. A t t h i s time there i s minimal i n formation p e r t a i n i n g t o the l a t t e r . I n one f i e l d study a p p r o x i mately 28 percent of the t o t a l a v a i l a b l e manganese was t r a n s ported through a watershed by humic m a t e r i a l (38). Studies of Fe, N i , Cu, C r , Co, and Mn t r a n s p o r t (39) suggest a major r o l e being played by c r y s t a l l i n e m a t e r i a l and surface c o a t i n g s . The same d i s t r i b u t i o n i s not observed i n other systems (40). I n any event t h e c o n t r o l s on the amount o f organic m a t e r i a l and the s t a b i l i t y o f formed metal complexes a r e such t h a t m e t a l - f u l v i c a c i d complexes may play an important r o l e i n the t r a n s p o r t o f t r a c e metals. I t i s l i k e l y , given system d i v e r s i t y , t h a t the maximum enhanced c a r r y i n g c a p a c i t y due t o organic complexation w i l l be approximately a f a c t o r o f 10 g r e a t e r than t h a t p r e d i c t e d by a t o t a l l y i n o r g a n i c model. This would place the concentrat i o n o f the t r a c e metals i n the 1 0 " t o 1 0 " molar c o n c e n t r a t i o n range. The t r a c e metals w i l l compete w i t h each other f o r the a v a i l a b l e complexation s i t e s . I r o n ( I I l ) forms some o f the more s t a b l e complexes and thus t h i s metal may " s a t u r a t e " the HA and FA c o o r d i n a t i o n s i t e s rendering them u n a v a i l a b l e t o metals such as lead and cadmium. This competition would as a consequence g r e a t l y reduce t h e e f f e c t i v e n e s s o f HA and FA i n the t r a n s p o r t of t r a c e metals through n a t u r a l water systems. 6

5

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

23.

pagenkopf

Metal-Ion Transport

383

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Gamble, D . S . , Schnitzer, M . , and Hoffman, I., Can. J. Chem., 48, 3197 (1970).

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Schnitzer, Μ., and Skinner, S . I . M . , S o i l Sci., 96, 86 (1963).

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Stevenson, F.J., "Environ. Biogeochem., Proc. Int. Symp., 2nd e d . , 1975 V o l . 2 Edited by J . O . Nriagu. Ann Arbor Sci., Ann Arbor, M I . , 1976 pp 519-540.

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Green, J.B., and (1977).

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MacCarthy, P . , and O'Cinneidi, S . , J. S o i l Sci., 25, 429 (1974).

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Beck, M . T . , Coordn. Chem. Revs., 3, 91 (1968).

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Jenne, E.A., In "Trace Inorganics in Water" Edited by R . F . Gould, Adv. Chem. Ser. No. 73, A . C . S . , Washington, D.C. 1968, p. 389.

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Guy, R . D . , Chakrabarti, C.L., and Schramm, L.L., Can. J. Chem., 53, 661 (1975).

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Kodama, H., and Schnitzer, M . , Can. J. S o i l Sci., 51, 509 (1971).

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Schnitzer, M . , and Kodoma, Η . , Clays and Clay Minerals, 20, 359 (1972).

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Pagenkopf, G . K . , and Brady, W., Unpublished experimental observations, 1978.

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Zajicek, O . T . , and Pojasek, R . B . , Water Resources Res., 12, 305 (1976).

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Discussion J . H. WEBER (University of New Hampshire): I have a question about molecular weights for fulvic acids; you mentioned a 1000 to 10,000 range. The samples we have done both for solid and for aquatic fulvic acids, and also recalculation of Schnitzer s data, showed a value of abou you mentioned. 1

PAGENKOPF: It demonstrates that these natural chelating agents are repetitive polymeric units that are degraded to smaller units. We have characterized a fulvic acid that we isolated from an Oregon s o i l that has an average formula weight of 2700. There's another value from France of around 1800, and your values are down in the 600 range. I don't disagree with that at a l l . If you take humic acids and you break them up, correspondingly smaller chelates are obtained. WEBER: The second question is how did you measure s t a b i l i t y constants for cobalt and nickel? PAGENKOPF: Those cobalt and nickel values are actually Malcolm's data, not mine. Our cadmium values were obtained by ion selective electrodes. WEBER: How did you treat your data? thing in this sytesm.

That's a very d i f f i c u l t

PAGENKOPF: When u t i l i z i n g the cadmium ion selective electrodes, we have a balance between complexation, s t a b i l i t y , hydrol y t i c properties of metals, and a workable range or a reasonable concentration range of reactants. For cadmium we can work in the 10" or 10~ M L range f a i r l y well. Through mass balance, we can graphically evaluate our average gram formula weight with a plot of the amount of material that complexed as a function of inverse of free metal concentration. We assume a stoichiometry of 1 to 1 which is j u s t i f i e d on the basis of mass balance. We extrapolate that to i n f i n i t e free metal concentration and that gives us a measure of the average gram formula weight. Then what we do is u t i l i z e that value and we go on to subsequently evaluate complexes of higher stoichiometry. 7

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A. AVDEEF ( U n i v e r s i t y of C a l i f o r n i a , B e r k e l e y ) : I s there any evidence that any of these systems c o n t a i n dihydroxy u n i t s ; c a t e c h o l s , f o r example? PAGENKOPF: Yes, I am sure there a r e some. From i n t e r p r e t a t i o n of c o n d i t i o n a l s t a b i l i t y constant data and corresponding pH change you can i n f e r something about t h e deprotonation of the groups. One o f the f i r s t models t h a t was proposed, and s t i l l a v i a b l e one, i s that mode of c o o r d i n a t i o n comparable t o s a l i c y l i c a c i d , where you have p h e n o l i c oxygen and a c a r b o x y l i c group. I n the pH p r o f i l e s two t h i n g s can happen. The a c i d i t y of these p h e n o l i c groups i s h i g h e r than we would expect, o r they don't part i c i p a t e t o the degree t h a t we t h i n k they do. I n other words, i f you look a t the change i n s t a b i l i t y constants over a pH range o f 5 t o 7.5, and i f a hydroge may be even two m e t a l s changes i n the c o n d i t i o n a l s t a b i l i t y constants. Over t h i s range, we see a change of 1.5 o r so pH u n i t s . Not q u i t e as much as expected i f the pK's of these p h e n o l i c groups a r e as h i g h as 9 o r 10. I f the pK's a r e low then i t i s a s i t u a t i o n d i f f e r e n t from anything we r e a l l y know much about. But I'm sure t h a t i n some systems of t h e donors i n v o l v e p h e n o l i c oxygen. AVDEEF:

What c o l o r a r e these complexes a t pH 7 t o 10?

PAGENKOPF: The l i g a n d s themselves a r e dark brown. We work at a range of a few m i l l i g r a m s per l i t e r , so we a r e working w i t h dark brown, reddish-brown s o l u t i o n . AVDEEF:

Are these t h i n g s t o x i c ?

PAGENKOPF: L e t me d e s c r i b e the experiments we have done. We t r i e d t o e s t a b l i s h the t o x i c i t y of t r a c e metal complexes t o f i s h . We f i n d t h a t they r e a l l y don't bother the f i s h v e r y much. I n f a c t , t o e s t a b l i s h t o x i c i t y you have t o get the c o n c e n t r a t i o n of the t o x i c a n t so h i g h you can't see the f i s h anymore. M. P. EASTMAN ( U n i v e r s i t y of Texas, E l Paso): Do you c l e a n up these humic a c i d s before you s t a r t working on them? That i s , how do you make sure you haven't got metal contamination? PAGENKOPF: That's a v e r y good p o i n t . I t ' s d i f f i c u l t t o address because we s t a r t out w i t h a f a i r l y s i z a b l e ash content. We go through a whole sequence of steps i n v o l v i n g s t r o n g a c i d treatment, d i a l y s i s a g a i n s t good c h e l a t i n g agents, and i o n chromatography, u n t i l we get the ash content down as low as poss i b l e . We a l s o check f o r i r o n content t o make sure we got out e v e r y t h i n g we can, otherwise we would have a l l our s i t e s f i l l e d up.

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What a r e some t y p i c a l values f o r ash content i r o n ?

PAGENKOPF: W e l l , we s t a r t out ash content o f 11%. You can get i t down t o l e s s than 1% o f you keep working on i t . WEBER: I have a comment about p u r i f y i n g these w i t h respect to metal i o n s . We d i d get our m a t e r i a l s ' ash content down t o about 1%. Emission spectrocopy on our samples showed predominatel y s i l i c o n , aluminum, and i r o n . What we found i s probably c l a y . By more c a r e f u l c e n t r i f u g i n g , and o c c a s i o n a l l y a treatment w i t h HF, we f i n d out we can get r i d of the s i l i c o n , aluminum, and i r o n . There are very few t r a c e m e t a l s , i t seems. PAGENKOPF: This a l l u d e s t o the p o i n t concerning t r a n s p o r t . Aluminum and i r o n can compet s u c c e s s f u l l w i t h thes othe trac metals. BRINCKMAN: Do you have any s p e c u l a t i o n o r any knowledge of work r e l a t i n g t o c o o r d i n a t i o n of organometal ions t o humâtes o r f u l v a t e s ? I'm t h i n k i n g o f course of these ions described [ c f . Tobias t h i s volume] as hard a c i d s . They p o s s i b l y could compete r a t h e r s e l e c t i v e l y w i t h some o f the donor types that you have i n d i c a t e d . Would they compete even w i t h i r o n ? PAGENKOPF: I can't r e c a l l any work. I t i s conceivable that they could show the same types of s t a b i l i t y , p a r t i c u l a r l y w i t h m u l t i p l e donor s i t e s o r anything not c o o r d i n a t e l y s a t u r a t e d . R E C E I V E D August 22, 1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

24 Organotins in B i o l o g y a n d the E n v i r o n m e n t J. J. ZUCKERMAN Department of Chemistry, University of Oklahoma, Norman, OK 73019 ROBERT P. REISDORF, HARRY V. ELLIS III, and RALPH R. WILKINSON Midwest Research Institute, 425 Volker Boulevard, Kansas City, MO 64110

Tin in the form o affected the course o of antiquity to the Tin Drum (2) of today. Implements of t i n alloy dating from about 3000 BC have been found at Ur, and t i n is mentioned in the Bible (3). Tinplate, tinware, pewter, bronze and brass, solder, bearing, bell and type metal, and toothpaste tubes are all examples of current use, and we are in contact with t i n all through our lives, from our tinplated babyfood cans through stannous fluoride-containing toothpastes and the dental amalgam in our teeth to the tinplate on our casket linings. Introduction Tin chemistry has been the subject of much research effort in the last few years. Elemental t i n possesses two allotropic modifications, forms a wide variety of intermetallic phases and inorganic compounds, and has an extensive organometallic chemistry. Basic studies in organotin chemistry are stimulated by the obvious close analogies and interesting differences with the even more extensive chemistry of the cognate organosilicon compounds, and with the vast body of organic chemistry, and also by the success with which a large number of modern physical techniques can be applied to organotin compounds. Tin possesses, for example, two spin of one half nuclides, tin-117 and tin-119, which have become important in nuclear magnetic resonance studies of tin-proton and tin-carbon coupling constants as well as more recently in the t i n chemical shifts themselves ( 4 , 5 ) ; ten stable isotopes (the largest number for any element), which allows easy identification of tin-bearing fragments in the mass spectrometer (6); the isomeric nuclide tin-119m, which with iron-57 is one of the two easiest to observe nuclear gamma ray (Mossbauer) resonances (7); and easily assignable tin-carbon stretching frequencies in the infrared and Raman (8). Useful chemical information is routinely 0-8412-0461-6/78/47-082-388$09.25/0 © 1978 American Chemical Society In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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obtained from t h i s b a t t e r y o f powerful techniques i n combination w i t h others such as X-ray and UV p h o t o e l e c t r o n spectroscopy ( 9 ) . X-ray, neutron and e l e c t r o n d i f f r a c t i o n techniques have been a p p l i e d t o s o l v e t h e s t r u c t u r e s o f n e a r l y 600 i n o r g a n i c and o r g a n o t i n compositions (10). Tin and i t s compounds are found i n two s t a b l e o x i d a t i o n s t a t e s , t i n ( I I ) and t i n ( I V ) , and assume a wide v a r i e t y o f s t r u c t u r a l types from the a l l o t r o p i e m o d i f i c a t i o n s o f the element and i t s a l l o y s t o compounds i n which the t i n atom i s two- t o e i g h t - coordinated i n n e u t r a l , c a t i o n i c and a n i o n i c species w i t h i n t r a - and i n t e r m o l e c u l a r a s s o c i a t i o n to g i v e dimers and h i g h e r oligomers and one-, two- and three-dimensional polymeric a r r a y s . Tin a l l o y s and i n t e r m e t a l l i c phases e x h i b i t s u p e r c o n d u c t i v i t y (Nb^Sn) (11), ferromagnetism (Cu MnSn) (12), and s erni conduct i v i t y (ZnSnAs ) (13). Polyatomi c h a r a c t e r i z e d t o Sn^~ (14) c a t i o n i c o r a n i o n i c , and both can e x i s t i n one c r y s t a l as i n t h e t e r p y r i d y l complex o f d i m e t h y l t i n d i c h l o r i d e which contains both a t i n - b e a r i n g anion and c a t i o n (15). A s s o c i a t e d polymers can be one- [(CH ) SnCN] (16), two- [ ( C H ) S n F ] (17, 18) and h e l i c a l , three-dimensional [(CH3) Sn]2NCN (19). Organotin compounds can take two- [ ( h - C H ) S n ] (20), t h r e e - [ { [ ( C H ) S i ] C H } S n ] (21), f o u r - [Ri+Sn] (10), f i v e - [ ( C H ) S n C l - C H N ( t r i g o n a l b i p y r a m i d a l ) (22) o r [ ( C G H O S n ] S n N 0 ( s q u a r e pyramidal) ( 2 3 ) ] , s i x it ( C H ) S n C l ] 2 " (24) ] and seven- [CH Sn(N0 ) ( 2 5 ) ] , coordinated forms. The s t r u c t u r e o f t i n ( I I ) d e r i v a t i v e s show t h e e f f e c t o f the s t e r e o c h e m i c a l l y a c t i v e lone p a i r o f e l e c t r o n s present i n t h i s o x i d a t i o n s t a t e as a space i n t h e c o o r d i n a t i o n sphere (26). 2

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The Organotin L i t e r a t u r e The l i t e r a t u r e o f o r g a n o t i n compounds i s now so vast t h a t some guidance f o r t h e i n t e r e s t e d reader i s i n order. Two important s i n g l e - a u t h o r works are a v a i l a b l e (27, 28) along w i t h a three-volume e d i t e d work (29), but these a l l date from 19701971. E x t e n s i v e reviews o f the formation and cleavage o f t h e bonds o f t i n t o carbon (30), the halogens and the halogenoids (31) were p u b l i s h e d i n 1968 and 1972, r e s p e c t i v e l y . A more recent work b r i n g s together t h e papers d e l i v e r e d at a 1976 Symposium on chemistry and a p p l i c a t i o n s (32). The s t r u c t u r a l data f o r over 250 o r g a n o t i n compounds have been reviewed i n 1978 (10). However, t h e d e f i n i t i v e c o m p i l a t i o n o f i n f o r m a t i o n on o r g a n o t i n compounds i s t o be found i n t h e Gmelin Handbuch der Anorganischen Chemie. The f i r s t f o u r volumes c o v e r i n g R^Sn (1975) ( 3 3 ) , R SnR (1975) (34), R SnR , R SnR R", RR SnR"R ", h e t e r o c y c l e s and s p i r a n e s (1976) (35) and o r g a n o t i n hydrides (1976) (36) have been p u b l i s h e d thus f a r . The p u b l i s h i n g program under t h e authorship o f H. Schumann and I . Schumann w i l l e v e n t u a l l y i n c l u d e a l l compounds i n which t i n i s bound t o carbon. I n the meantime, readers can keep abreast o f t h e l i t e r a t u r e u s i n g t h e Annual f

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Surveys f o r each year s i n c e 1964 p u b l i s h e d i n v a r i o u s forms a s s o c i a t e d w i t h the J o u r n a l of Organometallic Chemistry (37-48), and u s i n g the y e a r l y volumes on Organometallic Chemistry i n the S p e c i a l i s t P e r i o d i c a l Reports o f the Chemical S o c i e t y o f London (49-55). The manufacture and use o f s e l e c t e d a l k y l t i n compounds have been reviewed i n 1976 i n a U.S. Government r e p o r t (56). This review paper i s based upon two U.S. Government commissioned r e p o r t s : C r i t e r i a f o r a_ recommended standard... Occupational Exposure t o Organotin Compounds, from the N a t i o n a l I n s t i t u t e f o r Occupational S a f e t y and Health (NIOSH), November, 1976, under the e d i t o r s h i p o f E.S. Flowers (57). The S t a n f o r d Research I n s t i t u t e s t a f f developed the b a s i c i n f o r m a t i o n f o r t h i s r e p o r t . The second r e p o r t , Assessment o f the Need f o r , the Character o f , and the Impac S e l e c t e d Organotins. Phas L i m i t a t i o n s on Organotins, from the Environmental P r o t e c t i o n Agency (EPA), O f f i c e o f T o x i c Substances (OTS), J u l y , 1977, under the e d i t o r s h i p o f R.R. W i l k i n s o n and I.C. Smith of the Midwest Research I n s t i t u t e whose s t a f f developed the b a s i c i n f o r m a t i o n and wrote the r e p o r t (58). The EPA-OTS p r o j e c t o f f i c e r , P. H i l g a r d , has k i n d l y given p e r m i s s i o n t o quote from t h i s p r e l i m i n a r y d r a f t r e p o r t before i t s r e l e a s e by the agency. One author (J.J.Z.) was a c o n s u l t a n t i n the p r e p a r a t i o n of these documents f o r the government agencies. In a d d i t i o n , much u s e f u l i n f o r m a t i o n was shared by the p a r t i c i p a n t s at a Workshop on Organotins organized by M.L. Good i n February, 1978 under the sponsorship o f the U.S. O f f i c e of Naval Research (59). Historical U n t i l r e c e n t l y i t was g e n e r a l l y b e l i e v e d t h a t o r g a n o m e t a l l i c compounds, which are u s u a l l y a i r - and moisture s e n s i t i v e , were p u r e l y a r t i f i c i a l and s y n t h e t i c , and a t e x t p u b l i s h e d i n 1964 s t a t e d , The s i t u a t i o n r e g a r d i n g a p p l i c a t i o n s may be summed up by saying t h a t t h e r e are no o r g a n o m e t a l l i c compounds i n n a t u r e , t h e r e seemingly being no mechanism f o r t h e i r formation... (60). However, i t had been recognized e a r l y i n the 19th century t h a t cases o f a r s e n i c p o i s o n i n g could be t r a c e d t o the use o f domestic wallpapers c o n t a i n i n g Scheele's green (copper hydrogen a r s e n i t e ) and P a r i s or SchweinfUrter's green ( c u p r i c acetoa r s e n i t e ) dyes. Gmelin i n 1839 d e s c r i b e d a g a r l i c odor i n rooms i n which the symptoms developed (61), and i t was demonstrated i n 1872 t h a t moldy green wallpaper l i b e r a t e d an a r s e n i c - c o n t a i n i n g gas (62), but i t was the d e f i n i t i v e experiments o f Gosio i n 1897 t h a t e s t a b l i s h e d t h i s "Gosio-gas as an o r g a n o m e t a l l i c compound, an a l k y l a r s i n e . I t remained f o r Challenger t o i d e n t i f y the g a r l i c odor component as ( C H ) A s i n 1933 (64), and t o c o i n the term " b i o l o g i c a l m e t h y l a t i o n " f o r i t s p r o d u c t i o n . Despite continued p u b l i c a t i o n by Challenger (65, 66) on the ,f

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Organotins

391

subject o f b i o m e t h y l a t i o n , t h e c r y s t a l s t r u c t u r e o f t h e v i t a m i n B-12 (cobalamin) coenzyme 5,6-dimethylbenzimidazolylcobamide i n 1961, which showed the presence o f a cobalt-carbon bond (67), was viewed as a c u r i o s i t y a t t h e time. Meanwhile, the t r a g i c deaths o f r e s i d e n t s a t Minimata Bay, Japan became recognized as owing t o i n g e s t i o n o f methylmercury d e r i v a t i v e s formed from t h e i n o r g a n i c mercury e f f l u e n t o f a nearby f a c t o r y (68), and i n 1969 i t was demonstrated t h a t l i v i n g organisms have t h e a b i l i t y t o methylate mercury (69). Now the m e t h y l a t i o n o f metals and m e t a l l o i d s i n t h e environment i s recognized as an important route i n t h e i r m o b i l i z a t i o n . The r o l e played by microorganisms i n the b i o chemical t r a n s f o r m a t i o n s whereby elements are methylated i s being e l u c i d a t e d , and some o f the molecular mechanisms are beginning t o be grasped Organotins i n t h e Environment Production. The annual world consumption o f t i n i n a l l forms was ca. 200,000 tons (ca. 400 m i l l i o n l b s . o r ca. 180 m i l l i o n kg) i n 1976, but o f t h i s t o t a l o n l y ca. 55 m i l l i o n l b s . (ca. 25 m i l l i o n kg) was i n t h e form o f o r g a n o t i n compounds. These compounds were composed o f a weighted average o f ca. 31% t i n , and so o n l y ca. 17 m i l l i o n l b s . (ca. 7.7 m i l l i o n kg) o f t i n o r 4.26% o f the annual world p r o d u c t i o n o f t i n i s produced i n t h i s form. The U.S. consumption o f o r g a n o t i n compounds was ca. 24 m i l l i o n l b s . (ca. 11 m i l l i o n kg) i n 1976. Midwest Research I n s t i t u t e f o r c a s t s c a l l f o r an 11-13% annual growth f o r the next ten years (58). Table I l i s t s t h e estimated U.S. p r o d u c t i o n o f s e l e c t e d a k l y l t i n compounds f o r the p e r i o d 1965 t o 1976. The t o t a l weight o f these organotin compounds produced i n t h i s country d u r i n g t h i s 12-year p e r i o d i s ca. 185 m i l l i o n l b s . (ca. 84 m i l l i o n kg). Use. Over t w o - t h i r d s o f the t o t a l world annual p r o d u c t i o n o f o r g a n o t i n compounds i s devoted t o the thermal s t a b i l i z a t i o n o f p o l y v i n y l c h l o r i d e (PVC) p l a s t i c s (79). The mechanism o f PVC breakdown i s not e n t i r e l y c l e a r at p r e s e n t , but the most commonly accepted view i s t h a t t h e decomposition i s r e l a t e d t o a d e h y d r o c h l o r i n a t i o n r e a c t i o n at an a l l y l i c o r t e r t i a r y c h l o r i n e s i t e w i t h t h e formation o f a double bond. As t h e degradation continues, conjugated unsaturated systems are formed which d i m i n i s h o p t i c a l c l a r i t y and lend u n d e s i r a b l e c o l o r t o the p l a s t i c . As l i t t l e as 0.1% decomposition can lead t o b l a c k e n i n g . The d e h y d r o c h l o r i n a t i o n process i s a u t o c a t a l y t i c , and i n t h e p r o c e s s i n g o f u n p l a s t i c i z e d PVC r e s i n , temperatures w e l l i n excess o f those r e q u i r e d f o r the i n i t i a t i o n o f the degradative process are a t t a i n e d (>200°C). The mode o f a c t i o n o f t h e e f f e c t i v e s t a b i l i z e r s i s not completely known, but probably

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Bu IOMA

22.0

1.4 2.9 4.0 4.5 4.0 4.5 6.5 t o 8.0 8.0 t o 10.0

0.7

-

Me IOMA

4.33

0.45

3.0

12.9

0.22 0.22 0.48 0.52 0.57 0.59 0.62 0.26 0.22 0.21 0.20 0.22 0.33

f

3.70

1.20

0.16 0.20 0.32 0.37 0.56 0.62 0.37 0.50 0.60 0.90

-

_.

Oct. Bu Maieate IOMA

1.0 1.0 0.9 0.9 0.9 1.1 1.1 1.3 1.3 1.3 1.0 1.1 2.0

Bu LM

0.53

0.30

0.02 0.03 0.05 0.06 0.08 0.08 0.07 0.07 0.07 0.20

-

_

Oct. Maleate

8.0

27.8

2.2

0.6 0.9 1.2 1.6 2.0 2.4 2.8 2.5 3.0 3.5 3.0 4.3 6.0

DBTDL

0.0

0.8 0.5 0.4 0.5 0.0

-

-

-

Mixed metals

9.0

0.86 0.93 1.20 1.32 1.50 1.67 1.97 1.61 1.09 2.07 1.40 2.30 4.6

(S5

TBTO

1.08

2.0

0.01 0.02 0.05 0.08 0.12 0.30 0.50 1.0

-

TBTF

185.5

49.5 t o 55 .0

5.0 7.6 8.7 10.7 12.3 15.2 16.6 20.6 23.0 23.0 18.8 23.5 36.5 t o 39 .5

Total

Dibutyltin dilaurate Dibutyltin b i s (2 e t h y l hexoate) Bis(tributyltin)oxide Tributyltin fluoride

4.7 18.81

2.5

0.8 0.9 1.1 0.9 1.0 1.9

-

-

-

DBTH

Bu IOMA = B u t y l t i n i s o c t y l m e r c a p t o a c e t a t e p l u s blends DBTDL Me IOMA = M e t h y l t i n isooctylmercaptoacetate p l u s blends DBTH Bu LM = D i b u t y l t i n - b i s ( l a u r y l m e r c a p t i d e ) Bu Maleate = D i b u t y l t i n a l k y l m a l e a t e e s t e r s TBTO Oct. IOMA = D i ( n - o c t y l ) t i n - S , S - b i s ( i s o o c t y l m e r c a p t o a c e t a t e ) TBTF Oct. Maleate = D i ( n - o c t y l ) t i n maleate polymers taken from r e f s . 56 and 58.

Note:

T o t a l 87.5 (1965 1976)

1965 2.3 1966 4.6 1967 4.9 1968 6.2 1969 7.1 1970 8.3 8.2 1971 1972 10.5 1973 10.1 1974 9.3 1975 7.0 1976 9.0 1981 13.0 t o 14.5 1986 15.0 t o 18.5

Year

TABLE I , Estimated Annual U.S. Production o f S e l e c t e d A l k y l t i n Compounds ( M i l l i o n Pounds P e r Year)

ι

ο

>

> ο ο

C/î

r

Ρ

ο w ο > ο

*°

24.

Z U C K E R M A N ET

AL.

Organotins

393

i n v o l v e s exchange o f a l l y l i c c h l o r i d e atoms w i t h the a n i o n i c p o r t i o n o f the organotin compound, and the a b s o r p t i o n o f l i b e r a t e d hydrogen c h l o r i d e t o r e l e a s e compounds which can add across the unsaturated c e n t e r s . T y p i c a l s t a b i l i z e r s are d i a l k y l t i n compounds c o n t a i n i n g t h i o o r e s t e r groups. The o r i g i n a l patents i s s u e d t o V. Yngve of Carbide and Carbon Chemicals Corporation i n 1936 and based upon the d i s c o v e r i e s o f W.M. Quattlebaum, were f o r the a p p l i c a t i o n o f d i b u t y l compounds, but d i o c t y l t i n s are now i n use as w e l l . The a d d i t i o n o f small amounts o f m o n o a l k y l t i n s has a s y n e r g i s t i c e f f e c t . The groups attached t o the a l k y l t i n m o i e t i e s i n c l u d e the l a u r a t e and maleate, and s e v e r a l mercapto d e r i v a t i v e s d e r i v e d from o c t y l and i s o o c t y l e s t e r s o f t h i o g l y c o l i c a c i d . In the l a s t decade t h e r e has been a s h i f t of emphasis from f l e x i b l t r i g i d PVC p r o d u c t s th latte r e q u i r i n g much h i g h e r p r o c e s s i n b e t t e r s t a b i l i z a t i o n ha the d e s i r e d c o l o r l e s s n e s s and transparency f o r packaging f i l m s , p i p i n g , b o t t l e s and s i d i n g i s to be produced. D i m e t h y l t i n s , because o f t h e i r extremely great thermal s t a b i l i t y a l l o w the use o f high working temperatures and high working speeds, and t h e i r a p p l i c a t i o n may have economic advantages (80). Organotin compounds are a l s o used as c a t a l y s t s i n the production o f r i g i d polyurethane foam and f o r the room temperature v u l c a n i z a t i o n o f s i l i c o n e elastomers. B i o c i d a l and a n t h e l m i n t i c a p p l i c a t i o n s w i l l be d i s c u s s e d s e p a r a t e l y , below. Table I I l i s t s the estimated annual U.S. consumption o f s e l e c t e d a l k y l t i n compounds i n the f o u r use areas d i s c u s s e d above, p l u s miscellaneous uses and exports. The c a p i t a l value o f the organotin chemicals used i n PVC heat s t a b i l i z a t i o n was $50 m i l l i o n i n 1976, w i t h the t o t a l c a p i t a l v a l u e f o r a l l uses estimated at $67.7 m i l l i o n . F i n a l D i s p o s a l . Consumption o f commercial o r g a n o t i n chemicals i s given by s e c t o r f o r 1976 i n F i g u r e 1. The route f o r each use area from i n t r o d u c t i o n through consumption and r e l e a s e t o the environment i s given on a weight b a s i s . I n d u s t r i a l d i s p o s a l options i n c l u d e evaporation, b a c t e r i a l degradation s e t t l i n g ponds, sludge b u r i a l w i t h i n p r o p e r t y l i n e s , use o f c o n t r a c t d i s p o s a l s e r v i c e s , deep-well i n j e c t i o n , h y d r o l y s i s and p r e c i p i t a t i o n methods, discharge t o m u n i c i p a l treatment p l a n t s , NPDES ( N a t i o n a l P o l l u t i o n Discharge E l i m i n a t i o n System) p e r m i t s , and p o t e n t i a l r e c l a m a t i o n o r r e covery and r e c y c l i n g techniques. Midwest Research I n s t i t u t e estimates t h a t o n l y 0.5% o f p r o d u c t i o n , or ca. 0.12 m i l l i o n l b s . (ca. 0.054 m i l l i o n kg) are l o s t to the environment by these routes at the source o f manufacture. Consumer d i s p o s a l options i n c l u d e m u n i c i p a l sewers, municipal waste c o l l e c t i o n which reaches l a n d f i l l or i n c i n e r a t o r , normal weathering of the consumer product, and

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1981 1986

taken from r e f s . 56 and 58.

133.2

3.5 5.8 6.3 7.8 8.8 11.1 11.8 15.6 17.1 16.2 13.2 16.0 23 to 26 28 t o 33.5

Year

Total (1965-1976)

PVC heat stabilizer

30.1

0.5 0.7 1.0 1.4 1.8 2.2 2.6 3.1 3.7 4.4 3.7 5.0 7.5 10.0

Catalysts

14.6

0.50 0.60 0.70 0.80 0.90 1.1 1.3 1.5 1.7 2.0 1.5 2.0 5.0 10.0

Biocidal

2.5

0.15 0.16 0.17 0.18 0.19 0.21 0.22 0.23 0.24 0.24 0.20 0.27 0.35 0.50

Anthelmintic

4.6

0.36 0.33 0.50 0.52 0.60 0.57 0.67 0.16 0.26 0.19 0.20 0.20 0.60 1.0

185.0

5.0 7.6 8.7 10.7 12.3 15.2 16.6 20.6 23.0 23.0 18.8 23.5 36.5 to 39.5 50 to 55

Total

Grand t o t a l (1965-1976)

Miscellaneous excluding exports

TABLE I I . Estimated Annual U.S. Consumption o f Selected A l k y l t i n Compounds By Use Area (Quantities i n M i l l i o n Pounds)

24.

Z U C K E R M A N ET

AL.

Organotins

Domestic Production 23.5 M lbs

395

Organotin Compounds 24.1 M lbs

Imports 0.6 M lbs

Merchant Sales

ORGANOTIN COMPOUND

PVC Heat Stabilization

BulOMA MelOMA BuLM BuMoleare Oct. IOMA Oct. Maleate Mixed Metals DBTDL TBTO DBTH TBTF

9.0 4.5 1.1 0.2 0.6 0.1 0.5

Total Organotins

16.0 M lbs

Biocides Including Anti-Foulin Marin Pes Disinfectant

Miscellaneous Use Includin y

4.0

— —

0.3 0.8

1.5

—

1.0

—

0.5 2.0 M lbs

5.0 M lbs

0.3 M lbs

0.8 M lbs

24.1 M Pounds Assumed Rejection Rote 0.5% Equivalent to 0.12 M lbs Organotin Content

INDUSTRIAL DISPOSAL MODES FOR PURE CHEMICALS. FORMULATIONS AND REJECT PRODUCTS Hydrolysis & Sludge Burial Evaporation, Aeration Precipitation on_Pjroptrty & Settling Ponds Contract Disposal ("Potential Reclamation Deep-Well Injection NPDES Permit & Recycle Municipal Sewer

Ν on-Organotin Containing By-Products I |

24.0 Ml Pounds CONSUMER PRODUCTS DISPOSAL MODES Assumed 99.5% Municipal Waste Normal Weathering of Release to Marine Usage Rate Equivalent to Via Incineration Products Exposed Environment via 24.0 M lbs or Landfill Leaching, Hydrolysis. Organotin Content Municipal Sewer Oxidation, Bioolkylotion, etc

Assessment of the Need for Limitations on Organotins Figure 1.

Organotin chemicals consumption in 1976 (58)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

396

ORGANOMETALLOIDS

r e l e a s e t o the marine environment through l e a c h i n g . The 24 m i l l i o n l b s . (ca. 11 m i l l i o n kg) o f o r g a n o t i n compounds annually manufactured i n the U.S. w i l l e v e n t u a l l y reach the environment i n some form. The 24 m i l l i o n l b s . o f o r g a n o t i n s are formulated o r compounded i n t o perhaps 2,400 m i l l i o n l b s . (ca. 1,100 m i l l i o n kg) o f i n d u s t r i a l and commercial products which are r e d i s t r i b u t e d t o the environment. Table I I I shows the estimated q u a n t i t i e s o f organotins r e l e a s e d t o the environment i n 1976 by v a r i o u s r o u t e s which are shown s c h e m a t i c a l l y i n F i g u r e 2. Transport i n the Environment. T h i s s e c t i o n d i s c u s s e s the t r a n s f e r behavior o f organotin compounds i n the environment w i t h r e s p e c t t o v o l a t i l i t y , s o l u b i l i t y , bioaccumulation and bioconcentrat i o n . The i n d u s t r i a l l y importan g e n e r a l l y l i q u i d s and waxy s o l i d s or powders o f low v o l a t i l i t y . B o i l i n g p o i n t s , even at reduced p r e s s u r e s , are q u i t e h i g h , e.g., 400°C/10 t o r r f o r d i b u t y l t i n d i l a u r a t e and 180°C/2 t o r r f o r b i s ( t r i b u t y l t i n ) o x i d e (TBTOff and the vapor p r e s s u r e c a l c u l a t e d at 25°C based upon a molar heat o f v a p o r i z a t i o n o f 20.2 Kcal/m f o r TBTO® i s 1.6 χ 1 0 t o r r , which corresponds t o 510 mgm/m o f a i r (58). While t h i s exceeds the recommended NI0SH standard o f 0.1 mg/m analyzed as t i n f o r workplace a i r (57), a vapor p r e s s u r e o f t h i s small magnitude i s probably i n s u f f i c i e n t t o m o b i l i z e l a r g e amounts o f organotins i n the environment. In a d d i t i o n , organotin compounds adsorbed i n s o i l or d i s s o l v e d i n water would have an even s m a l l e r tendency t o escape t o the atmosphere. S o l u b i l i t y data are l i m i t e d , but the h i g h e r t r i a l k y l t i n compounds are n e a r l y i n s o l u b l e i n water [10 t o 50 ppm at ambient temperatures (98)] i n accord w i t h t h e i r hydrocarbon l i k e c h a r a c t e r . B i s ( t r i b u t y l t i n ) o x i d e and t r i b u t y l t i n f l u o r i d e are s o l u b l e i n sea water t o the extent o f 51 and 6 ppm, r e s p e c t i v e l y (99). S o l u b i l i t y i n common o r g a n i c s o l v e n t s and i n l i p i d s i s a f u n c t i o n o f the number o f o r g a n i c groups attached t o the t i n atom, and i s p r o p o r t i o n a l t o t h e i r bulk. The m e t h y l t i n compounds are the most water s o l u b l e o f the organotins. Leaching from s o i l s has been i n v e s t i g a t e d u s i n g carbon-14 l a b e l e d compounds. Even hot methanol treatment f a i l s t o remove t r i p h e n y l t i n a c e t a t e completely, and n e i t h e r t h i s f u n g i c i d e nor any o f i t s a b i o t i c t r a n s f o r m a t i o n products are leached over a six-week p e r i o d . Over 70% o f the a c t i v i t y was found i n the upper 4 cm o f the packed s o i l column used (93). Neutron a c t i v a t i o n analyses have been c a r r i e d out on u n s p e c i f i e d d r i e d water p l a n t m a t e r i a l , sediments and f i s h samples taken from a Bavarian r i v e r both up- and downstream from a f a c t o r y producing t i n compounds and u s i n g a c h l o r i n e a l k a l i - e l e c t r o l y s i s process i n v o l v i n g mercury. The r e s u l t s _ 3

3

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

taken from r e f . 58.

1.1 χ 10°

All other applications including export

c

0.5 χ 10

0.7 χ 106

Latex paints

Industrial and consumer slimicides and other biocides

0.8 χ 10

Antifouling paints

6

21 χ 10

6

Organotin content (lb)

Plastics, PVC, PU, silicones

Organotin bearing product

6

6

0.77 χ 10

6

0.475 χ 10°

0.5 χ 10

0.4 χ 10

16 χ 10

6

In use (lb)

6

0.34 χ 10

6

0.025 χ 10°

6

0.2 χ 10

0.4 χ 10

6

5 χ 10

Discarded (lb)

TABLE III Estimated Quantities of Organotins Released to the Environment f o r 1976 Various Routes

6

0.34 χ 10

landfill

dumped or leaked

J

2.5 χ 10

rivers and estuaries, sediments

ocean and estuarine water sediments

incinerated landfill

6

0.2 χ 10

6

0.4 χ 10

6

0.5 χ 10^ 4.5 χ 10

Environmental route and quantity (lb)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Total:

χ ΙΟ

6

lbs

Organotins Annually

24.1

Figure 2.

»»

Loss

Assessment of the Need for Limitations on Organotins

% Total Product Class

N o Transport O r

Leaching

Adsorption

Volatilization

Organotin environmental exposure (58)

(ZD

Κ

KEY:

GO CD

Ο

>

Ο Ο Ο

>

F

i

Ο

>

8

ο

00

Z U C K E R M A N ET

24.

AL.

399

Organotins

f o r the sediments were 0.9 and 112 ppm Hg and 16.6 and 69 ppm Sn up- and downstream, r e s p e c t i v e l y , on a dry weight b a s i s . The b i o c o n c e n t r a t i o n i n the water p l a n t s i s shown i n Table IV. TABLE IV Water p l a n t samples (dry weight b a s i s , ppm) Element

Origin

Upstream

Downstream

Apparent magnification factor

Sn

Alz

13

3,100

240

Sn

Alzkanal

14

2,370

170

Hg

Alz

230

180

Hg

Alzkanal

1.3

Both t i n and mercury were found i n f i s h meat and l i v e r s at low (ca. 1 ppm) c o n c e n t r a t i o n . The s p e c i e s present were not i d e n t i f i e d (100). Environmental Fate. Once i n the environment the o r g a n o t i n compounds are leached from consumer products by environmental f o r c e s such as heat, l i g h t , and the a c t i o n o f water, oxygen, ozone, carbon d i o x i d e and microorganisms. I t has been estimated t h a t ca. 5.0 m i l l i o n l b s . (ca. 2.3 m i l l i o n kg) o f organotins i n PVC are disposed o f a n n u a l l y by l a n d f i l l and i n c i n e r a t i o n and t h a t ca. 1.0 m i l l i o n l b s . (ca. 0.45 m i l l i o n kg) o f b i o c i d e s are r e l e a s e d a n n u a l l y t o the environment v i a m u n i c i p a l sewers, s u r f a c e waterways, harbors and the oceans (58). The human and e c o l o g i c a l s i g n i f i c a n c e o f these i n p u t s t o the environment depend upon the p e r s i s t e n c e o f the o r g a n o t i n s , t h e i r m o b i l i t y between media, and the a v a i l a b l e pathways t o s u s c e p t i b l e p o p u l a t i o n s o f the organotins themselves and t h e i r degradation products. Organotin compounds are s u b j e c t t o both chemical and b i o l o g i c a l degradation. Chemical Degradation. Carbon-tin bonds are t h e r m a l l y s t a b l e below 200°C, but are capable o f p o l a r i z a t i o n by a t t a c k i n g species i n e i t h e r d i r e c t i o n . Organotin compounds are thus s u s c e p t i b l e t o a t t a c k at the c a r b o n - t i n bond by both n u c l e o p h i l i c and e l e c t r o p h i l i c reagents, l e a d i n g t o h y d r o l y s i s , s o l v o l y s i s , a c i d i c and b a s i c r e a c t i o n s , h a l o g e n a t i o n , e t c . (27-32). The r e s u l t s o f s c a t t e r e d k i n e t i c s t u d i e s i n the l i t e r a t u r e on the cleavage o f a l k y l - , unsaturated and aromatic groups from t i n by hydrogen c h l o r i d e and metal h a l i d e s , Cr03 i n g l a c i a l a c e t i c a c i d , a l k a l i metal hydroxides i n water

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

400

AND

ORGANOMETALLOIDS

TABLE V .

Rt-action A,

Alkyltin,

Temperature R e a c t i o n media

Cç>

saturated + HgCl

(C H )^n 2

ι » if

5

C

|g"

2

25

>

H 0/'CI!,OII (30*/70%) CH,OII 0.51 2

x

( C H ) jSn + C H l l g C l 2

5

5

2

[ u . T . Ni ^ 1.25 χ ΙΟ" M 1.00 χ 10" * M [llgCl I 1

/

2

(C H ) Sn 5

2

f HC1

4

)

2

2

(C H ) Sn 9

4

(C !l ) SiiOAc + C H 4

Β·

9

3

4

Alkyltin.

2

2<»

1

M

> jCrO }1 - ί χ Κ Γ M [ O . T . I - Μ χ 10"J M 4

9

unsaturated CHiOH

(CH )3SnCH Clf-CH 3

2

J

II20/Cl I jOH (47./%X) [lICI J « 1 0 ' - Ι Ο " H fo.T. I - 5 χ 10" M

+ HCl

2

( C H ) S n C l + ai j

H C l In Cfcllfc I O . T . J ^ 2.18 χ 1 0 "

0

> < 0 A c

Η CrO^

4

>

C h l > t >

(C H« ),SnCl + C H

2

CII-CH-

a=

4

2

J

4

(CH ) S»CH -C-<:H 3

3

2

CH ( c n 3 ) jSnci

> HCl

2

2-4

>

25

3

H 0/CH OH (47./907.) [HCl I - Ι Ο " - Κ Γ M [ o . T . l -- 5 χ Ι Ο " M 2

3

2

Η αι3-^αι

4

4

2

ci, ( C H ) :ίι»Γ,Η ί;ΙΓΗ:ΐΐψ + NaOH 2

|

5

(c n ) SiiOII + φΰΗ ΰΙΓ-ΟΊΙ 2

5

>

2

3

2

H 0/CH-jOII

12.7

2

[O.T.J

2

I χ ΙΟ" M 4

(^CITOI-CHj C«

Alkyl-aryItius (ΰΗ ) $η-φ 3

+ HCl()

3

( C H ) jSii-OII + C H 3

6

(CHPjSn-φ

» NaOH

(OHj) jSnOH + C H h

b

>

2

4

H 0 / C H ,011 (407„/W»7.) [OH- I - i M ί υ . Τ . I - 4.8 χ 1 0 "

> 14

2

f i

(CH ) ,SnCH 4 + Ki)l! }

H 0 / C H ,()|| <40X/b0%) [o.T.J 4.8 χ Ι Ο " M

0.77 and 0.8b

*

4

75

2

(CH-j) jSnOll + CH

ll 0/DHSO (I4ÎL/807.) [ o i l - I - m-2 M [o.T.J I χ ΙΟ" M 2

4

a7

f o . T . I -·'· U r g a i i u t i n , mXes/l

4

.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

M

ZUCKERMAN ET AL.

24.

Organotins

S o l v o l y s i s o f Organotins References Reaction rate

I mole"

k

2

- 5.59

k

2

-

7.5

k

2

-

2.84

k

2

= 0.475

k

2

= 24.8

k

2

mole"

1

k = 300 t

k

t

=

228

min"

χ 1(Γ* I mole"

£ mole"

t mole

t

varies (25°C)

1

Half-life

raole"

1

sec"

1

3

x

10"

10-3

12.1

k,

566 x

x

sec"

1

min

8J

350

sec

32

- 1

82,

sec"

1

sec"

1

χ 10"

χ 10"

4

4

1

1.17

hr

80.7

sec

23

to

115

83

84

days 85

t

(40°C)

x

ki «

1

and

parameters

143

sec

from 9.2 to 46.0

1

other

min" m

l

f

r

1

2.3

l

10" * m i n "

10" * m i n - l

3

1

#

0

57

1.2

min m

i

n

min

min

QM

87

88

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

402

ORGANOMETALLOIDS

and aqueous p e r c h l o r i c a c i d are d i s p l a y e d i n Table V. Homolytic r e a c t i o n s i n v o l v i n g organotin compounds w i t h f r e e r a d i c a l s have been r e c e n t l y reviewed (81). A l l these s t u d i e s were o f course c a r r i e d out i n homogeneous media where i t i s found t h a t the cleavage o f the o r g a n i c groups from t i n i s always f i r s t order i n each r e a c t a n t . In p o l a r s o l v e n t s there i s probably i n i t i a l s o l v a t i o n o f the t i n compound, f o l l o w e d by e l e c t r o p h i l i c a t t a c k (S 2) on a carbon atom adjacent t o t i n . With a l k a l i there can be n u c l e o p h i l i c a t t a c k (S^2) on the t i n atom w i t h e x p u l s i o n o f a carbanion. Although some o r g a n o t i n compounds w i l l undergo unimolecular p h o t o l y s i s or t h e r m o l y s i s under m i l d c o n d i t i o n s , f r e e organotin r a d i c a l s are u s u a l l y formed by b i m o l e c u l a r r e a c t i o n w i t h some other r a d i c a l . The a t t a c k can be at the t i n - c a r b o n bond, o r elsewhere i n the molecule (81). From these and other s t u d i e p r o g r e s s i v e cleavage o upon the type o f organotin compound, the number o f organic s u b s t i t u e n t s , and the s o l v o l y t i c c o n d i t i o n s . The r e l a t i v e ease o f removal o f a l i p h a t i c groups decreases w i t h i n c r e a s i n g s i z e o f the group, but unsaturated and aromatic groups are cleaved more r a p i d l y . For the s e r i e s : E

Ri+Sn-H R S n X - ^ > R S n X 3

2

RSnX — ^ nXi*

2

3

S

(1)

the r e a c t i o n r a t e s are ki*»k3»k2^ki. Laboratory s o l v o l y t i c r e a c t i o n s g e n e r a l l y represent extreme pH c o n d i t i o n s CpH <1 o r > 14). H a l f - l i v e s range from one minute t o 115 days, depending upon these c o n d i t i o n s and s p e c i f i c o r g a n o t i n compounds s t u d i e d . The s o l v o l y s i s o f t e t r a a l k y l t i n s c a r r i e d out under l e s s severe c o n d i t i o n s (pH = 4 t o 10), may be s e v e r a l orders o f magnitude slower (10'** t o 10"" ), and these t e t r a a l k y l t i n s w i l l r e a c t 10 t o 100 times f a s t e r than t r i a l k y l t i n s . The s o l v o l y s i s r a t e s o f d i a l k y l t i n s again approach those o f the t e t r a a l k y l t i n s . The i n o r g a n i c a n i o n i c groups i n the o r g a n o t i n compounds r e a c t w i t h moisture and a i r t o cleave from t i n i n an h y d r o l y s i s o x i d a t i o n t o g i v e s t a n n o l s and oxides. In t h i s way s u c c e s s i v e r e a c t i o n o f both p a r t s o f the molecule leads e v e n t u a l l y t o completely i n o r g a n i c hydrated t i n o x i d e s . 6

B i o l o g i c a l Degradation. M i c r o b i a l a c t i o n i s a l s o s i g n i f i c a n t . Rate constants and h a l f - l i v e s have been estimated from l a b o r a t o r y s t u d i e s i n water and are l i s t e d i n Table VI (92). Other s t u d i e s have u t i l i z e d carbon-14 l a b e l e d t r i p h e n y l t i n acetate i n which the r e l e a s e o f C02 from s o i l samples was monitored i n the dark, and a h a l f - l i f e o f 140 days determined f o r c o n c e n t r a t i o n s o f 5 and 10 ppm (93). Using UV i r r a d i a t i o n f o r 10 minutes to one hour, degradation i n t o d i - and monophenyltin compounds was observed f o r the acetate (93, 94) and hydroxide (94). The degradation o f the c h l o r i d e on sugar beet leaves i n a green house environment has been i n v e s t i g a t e d u s i n g a t i n - 1 1 3 11+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

24.

ZUCKERMAN ET AL.

Organotins

403

TABLE VI Rate Constants and H a l f - L i v e s at 20°C f o r S e l e c t e d Organotin Compounds o f P o t e n t i a l Commercial I n t e r e s t i n D i s t i l l e d Water (92) Concentration range (mg/ft)

Compound TBTCP

Rate constants (day" )

Half-life (days)

1

2-4

0.038

18.2

0.2-0.4

0.035

19.8

1.5-3

0.607

1.14

0.213

3.25

T r i b u t y l t i n methacrylate Bu IOMA Diethyltin dicaprylate Dioctyltin bis-(isobutylmaleate)

13-4

l a b e l . The p a t t e r n o f conversion t o i n o r g a n i c t i n can be seen i n Table V I I . No measurable amounts o f a c i t i v t y were found i n TABLE V I I • Degradation o f T r i p h e n y l t i n C h l o r i d e on Sugar Beet Leaves i n a Greenhouse Environment (95)

Percentage o f t o t a l r a d i o a c t i v i t y a p p l i e d Experiment No.

Days a f t e r application

φ 8η

1 2 3 4 5 6 7 8

0 3 7 14 21 28 35 42

100 86 67 47 33 26 22 19

3

+3

+

Sn

+3 <|>Sn

10 13 9 7 4 2 <2

<1 1 1 1 1 1 1

+2

2

+4 Sn 3 16 38 55 60 65 67

Not extracted^/

1 3 5 4 9 10 12

+ 4

Hydrolyzed and aged <|>Sn and S n .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

404

ORGANOMETALLOIDS

the stems o f the p l a n t s o r i n the sugar beets d u r i n g the 42 days o f the experiments. A l l the a c t i v i t y could be accounted f o r . The apparent h a l f - l i f e was i n i t i a l l y two weeks, but the degradation r a t e slowed a f t e r t h i s (95). T r i b u t y l t i n f l u o r i d e , which i s used as an a n t i f o u l i n g agent, hydrolyzes very r a p i d l y i n low c o n c e n t r a t i o n i n sea water t o give the c h l o r i d e and oxide. Carbon d i o x i d e can r e a c t w i t h the oxide t o form the carbonate. U l t i m a t e l y , through the a c t i o n o f s u n l i g h t and oxygen, hydrated i n o r g a n i c t i n oxide i s formed i n a stepwise degradation sequence (96). While the v a r i o u s r e s u l t s from separate s t u d i e s disagree i n t h e i r d e t a i l s , i t i s c l e a r t h a t the conversion t o l e s s a l k y l a t e d and a r y l a t e d t i n s proceeds s e q u e n t i a l l y t o produce hydrated i n o r g a n i c t i n oxides w i t h h a l f - l i v e s ranging from seconds t o days, depending upon the c o n d i t i o n s . Tests on clay-base compounds disposed of i simulated s o i l l e a c h i n g c o n d i t i o n s , u s i n g carbon-14 l a b e l e d compounds, high F r e u n d l i c h isotherms were determined f o r d i f f e r e n t s o i l types suggesting r e t e n t i o n of 94.9 t o 99.2% o f the organotin compounds at t h e i r o r i g i n a l s i t e of placement. No more than 0.2% of the t e s t t r i o r g a n o t i n compounds were found i n the leachates (97). Biomethylation of Inorganic T i n . M i c r o b i a l aerobes can s o l u b i l i z e HgS ( s o l u b i l i t y product 10" M) i n the form o f H g by o x i d i z i n g the s u l f i d e through s u l f i t e t o s u l f a t e (101) , whence Hg * can be reduced t o mercury metal by b a c t e r i a l enzymatic a c t i o n and l i b e r a t e d t o the atmosphere from the hydrosphere because o f the considerable vapor pressure o f Hg°. An a l t e r n a t i v e d e t o x i f i c a t i o n mechanism converts H g t o methyland dimethylmercury (102, 103), the l a t t e r of which i s v o l a t i l e and l o s t t o the atmosphere. The s y n t h e s i s o f dimethylmercury i s ca. 6000 times slower than the s y n t h e s i s o f methylmercury (104). The chemistry, b i o c h e m i s t r y and t o x i c o l o g y o f t i n i s somewhat d i f f e r e n t , however, beginning w i t h the n o n - v o l a t i l i t y of the metal i t s e l f . M i c r o b i a l methylation of i n o r g a n i c t i n has been claimed f o r a Pseudomonas species i s o l a t e d from Chesapeake Bay i n a w i d e l y quoted conference r e p o r t i n 1974 (105). In the l a b o r a t o r y , t i n ( I I ) under n i t r o g e n at pH 1 i n 1.0 M aqueous s a l t s o l u t i o n i n the presence o f methylcobalamin at ca. 5 χ 10"44 w i t h a s i n g l e e l e c t r o n o x i d i z i n g agent such as i r o n ( I I I ) c h l o r i d e or aquocobalamin i s methylated during one day at 20°C. Carbon-14 l a b e l e d methylcobalamin showed no organic products r e s u l t i n g from the cleavage of the cobalt-carbon bond. T i n ( I V ) d i d not p a r t i c i p a t e . The r a t e of the methylation r e a c t i o n was measured i n 10- t o 100-fold excess o f t i n ( I I ) as l ^ M ^ s " which i s dependent upon the pH. In aqueous t a r t r a t e b u f f e r at pH as high as 5, carbon-cobalt bond cleavage 53

2 +

2

2 +

1

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

24.

Z U C K E R M A N ET

AL.

405

Organotins

was found t o occur (106). The mechanism f o r the m e t h y l a t i o n has been discussed i n terms o f the r e d u c t i o n p o t e n t i a l s f o r the v a r i o u s species i n v o l v e d (76). No evidence has been p r e v i o u s l y p u b l i s h e d e i t h e r f r o m the l a b o r a t o r y or Nature, however, f o r the m e t h y l a t i o r o f i n o r g a n i c t i n by the species d i s c u s s e d above past the T o n o m e t h y l stage (105, Γυο;. U n l i k e the m o n o m e t h y I m e r c u r y d e r i v a t i v e s which are deadly poisonous n e u r o t o x i n s , the l i p i d s o l u b i l i t y o f the monomethyltins i s too low, and they t r a v e l i n the u r i n a r y t r a c t where they can cause r e n a l problems. The monomethyltins are expected t o be more t o x i c g e n e r a l l y than the h i g h e r a l i p h a t i c d e r i v a t i v e s , but no data are yet a v a i l a b l e . Single-dose LDs values f o r mice are i n the range 1400-1520 mg/kg f o r η-butyl- and n - o c t y l t r i s ( 2 - e t h y l h e x y l m e r c a p t o a c e t a t e ) and n - b u t y l t i n t r i c h l o r i d e , and i s >6,000 mg/kg f o r n - b u t y l t i n a c i d (107 108) This compares w i t h L D 5 0 value a i d 117 f o r the t r i - n - b u t y l t i mg/kg f o r t e t r a - n - b u t y l t i n (117). A complex b i o g e o l o g i c a l c y c l e has been proposed f o r t i n i n v o l v i n g successive a l k y l a t i o n s which are as yet undemonstrated t o g i v e d i - , t r i - and t e t r a m e t h y l t i n species (76). The Pseudomonas b. s t r a i n o f b a c t e r i a found i n Chesapeake Bay gave evidence, however, of some conversion o f hydrated t i n ( I V ) c h l o r i d e t o d i m e t h y l t i n d i c h l o r i d e a f t e r 10 days i n c u b a t i o n at ambient temperature i n >2% oxygen as determined by comparison w i t h an a u t h e n t i c mass spectrum, but the parameters f o r r e p r o d u c a b i l i t y o f these experiments have not been worked out (105), and no r e f e r e e d p u b l i c a t i o n has yet appeared. 0

The Mercury-Tin Crossover System. The b i o l o g i c a l l y p r o duced m e t h y l t i n species d e s c r i b e d above was shown t o methylate Hg(II) i o n a f t e r e i g h t days o f i n c u b a t i o n as determined by mass spectrometry (105). This r e s u l t i s corroborated by an e a r l i e r o b s e r v a t i o n t h a t aqueous t r i m e t h y l t i n methylated mercury(II) i o n (113), and the recent r e s u l t s o f computer s t u d i e s i n which changes o f pH, p C l , temperature and i o n i c s t r e n g t h were imposed on aqueous l a b o r a t o r y systems o f p a i r s o f t i n ( I V ) and mercury(II) c a t i o n s between which methyl groups were being t r a n s f e r r e d (114). A r e p r e s e n t a t i o n o f the crossover scheme i s shown i n F i g u r e 3. B i o l o g i c a l E f f e c t s of Exposure Metabolism o f Organotin Compounds. T e t r a e t h y l t i n was shown t o undergo d e s t a n n y l a t i o n in_ v i v o by a r a t l i v e r microsomal enzyme system s u c c e s s i v e l y t o the t r i - ( 1 1 5 ) , di-(116) and monoethyl (117) d e r i v a t i v e s . Other t r i a l k y l t i n compounds behave s i m i l a r l y (116, 118). The t o t a l metabolic y i e l d was <10%, however. More r e c e n t l y , i t was demonstrated t h a t a

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

Figure 3.

Bimetallic mercury-tin "crossover" scheme (58)

Assessment of the Need for Limitations on Organotins

(100ppm) Pseudomonos b.

Adapted from: F.E. Brinckman and W.P. Iverson, 1975, (113)

Pseudomonas b

ζ ο

>

§

> ζ Ό

I

ο

> ζ

ο

§

24.

Z U C K E R M A N ET

AL.

Organotins

407

cytochrome P-450 monooxygenase enzyme and not a l i p i d peroxidase system was r e s p o n s i b l e f o r metabolism, and that carbon h y d r o x y l a t i o n occurred on the b u t y l groups of carbon-14 l a b e l e d t r i b u t y l t i n acetate at the a- to γ-positions (119, 120). The products were compared w i t h a u t h e n t i c samples s y n t h e s i z e d f o r the purpose, and s i m i l a r i n v i v o r e a c t i o n s were shown to occur i n mice (120). The primary hydroxylated metabolic products of t e t r a b u t y l t i n - 1 - **C were r a p i d l y destannylated to the t r i b u t y l t i n d e r i v a t i v e s (120). Successive i n v i v o d e s t a n n y l a t i o n of t r i c y c l o h e x y l t i n hydroxide u l t i m a t e l y y i e l d s i n o r g a n i c t i n ( I V ) (118), but more recent f i n d i n g s r e v e a l that a cytochrome P-450 dependent monooxygenase enzyme-induced h y d r o x y l a t i o n i s a major metabolic r e a c t i o n y i e l d i n g 2-, 3- and 4 - h y d r o x y c y c l o h e x y l t i n d e r i v a t i v e s as m e t a b o l i t e s (121, 122). Tin-113 l a b e l e d hydroxylated i n v i t r o , bu to g i v e s u b s t a n t i a l amounts of d i and monophenyl-derivatives (120). 1

Exposure to Organotin Compounds. The t o x i c response of the common guppy, L e b i s t e s r e t i c u l a t u s , to t r i b u t y l t i n compounds has been determined. Guppies appear to be f a t a l l y s e n s i t i v e to l e s s than 1 ppm of b i s ( t r i b u t y l t i n ) o x i d e (123). Tests on L e b i s t e s u s i n g t r i p h e n y l t i n hydroxide show that 0.1 ppm k i l l e d 43% a f t e r 19 hour exposure and 100% a f t e r 48 hours (124). T r i p h e n y l t i n acetate used to c o n t r o l the o p e r c u l a t e s n a i l L a n i s t e s ovum a l s o had d e l e t e r i o u s e f f e c t s upon germinating swamp r i c e , and s e v e r a l other t r i b u t y l t i n s have been t e s t e d f o r t h e i r p h y t o t o x i c i t i e s as w e l l as t h e i r m o l l u s c i c i d a l a c t i v i t y (125). T r i b u t y l - and t r i p h e n y l t i n s are a l s o e f f e c t i v e a g a i n s t algae and barnacles (126, 127, 128). T r i p r o p y l - , b u t y l - , and t r i p h e n y l t i n d e r i v a t i v e s are t o x i c to mollusks. Concentrations of t r i a l k y l t i n s of ca. 1.0 ppm are l e t h a l to A u s t r a l o r b i s (or Biompharlaria) g l a b r a t a (129). Values f o r b i s ( t r i b u t y l t i n ) oxide range between 0.05 and 0.10 ppm (125). Maximum t o x i c i t y t o a l l types o f l i f e occurs w i t h the t r i o r g a n o t i n d e r i v a t i v e s , but t h e r e are important v a r i a t i o n s w i t h i n t h i s c l a s s o f compounds. Mammaliam t o x i c i t y reaches a maximum w i t h the e t h y l group and f a l l s o f f r a p i d l y w i t h increased c h a i n l e n g t h as shown i n Table V I I I . I n s e c t s , on the other hand, are most a f f e c t e d by the t r i m e t h y l t i n s , and the t r i - n - p r o p y l and b u t y l t i n s are most e f f e c t i v e a g a i n s t f u n g i and b a c t e r i a (137, 137a, 138, 139). The t r i b u t y l and t r i p h e n y l t i n compounds, which are not p a r t i c u l a r l y hazardous to mammals ( L D 5 0 100-200 mg/kg), are very e f f e c t i v e b i o c i d e s a g a i n s t marine f o u l i n g organisms, f o r example, a l g a e , b a r n a c l e s , shrimp and tubeworms a t l e v e l s of 0.1 to 1.0 ppm (125). The comparative b a c t e r i c i d a l e f f e c t s of the Group IV d i - and t r i - o r g a n o d e r i v a t i v e s as shown i n Table IX (140). D i b u t y l t i n d i l a u r a t e c o n t r o l s the chicken p a r a s i t e R a i l l i e t i n a c e s t i c i l l u s a t dose

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

408

Table VIII.

ORAL L D

5 0

ORGANOMETALLOIDS

VALUES FOR ORGANOTIN COMPOUNDS

LD (me/kR) 5 0

Compound

Species

Butyltin trichloride Bu ty 1 t i n i sqoc ty Jmercap tpac ς ta te

Dibutyltin bis (îsooctylthio-

D i i u f y f t i ^ l i c h lor ide Dibutyltin dichioride Dibutyltin dichioride Dibutyltin dichioride Dibutyltin dichioride D i b u t y l t i n oxide D i b u t y l t i n bis(isoocty1) Dibutyltin dilaurate D i b u t y l t i n bis(nonylmaleate) D i b u t y l t i n bis(nonylmaleate) D i o c t y l t i n oxide D i o c t y l t i n maleate D i o c t y l t i n maleate D i o c t y l t i n bis(butylmaleate) D i o c t y l t i n bis(butylmaleate) D i o c t y l t i n bis(isooctylmaleate) D i o c t y l t i n bis(lsooctylmaleate)

References

1,261 1,400 1,520

Weisfeld (129a1

Rat Rat» male Rat» female

1,037 100 182 112

Weisfeld (129a)

Rat Rat Rat Rat Rat Rat Rat Mouse Rat Mouse Rat Mouse

520 200 175 120 170 2,500 4,500 2,250 2,030 3,750 2,760 2,700

Klimmer (1301 Calley et a l . (120) Klimmer (130) Klimmer (130) Klimmer (130) Klimmer (130) Klimmer (130) Pelikan et a l . (119) Klimmer (130) Pelikan e t a i . (110) Klimmer (130) Pelikan et a l . (110)

Rat

W e i s f e l d (129a) Barnes and Stoner (1958) Barnes and Stoner (1958) Stoner e t a l . (1955) Stoner et a l . (1955) Barnes and Stoner (1958) Barnes and Stoner (1958) Barnes and Stoner (1958) Klimmer (1969) Truhaut et a l . (1976) Sheldon (1975) Barnes and Stoner (1958) Klimmer (1963) Kimbrough (1976) Klimmer (1963) Marks e t a l . (1969) Marks et a l . (1969)

Me thy It i n isooctylthioglycolate Rat

Mouse Mouse

Rat

Pelikan and Cerny (115, 116) Pelikan and Cerny (115, 116)

Klimmer (130a) Mazaev et a l . (117)

Dimethyltin bis(isooctylthio-

glycolate) Trimethyltin acetate T r i e t h y i t i n acetate T r i e t h y l t i n sulfate T r i e t h y i t i n sulfate T r i p r o p y l t i n acetate T r i i s o p r o p y l t i n acetate T r i b u t y l t i n acetate Bis(tributyltin)oxide Bis(tributyltin)oxide Bis(tributyltin)oxide T r i h e x y l t i n acetate T r i p h e n y l t i n acetate T r i p h e n y l t i n acetate T r i p h e n y l t i n acetate T r i p h e n y l t i n hydroxide T r i p h e n y l t i n hydroxide

Rat Rat Rat Rabbit Rat Rat Rat Rat Rat Rat Rat Rat Guinea p i g Guinea p i g Rat, male Rat, female

1, "8Γ 9 4 6 10 118 44 380 132 180 234 1,000 136 24 21 171 268

Tetraethyltin Tetraethyltin Tetraethyltin Tetraethyltin Tetraethyltin

Rat, male Rat, female Mouse Guinea p i g Rabbit

9 16 40 40 7

Mazaev Mazaev Mazaev Mazaev Mazaev

et et et et et

al. al. al. al. al.

(1971) (1971) (1971) (1971) (1971)

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ZUCKERMAN ET AL.

24.

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409

l e v e l s o f 75 mg/kg without harm t o t h e chickens (141, 142) , and the e f f e c t on egg p r o d u c t i o n , f e r t i l i t y and h a t c h a b i l i t y was temporary (143). L D values f o r t r i c y c l o h e x y l t i n hydroxide 5 0

TABLE IX Comparative B a c t e r i c i d a l E f f e c t s o f Group IVA Organometals Figures represent t h e minimum c o n c e n t r a t i o n i n g/ml needed t o i n h i b i t a l l growth on Streptococcus l o r t i s (140).

R-MX

CH

3

C

H

2 5 n-C H

>500

>500 100

P 200 50

>500

200

1

50

5

20

0,,5

5

H

1

5

1

20

0,,2

5

2

10

5

50

0.,2

20

50

10

>500

1

>500

5

1

50

1

C

7

n-C H 6

H

Sn

50

*- 4 9 n-C H

6 5

Ge

5

3

C

R„MX.

u

13

2 >500

>500

toward q u a i l are i n the range 255-390 mg/kg w i t h no e f f e c t on egg p r o d u c t i o n , f e r t i l i t y o r h a t c h i n g noted at t h e 20 ppm d i e t a r y l e v e l (144), and toward dogs, c a t s and monkeys at >800 mg/kg (145). Sheep r e c e i v i n g intrarumenal i n j e c t i o n s o f t r i c y c l o h e x y l t i n hydroxide i n doses o f 15 mg/kg experienced no i l l e f f e c t s ; w i t h 25 mg/kg a t r a n s i t o r y anorexia set i n ; at 50 mg/kg r e v e r s i b l e CNS depression and d i a r r h e a , w h i l e four sheep dosed w i t h 150 mg/kg d i e d . Y e a r l i n g c a t t l e and goats can t o l e r a t e m u l t i p l e treatments o f up t o 0.1% w/v o f t r i c y c l o h e x y l t i n hydroxide i n a water spray on t h e hide w i t h no b e h a v i o r a l e f f e c t s , but one ewe aborted t w i n mid-term f e t u s e s eight days a f t e r a s i n g l e a p p l i c a t i o n o f a 28% s o l u t i o n and d i e d f i v e days l a t e r (146). Against t h e bollworm H e l i o t h i s zea and tobacco budworm H. v i r e s c e n s l a r v a e , f o l i a r spray o f t r i o r g a n o t i n compounds revealed L D 5 0 values o f 0.20 and 0.50 mg/kg, r e s p e c t i v e l y (147). B i s ( t r i b u t y l t i n ) o x i d e at 1% w/v i n wool k i l l e d 100% o f c l o t h e s moths T i n e o l a b i s s e l l i e l l l a r v a e without i n j e s t i o n (148). Other t r i o r g a n o t i n d e r i v a t i v e s showed values o f 0.25 t o 0.30 ppm against the mosquito Culex p i p i e n s l a r v a e compared w i t h 0.04 ppm f o r DDT (149, 150). Various t r i p h e n y l t i n d e r i v a t i v e s a c t as

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95% r e p r o d u c t i o n i n h i b i t o r s on the h o u s e f l y Musca domestica L. i n as low as 62 ppm d i e t a r y dose l e v e l s , w i t h L D 5 0 values o f 1,000 ppm (151), and act as chemosterilants toward the German cockroach B l a t t e l l a germanica L. and the confused f l o u r b e e t l e T r i b o l i u m confusum at 0.1% by weight i n the d i e t . J a c q u e l i n du V a l A n t i f e e d i n g e f f e c t s were a l s o noted on v a r i o u s l e p i d o t e r o u s l a r v a e i n c l u d i n g the cotton l e a f worm Prodenia l i t u r a F. and the Colorado b e e t l e L e p t i n o t a r s a decemleneata Say and A g r o t i s y p s i l o n Rott (152). Sugar beet leaves t r e a t e d w i t h a 0.1% w/v s o l u t i o n o f t r i p h e n y l t i n acetate and hydroxide stopped l a r v a e feeding. In 1973 the I n t e r n a t i o n a l T i n Research I n s t i t u t e organized a cooperative research p r o j e c t t o i n v e s t i g a t e the environmental behavior o f organotin compounds. The Organotin Environmental P r o j e c t , or ORTEP, i s funde o f organotin chemicals i and Japan. Human Exposure. Organotin compounds can be a s s i m i l a t e d by i n h a l a t i o n , i n g e s t i o n through food or water or by absorption through the s k i n . The l i p i d s o l u b l e d e r i v a t i v e s w i l l accumulate i n f a t t y t i s s u e . No data concerning the r a t e s o f metabolism degradation or e x c r e t i o n i n humans or t e s t animals are a v a i l a b l e . The t o t a l d a i l y i n t a k e f o r t i n i n the d i e t has been estimated t o be i n the range 187 t o 8,800 yg/day which corresponds t o an average o f 2.7 t o 126 yg/kg f o r an adult (153). T i n , presumably as i n o r g a n i c t i n , has been shown t o be an e s s e n t i a l growth f a c t o r i n the r a t Ç154). A harmful p h y s i o l o g i c a l e f f e c t was f i r s t n o t i c e d i n 1858 f o r a d i e t h y l t i n c h l o r i d e which had a " p o w e r f u l l y pungent odor" and, when heated, produced a vapor t h a t " p a i n f u l l y a t t a c k s the s k i n o f the f a c e " and caused f i t s o f sneezing (155). S i m i l a r e f f e c t s were experienced w i t h t r i e t h y i t i n c h l o r i d e and t e t r a e t h y l t i n (156). The vapors of t r i e t h y i t i n acetate were observed t o cause nausea, headache, general weakness, d i a r r h e a and a l b u m i n u r i a , and t e t r a e t h y l t i n caused headache (157). The s t e r n u t a t o r y , i r r i t a t i v e and l a c h r i m a t o r y p r o p e r t i e s o f t r i e t h y i t i n i o d i d e were s t u d i e s f o r p o s s i b l e chemical warfare a p p l i c a t i o n s , but none o f the e f f e c t s were considered potent enough and the i d e a was, m e r c i f u l l y , abandoned (158, 159, 160). Widespread p o i s o n i n g occurred, however, i n France and A l g e r i a i n 1954 as a r e s u l t o f t a k i n g S t a l i n o n capsules, each o f which was s t a t e d t o c o n t a i n 15 mg o f d i e t h y l t i n d i i o d i d e , f o r the systematic treatment o f s t a p h y l o c o c a l i n f e c t i o n s o f the s k i n (161). The i n c i d e n t i n v o l v e d 210 known cases o f harmful e f f e c t s and one hundred deaths. I t i s estimated t h a t the f a t a l doses o f the o r g a n o t i n were i n the range 380 t o 750 mg (162-171). The p r e p a r a t i o n may have a l s o contained t r i - , mono- and t e t r a e t h y l t i n (172). Adverse e f f e c t s produced by o c c u p a t i o n a l exposure t o

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

24.

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t r i p h e n y l t i n acetate used as an a g r i c u l t u r a l f u n g i c i d e i n Eastern Europe (172-176) i n c l u d e general m a l a i s e , headache, l o s s o f conciousness, e p i g a s t r i c p a i n , v o m i t i n g , i r r i t a t i o n of t h e s k i n , conjunctivae and mucosae, dyspepsia, d i a r r h e a , foggy v i s i o n , d i z z i n e s s , hyperglycemia, g l y c o s u r i a and damage t o the l i v e r shown by i n c r e a s e d c o l l a g e n , some f i b r o s i s and increased serum g l u t a m i c - p y r u v i c transmutase l e v e l s . A l l o f these e f f e c t s were r e v e r s i b l e i n a few week's time and complete recovery was e f f e c t e d . Organotins have been found t o be h i g h l y i r r i t a t i n g t o t h e s k i n . Experiments w i t h v o l u n t e e r s showed t h a t u n d i l u t e d b u t y l t i n d e r i v a t i v e s produced f o l l i c u l a r i n f l a m a t i o n and p u s t u l a t i o n . The l e s i o n s were most severe w i t h t r i b u t y l t i n c h l o r i d e which produced m i l d edema and i t c h i n g (176, 177). I n t h e most severe cases o f organotin p o i s o n i n g , involving peralkylate and abrupt v a r i a t i o n s i noted (177). The i l l n e s s l a s t e d 4-10 weeks. The one f a t a l i t y i n which o c c u p a t i o n a l exposure t o organotins has been i m p l i c a t e d i n v o l v e d a 29 year o l d woman drenched w i t h a s l u r r y o f t r i - and d i p h e n y I t i n c h l o r i d e at 175°F (80°C) causing f i r s t - d e g r e e thermal bums over 90% o f the body w i t h erythema and second- and t h i r d - d e g r e e burns s e t t i n g i n w i t h 85% desquamated s k i n . Death from r e n a l f a i l u r e s e t i n 12 days l a t e r , but the agent r e s p o n s i b l e cannot be determined from the a v a i l a b l e data (179). An a n a l y t i c a l method"based upon o b s e r v a t i o n o f SnH fluorescence i n an H - a i r flame has been a p p l i e d t o o r g a n o t i n compounds present i n human u r i n e from males age 25-47. Reduction o f t h e organotins t o t h e corresponding hydrides allows s p e c i a t i o n o f t h e t i n ( I V ) , mono-, d i - and t r i m e t h y l t i n d e r i v a t i v e s . Averages o f 11 determinations gave concentrations i n the ppb range f o r t i n ( I V ) (0.82 ppb; 8 2 % ) , mono-(0.090 ppb; 9%), di-(0.073 ppb; 7.3%) and t r i m e t h y l t i n (0.042 ppb; 4.2%). T o t a l t i n c o n s t i t u t e d 1.0 ppb (180). The same techniques were a p p l i e d t o r a i n (25 p p t r t o t a l t i n , 44% t i n ( I V ) , 24% mono-, 30% d i - and 0.88% t r i m e t h y l t i n ) t a p (9.2 p p t r t o t a l t i n , 24% t i n ( I V ) , 47% mono-, 14% d i - and 16% t r i m e t h y l t i n ) , f r e s h ([average o f 16 s i t e s around Tampa Bay, F l o r i d a ] 9.1 p p t r t o t a l t i n , 46% t i n ( I V ) , 22% mono-, 15% d i and 16% t r i m e t h y l t i n ) e s t u a r i n e ([average o f a dozen s i t e s around Tampa Bay, F l o r i d a ] 12 p p t r t o t a l t i n , 63% t i n ( I V ) , 19% mono-, 14% d i - and 3.7% t r i m e t h y l t i n ) and s a l i n e ([average o f a dozen F l o r i d a s i t e s ] 4.2 p p t r t o t a l t i n , 54% t i n ( I V ) , 15% mono-, 33% d i - and 12% t r i m e t h y l t i n ) waters. 2

Regulation o f Organotins. The U.S. Occupational S a f e t y and Health Act (OSHA) o f 1970 r e q u i r e s standards f o r the p r o t e c t i o n o f workers exposed t o hazards a t t h e i r workplace. The U.S. N a t i o n a l I n s t i t u t e s f o r Occupational S a f e t y and Health (NIOSH) has recommended a standard f o r o c c u p a t i o n a l exposure t o

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ORGANOMETALS AND

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organotin compounds. The recommended t h r e s h o l d l i m i t value (TLV) o f 0.1 mg/m on a time-weighted average, c a l c u l a t e d as elemental t i n has not yet been adopted (57). This standard was i t s e l f based upon antecedent documents. The American Conference of Governmental I n d u s t r i a l H y g i e n i s t s (ACGIH) e s t a b l i s h e d a TLV o f 0.1 mg/m measured as t i n i n 1965 f o r a l l organotin compounds i n the o c c u p a t i o n a l environment (186), and t h i s standard was r e a f f i r m e d i n 1971 by analogy w i t h the standards f o r mercury, t h a l l i u m and selenium because of a l a c k of p e r t i n e n t data (187). A separate ACGIH standard was proposed f o r t r i c y c l o h e x y l t i n hydroxide as 1.2 mg/m measured as t i n i n 1973, and the standard was adopted i n 1975 (188). In the German Democratic Republic the maximum a l l o w a b l e c o n c e n t r a t i o n o f organotins i s given as 0.1 mg/m (189), and Romania and Y u g o s l a v i a use the same f i g u r e f o r a TLV based upon the 1966 ACGIH valu standard,-29 CFR 1910.1000 c o n c e n t r a t i o n l i m i t of 0.1 mg/m measured as t i n , and i s based upon the 1965 ACGIH TLV (57). This value equates t o an exposure o f 0.02 mg/kg/day. The World Health O r g a n i z a t i o n i s c u r r e n t l y d r a f t i n g a review o f the environmental h e a l t h aspects o f t i n (191). The Midwest Research I n s t i t u t e r e p o r t recommended a maximum d a i l y dosage o f 0.02 mg/kg which i s the estimated dosage o f a person exposed t o 0.1 mg/m over an eight-hour p e r i o d f o r f i v e days per week (58). The C o u n c i l o f the European Communities l i s t e d organotin compounds as p a r t of a group o f substances s e l e c t e d on the b a s i s o f t h e i r t o x i c i t y , p e r s i s t e n c e and bioaccumulation t o which s t a t e s were d i r e c t e d t o apply a system o f zero-emission t o discharges i n t o ground water, and t o r e q u i r e p r i o r a u t h o r i z a t i o n by competent a u t h o r i t y o f the member s t a t e s f o r a l l discharges i n t o the aquatic environment of the Community (192). Russian authors have proposed standards of 20 m g / l i t e r f o r d i b u t y l t i n s u l f i d e (193), 2 m g / l i t e r f o r d i b u t y l t i n d i c h i o r i d e (193), and 0.2 m g / l i t e r f o r t e t r a e t h y l t i n (195) i n r e s e v o i r water based upon n o - e f f e c t doses found i n c h r o n i c toxicity testing. Both the NIOSH and Midwest Research I n s t i t u t e r e p o r t s recognize the strong dependence of the t o x i c i t y o f o r g a n o t i n compounds upon the' number o f organic s u b s t i t u e n t s and t h e i r nature. The s i n g l e standard t h a t i s recommended f o r airborne organotins does not r e f l e c t the v a r i e d t o x i c i t y and hazard o f these compounds. However, there i s l a c k o f adequate data upon which t o d i s t i n g u i s h q u a n t i t a t i v e l y between d i f f e r e n t compounds, and a l a c k o f a n a l y t i c a l techniques f o r the s p e c i a t i o n o f organotins i n low environmental c o n c e n t r a t i o n s . Another area f o r the r e g u l a t i o n of organotins i s i n t h e i r use as a d d i t i v e s i n packaging m a t e r i a l s f o r food and beverages. The Federal Food, Drug and Cosmetic Act was amended i n 1963 to a l l o w the i n t r o d u c t i o n o f d i b u t y l t i n d i l a u r a t e i n s i l i c o n e 3

3

3

3

3

3

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polymer compositions not t o exceed 1 p a r t of t i n per hundred of polymer (196). A subsequent amendment t o the act allowed the use o f a d i - n - o c t y l t i n S, S - b i s ( i s o o c t y l m e r c a p t o a c e t a t e ) f o r m u l a t i o n o f «15.1-16.1% by weight o f t i n i n PVC. The s t a r t i n g m a t e r i a l s f o r the s y n t h e s i s o f the mercaptoacetate d e r i v a t i v e were c o n t r o l l e d at not more than 5% o f the t r i c h l o r o and not l e s s than 95% o f the d i c h l o r o t i n . The Food and A g r i c u l t u r a l O r g a n i z a t i o n and the World Health O r g a n i z a t i o n have j o i n t l y recommended r e s i d u e l i m i t s o f 2 ppm f o r apples and pears, 0.2 ppm f o r meat and 0.05 ppm f o r m i l k (197), and acceptable d a i l y i n t a k e o f l e s s than 0.0075 mg/kg o f body weight f o r the p e s t i c i d e t r i c y c l o h e x y l t i n hydroxide (198). There are c u r r e n t l y no s p e c i f i c f e d e r a l r e s t r i c t i o n s on the t r a n s p o r t or h a n d l i n g o f organotin compounds. Some organotins are v o l u n t a r i l the U.S. Handling procedure s p i l l s are not l e g a l l y s p e c i f i e d . N e i t h e r the Hazardous Substances L i s t o f the Environmental P r o t e c t i o n Agency (EPA) nor the Carcinogenic Suspect Agent l i s t o f the Occupational Safety and Health A d m i n i s t r a t i o n (OSHA) c o n t a i n any organotin compounds. The EPA O f f i c e o f P e s t i c i d e s has r e g i s t e r e d b i s ( t r i b u t y l t i n ) oxide and t r i b u t y l t i n f l u o r i d e f o r use i n a n t i f o u l i n g p a i n t s . As f o r a i l p e s t i c i d e s , the l a b e l s o f the c o n t a i n e r s o f u n d i l u t e d organotin as w e l l as f i n i s h e d nroduct must show a n a l y s i s , contents, d i r e c t i o n s f o r use, a c c i d e n t a l contact remedies and c o n t a i n e r d i s p o s a l . B i s ( t r i n e o p h y l ) t i n oxide and t r i c y c l o h e x y l - and t r i p h e n y l t i n hydroxides have been r e g i s t e r e d by the EPA as a g r i c u l t u r a l chemicals (199). The Food and Drug A d m i n i s t r a t i o n code permits the use o f o r g a n o t i n s t a b i l i z e r s i n r i g i d PVC food c o n t a i n e r s , and i n PVC f o r food wrap, i n c l u d i n g d i - n - o c t y l t i n S,S b i s ( i s o o c t y l m e r c a p t o a c e t a t e ) and maleate polymer and b u t y l t h i o s t a n n o i c a c i d (200). The EPA allows use i n PVC p i p e and conduit f o r p o t a b l e water. Organotins have a l s o been approved as c a t a l y s t s and c u r i n g agents i n the p r o d u c t i o n o f polyurethane r e s i n s , s i l i c o n e polymers and PVC products f o r food packaging, and as adhesive p r e s e r v a t i v e s f o r food use (200). f

f

Water and Waste Treatment. A U.S. Patent has been i s s u e d f o r removal o f i n o r g a n i c and organolead compounds from the aqueous e f f l u e n t from the manufacture o f t e t r a a l k y l l e a d by treatment w i t h an a l k a l i metal borohydride t o form i n s o l u b l e lead products i n c l u d i n g h e x a a l k y l d i l e a d and l e a d metal which can be separated by s e t t l i n g (201). Russian authors have u t i l i z e d absorption onto a c t i v a t e d carbon, e x t r a c t i o n i n t o ether and e l e c t r o c h e m i c a l o x i d a t i o n methods f o r the d e t o x i f i c a t i o n o f waters p o l l u t e d by organotin compounds (202, 203). Anodic s t r i p p i n g polarography has been used t o determine organotin residues i n s u r f a c e waters (204).

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7. 8. 9.

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188. ACGIH, "Threshold Limit Values for Chemical Substances in the Workroom Air," p. 32, Cincinnati, OH, 1975. 189. Landa, Κ., Fejfusova, J. and Nedomlelova, R., Prac. Lek. (1973), 25, 391. 190. International Labor Office, "Permissable Levels of Toxic Substances in the Working Environment," Occupational Safety and Health Series, Vol. 20, pp, 239, 353, ILO, Geneva, (1970). 191. Vouk, V . B . , private communication, 1977, quoted in ref. 58, p. 344. 192. Off. J. Eur. Commun. (18 May, 1975), 19, 23. 193. Mazaev, V.T. and Shlepnina, T . G . , Gig. Sanit. (1973), 38, 10. 194. Mazaev, V . T . and Korolev, Α . Α . , Prom. Zagryaz. Vodoemov (1969), 15. 195. Skachkova, I . N . , Gig 196. Federal Register (31 July, 1963), 28, 7777. 197. Tricyclohexyltin hydroxide, in Joint Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues: 1973 Evaluations of Some Pesticide Residues in Food - the Monographs, WHO Pesticide Residues Series No. 3, pp. 440-52, WHO, Geneva, 1974. 198. Tricyclohexyltin hydroxide, in Joint Meeting of the FAO Working Party of Experts and the WHO Expert Group on Pesticide Residues: 1970 Evaluation of Some Pesticide Residues in Food - The Monographs, pp. 521-42, The FAO of the UN and the WHO, Rome, 1971. 199. Code of Federal Regulations, T i t l e No. 40, Protection of the Environment, SEctions 180.144 and 180.236 (1 July, 1976). 200. Code of Federal Regulations, T i t l e No. 21, Food and Drugs, Sections 121.2514, 121.2520, 121.2522, 121.2566 and 121.2602 (1 A p r i l , 1976). 201 Lores, C. and Moore, R . B . , U.S. Pat. 3,770,425 (6 Nov., 1973), Chem. Abstr. (1974), 80, 137055. 202. Chernega, L . G . , Kozyura, A . S . , Kazakova, A . A . , Sirak, L . D . , Kudenko, N.E. and Linchuk, K.F., Vodosnabzh. Kanaliz. Gidrotekh. Sooruzh. (1971), 13, 75; Chem. Abstr. (1972), 76, 158028. 203. Sirak, L . D . , Lutsenko, F . A . and Shkorbatova, T.L., Vodosnabzh. Kanaliz. Gidrotekh. Sooruzh. (1974), 17, 72; Chem. Abstr. (1975), 82, 34748. 204. Woggon, H. and Jehle, D . , Nahrung (1975), 19, 271.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

24.

Z U C K E R M A N ET

AL.

Organotins

423

Discussion W. H. RIDLEY ( U n i v e r s i t y of Minnesota): What i n t e r e s t s me i s the t o x i c i t y of the o r g a n o t i n s . For example, the case of b u t y l t i n s a f t e r they have been h y d r o x y l a t e d by a P450 mechanism that Dr. F i s h d e s c r i b e d . Is there any i n f o r m a t i o n on the t o x i c i t y of these m a t e r i a l s r e l a t i v e to the a l k y l s ? I r a i s e t h i s i s s u e be cause I t h i n k another of the f a c t o r s c o n t r o l l i n g the t o x i c i t y of these compounds, i n a d d i t i o n to s t e r i c c o n d i t i o n s , i s going to be t h e i r h y d r o p h o b i c i t y , or t h e i r p a r t i t i o n i n g between l i p i d and aqueous phases. ZUCKERMAN: I t h i n k t h a t ' s a good q u e s t i o n . Dr. F i s h , have you put these t h i n g s back i n t o bugs and seen what the e f f e c t s are? R. H. FISH ( U n i v e r s i t ed a paper w i t h Norman A l d r i d g e [Biochem. Pharmac. (1977), 26, 1997] where we examined the i n h i b i t i o n of o x i d a t i v e phosphoryla t i o n w i t h i n v i t r o experiments. I t was found that the (6-hydroxyb u t y l ) d i b u t y l t i n c h l o r i d e was a b e t t e r i n h i b i t o r i n those systems than t r i b u t y l t i n . However, E l l a Kimmell i n our l a b o r a t o r y d i d t o x i c i t y s t u d i e s and found these were s l i g h t l y l e s s t o x i c than t r i b u t y l t i n c h l o r i d e . So t h e r e i s a dichotomy where they are b e t t e r i n h i b i t o r s i n v i t r o but l e s s t o x i c i n the whole animal. ZUCKERMAN: A f t e r l i s t e n i n g to papers i n the symposium, I have l e a r n e d to ask "More t o x i c to what?" To comment on your q u e s t i o n , the molecules w i t h the t e r m i n a l hydroxide group would have one end which i s l i p i d - s o l u b l e and another end which i s w a t e r - s o l u b l e , l i k e a detergent molecule. Maybe the t r a n s p o r t through membranes i s more important than the t o x i c i t y . Maybe t h a t ' s a predominimating f a c t o r i n determining whether i t ' s going to be e f f e c t i v e as a t o x i c a n t . FISH: I t ' s i n t e r e s t i n g to p o i n t out that the γ-hydroxy species was l e s s a c t i v e than the δ-hydroxy compound, perhaps be cause you get a t r i g o n a l b i p y r a m i d a l i n t e r a c t i o n as i t ' s exchang ing C l f o r OH when i t goes across the membrane. Both compounds were b e t t e r than t r i b u t y l t i n , because there was a d e f i n i t e d i f f e r ence between the γ- and δ-hydroxy compounds. J . S. THAYER ( U n i v e r s i t y of C i n c i n n a t i ) : I t has been p r e sumed that o r g a n o t i n compounds i n the environment w i l l end up as SnO^. Because of the l e n g t h of time i t takes f o r t h i s process to occur, r e l a t i v e t o r e d i s t r i b u t i o n , e t c . , complete removal of a l l organic groups might not occur. You might get a tin-oxygen p o l y mer w i t h a number of organic groups remaining (perhaps averaging out t o l e s s than one group per t i n ) but w i t h a h i g h molecular weight and which s t i l l r e t a i n s some b i o a c t i v e p r o p e r t i e s .

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

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ORGANOMETALS AND

ORGANOMETALLOIDS

ZUCKERMAN: The higher the molecular weight, the more complex the p a r t i c l e , the f u r t h e r i t ' s removed from an environment which might be one that cleaves the organo groups. But at the same time, i f i t became that p a r t i c l e i t would be i n a sense removed from the environment. I f i t i s d e t o x i f i c a t i o n that we are a f t e r , maybe that i s as e f f e c t i v e as making something which analyses as Sn0 'H 0. 2

2

R. COHEN ( B e l l L a b o r a t o r i e s ) : Have these organotins been subjected to Ames t e a t s to determine t h e i r p o s s i b l e mutagenicity? Has there been e s t a b l i s h e d any mechanism of c o n c e n t r a t i o n along the food chain s i m i l a r to c h l o r i n a t e d hydrocarbons? A. CHEH ( U n i v e r s i t y of Minnesota) : The Ames t e s t does not work w e l l f o r metals. C i t r a t metal. F. E. BRINCKMAN ( N a t i o n a l Bureau of Standards): A p o s s i b l e source f o r f u r t h e r i n f o r m a t i o n would be Dr. Warren Iverson at our i n s t i t u t i o n , who i s concerned w i t h the a p p l i c a t i o n s of Ames-type, f a s t turnover microorganism t e s t s w i t h respect to organometals. ZUCKERMAN: To t u r n that question around; a t the ONR Organot i n Workshop at New Orleans [February, 1978], there was d i s c u s s i o n of the p o s s i b l e t h e r a p e u t i c uses of o r g a n o t i n compounds by analogy w i t h the square p l a n a r platinum complexes. For example, what would be the analogous t i n compound t h a t might be e f f e c t i v e i n those ways, yet get around some of the bad s i d e - e f f e c t s of p l a t i num therapy ( r e n a l f a i l u r e , e t c . )

Acknowledgment T h i s manuscript was based i n p a r t on NIOSH C r i t e r i a Document No. 77-115, and on work done at Midwest Research I n s t i t u t e by R. R. W i l k i n s o n under EPA c o n t r a c t number 68-01-4313. The f i g u r e s and t a b l e s were excerpted from Dr. Wilkinson's d r a f t r e p o r t by permission of P. H i l g a r d a t EPA and are not s u b j e c t t o U.S. c o p y r i g h t . Our work i s supported by the O f f i c e of Naval Research. R E C E I V E D September 18,

1978.

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

INDEX A Absorption of lea.d-fulvic acid complex 380 Absorption method, solute 318 Acetolysis of dialkylmercury cleaved group parameters in 217 compounds 214 leaving group parameters in 216 with ionization potential of dialkyl mercury compound, correlation of cleaved-group constant and leaving group constant in 228 of methyl-ethyllead compounds 217 Acetonitrile, rates of reactions of dialkylplatinum(II) complexes with hexachloroiridate(IV) in 224 Acid character, trends in stability: hard and soft 138 Acids, Brônsted 220 Acidity, Lewis 341 Acidity values for humic and fulvic acids 373 Activation parameters for transmethylation between metals in protic media 165 Active methionine 6 Activity coefficients, Debye-Huckel limiting law for 167 Activity rate theory, Brônsted and Bierrum 167 Additive energy effects 216 Adenosine-S'-phosphosulfate (APS) .. 28 Adenylic kinase 27 ADP-sulfurylase 27,28 Adsorption, surface 322 Adverse effects produced by occupational exposure to triphenyltin acetate 410,411 Aerobic alkylation of arsenic 94,104 mechanism of 108 0-Alanine 273 monochloramines of 266 and their monochloramines toward equilibrium, approach of a mixture of N H 274 Alga Tetraselmis chui, arsenic uptake and metabolism by 116 Algae, metabolism of arsenate by marine 117 3

Algal growth, arsenic incorporation and Algal toxicity testing, biological generation of volatile methyl alkyls for Alkyl acid, biological methylation of groups cleaved saturation pattern for halides, rate constants for reaction of Cr"[15]ane N with -mercury bond, rate constant for electrophilic protonolysis of .... -metal bonds, cleavages of metalloids, toxicity of volatile metals, toxicity of volatile radicals calculated ionization potentials of electron transfer oxidation of experimental ionization potentials of ionization of HOMO of ionization potentials of -substituted compounds, ionization potential of transfers from cobalt (III) to chromium4

2

117 44 3 218 218 238 227 231 40 40 211 223 211 211 216 210

(II) 230 homolytic displacement in 229 in organometals, mechanisms for 205 Alkylarsine 390 assays 98 biosynthesis of 98 compounds, volatile 99 derivatives, biosynthesis of 98 formed in cell extracts 99 by whole cells of Methanobacterium strain M.oH, synthesis of 100 Alkylated arsine, analysis of 99 Alkylation of arsenic, aerobic and anaerobic .. 94 of metalloids 30 of metals 30,97 Alkylators of metal ions, organosilanes as aquatic 149 Alkylcobalamins 33,34

425

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

426

ORGANOMETALS AND

ORGANOMETALLOIDS

Antifouling coatings, leaching model.. 359 Alkylcobalt complexes undergoing 359 oxidation-reduction 231 Antifouling paint 36 Alkyllead compounds 65 Antimonite 8 analysis of 40 Antimony Alkylmercurials 160,339 Antimony (III) tartrate showing pseudo trigonal bipyramid Alkylmercury iodides in aqueous per ( φ-tbp ) coordination, structure of 35 chloric acid, protonolysis of 217 APS (adenosine-5'-phosphosulfate) ,. 28 Alkylmercury iodides in sulfuric acid, protonolysis of 217 Aquated metal ions, influence of environmental parameters on Alkylmetal intermediate, inner-sphere 206 transmethylation between 158 Alkylthallium compounds 65,216 Aquated organoelement ions 159 Alkyltin compounds, estimated annual U.S. production of selected 392 Aquatic alkylators of metal ions, organosilanes as 149 Alkyltin compounds, U.S. consump tion of 394 Aquation numbers 159 Alkyltrimethyltin compounds 216 Aqueous Alum-A-Tox 363 chemistry of organolead compounds in presence of microorganisms 65 coatings containing organotin com pounds, parameters for 36 Amines, second-order rate constant organisms 65 for chlorination of 280 media, organo group acceptors in .. 151 Amines, second-order rate constants perchloric acid, protonolysis of for HOCl chlorination of 284 alkylmercury iodides in 217 Aminoacid(s) cadmium complexation by sulfhysolution, distributions of chlor amines in 274,275 dryl-containing 339 solution, kinetics of disproportionacomplexes, bond lengths in 350 tion in 264 containing selenium 11 transmethylation between tin (IV) lead complexation by sulfhydryland mercury (II), speciation containing 339 of products and reactants in ... 168 mercury complexation by sulfhy162 dryl-containing 339 Arrhenius equation Arsenate PhHg(II) complexes of sulfurbiological methylation of 2 containing 332 conversion to trimethylarsine, rate constants for direct transfer of chlorine from NH C1 to pep inhibitors of 49 tides and 287 by marine algae, metabolism of 117 second-order rate constants for reduction of 29 1,116 chlorination of 280, 284 Arsenic aerobic alkylation of 94 Ammonia, monochloramines of 266 aerobic methylation of 105 Ammoniacal chloramines, distribution mechanisms of 108 of 273 anaerobic alkylation of 94 Anaerobic compounds, methylation of 47,48,116 alkylation of arsenic 94 compounds in phospholipid fraction bacterial culture, sources of from Tetraselmis chui, chro Me Pbin 74 matographic separation and ecosystems, arsenic transformation detection of 124 in 102,105 -containing lipids reactions of ( C H ) C o L 248 characterization of 122 Anion on reaction rate constant for elemental analyses of 126 methylmercuric salt-methylcoisolation of 122 balamin reaction, effect of 190 Ankistrodesmus falcatus 43 -containing phospholipid fraction, chromatographic isolation of .. 123 Anodic oxidation 213 cycle, biological Ill of tetraalkyllead compounds 213 cycle in the environment 109 Antifoulant activity 359 incorporation and algal growth 117 Antifoulants, organotin 359 3

+

4

3

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

427

INDEX

Arsenic (continued) lability of transformed 103 metabolism by alga Tetraselmis chut 116 -methylating agent 105 methylation of 45,49,351 aerobic 105,108 compounds biological 116 Moira River area sediment 47 by pure bacteria 48 natural occurrence of methylated compounds of 17 pigments 39 -protein interactions, large-scale growth and 117 in respiratory processes, involve ment of 27 in sludge, transformation of transformation in anaerobic eco systems 102,105 uptake by the alga Tetraselmis chui 116 in instant ocean medium 118 As activity, distribution of 121 Arsenical liquid cultures of S. copuhriopsis brevicaulis, methanol in 7 Arsenical poisoning 39 Arsenite 36 biological methylation of 2 oxidation 27 Arsine 105 analysis of the alkylated 99 biosynthesis 98 Aspergillus niger 3,7 Associative bridging complexes 182 Atmospheric oxidation of trimethylarsine 9 Atomic absorption spectrophotometry 14 "Available" metals ions 16 74

Β Bj2

-dependent methyl transfer mecha nisms, in vitro mechanisms for -dependent methyl transfer to toxic metal ions, kinetic and mecha nistic studies on - E N Z binding in methionine syn thetase system in synthesis of methionine, role of .. system for methylation of homo cysteine Bacillus arsenoxydans

Bacteria characteristics of methane 95 function of methane 94 mercury-resistant 16 methanogenic 94,105 role of 104 methylation of arsenic compounds by pure 48 silicate 150 sulfate-reducing (Desulfovibrio) .... 30 Bacterial environment, detoxification of 78 growth by lead compound, inhibition of 67 growth by organolead compounds at various lead and nutrient concentrations, inhibition of ... 70 Bactericidal effects of group IVA

BALHa (British anti-Lewisite), complexes of 327 BALHa, organomercury derivatives of 330 "Base-off" complex 33,197 "Base-off" methyl-Bi2 55 "Base-on" complex 33 "Base-on" methyl-B 55 Batch-type reactor 296 Beaumont-Leys 15 Benzene oxidation in the presence of differ ent chloride ion concentrations 309 ozone to be decomposed per oxidation of 305 spiked to water of Lac de Bret by decomposition of ozone, elimination of 305 Best linearfitfor k (obs) vs. [Cl ] by six independent pair-wise rate constants 176 Binary mercury (II) derivatives 212 first vertical ionization potentials of 212 Binding preferences for inorganic mercury, cadmium, and lead 347 Binuclear complexes 66 Bioaccumulation 39,314 Biochemical oxidation reactions 24 67 55 Biocides Bioconcentration factors for chlorobenzenes and chlorophenols 314 162 54 Biogenesis of organometals Biological arsenic cycle Ill 31 behavior of diphenylmercury 333 31 behavior of mercury compounds .... 327 conditions, rates of methylation 35 under 198 27 J2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

-

428

ORGANOMETALS AND

Biological (continued) degradation of organo derivatives of mercury 16 degradation of organotins 402 effects of exposure on organotins ... 405 generation of volatile methyl alkyls for algal toxicity testing 44 methylating agents 351 methylation 1,390 of alkyl acid 3 arsenate 2 of arsenic compounds 116 of arsenite 2 of dialkylarsonic acid 3 of elements 39 in the environment, occurrence of 39 mechanism of 4 production of Me Pb 7 Biology, organotins in 388 Biomethylation of Et PbCl 74 of Et PbX 72 of inorganic tin 404 of Me PbX 71 mechanisms for 55 of metals 158 of metalloids 158 of organolead compounds 68 of Pb 68,70 significance of 78 of TT 73 significance of 78 Biomolecular rate effects of ionic strength on 166 effects of salinity on 166 law 162 Biomolecules, stability with 140 Bioorganotin chemistry: situselectivity in the monoxygenase enzyme reactions of cyclohexyltin compounds 82 Bioorganotin chemistry: stereoselectivity in the monoxygenase enzyme reactions of cyclohexyltin compounds 82 Biosynthesis of alkylarsine(s) 98 derivatives 98 arsine 98 of coenzyme M 12 of dimethyl arsine, proposed pathway for 103 methane 96,104 role of CoM in 100 of organometallic compounds 1 of organometalloidal compounds .... 1 requirements for 98

Biotransformations of sulfur as evolutionary prototypes 23 Biotransport 314 Bond lengths in amino acid complexes 350 Brain, mercury in 328,334 Brain tissue, mercury in 330 of rats 335 Breakpoint chlorination, relationship between chlorine dosage and residual chlorine for 282 Bridges, mercapto 346 Bridging complexes, associative 182 Bridging in organolead compounds ... 66 British anti-Lewisite ( B A L H ) , complexes of 327 Brônsted acids 220 and Bierrum activity rate theory ... 167

ORGANOMETALLOIDS

3

4

3

3

Buffer systems, chloride Buffering, metal-ion f-Butyl hydroperoxide and C r

172 172 239

C

3

2+

aq

2+

[ C ] methylcobalamin 99 Cacodylate 109 Cacodylic acid 10 Cadmium binding preferences for 347 complexation by sulfhydryl-containing amino acids 339 hazards 15 poisoning 347 Candida humicola 49,105,198 extracts, ion-exchange separation of 110 Carbanion methyl transfer 55,56 Carbon hydroxylation 82 -metal bond 30 electrophilic cleavage of 226 formation of 33 -metalloid bond 30 formation of 33 -tin bonds 399 Cation(s) methylmercury 298 organometallic 130 at 25°, hydrolysis constants for univalent 134 in aqueous media, chemistry of .. 130 in aqueous solution, complexation of 138 with organic ligands, stability of constants of 142 organotin 298 -radical of dialkylmercury 215 radical, fragmentation of 220 14

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

INDEX

429

Cd methane evolution study for the reactions of (CH ) CoL with .. 256 reaction of ( C H ) C o L with 258 reactions with excess 248 Cell extracts, alkylarsine formed in .... 99 (CH ) CoL anaerobic reactions of 248 by H 0 , demethylation of 249 reaction(s) of 250,253 with C d 258 methane evolution study for ... 256 kinetic data for methane evolution during 251 rate of methane evolution for 253 with Pb 256 with Zn 258 reactions with excess 25 C H H g (methylmercury) 33 -mercaptalbumin complex 341 stability constants for 141 CH Hg( II)-pyridine system, Raman perturbation difference spectra for 145 (CH ) Pb with carboxylic acids, stability constants for 144 ( C H ) P b hydrolysis at 25° 138 (CH ) Sn * hydrolysis at 25° 138 Charge neutralization 374 Chelating agents 14 interactions between trace metals and 372 Chemical degradation of organotins 399 disproportionation, production of Me Pb by 44 production of Me Pb 71 speciation 380 Chemistry, mercury (II) thiolate 327 Chemistry, tin 388 CHEMSPECIES 160 determinations of mercury reactant species 168 determinations of methyltin reactant species 168 program 169 calculations at constant ionic strength and p H 170 Chloramines 264 distribution of 273 in aqueous solution 274 equilibria 264 rate constants for hydrolysis of 285 toxicity of 279 to aquatic life 264 ChloreUa pyrenoidosa 49 2+

3

3

3

2

2

3

+

2+

2+

2

3

3

3

3

3

2

3

2

2+

2

4

4

2

Chloride(s) buffer systems 172 ion concentrations, benzene oxidation in presence of different ... 309 organotin 191 Chlorination 278 of amines, second-order rate constants for 280,284 of amino acids, second-order rate constants for 280 reactions, monochloramine formation in 281 relationship between chlorine and residual chlorine for breakpoint 282 of water as means of disinfection .. 264 Chlorine 278 distribution of millimolar 273 dosage and residual chlorine for relationship between -methyl exchange from NH C1 to amino acids and peptides, rate constants for direct transfer of Chloro complexing N-Chloro compounds in water treatment, formation of N-Chloro-0-alanine Chlorobenzenes, bioconcentration factors for Chloroelectrophiles, formation constants for N-Chloroglycylglyeine determination of disproportionation equilibrium constant for Chlorophenols, bioconcentration factors for Chloro species, methyltin and mercury Chromatographic isolation of arseniccontaining phospholipid fraction Chromatographic separation of arsenic compounds in phospholipid fraction isolation from Tetraselmis chui Chromatography, thin-layer Chromium (II), alkyltransfers from cobalt(III) to [Cl"], statistical analysis of the dependence of k (obs) on C l transfer reactions of NH C1 C l , kinetics of hydrolysis of C l , reactions of Cleavages of alkyl-metal bonds of dialkyImercury by hexachloroiridate(IV) 3

+

2

+

282 195

2

2

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

287 139 278 274 314 182 274 269 314 177 123

124 8 230 174 289 279 279 231 221

430

ORGANOMETALS AND

Cleavages (continued) of dialkylmercury(II) by hexachloroiridate 226 exclusive 222 of the metal-carbon bonds, reactions involving 131 preferential 222 Cleaved alkyl groups 218 Cleaved group constant and leaving group constant in acetolysis with ionization potential of dialkylmercury compound, correlation of 228 effects 216,227 parameters in acetolysis of dialkylmercury 217 Co-C bond cleavage of methyl-Bi , reductiv heterolytic cleavage of 5 homolytic cleavage of 55 influence of corrin-ring conformation on stability of 58 of methyl-Bi2 electrophilic attack on 55 free radical attack on 55 "redox switch" mechanism for attack on 58 CoM in methane biosynthesis, role of 100 Coating(s) containing organotin compounds, parameters for Alum-A-Tox .... 367 continuous contact 360 leaching model for antifouling ... 359 surfaces, release mechanisms of organotin toxicants from 359 Cobalt chelates 236 Cobalt(I), nucleophilic pathways via 240 Cobalt ( III ) to chromium ( II ), alkyl transfers from 230 Cochromatography, T L C 84 Coefficients, partition 158 determination of 158 Coenzyme M (2-mercaptoethanesulphonic acid) 11 biosynthesis of 12 and derivatives 12 Coenzyme Q (ubiquinones) 25 Cofactor, methyl transfer 11 Commercial organotin chemicals, consumption of 395 Complex dissociation, rate of 377 formation between mercury compounds and thiols 327 formation, rate of 377

ORGANOMETALLOIDS

Complexation of Fe( III ) with fulvic acid of trace metals by humic and fulvic acids, conditional stability constants for Complexing capacity of HA and FA .. Complexing ligand Conditional stability constants for complexation of trace metals by humic and fulvic acids Consumer disposal options for organotins Continuous contact coatings and leaching Coordination spheres of organometal ions, hydrolysis of water in 4-Coordinate organolead compounds Coordinated solvent, proton transfer

374 377 374 381 380 376 374 393 360 159 215

2

Correlation matrix for regression 175 Corrin macrocycle 58 -ring conformation on the stability of the Co-C bond, influence of 58 -ring isomerizations 58 Coulombic repulsions 168 Cr [15]ane N with alkyl halides, rate constants for reaction of 238 Cr \ f-butyl hydroperoxide and 239 Crossover system, mercury-tin 405,406 Crystal structures of simple thiolates Hg(SR) 328 Cu-HA complexes, electron paramagnetic resonance studies of .... 377 Culex pipiens 409 Cyclohexyldiphenyltin acetate 90 Cyclohexyltin compounds, bioorganotin chemistry: stereoselectivity and situselectivity in monooxygenase enzyme reactions of 82 Cyclohexyltriphenyltin 90 Cysteine 339 L-Cysteine complexes 330,342 Cytochrome -linked oxidative phosphorylation .. 26 P-450 monooxygenase enzyme reactions 87 system, P-450 27 n

aq

4

2 +

2

2

D

Dealkylation reactions of organocobalt compounds Debye-Hiickel extensions of the Brônsted equation Debye-Hiickel limiting law for activity coefficients Decaying plants, leaching of

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

247 173 167 372

INDEX

431

Decomposition of MeTlX 76 Decomposition of organolead compounds in water 65 Degradation of organo derivatives of mercury, biological 16 Degradation of triphenyltin chloride on sugar beet leaves in a greenhouse environment 403 Dehydrogenations 24 Demethylation of (CH )oCoL by H 0 249 of lead 351 of Me Sn 165 metathetical 158,196 of methylcobalamin 188 rates of methylmetal donors, reduction of 168 redox 197 reductive 15 of silicon 15 Destannylation of tricyclohexyltin hydroxide, in vivo 407 Desulforibrio ( sulfate-reducing bacteria) 30 Detoxification of bacterial environment 78 Detoxification process 30,39 Dialkylarsonic acid, biological methylation of 3 Dialkyl ( bis-phosphine ) platinum ( II ) complexes 223 Dialkylmercury in acetic acid solutions, protonolysis of 214 cation-radical of 215 cleaved group parameters in acetolysis of 217 compounds 207,212,221 acetolysis of 214 correlation of cleaved-group constant and leaving group constant in acetolysis with ionization potential of 228 electrophilic protonolysis of 207 vertical ionization potentials of .... 208 generalized equation for protonolysis of 218 by hexachloroiridate ( IV ), cleavage of 221 leaving group parameters in acetolysis of 216 Dialkylmercury (II) compounds, protonolysis of 131 Dialkylmercury (II) by hexachloroiridate, cleavage of 226 Dialkylplatinum(II) complexes with hexachloroiridate (IV) in acetonitrile, rates of reactions of 224 2

3

3

3

+

+

Dichloramine(s) (NHC1 ) 266,278 formation 269,271 reactions of 287 Diethylmercury, thermal composition of 323 Diffusion, Fick's First Law of 361 Dimethylarsine ( Me AsH ) proposed pathway for the biosynthesis of 103 synthesis 99 Dimethylgold(III) compounds 193 Dimethylmercury partition coefficients in (Table I) distilled water, (Table II) sea water 321 Dimethylselenide 3 Dimethyltelluride 3 Diorganothallium compounds, inhibition of bacterial growth by 69 2

2

biological behavior of Direct reaction(s) of ozone with organomercurials of ozone with solutes in water Direct transfer of chlorine from NH C1 to amino acids and peptides, rate constants for Disinfection, chlorination of water as a means of Disproportionation in aqueous solution, kinetics of equilibrium constant of N-chloroglycylglycine, determination of kinetics of of MeTlX from -d [monochloramine]/dt = k i s [monochloramine] [Hmonochloramine ], rate constants for Distilled water, dimethylmercury partition coefficients in 2,2'-Dithiodiethane sulfonic acid Dithionite Double two-jet tangential mixing system · DSS (sodium 2,2-dimethyl-2-silapenpentane-5-sulfonate) 3

333 293 299 295 297

+

2

287 264 264 269 271 77

D

+

276 321 100 29 265 152

£ ( E ° ) standard reduction potential Edwards oxybase equation Electrolytes, inorganic Electron detachment from tetraalkyllead donors, organometals as paramagnetic resonance studies of Cu-HA complexes

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

57 219 167 213 207

432

ORGANOMETALS A N D ORGANOMETALLOIDS

Electron transfer cleavage of organometals with hexachloroiridate ( IV ) 219 mechanism, delineation of 226 oxidation of alkyl radical 223 oxidation of same organomer curials with hexachloroiridate(IV) 207 processes between metal com plexes 206 processes in electrophilic substi tutions 228 Electronegativities of alkyl groups .... 212 Electrophilic attack 247 on the Co-C bond of methyl-Bi 55 cleavage of carbon-metal bond 226 cleavage of organometals 214 mechanism, delineation of 22 pathways 241 protonolysis of alkyl-mercury bond, rate constant for 227 protonolysis of dialkylmercury compounds 207 reactions, linear free-energy corre lations for 242 reagents 399 substitutions, electron-transfer processes in 228 Elemental analyses of arsenic-contain ing lipids 126 Elemental analysis of humic and fulvic acids 373 Elements, biological methylation of .. 39 Elements in the environment, occur rence of biological methylation of 39 Elimination lines 296 Elimination of toxic methylelement species 158 Energy effects, additive and saturated 216 Environment arsenic cycle in 109 organotins in 388,391 organotins released to 397 transport in 396 Environmental fate of organotins 399 parameters, assessing influences of .. 158 parameters on transmethylation between aquated metal ions, influence of 158 significance of organosilicon com pounds 153 ENZ ( N -methyltetrahydrofolatehomocysteine cobalamin methyltransferase) 31 Enzyme Β 24 2

5

Equation, Arrhenius Equilibration cell Equilibria chloramine summary of Equilibrium, approach of a mixture of N H , β-alanine, and their monochloramines toward Equilibrium constant of N-chloroglycylglycine, determination of disproportionation Eschenchia coli Et PbCl, biomethylation of Et PbX, biomethylation of Ethionine Ethylarsines Ethylenediamine complexes, stability constants for

162 315 266 264 268

3

3

3

Evolutionary development, silicon and Evolutionary prototypes, biotrans formations of sulfur in Exclusive cleavage Exposure on organotins, biological effects of Exposure to organotin compounds .... Extraction method, solute

274 269 49 74 72 109 109 347 150 23 222 405 407 319

F FA (see Fulvic acid) Faecal excretion of mercury from rats 334 Fatty acids of lipids from Tetraselmis chui 125 Fatty tissue, mercury in 333,334 of rats 335 Fe(III) with fulvic acid, complexa tion of 377 Fe(III), rate of water loss from 377 Fick's First Law of Diffusion 361 First-order rate constant for formation of NHoCl from hypochlorous acid 282 First Law of Diffusion, Ficks 361 Flocculation 377 Formation constants for chloroelectrophiles 182 mercury (II) species in water 161 tin(IV) species in water 161 Fouling organisms 359 Fragmentation of cation-radical 220 Free -energy correlations for electrophilic reactions, linear 242 -energy relations 140 radical attack on the Co-C bond of methyl-Bi2 55 radicals, photochemical routes via .. 240

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

433

INDEX

Hexachloroiridate ( IV ) in acetonitrile, rates of reactions of dialkylplatinum ( II ) complexes with 224 cleavage of dialkylmercury by 221 electron transfer cleavage of organometals with ! 219 electron transfer oxidation of same 374 organomercurials with 207 373 rate constants for oxidation of 372 R PtL by 224 374 rates of oxidative cleavage of tetra374 alkylleads by 220 selectivities of oxidative cleavage of G tetraalkylleads by 220 Gas law, ideal 318 Hexamethyldisiloxane 151 GHocfodium roseum 108 Hg(II) in water, transmethylation Glutathione 341 between Sn(IV) and 160 Glycine 27 Glycylglycine 27 by Me Sn in natural waters, monochloramines of 266 mechanistic considerations of Gosio gas 1,39,105,390 several pathways for methylaGreenhouse environment, degradation tion of 177 of triphenyltin chloride on sugar species by Me Sn , reaction pathbeet leaves in a 403 ways for methylation of 173 Grignard reagents 216,237 three classes of behavior for rates or Group effects, cleaved and leaving .... 227 transmethylation between Group IVA organometals, bactericidal Me Sn and 170 effects of 409 HgCl from freshwater aquaria, transGrowth by Tetraselmis chui in instant formation of 40 ocean medium, large-scale 118 HgCl in protic solutions 165 HgCln, stgma-bonded pyridinomethvl H derivatives of transition metals by 174 HgR' (leaving group effects) 214 H abstraction 89 Highest occupied molecular orbital HA (see Humic acid) (HOMO) 211 H 0\ demethylation of ( C H ) C o L of alkyl radicals, ionization of 211 by 249 HOCl chlorination of amines and Half-fives for organotin compounds .. 403 monochloramines, second-order Hard acid character, trends in rate constants for 284 stability 138 HOCl reactions 281 Heavy metal(s) 14 with monochloramines, protonation pollution of natural waters, manand rate constants for 283 made 339 HOMO (see Highest occupied molecsynthesis 339 ular orbital) toxicology 339 30,339 transport 339 Homocysteine "inorganic" complexes of 344,346 He(I) photoelectron spectra of first methylation of 97 bands in series of organoB system for 35 mercurials 209 342 Heliothis zea 409 DL-Homocysteine complexes 378 Heme-iron-monooxygen complex 82 Homogeneous phase reactions Heterogeneous phase interactions 379 Homolytic bond cleavage 247 Heterogeneous reactions 130 cleavage of the Co-C bond 55 Heterolytic cleavage of the Co-C displacements in alkyl transfers 229 bond 55 Heterolytic reactions 241 Human exposure to organotin compounds 410 Hexachloroiridate, cleavage of dialkyl372 mercury (II) by 226 Humâtes

Freshwater aquaria, transformation of HgCl from Fulvic acid (FA) acidity value for complexation of Fe(III) with complexing capacity of conaitional stability constants for complexation of trace metals by elemental analysis of metal ion transport mediated by .... molecular weights of potentiometric titrations of 2

40 372 373 377 381

2

2

3

3

+

+

2

2

3

3

2

i 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

434

ORGANOMETALS AND

Humic acid (HA) 372 acidity value for 373 complexing capacity of 381 conditional stability constants for complexation of trace metals by 374 elemental analysis of 373 metal ion transport mediated by .... 372 molecular weights of 374 potentiometric titrations of 374 Hydrogen peroxide 295 on the oxidation competition value, Ω, effect of 306 Hydrogen sulfide 4 Hydrolysis 133 of chloramines, rate constants for .. 285 of C l , kinetics of 279 constants ...130,136 for univalent organometallic cations at 25° 13 of metal species 16 reactions 285 of water in coordination spheres of organometal ions 159 Hydrophobicity 314 Hydroxy species 172 ets-Hydroxycyclohexyltin isomer 83 irans-Hydroxyeyclohexyltin isomer .... 83 Hydroxyl-radical initiated oxidations of trace impurities in water 292 Hydroxylamine 285 Hydroxylation, carbon82 Hydrozines, organic 239 Hypochlorous acid,first-orderrate constant for formation of NH C1 from 282

Inhibitors of arsenate conversion to trimethylarsine 49 Inner-sphere alkylmetal intermediate 206 complex 375,377 mechanisms 206 Inorganic complexes of homocysteine 344,346 complexes in natural waters 172 compounds, removal of 413 electrolytes 167 oxy compounds, rate constants for reaction of methylcobalamin with 189 reduction of sulfite 29 tin, biomethylation of 404 Instant ocean medium, arsenic uptake by Tetraselmis chui in 118

2

2

I

Ideal gas law In vitro mechanisms for Bi -dependent methyl transfer mechanisms .... reactions of organotin compounds with monooxygenase enzymes .. transmethylations In vivo destannylation of tricyclohexyltin hydroxide kinetics methylation of metal ions Industrial disposal options for organotins Inert pair effect Inhibition of bacterial growth by diorganothallium compounds lead compound organolead compounds at various lead and nutrient concen trations

318

2

55 82 33 407 198 75 393 77

ORGANOMETALLOIDS

Interactions, heterogeneous phase 379 Ion(s) aquated organoelement 159 effects, specific 167 -exchange separation of Candida humicota extracts 110 hydrolysis of water in coordination spheres of organometal 159 -pair-like transition states 166 sigma-bonded organometallic 159 Ionic complexes, stability constants for formation of 330 Ionic strength effect on biomolecular rate 166 effect on rate of reaction 167 reaction rate, influence of 163 Ionization of HOMO of alkyl radicals 211 potentials 207 of alkyl radicals 216 calculated 211 experimental 211 of alkyl-substituted compounds .. 210 of binary mercury (II) deriva tives, first vertical 212 of dialkylmercury compound, correlation of cleaved-group constant and leaving group constant in acetolysis with .... 228 of dialkylmercury compounds, vertical 208 of organolead compounds 213 process in organometals 211 Isoelectronic Hg , methylations of 78 Isomer, cw-hydroxycyclohexyltin 83 Isomer, frans-hydroxycyclohexyltin .... 83 Isomerizations, corrin-ring 58 Isotope effect, kinetic 214,217 Itai-Itai disease 15 2+

69 67 70

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

INDEX

435

κ k based on the reaction pair model, estimation of k (obs) on [Cl~], statistical analysis of the dependence of kois ···· rate constants for monochloramine disproportionation K PtCl (potassium tetrachloroplatinate) -methylcobalamin reaction, data for 2

2

2

4

KoPtCle

178 174 273 286 194 194

191

-methylcobalamin reaction, kinetics plot of 192 K , determination of 268 DT

K KHYD,

273

H

confirmation of 270 K M D , determination of 26 Kinetic(s) data for methane evolution during the reactions of ( C H ) CoL .... 251 of disproportionation 271 in aqueous solution 264 of hydrolysis of C l 279 in vivo 198 isotope effect 214,217 parameters 179 plot of K PtCl methylcobalamin reaction 192 of the reactions of ( C H ) CoL with excess C d and Zn 255 salt effect, primary 167 3

2

2

2

e

3

2+

2

2 +

L

Lac de Bret by decomposition of ozone, elimination of benzene spiked to water of Lac de Bret, elimination of different types of solutes spiked into water of Lake Zurich water upon decomposi tion, elimination of trace impurities in Large-scale algal growth and arsenicprotein interactions Large-scale growth by Tetraselmis chui in instant ocean medium Leach tests, static Leaching continuous contact model for antifouling coatings process results for the tributyltin compounds

from soils of soil and decaying plants

305 306

Lead 16 binding preferences for 347 complexation by sulfhydryl-containing amino acids 339 compound, inhibition of bacterial growth by 67 demethylation of 351 -fulvic acid complex, absorption of 380 methylation of 42, 351 in lake sediments 42 organocompounds of 65 plant uptake of 16 Leaving group constant in acetolysis with ioniza tion potential of dialkylmercury compound, correlation of cleaved-group constant and 228 effects (HgR') 214,227 216 Lebistes reticulatus 407 Lewis acidity 341 Ligand(s) complexing 380 pre-equilibrium distribution of 160 stability constants of organometallic cations with organic ligands .... 142 stability with related 140 trans effect 132 Limiting law for activity coefficients, Debye-Hiickel 167 Linear energy relation, Stock and Brown 298 Linear free-energy correlations for electrophilic reactions 242 Lipid(s) Arsenic-containing characterization of 122 elemental analyses of 126 isolation of 122 solubility 139 of the monomethyltins 405 from Tetraselmis chui, fatty acids of 125

304 M

117

M, coenzyme (2-mercaptoethanesulfonic acid) 11 118 363 M.oH, synthesis of alkylarsine by whole cells of Methanobacterium strain 100 360 407 361 Mammalian toxicity 359 Man-made heavy metal pollution of 360 natural waters 339 Man-made organosilicon compounds .. 153 363,364 Marine algae, metabolism of arsenate 396 by 117 372 Me AsH (dimethylarsine) 45 2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS AND

436 Me Hg partitions 158 Me Pb (trimethyllead) 41 Me Pb (tetramethyllead) 41,72 in anaerobic bacterial culture, sources of 74 chemical and biological production of 71 by chemical disproportionation, production of 44 by methylation, production of 44 on Scenedesmus quadricauda, toxicity of 43 Me PbX 66 biomethylation of 71 Me Sn demethylation of 165 and Hg , three classes of behavior for rates or transmethylation between 17 in natural waters, mechanistic considerations of several pathways for methylation of 177 reaction pathways for methylation of H g species by 173 MeTP, methylation of 78 MeTlX , disproportionation of 77 MeTlX in solution, behavior of 76 Mean lifetime of a metal complex 382 Mechanistic pathways accompanying solvent changes 164 Mercaptalbumin-CH Hg complex .... 341 Mercapto bridges 346 2-Mercaptoethanesulfonic acid (Coenzyme M) .11,100 Mercuric salts, transfer of organo groups to 153 Mercury binding preferences for inorganic .. 347 biological degradation of organo derivatives of 16 in brain 328,334 in brain tissue 330 of rats 335 chloro species 177 complexation by sulfhydryl-containing amino acids 339 compounds, biological behavior of .. 327 compounds and thiols, complex formation between 327 in fatty tissue 333,334 of rats 335 methylation of 40 poisoning in humans, treatment of .. 327 from rats, urinary and faecal excretion of 334 reactant species, CHEMSPECIES determination of 168 -resistant bacteria 16 2

3

+

4

3

3

+

2+

2+

2

2

3

+

ORGANOMETALLOIDS

Mercury (continued) -sulfur interactions in thiol complexes 341 -tin crossover system 405,406 Mercury (II) derivatives, binary 212 first vertical ionization potentials 212 speciation of products in aqueous transmethylation between tin(IV) and 168 speciation of reactants in aqueous transmethylation between tin(IV) and 168 species in water, formation constants for 161 thiolate chemistry 327 Metabisulfite 29 of organotin compounds 405 of selenium compounds 10 of sulfur compounds in mold cultures 3 Metal(s) alkylation of 30,97 biomethylation of 158 -carbon bonds 30 reactions involving cleavage of .... 131 remain intact, reactions in which 133 complex, mean life time of 382 complexes, electron transfer process between 206 compounds, rate constants for oxidative reaction of methylcobalamin with 195 heavy 14 ion(s) available 16 buffer 382 buffering 172 concentration, second-order rate constants as a function of .... 257 in vivo methylation of 75 influence of environmental parameters on transmethylation between aquated 158 kinetic studies on B -dependent methyl transfer to toxic 54 mechanistic studies on B dependent methyl transfer to toxic 54 by methylcobalamin, mechanisms for methylation of 205 nonavailable 16 organosilanes as aquatic alkylators of 149 transport mediated by humic and fulvic acids 372 i2

i2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

INDEX

437

Metal(s) (continued) nucleophile 34 pollution, determination of total ... 14 in protic media, comparison of activation parameters for transmethylation between 165 in solis, toxic 14 species, hydrolysis of 169 toxicity or volatile alkyl 40 Metal (II) complexes 240 Metalloid(s) 23 alkylation of 30 biomethylation of 158 -carbon bond 30 nucleophile 34 toxicity of volatile alkyl 40 Metathetical demethylation 158,19 exchange 18 reaction of methylcobalamin organometals, rate constants for 189 Methane bacteria, characteristics of 95 bacteria, function of 94 biosynthesis 96,104 pathway for 100 role of CoM in 100 evolution 252 during reactions of (CH ) CoL, kinetic data for 251 for reactions of (CH ) CoL, rate of 253 with PB 256 study for reaction of (CH ) CoL with Cd 256 formation of 17 Methanethiol 4 Methane-bacterium 5,8,49

Methyl (continued) -Bi2

^base-oflT 55 "base-on" 55 complex, P t " C l 60 electrophilic attack on Co-C bond of 55 free radical attack on Co-C bond of 55 redox switch mechanism for attack on Co-C bond of 58 reductive Co-C bond cleavage of 59 carbonium ion transfer 197 -chlorine exchange 195 -cobalt bond 56,196 -ethyllead compounds, acetolysis of 217 -ethyllead derivatives 219 2

4

, transfer carbanion 55,56 cofactor 11 mechanisms, in vitro mechanisms for B -dependent 55 to toxic metal ions, kinetic and mechanistic studies on B i dependent 54 Methylamine, monochloramines of .... 266 Methylarsenic acids, analysis of 40 Methylarsines, analysis of 40 Methylated compounds of arsenic, natural occurrence of 17 N-Methylated compounds 76 Methylating agents, biological 351 Methylation(s) of arsenic 45, 351 aerobic 105 compounds in Moira River area omelianskii 96 sediment 47 strain M.oH 96 compounds by pure bacteria 48 synthesis of alkylarsine by whole biological 1,390 cells of 100 of alkyl acid 3 Methanogenic bacteria 94,105 of arsenate 2 role of 104 of arsenic compounds 116 Methanol in arsenical liquid cultures of arsenite 2 of Scopuforiopsis brevicaulis 7 of dialkylarsonic acid 3 Methanosarcina barkerii 96 of elements in the environment, Methionine 6,30,108 occurrence of 39 active 6 mechanism of 4 biosynthetic pathways 97 under biological conditions, rates of 198 of Hg by Me Sn in natural methyl JL09 role of B in synthesis of 31 waters, mechanistic considerasynthetase system, B -ENZ tions of several pathways for .. 177 binding in 31 of Hg species by Me Sn , reaction Methyl pathways for 173 of homocysteine 97 alkyls for algal toxicity testing, B system for 35 biological generation of volatile 44 3

3

i2

2

2

2

2+

3

2

2+

2+

+

3

i2

i2

2+

+

3

i2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ORGANOMETALS

438 Methylation ( s ) ( continued ) of isoelectronic H g 78 of lead 41,351 in lake sediments 42 of MeTl 78 of mercury 40 of metal ions, in vivo 75 of metal ions by methylcobalamin, mechanisms for 205 by natural organisms 198 oxidative 75 production of Me Pb by 44 for selected elements, relationship between reduction potential and mechanism of 57 selective 4 of selenate 3 of selenite 3 of selenium 7,4 compounds in Sudbury are sediment 46 successive 193 of tellurite 3 Methylcobalamin .73,96,116,205,235,342 demethylation of 188 with inorganic oxy compounds, rate constants for reaction of 189 - K P t C l reaction, data for 194 mechanisms for methylation of metal ions by 205 with metal compounds, rate con stants for oxidative reaction of 195 -methylmercuric salt reaction, effect of anion on reaction rate con stant for 190 with organometals, rate constants for metathetical reaction of ... 189 oxidative reaction with 195 rate constants for successive reac tions with 191 reaction of K PtCl 194 Methylcobaloxime 240 Methylcorrinoid (vitamin B ) derivatives 205 Methylelement species, elimination of toxic 158 Methyllead 339 Methylmercuric salt-methylcobalamin reaction, effect of anion on reac tion rate constant for 190 Methylmercury (CH Hg ) 339 cation 298 chloride 298, 308 hydroxide 293,298,308 mineralization of 303,306 mineralization 309 Methylmercury (II) poisoning 328 2+

2+

4

2

4

2

4

i2

3

+

A N D ORGANOMETALLOIDS

Methylmetal donors, reduction of demethylation rates of 168 Methylselenides, analysis of 40 Methylthallium compounds, redistri bution reactions of 66 Methylthallium diacetate 191 2- ( Methylthio ) -ethane sulfonic acid .. 100 Methyltin chloro species 177 Methyltin reactant species, C H E M SPECIES determinations of 168 Methyltransferase 31 Meyer reaction 109 Microorganisms, aqueous chemistry of organolead and organothallium compounds in presence of 65 Micropollutants in water, oxidation competition values for elimina tion of 304 Mineralization of methylmercury hydroxide 303,306 Mobilization of trace metals 380 Moira River area sediment, methylations of arsenic compounds in 47 Mold cultures, metabolism of sulfur compounds in 3 Molecular weights of humic and fulvic acids 374 Monoalkyllead 43 -d [ Monochloramine] /dt = k i [ monochloramine ] [ H-monochloramine ], rate constants for disproportionation from 276 Monochloramine(s) (NH C1) 274,278 of β-alanine 266 of ammonia 266 disproportionation ( k ) , rate constants for 286 toward equilibrium, approach of mixture of N H , β-alanine, and their 274 formation in chlorination reactions .. 281 of glycylglycine 266 of methylamine 266 protonation constants 276 for HOCl reaction with 283 rate constants for HOCl reaction with 283 reactions of 283 second-order rate constants for HOCl chlorination of 284 solutions 266 Monomethylbismuth ( IV ) compounds 193 Monomethyllead(IV) compounds 193 Monomethylthallium compounds 76 Monomethyltins, lipid solubility of .... 405 D

S

+

2

DiS

3

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

439

INDEX

Mononuclear complexes Monooxygenase enzyme(s) in vitro reactions of organotin compounds with reactions of cyclohexyltin com pounds, bioorganotin chem istry: stereoselectivity and situselectivity in reactions, cytochrome P-450 Multiregression analysis program Ν

66 82

82 87 175

Nucleophilic attack resistance of organometallic ions to pathways via cobalt(I) reagents

+

2+

Occupational exposure to triphenyltin acetate, adverse effects produced by 410,411 Octanol/water/air systems, partition of organoelements in 314 n-Octanol/water partition coefficient 317,320 n-Octanol/water system, partition

3

3

2

+

3

3

133 240 399

Ο

N -Methyltetrahydrofolate-homocysteine cobalamin methyltransferase (ENZ) 31 NAD (nicotinamide adenine dinucleotide) .....25,32 National Pollution Discharge Elimina tion System (NPDES) 39 consumption, rate of Natural organisms, methylation by .... 198 radical(s) Natural waters 380 reactions inorganic complexes in 172 oxidations initiated by man-made heavy metal pollution of 339 reaction rate constants of mechanistic considerations of sev trapping eral pathways for methylation of Hg by Me Sn* in 177 Organic hydrazines v. NC1 (trichloramine) 278 trace impurities in water, ozone Neighboring group effect 241 initiated, and hydroxyl-radical Neurospora Crassa 339 initiated oxidations of Neutral complexes, stability constants -water partition coefficient for formation of 330 Neutralization, charge 374 Organisms, fouling Neutron activation analyses 396 Organisms, methylation by natural .... Organo group(s) N H C I 2 (dichloramine) 278 acceptors in aqueous and non NH C1 (monochloramine) 278 aqueous media Cl transfer reactions of 289 donor, silicon as from hypochlorous acid, first-order to mercuric salts, transfer of rate constant for 282 transfer reactions N H , β-alanine, and their monochlor transfer from silicon amines toward equilibrium, approach of mixture of 274 Organo derivatives of mercury, biological degradation of NH C1 to amino acids and peptides, Organochromium compounds rate constants for direct transfer of chlorine from 287 Organocobalt compounds dealkylation reactions of Nicotinamide adenine dinucleotide (NAD ) 25,32 Organocobalt (III) complexes Organocompounds of lead Nitrosoisobutane, spin-trapping experiments with 221 Organoelement ions, aquated Organoelements in octanol/water/air Non-aqueous media, organo group systems, partition of acceptors in 151 Nonavailable metal ions 16 Organofluorosilicates Nonmetals 23 Organoiron compounds Organolead compounds NPDES (National Pollution Dis biomethylation of charge Elimination System ) 393 bridging in Nucleophiles, metal and metalloid 34 4-coordinate Nucleophiles, organometallic 219 5

247

+

+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

300 293 293 299 301 89 239 292 314 359 198 151 150 153 150 150 16 235 235 247 229 65 159 314 151 235 68 66 215

440

ORGANOMETALS AND

Organolead compounds (continued) ionization potentials of oxidation potentials of in presence of microorganisms, aqueous chemistry of removal of toxicity of at various lead and nutrient concentrations, inhibition of bacterial growth by in water, decomposition of Organomercurials direct reactions of ozone with He(I) photoelectron spectra of first bands in series of with hexachloroiridate (IV), electron transfer oxidation of same Organomercury derivatives of B A L H Organometals bactericidal effects of group IV biogenesis of compounds as electron donors electrophilic cleavage of with hexachloroiridate (IV), electron transfer cleavage of ionization process in ions, hydrolysis of water in coordination spheres of mechanisms for alkyl transfers in .... rate constants for metathetical reaction of methylcobalamin with Organometallic cations in aqueous media, chemistry of .... in aqueous solution, complexation with organic ligands, stability constants of at 25°, hydrolysis constants for univalent complexes, sigma-bonded compound formation of intermediates in protic medium, unstable ions to nucleophilic attack, resistance of ions, sigma-bonaea nucleophiles toxicants trace impurities in water, hydroxylradical initiated oxidations of .. trace impurities in water, ozone initiated oxidations of Organometalloidal compounds, biosynthesis of

213 213 65 413 67 70 65 299 299 209 207 330 162 314 207 214 219 211 159 205 189 130 130 138 142 134 235 390 39 247 133 159 219 361 292 292 1

ORGANOMETALLOIDS

Organometalloids, formation of Organoselenium compound, volatile .. Organosilanes as aquatic alkylators of metal ions Organosilicon compounds environmental significance of man-made toxic Organothallium compounds in presence of microorganisms, aqueous chemistry of Organothallium compounds, toxicity of Organotin(s) antifoulants biological degradation of biological effects of exposure on .... in biology

39 45 149 149 153 153 150 65 67 359 402 405 388

chemical degradation of 399 chemicals, consumption of commercial 395 chlorides 191 compounds 295 exposure to 407 half-lives for 403 human exposure to 410 metabolism of 405 with monooxygenase enzymes, in vitro reactions of 82 parameters for Alum-A-Tox coatings containing 367 rate constants for 403 toxicity of 407 transfer behavior of 396 consumer disposal options for 393 in the environment 388,391 environmental fate of 399 final disposal of 393 industrial disposal options for 393 literature 389 production of 391 regulation of 411 released to the environment 397 as stabilizers 393 toxicants from coating surfaces, release mechanisms of 359 use of 391 Outer-sphere complex 375 Outer-sphere mechanisms 206 Oxidation of alkyl radicals, electron transfer .. 223 anodic 213 of tetraalkyllead compounds 213 arsenite 27 of benzene, ozone to be decomposed per 305

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

441

INDEX

Oxidation (continued) competition value ( Qm ) 300,309 effect of hydrogen peroxide on .... 306 for elimination of micropollutants in water 304 initiated by O H radical reactions .... 299 of organic trace impurities in water, ozone initiated 292 of same organomercurials with hexachloroiridate ( IV ), electron transfer 207 of organometallic trace impurities in water, hydroxyl-radical initiated 292 of organometallic trace impurities in water, ozone initiated 292 potentials of organolead compounds ^13 in the presence of different chloride ion concentrations, benzen of R PtL by hexachloroiridate(IV), rate constants for 224 reactions, biochemical 23 -reduction, alkylcobalt complexes undergoing 231 -reduction reactions 54 Oxidative cleavage of tetraalkylleads by hexa chloroiridate (IV), selectivities and rates of 220 methylation 75 phosphorylation chain, cytochromelinked 26 reaction with methylcobalamin 195 with metal compounds, rate con stants for 195 Oxo-species 172 Oxybase equation, Edwards 219 Oxygen insertions 24 Ozonation 292,299 Ozone to be decomposed per oxidation of benzene 305 decomposition of 293,299 in different types of water, halflife of 294 elimination of benzene spiked to water of Lac de Bret by com position of 305 initiated oxidations of organic trace initiated oxidations of organometal lic trace impurities in water .... 292 with organomercurials, direct reac tions of 299 with solutes, direct reactions of 295 in water 297 in water, reactions initiated by 294 impurities in water 292 2

2

Ρ P-450 cytochrome system 27 monooxygenase enzyme reactions, cytochrome 87 monooxygenase enzyme system 83 Paint, antifouling 359 Pair-wise rate constants, best linear fit for k (obs) vs. [Cl"] by six independent 176 PAPS ( 3'-phosphoadenosine-5'-phosphosulfate) 29,32 PAPS-reductase 29 Parameters, kinetics 179 Partition coefficients) 158 determination of 158 2

mercury 321 n-octanol/air 320 n-octanol/water 317 in n-octanol/water system 314 organic/water 314 in sea water, dimethylmercury .... 321 water/air 317 Me Hg 158 of organoelements in octanol/ water/air systems 314 Pathway for methane biosynthesis 100 Pb ( II )-penicillamine complex 351 Pb biomethylation of 68, 70 rate of methane evolution for reac tion of ( C H ) C o L with 256 reactions with excess 248 significance of biomethylation of .... 78 Pénicillium brevicaulis 2 chrysogenum 3 notatum 105 Peptides, rate constants for direct transfer of chlorine from NH C1* to amino acids and 287 Perturbation difference spectroscopy, Raman 146 pH, species distribution as function of 137 PhHg(II) complexes of sulfur-containing amino acids 332 Phenyl-i-butylnitrone, spin-trapping experiments with 221 Phenylmercury 334 Phenylmercury(II) thiolates, decomposition of 332 Phosphate 49 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) 29,32 2

2+

3

2

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

3

442

ORGANOMETALS AND

Phospholipid fraction chromatographic isolation of arsenic-containing isolation from Tetraselmis chui, chromatographic separation of arsenic compounds in isolation from Tetraselmis chui, direction of arsenic compounds in Photochemical routes via free radicals Photoelectron spectra of first bands in series of organomercurials, He(I ) Pigments, arsenic Plant uptake of lead Plastics, polyvinyl chloride (PVC) .... Plug-type reactor Poisoning, arsenical Pollution of natural waters, man-made heavy metal Polyvinyl chloride (PVC) plastics Positive methyl group Potassium tetrachloroplatinate (K PtCl ) Potentiometric titrations of HA and FA Pseudonutrients phosphorus nutrient sulfur nutrient Pre-equilibrium distribution of ligands Preferential cleavage Primary kinetic salt effect Protic media comparison of activation parameters for transmethylation between metals in pathways for formation of transition metal-carbon bonds in unstable organometallic intermediates in Protic solutions, HgCl in Proto-demercuration Proton transfer from coordinated solvent Protonation constants for HOCl reaction with monochloroamines Protonation constants of monochloramines Protonolysis of alkyl-mercury bond, rate constant for electrophilic of alkylmercury iodides in aqueous perchloric acid of alkylmercury iodides in sulfuric acid of dialkylmercury in acetic acid solutions compounds, electrophilic 2

4

2

123

Protonolysis (continued) of dialkylmercury (continued) generalized equation for of dialkylmercury(II) compounds .. Pt Cl -methyl-Bi complex PVC (polyvinyl chloride) plastics Pyridino-methyl derivatives of transition metals by HgCl„ and T1C1„, sigrafl-bonded Pyrophosphatase n

124 124 240 209 39 16 391 296 39 33 391 5

374 23 23 23 160 222 167

4

2

2

218 131 58 60 391 174 28

R

R (cleaved group effects)

216

R-ML.5 complexes

235

rate constants for oxidation of .... R PtL , fate of Radical mechanism, two-step scavengers -type reaction Raillietina cesticillus Raman perturbation difference spectra for CH Hg( II)-pyridine system Raman perturbation difference spectroscopy Rate constant(s) best linear fit for k (obs) vs. [Cl"] by six independent pair-wise .. for chlorination of amines, secondorder for chlorination of amines and amino acids, second-order for direct transfer of chlorine from NH C1 to amino acids and peptides for disproportionation from -d[monoehloramine]/dt = k D is [monochloramine] [Hmonochloramine*] for electrophilic protonolysis of alkyl-mercury bond for formation of NH C1 from hypochlorous acid, first-order as function of metal ion concentration, second-order for HOCl chlorination of amines and monochloramines, secondorder from HOCl reaction with monochloramines for hydrolysis of chloramines

224 225

2

194

ORGANOMETALLOIDS

2

+

238 296 307 407

3

145 146

2

165 235 247 165 214 133 283 276

3

176 284 280

+

287

276 227

2

227 217 217 214 207

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

282 257 284 283 285

443

INDEX

Rate constant ( s ) ( continued ) for metathetical reaction of methylcobalamin with organometals .. 189 for monochloramine disproportionation (k ) 286 for O H ' radical reactions, reaction .. 301 for organotin compounds 402 for oxidation of R PtL2 by hexachloroiridate (IV) 224 for oxidative reaction of methylcobalamin with metal compounds 195 for reaction of Cr [15]ane N with alkyl halides 238 for reaction of methylcobalamin with inorganic oxy compounds 189 for successive reactions with methylcobalamin 191 Rate law, biomolecular 16 Rats faecal excretion from 334 mercury in brain tissue of 335 mercury in fatty tissue of 335 urinary excretion from 334 Reaction(s) of ( C H ) CoL, overall 253 ofCl 279 of dichloramines 287 direct 293 effect of ionic strength on rate of .... 167 with excess Cd 248 (CH ) CoL 252 Pb 248 Zn 248 of HOCl 281 hydrolysis 285 initiated by ozone in water 294 involving cleavage of metal-carbon bonds 131 in which metal-carbon bonds remain intact 133 with methylcobalamin, rate constants for successive 191 OH- radical 293 pair model, estimation of k based on 17 pathways for methylation of H g species by Me Sn 173 radical-type 307 rate constant for methylmercuric saltmethylcobalamin reaction, effect of anion on 190 constants of OH* radical reactions 301 influence of ionic strength on 163 influence of salinity on 163 successive 191 DIS

2

n

3

4

2 +

2

2

2+

3

2

Reactor, batch-type 296 Reactor, plug-type 296 Redistribution reactions of methylthallium compounds 66 Redox conditions 55 in a specific environment 54 demethylation 197 switch mechanism 55,197 for attack on Co-C bond of methyl 58 Reduction of arsenate 29 of demethylation rates of methylmetal donors 168 potentials, standard 272 of sulfate 28 of sulfite, inorganic 29 methyl-B Reductive demethylation Regression, correlation matrix for Regulation of organotins Related ligands, stability with Release mechanisms of organotin toxicants from coating surfaces .. Residual chlorine for breakpoint chlorination, relationship between chlorine dosage and Respiration chains, evolution of Respiratory processes, involvement of arsenic in Repulsions, coulombic

59 158 175 411 140 359 282 23 27 168

2+

2+

2

2+

3

+

S

S-adenosylmethionine (SAM) SAM (S-adenosylmethionine)

6,8,31, 34,35,108 6,8,31, 34,35,108

Salinity on biomolecular rate, effects of 166 Salinity on reaction rate influence of .. 163 Salt effect, primary kinetic 167 Saturated energy effects 216 "Saturation" effect 218 Saturation pattern for alkyl groups .... 218 Scenedesmus quadricauda, toxicity of Me Pb on 43 Schizophyllum commune 4 Scopulariopsis brevicaulis 2,45,105 methanol in arsenical liquid cultures of 7 S 2-type mechanism 33 Sea water, dimethylmercury partition coefficients in 321 Second-order law 160 4

E

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

444

ORGANOMETALS AND

Second-order rate constants for chlorination of amines 284 and amino acids 280 as a function of metal ion concen tration 257 for HOCl chlorination of amines and monochloramines 284 Sediment-lake water system 40 Selective methylation 4 Selenate 49 methylation of 3 Selenite 36 methylation of 3,7,43 Selenium 1,34,39 amino acids containing 11 compound(s) metabolism of 10 production of 4 in Sudbury area lake sediment methylation of 46 volatile 43 Selenomethionine ., 11 Sewage sludge 102 Stgma-bonded organometallic complexes 235 organometallic ions 159 pyridino-methyl derivatives of tran sition metals by HgCl T1C1„ .. 174 Silicate bacteria 150 Silicon demethylation of 152 distribution 149 and evolutionary development 150 occurrence 149 as an organo group donor 150 organo group transfer from 150 role of 150 Silicones, applications of 154 Situselectivity in the monooxygenase enzyme reactions of cyclohexyltin compounds, bioorganotin chemistry 82 Sludge, transformation of arsenic in .... 103 S 2 mechanisms 34 Sn(II)-CH B reaction 197 Sn(IV) and Hg(II) in water, trans methylation between 160 Sodium cacodylate 2 2,2-dimethyl-2-silapentane-5-sulfonate(DSS) 152 methylarsenate 2 3-trimethylsilypropionate-d (TSP) 152 Soft acid character, trends in stability 138 Soil, leaching 372,396 Solubility, lipid 139

Solute absorption method extraction method spiked into water of Lac de Bret, elimination of different types of Solvent changes, mechanistic path ways accompanying Solvent systems, T L C Speciation, chemical Species distribution as function of pH Specific ion effects Spin-trapping experiments with nitrosoisobutane and phenyl-f-butylnitrone Stability with biomolecules constants for C H H g

n

N

3

12

4

ORGANOMETALLOEDS

318 319 306 164 84 380 137 167 221 140 130 141

acids 144 for complexation of trace metals by humic and fulvic acids, conditional 374 conditional 376 for ethylenediamine complexes .. 347 for formation of ionic complexes .. 330 for formation of neutral complexes 330 of organometallic cations with organic ligands 142 hard acid character, trends in 138 with related ligands 140 soft acid character, trends in 138 Stabilizers, organotins as 393 Standard reduction potential ( E ° ) ...57,272 and mechanism of methylation for selected elements, relationship between 57 Static leach tests 363 Stereoselectivity in monooxygenase enzyme reactions of cyclohexyltin compounds, bioorganotin chemistry 82 Steric ( E ) constants, correlation of parameters with Taft polar ( σ * ) and 227 Stock and Brown linear energy relation 298 Streptococcus lortis 409 Successive reactions 191 with methylcobalamin, rate con stants for 191 Successive methylation 193 Sudbury area lake sediment, methyla tion of selenium compounds in .... 46 Sugar beet leaves in a greenhouse environment, degradation of tri phenyltin chloride on 403 8

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

445

INDEX

Sulfate-reducing bacteria (Desulfovibrio) Sulfate, reduction of Sulfhydryl-containing amino acids cadmium complexation by lead complexation by mercury complexation by Sulfide oxidase . Sulfite, inorganic reduction of Sulfokinase Sulfur biotransformation of compounds in mold cultures, metabolism of -containing amino acids, PhHg(II) complexes of Surface adsorption Synthesis of alkylarsine by whole cells o Methane-bacterium strain M.oH dimethylarsine heavy metal of methionine, role of B in J 2

30 28 339 339 339 26 29 29 23 3 332 322

100 99 339 31

Τ Taft polar ( σ * ) and steric (E ) con stants, correlation of parameters with 227 Taft relationship 208 Tartar emetic 9 Taurine 13 TeTlX , decomposition of 76 Tellurate 49 Tellurite 36 methylation of 3 Tellurium 1,34,39 Temperature(s) partition coefficients at different 319 transmethylation, effects of 162,163 variation method 320 Tetraalkyllead compounds 212,219 anodic oxidation of 213 electron detachment from 213 by hexachloroiridate (IV), selectivities and rates of oxidative cleavage of 220 Tetraalkyltins 160 Tetrachloroethylene 306 Tetraethyltin 405 Tetrahydrofolic acid 32 Tetramethylene dicobalamin 241 Tetramethyllead (Me Pb) 41 Tetraselmis chui arsenic uptake and metabolism by alga 116 8

2

4

Tetraselmis chui (continued) chromatographic separation of arsenic compounds in phospho lipid fraction isolation from detection of arsenic compounds in phospholipid fraction isolation from fatty acids of lipids from in instant ocean medium, arsenic uptake and large-scale growth by.. Thin-layer chromatography Thiobacillus(i) respiration in thiooxidans thioparus Thiol complexes formation between mercury com

124 124 125

118

8 25 25 26 26 327

341 Thiolates Hg(SR) , crystal structures of simple 328 Thiosulfate 29 reductase 26 Tin 388 biomethylation of inorganic 404 chemistry 388 crossover system, mercury405,406 Tin (IV) and mercury (II), speciation of reactants and products in aqueous transmethylation between 168 Tin (IV) species in water, formation constants for 161 Tineola bisselliell 409 Tl\ biomethylation of 73 Tl\ significance of biomethylation of .. 78 TlCln, sigma-bonded pyridinomethyl derivatives of transition metals by 174 T L C cochromatography and solvent systems 84 Toluene 306 Toxic metal ions, kinetic and mechanistic studies on Bi -dependent methyl-transfer to 54 metals in soils 14 methylelement species, elimination 158 organosilicon compounds 150 Toxicants, organometallic 361 Toxicity of chloramines 279 to aquatic life 264 mammaliam 407 of Me Pb on Scenedesmus quadricauda 43 of organolead and organothallium compounds 67 2

2

4

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

446

ORGANOMETALS A N D ORGANOMETALLOIDS

Toxicity (continued) of organotin compounds 407 testing, biological generation of volatile methyl alkyls for algal 44 of volatile alkyl metals and metalloids 40 Toxicology, heavy metal 339 Trace impurities in Lake Zurich water upon decomposition of, élimination of 304 Trace metal(s) and chelating agents, interactions between 372 concentrations, predicted total by humic and fulvic acids, conditional stability constants for complexation of 374 mobilization of 38 transport 379,38 Trans effect(s) 132 ligand 132 Transalkylation 66 Transfer behavior of organotin compounds .. 396 of organogroups to mercuric salts .. 153 reactions of NH C1, CP 289 reactions, organo group 150 Transformation of arsenic in sludge .. 103 Transformation of HgCl from freshwater aquaria 40 Transition metal ( s ) -carbon bonds in protic media, pathways for formation of 235 by HgCl , sigwui-bonded pyridinomethyl derivatives of 174 by TlCln, sigma-bonded pyridinomethyl derivatives of 174 Transition states, ion-pair-like 166 Transmetallation 205 Transmethylation ( s ) between aquated metal ions, influence of environmental parameters on 158 between Me Sn and Hg *, three classes of behavior for rates of 170 between metals in protic media, comparison of activation parameters for 165 between Sn(IV) and HG(II) in water 160 between tin(IV) and mercury(II), speciation of reactants and products in 168 effects of temperature on 162,163 in vitro 33 reaction, changes in pH for typical 171

Transport 381 in the environment 396 heavy metal 339 of trace metals 379,380 Trialkyltin compounds 396 Tributyltin chloride 90 Tributyltin compounds 407 leaching results for 364 Trichloramine (NC1 ) 278 Tricyclohexyltin hydroxide 409 in vivo destannylation of 407 Triethyitin acetate 410 Trimethylarsine 2,39,45,105,108,116 atmospheric oxidation of 9 inhibitors of arsenate conversion to 49 oxide 10 Trimethyllead (Me Pb ) 41 Triphenyltin

2

3

chloride 90 on sugar beet leaves in a greenhouse environment, degradation of 403 derivatives 409 TSP (sodium 3-trimethylsilypropionate-d ) 152 Two-step radical mechanism 238 4

U

2

n

3

+

2

+

3

Ubiquinones ( coenzyme Q ) 25 Univalent organometallic cations at 25°, hydrolysis constants for 134 Unstable organometallic intermediates in protic medium 247 Urinary excretion of mercury from rats 334

V Vertical ionization potentials of dialkylmercury compounds Vitamin B ( methyIcorrinoid ) derivatives Volatile alkylarsine compounds 12

208 205 99

W Waste treatment, water and 413 Water -air partition coefficient 317 in coordination spheres of organometal ions, hydrolysis of 159 upon decomposition of, elimination of trace impurities in Lake Zurich 304

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

INDEX

447

Water (continued) dimethylmercury partition coeffi cients in distilled and sea direct reactions of ozone with solutes in formation constants for mercury(II) and tin (IV) species in halflife of ozone in different types of hydroxyl-radical initiated oxidations of organometallic and organic trace impurities in inorganic complexes in natural of Lac de Bret by decomposition of ozone, elimination of benzene spiked to of Lac de Bret, elimination of differ ent types of solutes spiked into loss from Fe(III), rate of loss values, characteristic man-made heavy metal pollution of natural as means of disinfection, chlorina tion of

321

Water (continued) mechanistic considerations of several pathways for methyla tion of Hg by Me Sn* in natural natural oxidation competition values for the elimination of micropollutants in ozone initiated oxidations of organic and organometallic trace impurities in plant samples reactions initiated by ozone in transmethylation between Sn(IV) andHg(II)in treatment, formation of N-chloro compounds in 2+

297 161 294 292 172 305 306 37 37 339

177 380 304 292 399 294 160 278

Ζ Zn , reaction of ( C H ) C o L with Zn , reactions with excess 2+

264

3

3

2

2+

In Organometals and Organometalloids; Brinckman, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

258 248