High performance mass spectrometry: Chemical applications

High Performance Mass Spectrometry: Chemical Applications Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.fw001

Michael L. Gross, EDITOR University of Nebraska

A symposium co-sponsored by the University of Nebraska—Lincoln, the National Science Foundation, ΑΕΙ Scientific, and INCOS Corp., Lincoln, November 3-5, 1976.

ACS

SYMPOSIUM

SERIES

AMERICAN CHEMICAL SOCIETY

WASHINGTON, D. C.

1978

70

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.fw001

Library of Congress Data Main entry under title: High performance mass spectrometry. (ACS symposium series; 70 ISSN 0097-6156) Includes bibliographies and index. 1. Mass spectrometry—Congresses. I. Gross, Michael L. II. University of Nebraska— Lincoln. III. Series: American Chemical Society. ACS symposium series; 70. QD96.M3H53 543'.085 78-789 ISBN 0-8412-0422-5 ASCMC8 70 1-358 1978

Copyright © 1978 American Chemical Society All Rights Reserved. The appearance of the code at the bottom of thefirstpage 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 a n d / o rnamesof 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, reproduce, use, or sell any patented invention or copyrighted work that may in any way be related thereto. PRINTED IN THE UNITED STATES OF AMERICA

ACS Symposium Series

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.fw001

Robert F . G o u l d , Editor

Advisory Board Kenneth B. Bischoff

Nina I. McClelland

Donald G. Crosby

John B. Pfeiffer

Jeremiah P. Freeman

Joseph V. Rodricks

E. Desmond Goddard

F. Sherwood Rowland

Jack Halpern

Alan C. Sartorelli

Robert A. Hofstader

Raymond B. Seymour

James P. Lodge

Roy L. Whistler

John L. Margrave

Aaron Wold

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.fw001

FOREWORD The ACS S Y M P O S I U M S E R I E S was founded in 1974 to provide a medium for publishing symposia quickly in book form. The format of the S E R I E S parallels that of the continuing A D V A N C E S I N C H E M I S T R Y S E R I E S except that in order to save time the papers are not typeset but are reproduced as they are submitted by the authors in camera-ready form. As a further means of saving time, the papers are not edited or reviewed except by the symposium chairman, who becomes editor of the book. Papers published in the ACS S Y M P O S I U M S E R I E S are original contributions not published elsewhere in whole or major part and include reports of research as well as reviews since symposia may embrace both types of presentation.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.pr001

PREFACE A4Tass spectrometry has emerged as a mature scientific discipline in chemistry. Investigators no longer are limited to slow scans at low resolution of volatile samples ionized by electron impact. In recent years, a number of significant developments have occurred that are considered examples of "High Performance Mass SpectrometryThese include chemical and field ionization, ultra-high resolution, new methods of defocused metastable scans, collisional activation spectrometry, field ionization kinetics, and new techniques in gas chromatography/mass spectrometry and sample introduction. To provide a forum for discussing the chemical applications of these techniques, a symposium was held by the Department of Chemistry, University of Nebraska, Lincoln, Nebraska, Nov. 3-5, 1976. The papers presented at that symposium have been updated during the past year (1977) and are collected in this volume. The primary objective of this volume is to survey current research in high performance mass spectrometry. Solution to problems in chemical analysis is one major theme. Complete identification and quantitation of trace amounts of materials in biological and environmental systems requires many of the methods of high performance mass spectrometry: GC/MS, exact mass measurements, and improved methods of sample vaporization and ionization. Another emphasis is the determination of structure and properties of gas-phase ions. This research is important in understanding the intrinsic properties of these species in the absence of solvent. Moreover, a thorough understanding of the mechanism of mass spectral fragmentations must rely on these fundamental studies. Accordingly, the volume has been divided into two sections. The first includes chapters describing methods for acquiring metastable ion data that relate to stable and low-energy decomposing ions and the application of these methods for determining ion structures, properties, and potential energy surfaces. By way of contrast, the capability to investigate extremely rapid ionic reactions using field ionization kinetics is described. The second section is a survey of analytical applications that can be explored with high performance mass spectrometry. General applications on qualitative and quantitative analyses using high resolution with vii

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.pr001

direct inlet and G L C methods of sample introduction are described. Furthermore, selective methods of chemical ionization and the development of simultaneous recording of positive and negative ion chemical ionization are also reviewed. The application of mass spectrometry to important problems in biochemistry and pharmaceutical chemistry are discussed in four of the chapters. In particular, methods of obtaining specificity in biological assays and the use of field desorption and an alternative to field desorption for handling nonvolatile materials are covered. Petroleum and solid state analysis and the use of ultra-high resolution, metastable methods, and spark source ionization are discussed for the analysis of complex mixtures in three chapters. The last two chapters are illustrative of two of the methods currently used in computer-assisted spectral interpretation. They are included because high performance techniques in mass spectrometry can produce tremendous quantities of data that place onerous interpretation demands on the user. This volume and the original symposium are intended to introduce the various aspects of high performance mass spectrometry and to provide a review of the current state of knowledge. Our hope is that the book will be useful to scientists with a modest background in mass spectrometry who wish to make use of the technique in their own research and to the expert who is interested in a critical review. At the opening remarks session of the symposium, G. G. Meisels, Chairman of the Chemistry Department at the University of Nebraska, offered an alternate definition of high performance mass spectrometry. He said that high performance mass spectrometry is a branch of research practiced by high performance scientists. Indeed, this volume is a collection of papers by many of the "highest performance mass spectroscopists at work today. I must acknowledge their cooperation in assembling this book. Moreover, I wish to thank Jan Deshayes for assisting in the organization of the symposium and overseeing the typing of the majority of manuscripts. The manuscripts were typed and assembled by Kathy Steen, Velaine Zbytniuk, and Sharon Coufal. Many of the conference details were handled by my graduate students: David Russell, David Hilker, and Stan Wojinski. I am also indebted to these persons for their efforts. F. H. Field and T. L. Isenhour presented plenary lectures at the symposium, but the press of other duties did not allow them to contribute to this volume. However, I am indebted to them for their participation. ,,

viii

Finally, the symposium was made possible because of generous support from the National Science Foundation, the University of Nebraska Research Council, Kratos-AEI Scientific Apparatus, and the INCOS Corp. Their contributions are gratefully acknowledged.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.pr001

University of Nebraska MICHAEL L. GROSS Lincoln, Nebraska December 30, 1977

ix

1 Observation of Metastable Transitions in a High Performance Mass Spectrometer K. R. JENNINGS

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

Department of Molecular Sciences, University of Warwick, Coventry, United Kingdom

A metastable transition is the unimolecular or collision induced decomposition of an ion after leaving the source exit s l i t and before reaching the collector of a mass spectrometer. The daughter ions produced in these decompositions give rise to metastable peaks in mass spectra produced in a magnetic deflection instrument. During the past ten years, various methods of observing metastable transitions in high performance double focussing instruments of various geometries have been introduced (1,2,3,4). This article aims to give a comparative account of these methods together with illustrations of the use of some of them in the author's laboratory. No single method has established i t s e l f as ideal for a l l applications, and before considering the methods in detail, one must be clear what information is required or may be obtained from a study of metastable transitions. If one is concerned with obtaining detailed information about the potential energy surface over which a particular decomposition occurs, the method must be capable of yielding information on peak shapes, and if possible, the energy resolution should be high enough to reveal any structure in the peak. On the other hand, if one's prime aim is to establish whether or not there is a metastable peak arising from the process m ->m or alternatively to assign as precisely as possible the mass of either m or m when one of them is known, a method which produces a very narrow peak, the position of which on the mass or voltage scale can be measured with high precision, is to be preferred. The choice of method may also be influenced by a consideration of whether one is particularly interested in collision-induced decompositions or whether one particularly wishes to avoid them. Other factors such as sensitivity, rapidity of scan, +

1

+

2

+

1

©0-8412-0422-5/78/47-070-003$05.00/0

+

2

4

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PERFORMANCE

MASS

SPECTROMETRY

d i s c r i m i n a t i o n e f f e c t s and the i n t e r p r e t a t i o n o f t i v e peak i n t e n s i t i e s must a l s o be c o n s i d e r e d .

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

Methods o f O b s e r v i n g Applications.

Metastable

T r a n s i t i o n s and

rela­ their

I n a d o u b l e f o c u s s i n g i n s t r u m e n t , the t h r e e pos­ s i b l e v a r i a b l e s a r e V, the a c c e l e r a t i n g v o l t a g e , E, the e l e c t r i c s e c t o r v o l t a g e and B, the m a g n e t i c f i e l d s t r e n g t h . These may be scanned i n v a r i o u s ways t o a l l o w the c o l l e c t i o n o f d a u g h t e r i o n s formed i n metas­ t a b l e t r a n s i t i o n s w h i c h o c c u r i n the f i e l d f r e e r e g i o n s between the s o u r c e and the f i r s t s e c t o r and between the two s e c t o r s . The major c h a r a c t e r i s t i c s o f the f i v e methods w h i c h have so f a r been used a r e summarized i n T a b l e I . In d i s c u s s i n g these methods, i t w i l l be as­ sumed, u n l e s s o t h e r w i s e s t a t e d , t h a t the mass s p e c t r o ­ meter has a geometry i n w h i c h the e l e c t r i c s e c t o r p r e ­ cedes the m a g n e t i c s e c t o r . The f i r s t method s i m p l y makes use o f the o f t e n d i f f u s e peaks o f low i n t e n s i t y w h i c h a r e o b s e r v e d i n a normal mass spectrum i n w h i c h Β i s scanned w i t h V and Ε f i x e d . The m e t a s t a b l e peaks may be masked by i n t e n s e normal p e a k s , and assignment i s u s u a l l y not d i f f i c u l t f o r peaks g i v e n by a low m o l e c u l a r w e i g h t compound. However, i t becomes i n c r e a s i n g l y d i f f i c u l t to a s s i g n low i n t e n s i t y m e t a s t a b l e peaks i n the mass spectrum o f a compound o f h i g h m o l e c u l a r w e i g h t . I f o n l y the more i n t e n s e m e t a s t a b l e peaks are o f i n t e r e s t , few problems a r e e n c o u n t e r e d , and the method has the advantage t h a t the normal mass spectrum and m e t a s t a b l e peaks a r e ob­ t a i n e d i n a s i n g l e scan. One o f the most w i d e l y used methods i s t h a t i n w h i c h the a c c e l e r a t i n g v o l t a g e V i s scanned w i t h Ε and Β fixed. In t h i s method the d a u g h t e r i o n m i s selec­ t e d under normal o p e r a t i n g c o n d i t i o n s but w i t h V and Ε s e t a t t y p i c a l l y h a l f the maximum v a l u e . A s c a n o f V i s t h e n i n i t i a t e d and a peak i s o b t a i n e d whenever d i f f e r e n t p r e c u r s o r i o n s m i f u l f i l l the r e q u i r e m e n t that V /V„ = m /m (1) +

2

+

1

1

2

where V i s the a c c e l e r a t i n g v o l t a g e r e q u i r e d f o r the c o l l e c t i o n of m i o n s formed i n the s o u r c e and V i s the v a l u e r e q u i r e d t o t r a n s m i t m i o n s formed from m i i o n s i n the f i e l d - f r e e r e g i o n between the source and e l e c t r i c s e c t o r . T h e r e f o r e , the method i s w e l l s u i t e d to g i v e i n f o r m a t i o n on p r e c u r s o r i o n s o f a g i v e n daugh­ t e r i o n . The s i g n a l i s p r o d u c e d by the c o l l e c t i o n o f d a u g h t e r i o n s o f a f i x e d mass and energy, d e f i n e d by 0

+

2

x

+

2

+

Metastable Transitions

JENNINGS

Table I.

Scan

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

Β

C h a r a c t e r i s t i c s o f D i f f e r e n t Methods f o r Observation of Metastable Transitions.

Fixed

Ease o f KE Assignment R e l e a s e

V, Ε

Often D i f ­ ficult

Ε, Β

Usually to nearest nominal mass

Yes

i) D i f f i c u l t i i ) Usually to nearest nominal mass

Yes

V, Β

Yes

Feature 2

G i v e s m /mi r a t i o . Low i n t e n s i t y r e l a ­ t i v e t o normal peaks. O v e r l a p pro­ blems. 2

G i v e s a l l mi o f s e l e c t e d m . Range l i m i t e d by p r a c t i ­ c a l Vi/Vo r a t i o . Source c o n d i t i o n s vary during scan. +

2

i ) Ε p r e c e d e s B: g i v e s a l l mi/m r a t i o s w i t h o u t mass a n a l y s i s . Requires EM between s e c t o r s , i i ) Β p r e c e d e s E: gives a l l m from s e l e c t e d m i . Wide range; c o n s t a n t source c o n d i t i o n s . 2

+

2 +

V V E

Β

Good; peaks narrow

No

+

Gives a l l m from s e l e c t e d m i . Range l i m i t e d t o mi/m ~3. Source c o n d i t i o n s vary during scan. 2 +

2

Β/Ε

V

Good; narrow peaks

No

+

Gives a l l m from s e l e c t e d m i . Wide range; c o n s t a n t source c o n d i t i o n s . 2 +

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

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HIGH

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the s e l e c t e d v a l u e s o f Β and E. The spectrum i s an energy spectrum o f p r e c u r s o r i o n s w h i c h fragment t o y i e l d t h e s e daughter i o n s , and t h i s i s r e a d i l y used t o g i v e t h e masses o f p r e c u r s o r i o n s by means o f e q u a t i o n (1). I f t h e f r a g m e n t a t i o n i s accompanied by t h e r e l e a s e o f t r a n s l a t i o n a l energy, t h e m e t a s t a b l e peak i s b r o a d ­ ened. I f t h e 3 - s l i t w i d t h i s r e d u c e d i n an i n s t r u m e n t o f N i e r - J o h n s o n geometry, t h e i n c r e a s e d d i s c r i m i n a t i o n a t t h e β-slit causes t h e peak-shape t o change and f a c i l i t a t e s t h e e v a l u a t i o n o f t h e energy r e l e a s e . Un­ der such c o n d i t i o n s , t h e i n t e n s i t y i s r e d u c e d b u t s i g n a l a v e r a g i n g may be used t o improve t h e s i g n a l - t o n o i s e r a t i o , and, i n c e r t a i n c a s e s , t h i s has r e v e a l e d f i n e s t r u c t u r e i n m e t a s t a b l e peaks. S e v e r a l fragmen­ t a t i o n s which l e a d t o the p r o d u c t i o n o f 0 Η ions y i e l d m e t a s t a b l e peaks w h i c h p o s s e s s f i n e s t r u c t u r e (5J). The s i g n a l g i v e n by t h e Ci»rU i o n s formed i n t h e process +

3

3

+

C

H

7 7

+ +

*

C

H

4 4

+

+

C

H

3 3

+

i s r e p r o d u c e d i n F i g u r e 1. T h i s peak s t r u c t u r e i s r a t i o n a l i z e d by assuming t h a t t h e two p r o c e s s e s y i e l d l i n e a r and c y c l i c forms o f t h e C H ions, the enthal­ p i e s o f f o r m a t i o n o f w h i c h d i f f e r by 1.09 eV. The d i f f e r e n c e i n e n e r g i e s r e l e a s e d i n t h e two p r o c e s s e s w h i c h g i v e r i s e t o t h e two components o f t h e peak i s 0.52 eV. T h i s i n d i c a t e s t h a t a p p r o x i m a t e l y h a l f o f t h e d i f f e r e n c e i n e n t h a l p i e s o f f o r m a t i o n appears as t h e difference i n energies released. A s i m i l a r conclusion i s r e a c h e d from t h e s t r u c t u r e i n t h e m e t a s t a b l e peak a r i s i n g from t h e p r o c e s s +

3

C

H

5 5

+

*

C

H

3 3

+

+

3

C

H

2 2

^

A f u r t h e r use o f t h i s type o f s c a n has been i n t h e i n v e s t i g a t i o n o f t h e energy r e l e a s e w h i c h accompanies the f r a g m e n t a t i o n o f an i o n formed i n an i o n - m o l e c u l e r e a c t i o n i n a h i g h p r e s s u r e source. For t h i s type o f e x p e r i m e n t , t h e c o n d i t i o n s r e q u i r e c a r e f u l adjustment s i n c e i f the pressure i s too low, the y i e l d o f f r a g ­ menting i o n i s low and i f t h e p r e s s u r e i s t o o h i g h , c o l l i s i o n - i n d u c e d decompositions occur o u t s i d e the s o u r c e and mask t h e peak g i v e n by t h e u n i m o l e c u l a r decomposition. I n a s t u d y (6) o f t h e f r a g m e n t a t i o n o f the C H 3 O H 2 " i o n , i t was founcT t h a t b e s t r e s u l t s were o b t a i n e d w i t h a s o u r c e p r e s s u r e o f hydrogen o f 0.05 Torr w i t h a t r a c e o f methanol. M e t a s t a b l e peaks a r i s i n g from two f r a g m e n t a t i o n s c o u l d be o b s e r v e d 4

1.

Metastable Transitions

JENNINGS

CH OH

+

2

H

+ 3

+ CH OH 3

-

H

2

+

2

(4a)

[CH OH ]-<^ 3

2

CH

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

+ H

+

+ 3

+ H0 2

(4b)

The b r o a d m e t a s t a b l e peak a t t r i b u t e d t o r e a c t i o n (4a) i n d i c a t e s t h a t i t o c c u r s w i t h t h e r e l e a s e o f 0.93 eV o f t r a n s l a t i o n a l energy, i n e x c e l l e n t agreement w i t h a v a l u e o f 1.1 eV c a l c u l a t e d from r e s u l t s based on ICR s p e c t r o m e t r y and t h e q u a s i e q u i l i b r i u m t h e o r y (OET) o f mass s p e c t r a ( 7 ) . The m e t a s t a b l e peak a r i s i n g from r e a c t i o n (4b) Ts v e r y narrow and i s c o n s i s t e n t w i t h t h e r e l e a s e o f o n l y 0.0016 eV o f t r a n s l a t i o n a l energy. The e f f e c t o f t h e β-slitwidth on s e n s i t i v i t y and on t h e ease o f assignment o f p r e c u r s o r i o n masses has been s t u d i e d on an ΑΕΙ MS9 i n s t r u m e n t , o f N i e r - J o h n s o n geometry (81). The s t a n d a r d ^ - s l i t w i d t h i n such an i n s t r u m e n t i s 0.508 cm. which has an energy bandpass o f ± 0.661 o f t h e n o m i n a l energy o f t h e i o n beam. I f energy r e l e a s e i n a m e t a s t a b l e t r a n s i t i o n i s s u f f i ­ c i e n t l y l a r g e t o produce a beam w i t h a s p r e a d i n energy at t h e β-slit w h i c h i s g r e a t e r t h a n t h i s energy band­ p a s s , some o f t h e beam i s l o s t w i t h a consequent r e d u c ­ t i o n i n s i g n a l i n t e n s i t y . Any r e d u c t i o n i n t h e βs l i t w i d t h r e s u l t s i n a further loss of s i g n a l . I f on the o t h e r hand t h e energy s p r e a d w i t h i n t h e beam i s l e s s t h a n t h a t p a s s e d by t h e β-slit, t h e s l i t w i d t h may be r e d u c e d w i t h o u t l o s s o f s e n s i t i v i t y u n t i l t h e two become comparable a f t e r w h i c h any f u r t h e r r e d u c t i o n i n s l i t w i d t h leads to a f a l l i n s e n s i t i v i t y . Consequent­ l y , i f one w i s h e s t o compare t h e r e l a t i v e i n t e n s i t i e s of t h e peaks g i v e n by two m e t a s t a b l e t r a n s i t i o n s , i t i s u s u a l l y necessary to s p e c i f y the 3 - s l i t w i d t h at which the measurements a r e t a k e n . F o r example, i n F i g u r e 2, the two s i g n a l s a r e n o r m a l i z e d t o be e q u a l a t a s l i t ­ w i d t h o f 0.508 cm., b u t a t any l o w e r s l i t w i d t h t h e y a r e c l e a r l y unequal. S i m i l a r c o n s i d e r a t i o n s a p p l y when one r e d u c e s t h e β-slitwidth i n an a t t e m p t t o reduce t h e o v e r l a p p i n g o f m e t a s t a b l e peaks i n o r d e r t o a s s i g n masses o f p r e c u r s o r i o n s more r e a d i l y . F o r example, i f an i n t e n s e , broad peak i s o b s e r v e d f o r t h e t r a n s i t i o n i i m , i t may be d i f f i c u l t t o o b s e r v e a low i n t e n s i t y s i g n a l f o r t h e transition (mi-l) -* m . I f a m e t a s t a b l e peak i s i n t r i n s i c a l l y b r o a d owing t o t h e r e l e a s e o f energy i n the f r a g m e n t a t i o n , a r e d u c t i o n o f t h e β-slitwidth r e d u c e s t h e i n t e n s i t y o f t h e peak b u t n o t i t s w i d t h so t h a t a " p r e c u r s o r mass r e s o l v i n g power based on a 5% a d j a c e n t peak c o n t r i b u t i o n r i s e s v e r y l i t t l e as t h e s l i t w i d t h i s d e c r e a s e d . I f t h e energy r e l e a s e i s s m a l l +

+

2

+

+

2

11

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

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Organic Mass Spectrometry

Figure 1. Typical peak shape for transition C H *+ -» 7

Figure 2. Effect of β-slitwidth W on sensi­ tivity S for two metastable transitions; the points are experimental data, and the lines are calculated assuming a rectangular beam profile.

7

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

1.

9

Metastable Transitions

JENNINGS

so t h a t t h e energy s p r e a d i n t h e beam i s l e s s t h a n t h e energy bandpass o f t h e β-slit, a s u b s t a n t i a l improve­ ment i n " p r e c u r s o r mass r e s o l v i n g power" i s o b s e r v e d as the 3 - s l i t w i d t h i s reduced. R e s u l t s obtained f o r a number o f m e t a s t a b l e t r a n s i t i o n s a r e i l l u s t r a t e d i n F i g u r e 3. The main advantages o f t h e a c c e l e r a t i n g v o l t a g e scan method o f o b s e r v i n g m e t a s t a b l e t r a n s i t i o n s a r e i t s s i m p l i c i t y and s e n s i t i v i t y c o u p l e d w i t h i t s a b i l i t y t o g i v e d e t a i l e d i n f o r m a t i o n on energy r e l e a s e i n f r a g ­ mentations. I t s major d i s a d v a n t a g e s a r e t h a t t h e p r a c t i c a l range over w h i c h Vi/Vo may be v a r i e d i s l i m i t e d t o about f o u r and t h a t t h e s o u r c e t u n i n g c h a r ­ a c t e r i s t i c s may change d u r i n g t h e s c a n t h e r e b y a l t e r i n g t h e e f f i c i e n c y o f e x t r a c t i o n o f i o n s from t h e s o u r c e . The l a t t e r problem c a n be overcome t o a l a r g e e x t e n t by a d j u s t i n g t h e t u n i n g so t h a t i t i s r e l a t i v e l y i n s e n s i ­ t i v e t o V i a l t h o u g h t h i s u s u a l l y e n t a i l s some s a c r i f i c e of s e n s i t i v i t y . I n some a p p l i c a t i o n s , t h e b r o a d peaks produced by t h i s s c a n , even a t reduced β-slitwidths, may cause some u n c e r t a i n t y i n t h e assignment o f p r e c u r ­ sor i o n masses, p a r t i c u l a r l y i f t h e scan i s used t o study c o l l i s i o n induced decompositions. The t h i r d g e n e r a l method i n w h i c h t h e e l e c t r i c s e c t o r v o l t a g e Ε i s scanned a t c o n s t a n t V and Β s h a r e s many o f t h e advantages and d i s a d v a n t a g e s o f t h e p r e ­ v i o u s method, e s p e c i a l l y when used w i t h an i n s t r u m e n t of r e v e r s e d geometry ( 4 ) . I t makes use o f t h e f a c t that i f m i i i n tEe f i e l d - f r e e region preceding the e l e c t r i c s e c t o r , m a r e t r a n s m i t t e d when +

+

2

+

2

m /m 1

2

=

E /E 1

(5)

2

where E i and E a r e t h e e l e c t r i c s e c t o r v o l t a g e s r e ­ q u i r e d t o t r a n s m i t i o n s m i (main beam) and m . I n i n s t r u m e n t s o f N i e r - J o h n s o n geometry, t h e method has n o t been w i d e l y a p p l i e d s i n c e i t r e q u i r e s t h e u s e o f a s e n s i t i v e d e t e c t o r between t h e two s e c t o r s . Even t h e n , w i t h o u t mass a n a l y s i s o f t h e p r i m a r y i o n beam, peaks a r e o b s e r v e d f o r a l l t r a n s i t i o n s f o r which e q u a t i o n (5) i s s a t i s f i e d , i . e . , without s e l e c t i o n of either i i or m . A l t h o u g h assignment i s n o t d i f f i c u l t f o r s i m p l e compounds, i t becomes much more d i f f i c u l t as t h e com­ p l e x i t y o f t h e m o l e c u l e i n c r e a s e s . N e v e r t h e l e s s , such a d i s p l a y , known as an i o n k i n e t i c energy (IKE) s p e c t r u m , may have a p p l i c a t i o n s as a " f i n g e r p r i n t " spectrum. In a r e v e r s e geometry i n s t r u m e n t , however, t h e main beam i s m a s s - a n a l y z e d by p a s s i n g i t t h r o u g h a m a g n e t i c s e c t o r b e f o r e t h e e l e c t r i c s e c t o r so t h a t m i i s s e l e c t e d by a d j u s t i n g t h e m a g n e t i c f i e l d . Decompo2

+

+

2

+

+

2

+

10

HIGH

PERFORMANCE

MASS

SPECTROMETRY

+

s i t i o n s o f m i i o n s i n the f i e l d - f r e e r e g i o n between the two s e c t o r s g i v e r i s e to v a r i o u s d a u g h t e r i o n s m2 w h i c h are s e l e c t e d by s c a n n i n g the e l e c t r i c s e c t o r v o l t a g e E. The peak-shape c h a r a c t e r i s t i c s and o t h e r f e a t u r e s a r e v e r y s i m i l a r t o those o f the V s c a n method e x c e p t t h a t one o b t a i n s i n f o r m a t i o n on the p r o d u c t s g i v e n by the f r a g m e n t a t i o n o f a p a r t i c u l a r i o n m i r a t h e r t h a n on a l l p a r e n t i o n s o f a p a r t i c u l a r d a u g h t e r ion m . The r e s u l t i n g spectrum i s a m a s s - a n a l y z e d i o n k i n e t i c energy (MIKE) s p e c t r u m . Two advantages o f t h i s method o v e r the V s c a n method a r e t h a t the s o u r c e c o n d i t i o n s a r e c o n s t a n t t h r o u g h o u t the s c a n so t h a t i t can be t u n e d f o r maximum s e n s i t i v i t y a t the maximum p r a c t i c a l v a l u e o f V, and the range o f E i / E w h i c h i s p r a c t i c a b l e i s s u b s t a n t i a l l y g r e a t e r t h a n the range o f V i / V o i n the p r e v i o u s method. Problems a s s o c i a t e d w i t h d e c o m p o s i t i o n d u r i n g a c c e l e r a t i o n a r e absent and c o l ­ l i s i o n - i n d u c e d d e c o m p o s i t i o n s o f p r o d u c t s for«med i n i o n - m o l e c u l e r e a c t i o n s i n a h i g h p r e s s u r e source a r e l e s s l i k e l y t o mask peaks a r i s i n g from u n i m o l e c u l a r decompositions. Set a g a i n s t t h e s e a d v a n t a g e s , however, i s the f a c t t h a t s i n c e o b s e r v a t i o n s a r e made s u b s t a n ­ t i a l l y l a t e r i n the i o n f l i g h t p a t h t h a n i n the V s c a n method, a s m a l l e r number o f i o n s , i n g e n e r a l , w i l l decompose i n t h e f i e l d - f r e e r e g i o n b e f o r e the e l e c t r i c s e c t o r o f a r e v e r s e geometry i n s t r u m e n t t h a n i n the same r e g i o n o f an i n s t r u m e n t o f N i e r - J o h n s o n geometry. T h e r e f o r e , the s e n s i t i v i t y i s l o w e r . In a d d i t i o n , a t h i g h v a l u e s o f E i / E , the energy o f the t r a n s m i t t e d m i o n s i s low, t h e r e b y l e a d i n g t o a r e d u c e d g a i n a t the e l e c t r o n m u l t i p l i e r so t h a t the w i d e r range i s o b t a i n e d t o some e x t e n t a t the expense o f s e n s i t i v i t y . A p p l i c a ­ t i o n s o f t h i s method a r e d i s c u s s e d by o t h e r a u t h o r s e l s e w h e r e i n t h i s volume. The l a s t two methods d i f f e r from those d e s c r i b e d above i n t h a t two o f the t h r e e p a r a m e t e r s V, Ε and Β a r e l i n k e d t o g e t h e r and scanned w h i l e the t h i r d i s h e l d constant. Each has the f e a t u r e o f g i v i n g narrow meta­ s t a b l e peaks comparable w i t h peaks g i v e n by i o n s formed i n t h e s o u r c e i n a normal mass spectrum so t h a t , i n e f f e c t , a h i g h r e s o l u t i o n spectrum o f m e t a s t a b l e peaks i s obtained. I n each s c a n , peaks a r e g i v e n by d a u g h t e r i o n s formed from a chosen p a r e n t i o n m i and the meta­ s t a b l e t r a n s i t i o n s a r e r e a d i l y a s s i g n e d . N e i t h e r method g i v e s any i n f o r m a t i o n on peak shape and hence no i n ­ f o r m a t i o n on the r e l e a s e o f t r a n s l a t i o n a l energy i n a f r a g m e n t a t i o n can be deduced. In the f i r s t o f the two l i n k e d scans Β i s h e l d c o n s t a n t and the a c c e l e r a t i n g v o l t a g e V and £he e l e c ­ t r i c s e c t o r v o l t a g e Ε a r e l i n k e d such t h a t V^/E i s +

+

+

2

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

2

+

2

2

+

1.

Metastable Transitions

JENNINGS

11

constant throughout the scan ( 9 ) . Since Ε i s d i r e c t l y p r o p o r t i o n a l t o V , t h e energy o f i o n s t r a n s m i t t e d by t}ie e l e c t r i c s e c t o r , V^/E i s e q u i v a l e n t t o m a i n t a i n i n g VW constant d u r i n g the scan. A t one p o i n t d u r i n g t h e s c a n , a t t h e c r o s s - o v e r p o i n t , V - V* as shown i n F i g u r e 4, t h e main beam i s t r a n s m i t t e d and t h e p a r e n t ion i i i s s e l e c t e d by a d j u s t i n g t h e m a g n e t i c f i e l d B. I f t h i s i o n fragments t o g i v e m i n the f i e l d - f r e e r e g i o n between t h e s o u r c e and e l e c t r i c s e c t o r , m ions are t r a n s m i t t e d by t h e e l e c t r i c s e c t o r when e

+

+

2

+

2

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

Vj

=

(m /m )V 2

1

(6)

1

where V i i s t h e a c c e l e r a t i n g v o l t a g e a c t u a l l y a p p l i e d t o t h e m i i o n s when m ions are transmitted. In order f o r these m i o n s t o be c o l l e c t e d a t t h e f i x e d magnetic f i e l d s t r e n g t h Β +

+

2

+

2

#

where vî = V a t t h e c r o s s o v e r p o i n t . tions are s a t i s f i e d Vj/Vj

%

=

(1/Vj)

=

kCl/v/)^

%

V /E 1

When b o t h equa(8)

2

In t h e s c a n , Ε and hence V* i s d i r e c t l y p r o p o r t i o n a l t o t h e t i m e t w h i c h has e l a p s e d s i n c e t h e i n i t i a t i o n o f the s c a n so t h a t m

2

=

m t /t 1

1

2

=

K/t

2

(9)

where t i and t a r e t h e t i m e s a f t e r i n i t i a t i o n o f t h e s c a n a t w h i c h m i and m are c o l l e c t e d . T h i s t y p e o f s c a n has been used on t h e ΑΕΙ MS50 i n s t r u m e n t w i t h VÎ = 2kV. When V r e a c h e s i t s i n s t r u m e n t a l maximum v a l u e o f 8kV, V = 4kV so t h a t t h e minimum v a l u e o f m /mi = 0 . 5 f o r a m e t a s t a b l e peak t o be o b s e r v a b l e . I f the crossover point i s s e t at a l o w e r v a l u e i n t h e r e g i o n o f l k V , t h e range c a n be e x t e n d e d so t h a t t h e minimum v a l u e o f m /mi i s app r o x i m a t e l y 0.33 b u t p r a c t i c a l problems may a r i s e i n m a i n t a i n i n g source s e n s i t i v i t y a t low a c c e l e r a t i n g voltages. T h i s i l l u s t r a t e s two o f t h e main d i s a d v a n t a g e s o f t h e method, l i m i t e d range and v a r i a t i o n o f s o u r c e t u n i n g c o n d i t i o n s d u r i n g t h e scan. In a d d i t i o n , a narrow β-slitwidth i s r e q u i r e d t o e l i m i n a t e peaks a r i s i n g from p a r e n t i o n s o f mass ( m i + l ) o r ( m i - l ) , 2

+

+

2

2

2

+

+

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

HIGH

•050"

PERFORMANCE

IOO* VV

,5

· °"

2

0

MASS

SPECTROMETRY

0

Figure 3. Effect of β-slitwidth W on precursor mass resolution R for various meta­ stable transitions

Scan time (arbj International Journal of Mass Spectrometry and Ion Physics

Figure 4. Plot of voltage vs. scan-time showing the cross-over point at V · (2kV) t

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

1.

Metastable Transitions

JENNINGS

13

but one cannot e l i m i n a t e low i n t e n s i t y s p u r i o u s peaks w h i c h o c c a s i o n a l l y a r i s e from d e c o m p o s i t i o n s w h i c h occur i n the a c c e l e r a t i n g r e g i o n . D e s p i t e these d i s a d v a n t a g e s , t h i s l i n k e d s c a n has p r o v e d v e r y u s e f u l i n t h e i n v e s t i g a t i o n o f t h e fragmen­ t a t i o n o f the m o l e c u l a r i o n s o f a s e r i e s o f s u b s t i t u t e d t e t r a f l u o r o c y c l o b u t a n e s ( 1 0 ) . The r e a c t i o n s o f f l u o r o e t h y l e n e and f l u o r o p r o p e n e m o l e c u l a r i o n s w i t h f l u o r o o l e f i n s s t u d i e d u s i n g ICR s p e c t r o s c o p y have been i n t e r ­ p r e t e d as p r o c e d i n g t h r o u g h a r e a c t i o n complex h a v i n g a c y c l o b u t a n e s t r u c t u r e and t h e f r a g m e n t a t i o n s o f t h e m o l e c u l a r i o n s o f t h e f l u o r o c y c l o b u t a n e s were shown t o be c o n s i s t e n t w i t h t h i s h y p o t h e s i s . Metastable t r a n s i ­ t i o n s o f d e u t e r a t e d m o l e c u l a r i o n s showed t h a t t h e s p e c i f i c i t y of the l a b e l l i n g i s retained i n t h e i r frag­ m e n t a t i o n so t h a t , f o r example, peaks were o b s e r v e d f o r the f r a g m e n t a t i o n s

F

D

In t h e second o f t h e l i n k e d s c a n s , t h e a c c e l e r a ­ t i n g v o l t a g e V i s h e l d c o n s t a n t and the m a g n e t i c f i e l d Β and e l e c t r i c s e c t o r v o l t a g e Ε a r e scanned such t h a t B/E i s c o n s t a n t t h r o u g h o u t t h e s c a n ( 1 1 ) . A p r o t o t y p e o f t h i s s c a n has r e c e n t l y been f i t t e d t o the Warwick MS50 i n s t r u m e n t , and a s c h e m a t i c o f t h e c i r c u i t i s shown i n F i g u r e 5. The m a g n e t i c f i e l d i s a d j u s t e d so t h a t t h e i o n m i i s c o l l e c t e d under normal o p e r a t i n g c o n d i t i o n s , and t h e e l e c t r i c s e c t o r v o l t a g e Ε i s mea­ s u r e d b y means o f a d i g i t a l v o l t m e t e r . The l i n k e d s c a n i s t h e n s w i t c h e d i n so t h a t t h e e l e c t r i c s e c t o r r e f e r ­ ence v o l t a g e i s c o n t r o l l e d by t h e o u t p u t o f t h e f i e l d monitor. The v a r i a b l e g a i n a m p l i f i e r i s a d j u s t e d so t h a t Ε i s i d e n t i c a l t o t h a t used i n normal o p e r a t i o n so that i i i o n s a r e a g a i n c o l l e c t e d . The s c a n i s t h e n i n i t i a t e d , and as Β and Ε f a l l , B/E remains c o n s t a n t as shown i n F i g u r e 6. Under normal o p e r a t i n g c o n d i t i o n s , i o n s mi sub­ j e c t e d t o an a c c e l e r a t i n g v o l t a g e V w i l l pass t h r o u g h an e l e c t r i c s e c t o r o f r a d i u s R w i t h v e l o c i t y v when the e l e c t r i c f i e l d E i s such t h a t +

+

+

x

0

m ν 1

/R = eE

Ί

or

2

+

2V =

REQ

(ID

s i n c e Ve = ^ m i V i . The m i o n s a r e c o l l e c t e d i f they pass t h r o u g h a m a g n e t i c f i e l d o f s t r e n g t h B i such t h a t x

HIGH

PRIMARY REFERENCE -20V

E S A SUPPLY

PERFORMANCE

MASS

ACCELERATING VOLTAGE POWER SUPPLY

-20V (MAIN BEAM) FIELD

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

MONITOR

B/E SCAN

Figure 5. Circuit used for B/E linked scan

Figure 6. Plot of B/E scan showing normal scan at E and Β and Ε values for collection of m * formed from various precursors 0

2

SPECTROMETRY

1.

2

m v /r 1

1

15

Metastable Transitions

JENNINGS

=

B ev 1

2

1

2

2

2

o r n^/e = r B / 2 V = r B / R E C I 2) 1

1

Q

where r i s t h e r a d i u s o f t h e m a g n e t i c s e c t o r . I f m i ·> m o c c u r s i n t h e f i e l d - f r e e r e g i o n be­ tween t h e s o u r c e and e l e c t r i c s e c t o r , m ions of v e l o c i t y v i a r e t r a n s m i t t e d by t h e e l e c t r i c s e c t o r o n l y if +

+

2

+

2

E

=

2

(m /m )E 2

1

(13)

0

and by t h e m a g n e t i c s e c t o r o n l y i f

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

m

v

2 l

/

r =

B

2

e

v

o

l

r

B

2

=

m

m

B

( 2/ l^ i

(

1 4

)

Hence b o t h Ε and Β need t o be r e d u c e d by t h e same fraction to (m /ii) of their o r i g i n a l value. Hence, the l i n k e d s c a n o f B/E h e l d c o n s t a n t a l l o w s a l l daugh­ ter ions m from t h e s e l e c t e d m i i o n t o be c o l l e c t e d i n t u r n . The s c a n has t h e advantage t h a t t h e s o u r c e e x t r a c t i o n e f f i c i e n c y i s constant since V i s not var­ i e d , and t h e range i s l i m i t e d o n l y by t h e range o v e r w h i c h t h e H a l l probe i s l i n e a r i n B. The s e n s i t i v i t y i s h i g h since products of decompositions i n the f i r s t f i e l d f r e e r e g i o n a r e c o l l e c t e d , b u t , as i n t h e s c a n o f Ε i n a r e v e r s e geometry i n s t r u m e n t , t h e r e s p o n s e o f t h e e l e c t r o n m u l t i p l i e r w i l l f a l l as t h e v a l u e o f Ε f a l l s . The r e l a t i v e i n t e n s i t i e s o f peaks w i t h i n a g i v e n scan w i l l depend on t h e energy r e l e a s e f o r each decomposi­ t i o n , t h e l i n e a r i t y o f t h e H a l l p r o b e , and t h e f a l l o f f i n s e n s i t i v i t y . N e v e r t h e l e s s , t h e narrow peaks and ease o f assignment make t h e scan i d e a l f o r a p p l i c a t i o n s i n w h i c h one m e r e l y wants t o a s c e r t a i n whether o r n o t there i s a metastable t r a n s i t i o n f o r the process m i m . I f one c o n s i d e r s t h e f o r m a t i o n o f m i o n s from a s e r i e s o f p a r e n t i o n s , t h e p a r t i c u l a r v a l u e s o f B/E w h i c h a r e r e q u i r e d f o r t h e i r c o l l e c t i o n a r e g i v e n by 2

+

+

2

+

+

2

+

2

m /e 2

=

2

(r B

2 2

)/E

(15)

2

and s o form a p a r a b o l a as shown i n F i g u r e 6. The v a l u e required f o r the c o l l e c t i o n of m from a p a r t i c u l a r m i i s found a t t h e i n t e r s e c t i o n o f t h e l i n e a r B/E p l o t and t h e p a r a b o l a . One c a n show t h a t t h e v a l u e o f Β i s t h a t a t w h i c h t h e m e t a s t a b l e peak would appear i n a normal mass s p e c t r u m , i . e . , a t an a p p a r e n t mass o f m / m i . When s c a n n i n g t o o b t a i n d a u g h t e r i o n s from a p a r t i c u l a r p a r e n t i o n m i , one may o b t a i n s p u r i o u s peaks o f low i n t e n s i t y i f t h e r e i s an i n t e n s e s i g n a l +

2

+

2

2

+

16

HIGH

+

PERFORMANCE

MASS

SPECTROMETRY

+

a r i s i n g from ( m i + l ) •> m or i f there i s s i g n i f i c a n t r e l e a s e o f i n t e r n a l energy. Such peaks can u s u a l l y be r e c o g n i z e d w i t h o u t d i f f i c u l t y and a r e , i n any c a s e , m i n i m i z e d by r e d u c i n g the $ - s l i t w i d t h . When used t o s t u d y c o l l i s i o n - i n d u c e d decomposi­ t i o n s , e i t h e r b y r a i s i n g the a n a l y z e r tube p r e s s u r e o r by u s i n g a c o l l i s i o n chamber between the s o u r c e and e l e c t r i c s e c t o r , t h i s scan s t i l l g i v e s sharp peaks and assignment i s t h e r e b y s i m p l i f i e d . For example, t h e c o l l i s i o n - i n d u c e d d e c o m p o s i t i o n o f the t o l u e n e molecu­ l a r i o n gave many sharp peaks down t o masses as low as m/e = 25, C H . I t has a l s o been used i n a s t u d y (12) o f t h e r e a c t i o n between the v i n y l m e t h y l e t h e r molecu­ l a r i o n and 1,3-butadiene i n which methanol i s e l i m i ­ n a t e d t o y i e l d what i s c o n s i d e r e d t o be the 1 , 3 - c y c l o hexadiene m o l e c u l a r i o n . The p r o d u c t s o b t a i n e d by t h e c o l l i s i o n - i n d u c e d d e c o m p o s i t i o n o f t h i s i o n produced by ion-molecule r e a c t i o n s i n a h i g h p r e s s u r e source a r e v e r y s i m i l a r t o those g i v e n by the 1 , 3 - c y c l o h e x a d i e n e m o l e c u l a r i o n when t h i s compound i s i n t r o d u c e d d i r e c t l y i n t o the s o u r c e , t h e r e b y s u p p o r t i n g t h i s s u g g e s t i o n . 2

+

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

2

Conclusion. In t h e above a c c o u n t , we have a t t e m p t e d t o p o i n t out t h e advantages and d i s a d v a n t a g e s o f the v a r i o u s methods o f o b s e r v i n g the p r o d u c t s o f m e t a s t a b l e t r a n s i ­ t i o n s and i t i s c l e a r t h a t a l l have t h e i r uses i n particular situations. For most a p p l i c a t i o n s , a V scan ( N i e r - J o h n s o n geometry) o r Ε s c a n ( r e v e r s e geometry) t o g e t h e r w i t h a l i n k e d s c a n , p r e f e r a b l y the B/E s c a n because o f i t s g r e a t e r r a n g e , w i l l g i v e the r e q u i r e d i n f o r m a t i o n . The methods s h o u l d be r e g a r d e d as comple­ mentary r a t h e r than i n c o m p e t i t i o n .

Literature Cited. 1. 2. 3. 4.

Cooks, R.G., Beynon, J.H., Caprioli, R.M. and Lester, G.R., "Metastable Ions", (Elsevier Scientific Publishing Co.), Amsterdam, 1973. Jennings, K.R. in "Mass Spectrometry, Techniques, and Applications", p. 419 (Ed. G. W. A. Milne, Wiley Interscience), New York, 1971. Holmes, J.L. and Benoit, F.M. in MTP Int. Rev. of Sci. Physical Chemistry Series 1 (1972) 5, 259. (Ed. A. Maccoll, Butterworths), London. Beynon, J.H. and Cooks, R.G. in TMP Int. Rev. of Sci. Physical Chemistry Series 2, (1975), 5, 159. (Ed. A. Maccoll, Butterworths), London.

1.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch001

5.

JENNINGS

Metastable Transitions

17

Sen Sharma, D.K., Jennings, K.R. and Beynon, J.H., Organic Mass Spectrom., (1976), 11, 319. 6. Huntress, W.T., J r . , Sen Sharma, D.K., Jennings, K.R. and Bowers, M.T., Int. J. Mass Spectrom Ion Phys. (submitted for publication). 7. Bowers, M.T., Chesnavich, W.J. and Huntress, W.T., Jr., Int. J. Mass Spectrom Ion Phys., (1973), 12 357. 8. Jones, S., Elliott, R.M. and Jennings, K.R., unpublished work. 9. Weston, A.F., Jennings, K.R., Evans, S. and Elliott, R.M., Int. J. Mass Spectrom Ion Phys. (1976), 20, 317. 10. Derai, R., Ferrer-Correia, A.J.V., Mitchum, R.K., and Jennings, K.R., unpublished work. 11. Bruins, A.P., Jennings, K.R., Evans, S., Int. J. Mass Spectrom. Ion Phys. (in press). 12. van Doorn, R., Nibbering, N.M.M., Ferrer-Correia, A.J.V. and Jennings, K.R., unpublished work. Received December 30, 1977

2 Potential Energy Surfaces for Unimolecular Reactions of Organic Ions RICHARD D. BOWEN and DUDLEY H. WILLIAMS

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

University Chemical Laboratory, Cambridge, United Kingdom

In s t u d y i n g t h e r e a c t i o n s undergone by charged s p e c i e s i t i s o f t e n advantageous t o examine t h e chemis t r y u s i n g i o n beams. Such methods f a c i l i t a t e a t i g h t e r c o n t r o l o f the chemistry than i s p o s s i b l e i n c l a s s i c a l experiments i n s o l u t i o n . F o r i n s t a n c e , comp l i c a t i o n s caused by s o l v a t i o n a r e c o m p l e t e l y e l i m i n a t e d , and t h e o c c u r r e n c e o f r e a c t i o n s i s e a s i l y d e t e c t e d by t h e appearance o f m e t a s t a b l e peaks i n t h e mass spectrum. The i m p o r t a n c e o f m e t a s t a b l e peaks i n mass s p e c t r o m e t r y has been d i s c u s s e d i n d e t a i l ( 1 - 3 ) ; i n t h e p r e s e n t c o n t e x t t h i s i m p o r t a n c e a r i s e s because metast a b l e peaks a r e u s u a l l y produced by t h e s l o w , u n i molecular decompositions of ions having a w e l l - d e f i n e d range o f i n t e r n a l e n e r g y , j u s t above t h e t h r e s h o l d f o r r e a c t i o n . A l t h o u g h c l e a r l y d e f i n e d examples o f t h e i n t e r v e n t i o n o f i s o l a t e d s t a t e s a r e known ( 4 ) , such cases are probably the e x c e p t i o n r a t h e r than the r u l e . Indeed, t h e u n i m o l e c u l a r c h e m i s t r y o f e l e v e n members o f the C

H

n 2n l +

C

n = 2

1 2

- >

homologous s e r i e s o f i o n s c a n be e i t h e r r a t i o n a l i z e d o r p r e d i c t e d without invoking the i n t e r v e n t i o n o f i s o l a t e d s t a t e s ( 5 ) . A consequence o f t h e f a c t t h a t m e t a s t a b l e d i s s o c i a t i o n s u s u a l l y o c c u r w i t h l i t t l e e x c e s s energy i n the t r a n s i t i o n state i s that the a b i l i t y o f possible decay c h a n n e l s t o compete a g a i n s t one a n o t h e r i s c r i t i c a l l y dependent on t h e a c t i v a t i o n e n e r g i e s f o r t h e p r o c e s s e s concerned ( 6 ) . T h i s i s e l e g a n t l y demonstrat e d by t h e o c c u r r e n c e o f i s o t o p e e f f e c t s i n t h e decomp o s i t i o n o f s u i t a b l y l a b e l l e d i o n s . These i s o t o p e e f f e c t s span t h e e n t i r e range o f t h o s e known i n s o l u t i o n c h e m i s t r y , and i n some cases a r e s p e c t a c u l a r l y large. For instance, the metastable decompositions o f a l l t h e v a r i o u s D - l a b e l l e d methanes have been documen-©0-8412-0422-5/78/47-070-018$10.00/0

2.

BOWEN

Unimolecuhr

AND WILLIAMS

Reactions of Organic Ions

19

t e d ( 7 ) , and, a l t h o u g h c a l c u l a t i o n s i n d i c a t e t h a t t h e t h r e s h o l d f o r l o s s o f ϋ· from t h e m o l e c u l a r i o n s i s o n l y 0.08 eV above t h a t f o r Η· l o s s , t h e energy d i s ­ c r i m i n a t i o n i s so s t r o n g t h a t l o s s o f ϋ· i s n o t o b s e r v e d e x c e p t from CDi^. S t u d i e s o f l a b e l l e d ethane and propane have a l s o been r e p o r t e d ( 8 - 1 0 ) , and f o r CD CHt t h e r a t i o o f H :D l o s s i s ca."150:1 w h i l e t h a t f o r Η·:ϋ· l o s s from C D C H i s > 6UÏÏ:1. I n a d d i t i o n t o c o n c l u s i o n s based on t h e r e l a t i v e abundances o f m e t a s t a b l e p e a k s , u s e f u l i n f o r m a t i o n c o n c e r n i n g t h e t r a n s i t i o n s t a t e s f o r r e a c t i o n s c a n somet i m e s be deduced from t h e shapes o f m e t a s t a b l e p e a k s . A n e c e s s a r y ( b u t n o t s u f f i c i e n t ) c o n d i t i o n f o r decomp o s i t i o n o f i s o m e r i c i o n s o v e r t h e same p o t e n t i a l surface, with c l o s e l y similar i n t e r n a l energies, i s t h a t t h e m e t a s t a b l e peaks f o r t h e d i s s o c i a t i o n ( s ) o f such i o n s must be t h e same shape. F o r i n s t a n c e e v i dence has b e e n p r e s e n t e d (11) w h i c h s t r o n g l y s u g g e s t s t h a t t h e C H 0 i o n s i n t h e mass s p e c t r a o f p h e n o l ( J ) and t r o p o l o n e ( 2 ) , w h i c h decompose by l o s s o f CO i n m e t a s t a b l e t r a n s i t i o n s , have t h e same s t r u c t u r e ( o r m i x t u r e o f s t r u c t u r e s ) . I n each c a s e , t h e m e t a s t a b l e peak f o r t h e r e a c t i o n +

3

2

2

t

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

3

3

+

6

6

C H 0Î 6

6

C H i 5

6

+

CO

i s t h e same shape ( 1 1 ) . OH

2 C o n v e r s e l y , i f t h e m e t a s t a b l e peaks f o r d i s s o c i a t i o n o f isomeric ions are d i f f e r e n t , t h i s c o n s t i t u t e s s t r o n g e v i d e n c e t h a t t h e decay c h a n n e l s , t h r o u g h w h i c h reaction i s occurring, are d i f f e r e n t . A c l a s s i c case i s the decomposition o f the molecular ions o f the i s o m e r i c n i t r o p h e n o l s v i a e l i m i n a t i o n o f NO. I n t h e c a s e s o f o- and £-nitrophenol m o l e c u l a r i o n s t h e met a s t a b l e peak f o r NO l o s s i s b r o a d and f l a t - t o p p e d , whereas f o r m - n i t r o p h e n o l t h e peak i s g a u s s i a n ( 1 2 ) .

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

20

HIGH

3c

PERFORMANCE

4c

MASS

SPECTROMETRY

5c

C l e a r l y , t h e r e i s a fundamental d i f f e r e n c e i n t h e p o t e n t i a l s u r f a c e o v e r w h i c h t h e m o l e c u l a r i o n o f mn i t r o p h e n o l (3b) decomposes. C o n s i d e r a t i o n o f t h e p l a u s i b l e p r o d u c t s t r u c t u r e s ( 4 a , b, c) r e v e a l s t h a t the charge can be more e f f e c t i v e l y ~ d e I o c a l i z e d i n 4a and 4c v i a a " c l a s s i c a l resonance e f f e c t " . Furthermore, t h e d i f f e r e n t m e t a s t a b l e peaks f o r NO l o s s i n d i c a t e t h a t 3b does n o t e q u i l i b r a t e w i t h e i t h e r 3a o r 3c prior~£o u n i m o l e c u l a r decomposition. The Concept o f t h e P o t e n t i a l S u r f a c e . A r e l a t i v e l y s i m p l e and e l e g a n t method o f summ a r i z i n g t h e c h e m i s t r y o f a g i v e n system i s t h e cons t r u c t i o n o f t h e p o t e n t i a l s u r f a c e over w h i c h t h e i o n s decompose ( 1 3 ) . The method may be used when o n l y one e l e c t r o n i c s t a t e i s i n v o l v e d (an a d i a b a t i c s u r f a c e ) and can be extended t o i n c l u d e cases where more t h a n one e l e c t r o n i c s t a t e i s i n v o l v e d (a d i a b a t i c s u r f a c e ) . The l a t t e r must be employed when " c r o s s i n g s " o c c u r (14)·

The c o n s t r u c t i o n o f t h e p o t e n t i a l s u r f a c e f o r an i o n i c system a l s o e n a b l e s t h e c h e m i s t r y t o be c l e a r l y understood. For i n s t a n c e , consider t y o i s o m e r i c ions A+ and B+, w h i c h can decompose i n t o C +D and E +F,

2.

BOWEN

Unimolecular Reactions of Organic Ions

AND WILLIAMS

respectively. Clearly i f t h e a c t i v a t i o n energies f o r i s o m e r i z a t i o n o f A and Β a r e l e s s t h a n t h o s e needed to cause d i s s o c i a t i o n o f e i t h e r A o r B t h e n a t energies a p p r o p r i a t e t o slow r e a c t i o n s , r a p i d e q u i l i ­ b r a t i o n o f A and B w i l l o c c u r p r i o r t o m e t a s t a b l e t r a n s i t i o n s ( F i g . 1 ) . C o n s e q u e n t l y , t h e slow r e a c t i o n s undergone by i o n s on such a s u r f a c e w i l l r e f l e c t tlje r e l a t i v e a c t i v a t i o n e n e r g i e s f o r d i s s o c i a t i o n t o C +D and E +F, i r r e s p e c t i v e o f whether t h e i o n s a r e i n i ­ t i a l l y formed as A o r B . An example o f t h i s s i t u ­ a t i o n i s the p o t e n t i a l s u r f a c e f o r decomposition o f C H! i n t o C»H + C Hi» and C H + C H . Irres­ p e c t i v e o f t h e p r e c u r s o r used t o g e n e r a t e C 6 H , such i o n s always undergo d e c o m p o s i t i o n i n a p p r o x i m a t e l y t h e same r a t i o (1.6:1 f a v o r i n g C H l o s s ) (6) t h u s i n d i ­ c a t i n g that the a c t i v a t i o n energies f o r i n t e r c o n v e r s i o n of a l l t h e a c c e s s i b l e c o n f i g u r a t i o n s o f C H i a r e l e s s t h a n t h o s e f o r d e c o m p o s i t i o n . A s i m i l a r ca§e o c c u r s i n 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 o f Ci*H where n e a r l y a l l t h e m e t a s t a b l e i o n c u r r e n t i s due t o CHi* l o s s (15) a l t h o u g h a s m a l l and a l m o s t c o n s t a n t p e r c e n t a g e i s due t o C Hi* l o s s (15J) . R a p i d e q u i l i b r i t i o n of a l l the p o s s i b l e structures of ^ Η ( F i g . 2) r e q u i r e s t h a t complete l o s s o f i d e n t i t y o f a l l c a r b o n and hydrogen atoms i n l a b e l l e d C»*H i o n s must precede 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 . T h i s i s borne o u t by D and C l a b e l l i n g s t u d i e s , which e s t a b l i s h s t a t i s t i c a l l o s s of CHi* i n m e t a s t a b l e t r a n s i t i o n s , i r r e s p e c t i v e o f t h e p r e c u r s o r s t r u c t u r e (15). T h i s l o s s o f i d e n t i t y o f t h e atoms o f l a b e l l e d i o n s i s sometimes r e f e r r e d t o as " s c r a m b l i n g " o r "randomization". Such e x p r e s s i o n s s h o u l d be used w i t h c a u t i o n , f o r t h e y may appear t o i m p l y t h a t t h e chemis­ t r y o f t h e system i s n o t u n d e r s t o o d , whereas i n f a c t , r e f e r e n c e t o a s u i t a b l e p o t e n t i a l s u r f a c e (e.g. F i g . 2 above) r e a d i l y e x p l a i n s t h e c h e m i s t r y . F u r t h e r m o r e , i t i s important t o grasp t h a t i t i s the r a p i d e q u i l i ­ b r a t i o n o f v a r i o u s i s o m e r i c s t r u c t u r e s w h i c h causes t h e l o s s o f i d e n t i t y o f atoms i n l a b e l l e d s p e c i e s and n o t the p r e s e n c e o f a s u i t a b l e s y m m e t r i c a l i o n on t h e potential surface. That t h e p r e s e n c e o f such a sym­ m e t r i c a l i o n i s n o t a p r e r e q u i s i t e i s e v i d e n t from t h e Ci*H case c o n s i d e r e d above, where l o s s o f i d e n t i t y o f a l l hydrogen and c a r b o n atoms o c c u r s p r i o r t o m e t a s t ­ a b l e t r a n s i t i o n s , even though no s t r u c t u r e f o r C^Hg* e x i s t s i n w h i c h a l l t h e hydrogen and c a r b o n atoms a r e equivalent. In a d d i t i o n t o t h e c r i t e r i o n o f m e t a s t a b l e abun­ dances (16), and l a b e l l i n g s t u d i e s , o t h e r i m p o r t a n t methods a r e a v a i l a b l e w h i c h a s s i s t i n t h e c o n s t r u c t i o n +

+

+

+

+

+

+

+

6

3

+

+

9

+

2

3

7

3

6

i 3

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

21

3

6

+

6

3

9

2

+

9

+

9

1 3

+

9

22

HIGH

PERFORMANCE

MASS

SPECTROMETRY

of p o t e n t i a l s u r f a c e s . These a r e C o l l i s i o n a l A c t i v a t i o n ( C A ) , I o n C y c l o t r o n Resonance (ICR) and energy measurements o f v a r i o u s k i n d s . The f i r s t two t e c h n i q u e s p e r m i t t h e d e t e c t i o n o f any i o n w h i c h e x i s t s i n a s i g n i f i c a n t w e l l on t h e p o t e n t i a l s u r f a c e . Thus, f o r i n s t a n c e , f o r C 2 H 0 , CA s t u d i e s i n d i c a t e o n l y two s t r u c t u r e s , p r e s u m a b l y 6 and 7, w h i c h e x i s t i n r e l a t i v e l y deep p o t e n t i a l w e l l s (17) ; t h i s i s i n agreement w i t h a s t u d y o f t h e m e t a s t a b l e d e c o m p o s i t i o n s o f the i o n (!L8) and w i t h a p r e v i o u s ICR s t u d y (19J) . + + CH CH=OH CH 0=CH +

5

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

3

3

2

S i m i l a r c o n c l u s i o n s have a l s o been r e a c h e d i n t h e C H 0 system (2£) ; and t h e C H N and C H N systems ( 2 1 ) , where once a g a i n t h e onium type i o n s (8-11; 14-18) appear t o e x i s t i n p o t e n t i a l w e l l s : + + • + CH CH CH=OH (CH ) C=OH CH CH 0=CH CH CH=OCH +

3

7

2

+

6

3

8

a n d

3

2

3

2

8

3

9 + CH CH=NH 3

2

11

+ CH NH=CH

2

3

3

2

13

+

+

CH CH CH=NH 2

3

10

12 3

2

(CH ) C=NH

2

3

14

2

+

CH CH NH=CH

2

3

2

15

+ CH CH=NHCH 3

3

2

16 + (CH ) N=CH 3

17

2

2

18

I t s h o u l d be n o t e d , however, t h a t t h e d i f f e r e n c e i n CA s p e c t r a o f two i o n s does n o t n e c e s s a r i l y p r e clude i s o m e r i z a t i o n p r i o r to metastable d i s s o c i a t i o n s . T h i s i s because t h e a c t i v a t i o n e n e r g i e s f o r i n t e r c o n v e r s i o n o f t h e i o n s may be l e s s t h a n t h o s e f o r d i s s o c i a t i o n b u t n e v e r t h e l e s s l a r g e enough t o cause c o n s i d e r a b l e d i f f e r e n c e s i n t h e CA s p e c t r a . An example o f t h i s s i t u a t i o n i s found i n t h e C H e N system where i o n s o f s t r u c t u r e s 14 and 15 have d i f f e r e n t CA s p e c t r a (21) a l t h o u g h an e a r l i e r m e t a s t a b l e i o n s t u d y r e v e a l s tïïât t h e s e i o n s decompose over t h e same s u r f a c e i n metastable t r a n s i t i o n s (22). +

3

2.

BOWEN

23

Unimolecular Reactions of Organic Ions

AND WILLIAMS

CA s p e c t r o s c o p y has a l s o been a p p l i e d t o t h e long-standing "benzyl versus t r o p y l i u m " problem (23^ 2£) ; s e v e r a l C H s p e c i e s w i t h d i f f e r e n t CA spect r a a r e o b s e r v e d ( 2 3 ) . E l e g a n t r e s u l t s stem from a d e u t e r i u m l a b e l l i n g s t u d y (24) where C H s D ions o f n o m i n a l s t r u c t u r e 1§ a r e o b s e r v e d t o l o s e :CD i n CA s p e c t r o s c o p y , thus p r o v i n g t h a t such low energy i o n s do n o t c o l l a p s e t o t r o p y l i u m s t r u c t u r e s . These s t u d i e s (23,24-), t o g e t h e r w i t h ICR work (2_5) w h i c h r e v e a l s tHât two d i s t i n c t C H p o p u l a t i o n s (presumab l y b e n z y l and t r o p y l i u m ) , w i t h d i f f e r e n t r e a c t i v i t i e s , e x i s t (25), c o n s t i t u t e strong evidence i n favor of b o t h t r o p y l i u m and b e n z y l c a t i o n s e x i s t i n g i n p o t e n t i a l w e l l s i n t h e gas phase. +

7

7

+

7

2

2

+

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

7

7

+

19 N e v e r t h e l e s s , s t u d i e s on h i g h e r energy i o n s (met a s t a b l e and s o u r c e r e a c t i o n s ) produced from 2 , 6 - C t o l u e n e (20) ( 2 6 ) , t h e t r o p y l i u m s a l t (21) (27) and d o u b l y l a b e l l e c T c y c l o h e p t a t r i e n e (28) s u g g e s t i s o m e r i z a t i o n o f benzyl to tropylium (or e q u i l i b r a t i o n of the two (2Ί5)) o c c u r s . T h i s i s because 20, f o r i n s t a n c e , fragments t o y i e l d some u n l a b e l l e d C s H and C H * . This i s not c o n s i s t e n t with simple c o l l a p s e to a 13

2

+

5

1 3

2

2

20 t r o p y l i u m i o n w h i c h t h e n r e a c t s w i t h o u t rearrangement s i n c e i o n s such as t h e c a t i o n o f 21 can o n l y l o s e C H or C C H without p r i o r rearrangement. The use o f energy measurements, w h i c h y i e l d h e a t s o f f o r m a t i o n (ΔΗ-f) o f s p e c i e s o f i n t e r e s t , i n con­ s t r u c t i n g p o t e n t i a l s u r f a c e s i s i n many ways s e l f evident. Where r e l i a b l e v a l u e s a r e a v a i l a b l e ( f o r i n s t a n c e : s e v e r a l s a t u r a t e d a l k y l i o n s ( 2 9 , 3 0 ) , some u n s a t u r a t e d carbonium i o n s (31-34) and v a r i o u s o t h e r s p e c i e s ( 3 5 - 3 8 ) ) , t h e r e l a t i v e l e v e l s o f r e a c t a n t s and p r o d u c t c o m b i n a t i o n s on a p o t e n t i a l s u r f a c e can be accurately assigned. A case where t h i s i s p o s s i b l e i s 2

1 3

2

2

24

HIGH

PERFORMANCE MASS

SPECTROMETRY

the (\Η + s u r f a c e r e f e r r e d t o abçve, where t h e h e a t s o f f o r m a t i o n o f t h e i s o m e r s o f Ci»H (29), product ions (29,31) and n e u t r a l s (38) a r e a l l a v a i l a b l e . In cases wïïëre t h e r e i s i n c o m p l e t e d a t a c o n c e r n i n g t h e h e a t s o f f o r m a t i o n o f t h e s p e c i e s o f i n t e r e s t , appearance pot e n t i a l (AP) measurements may be made. However, on conventional instruments there are systematic errors a s s o c i a t e d w i t h AP d e t e r m i n a t i o n s , and s i g n i f i c a n t e r r o r s a r e l i k e l y t o o c c u r . Many o f t h e d i f f i c u l t i e s a s s o c i a t e d w i t h AP measurements a r e e s s e n t i a l l y i n s t r u m e n t a l i n n a t u r e and have been d i s c u s s e d r e c e n t l y (39,40). AP measurements u s i n g c o n v e n t i o n a l mass spect r o m e t e r s may be u s e f u l i n d e t e r m i n i n g rough A H v a l u e s , but i n v i e w o f t h e d i f f i c u l t i e s a t t e n d i n g such measurements (3J9,40), t h e y s h o u l d n o t be r e g a r d e d a s b e i n g a c c u r a t e tô~T)etter t h a n ( s a y ) ±10 k c a l m o l " . Other ways around t h e p r o b l e m o f o b t a i n i n g ΔΗ^ v a l u e s f o r relevant species are calculations (41), estimation t e c h n i q u e s (5,42,£3), and p r o t o n a f f i n i t y (PA) mea­ surements (37,3T). The f i r s t two a r e e s p e c i a l l y use­ f u l i n c a s e s wKêre t h e s p e c i e s o f i n t e r e s t a r e unl i k e l y t o be a c c e s s i b l e v i a e x p e r i m e n t a l AP o r PA d e t e r m i n a t i o n , e.g., t h e 3 - h y d r o x y - l - p r o p y l c a t i o n ( 2 2 ) . The l a s t method i s o f t e n u s e f u l when t h e r e q u i s i t e c a t i o n cannot be g e n e r a t e d v i a d i r e c t i o n i z a t i o n o f t h e c o r r e s p o n d i n g r a d i c a l and i s c a p a b l e o f y i e l d i n g accurate r e s u l t s . An i n g e n i o u s a p p l i c a t i o n o f t h e t e c h n i q u e i s t h e d e t e r m i n a t i o n o f t h e h e a t o f format i o n o f t h e 2 - p r o p e n y l c a t i o n (23) by p r o t o n a t i o n o f propyne ( 4 4 ) . 9

9

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

f

1

+

+

CH CH CH 0H 2

2

22

2

CH C=CH 3

2

23

When t h e methods o u t l i n e d above a r e a p p l i e d , t h r e e b a s i c t y p e s o f p o t e n t i a l s u r f a c e s a r e found t o occur. Complete E q u i l i b r a t i o n o f Isomers P r i o r t o Unimolecul a r Decomposition. T h i s c o r r e s p o n d s t o t h e g e n e r a l form o f p o t e n t i a l s u r f a c e shown i n F i g u r e 1. Here t h e a c t i v a t i o n energ i e s f o r i s o m e r i z a t i o n processes are l e s s than those f o r d i s s o c i a t i o n , and d e c o m p o s i t i o n o c c u r s o v e r t h e same s u r f a c e , from t h e same i o n ( o r i o n s ) i r r e s p e c t i v e of t h e o r i g i n o f t h e i o n under s t u d y . Examples o f t h i s g e n e r a l case a r e numerous, f o r i n s t a n c e t h e Ci»H +

9

2.

BOWEN

AND WILLIAMS

+

25

(15) and C H i (6) i s o m e r s r e f e r r e d t o above. Four g e n e r a l c r i t e r i a o f e x p e r i m e n t a l measurements must be s a t i s f i e d b e f o r e t h i s k i n d o f s u r f a c e may be s a f e l y assigned t o a given i o n . ( i ) The c r i t e r i o n o f m e t a s t a b l e abundances (ljS) must h o l d good, i . e . t h e d e c o m p o s i t i o n o f i o n s gener­ a t e d i n i t i a l l y as d i f f e r e n t s t r u c t u r e s must o c c u r t h r o u g h t h e same c h a n n e l ( s ) and i n s i m i l a r r a t i o s . However, some changes i n t h e r a t i o s o f i o n s decompo­ s i n g t h r o u g h t h e v a r i o u s c h a n n e l s may be o b s e r v e d ; t h e s e changes r e f l e c t t h e s l i g h t d i f f e r e n c e s i n i n t e r ­ n a l e n e r g i e s o f i o n s produced f r o m d i f f e r e n t p r e c u r s o r s (16) . (ii) The m e t a s t a b l e peak shapes must be t h e same f o r each d e c o m p o s i t i o n c h a n n e l , i r r e s p e c t i v e o f t h e precursor o f the ion. (iii) The AP's f o r each d e c o m p o s i t i o n channel must be t h e same ( a f t e r s u i t a b l e c o r r e c t i o n s have been made t o compensate f o r t h e d i f f e r e n t h e a t s o f formation of precursors) i r r e s p e c t i v e of the o r i g i n o f t h e i o n s under s t u d y . (iv) There must be l o s s o f i d e n t i t y o f some atoms i n l a b e l l e d i o n s , i . e . , t h e d e c o m p o s i t i o n o f l a b e l l e d i o n s must be s t a t i s t i c a l , o r must be c a p a b l e o f b e i n g i n t e r p r e t e d i n terms o f s t a t i s t i c a l s e l e c t i o n o f t h e n e c e s s a r y atoms t o g e t h e r w i t h an i s o t o p e e f f e c t . When i s o t o p e e f f e c t s a r e i n o p e r a t i o n , they must be the same f o r i o n s g e n e r a t e d from d i f f e r e n t p r e c u r s o r s . Whereas t h e t h i r d c r i t e r i o n i s l e s s r e l i a b l e when the AP measurements a r e made u s i n g c o n v e n t i o n a l mass s p e c t r o m e t e r s because o f t h e s y s t e m a t i c e r r o r s w h i c h may c o m p l i c a t e t h e a n a l y s i s ( 3 9 , 4 0 ) , t h e o t h e r t h r e e a r e s u i t a b l e f o r work u s i n g s t a n d a r d mass spectrome­ ters. An i n t e r e s t i n g example o f t h e i m p o r t a n c e o f con­ s i d e r i n g i s o t o p e e f f e c t s i n c o n j u n c t i o n w i t h complete e q u i l i b r a t i o n o f t h e atoms i n l a b e l l e d i o n s i s f u r ­ n i s h e d by two independent s t u d i e s (45,46) o f t h e c o m p e t i t i v e l o s s o f Η· and D« from t E e m o l e c u l a r i o n s of l a b e l l e d toluenes. For the three precursors 24-26, l o s s o f Η· and D» i n m e t a s t a b l e t r a n s i t i o n s from t h e m o l e c u l a r i o n s c a n be a c c o u n t e d f o r i f t h e l o s s o f hydrogen r a d i c a l i s assumed t o be s t a t i s t i c a l w i t h an i s o t o p e e f f e c t o f 2.8:1 (45) o r 3.5:1 (46) i n f a v o r o f Η· l o s s . The s l i g h t cTTscrepancy between the two v a l u e s found i n t h e two s t u d i e s i s presumably due t o a p o p u l a t i o n o f i o n s w i t h l o n g e r l i f e t i m e s (and hence lower i n t e r n a l e n e r g i e s ) i n t h e l a t t e r s t u d y ( 4 6 ) . S i m i l a r r e s u l t s a r e found (45) f o r t h e l a b e l l e c T ~ c y c l o h e p t a t r i e n e m o l e c u l a r i o n s T7 and 28; 6

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

Unimolecular Reactions of Organic Ions

3

26

HIGH

PERFORMANCE

MASS

SPECTROMETRY

t h i s i s c o n s i s t e n t w i t h e q u i l i b r a t i o n of the toluene and c y c l o h e p t a t r i e n e m o l e c u l a r i o n s p r i o r t o m e t a s t a ­ b l e d e c o m p o s i t i o n s (see c r i t e r i o n ( i v ) above).

24

25

26

27

28

Perhaps t h e b e s t example o f t h e j o i n t a p p l i c | t i o n of the c r i t e r i a i s a d e f i n i t i v e study o f the 0 Η · r a d i c a l c a t i o n s (47). In t h i s study the metastable abundances, peak sïïapes and t h e appearance p o t e n t i a l s f o r the v a r i o u s decomposition channels o f C H * ions g e n e r a t e d from propene and c y c l o p r o p a n e a r e shown t o be c o n s i s t e n t w i t h complete e q u i l i b r a t i o n o f t h e two p o s s i b l e structures o f the molecular i o n p r i o r to metastable t r a n s i t i o n s . Other members o f t h e H * homologous s e r i e s o f r a d i c a l c a t i o n s behave s i m i l a r l y (48,49). Other examples o f t h e a p p l i c a t i o n o f t h e c r i t e r i o n o f m e t a s t a b l e abundances (16) t o show complete e q u i l i bration of a l l accessible reactant configurations prior to m e t a s t a b l e d e c o m p o s i t i o n s i n c l u d e some C Η and C H 2 _ i o n s ( 5 0 ) . '

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

3

3

6

6

+

c

n

2 n

η

n

n

n

Δ η

λ

3

No E q u i l i b r a t i o n o f Isomers P r i o r t o U n i m o l e c u l a r Decomposition? T h i s c o r r e s p o n d s t o t h e g e n e r a l form o f p o t e n t i a l s u r f a c e i l l u s t r a t e d i n F i g u r e 3. Here t h e a c t i v a t i o n energies f o r i s o m e r i z a t i o n processes are g r e a t e r than t h o s e f o r d i s s o c i a t i o n , and d e c o m p o s i t i o n o c c u r s over two s e p a r a t e p o t e n t i a l s u r f a c e s . D e c o m p o s i t i o n o v e r t h i s g e n e r a l p o t e n t i a l s u r f a c e can be d e t e c t e d by t h e following observations: (1) The d e c o m p o s i t i o n ( s ) o f i o n s on t h e two s e p a r a t e " h a l v e s o f t h e s u r f a c e w i l l i n g e n e r a l be d i f f e r e n t b o t h i n t h e n a t u r e o f t h e r e a c t i o n ( s ) under­ gone and i n t h e e x t e n t t o w h i c h any common r e a c t i o n s occur. (ii) The shapes o f t h e m e t a s t a b l e peaks f o r any common r e a c t i o n s w i l l n o t , i n g e n e r a l , be t h e same. Indeed, i n some c a s e s (12^, 5 ^ ) , d r a s t i c d i f f e r e n c e s a r e observed. (iii) The AP's f o r any common d e c o m p o s i t i o n s w i l l be d i f f e r e n t i n g e n e r a l . 1 1

BOWEN

AND WILLIAMS

unimolecular Reactions of Organic Ions

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

Accounts of Chemical Research

Figure 1. Potential energy surface corresponding to complete equilibration to two ions, A* and B*, prior to slow unimolecular decomposition 231 CH CH 3

/ ^

208

2

+ CH =CH 2

2

+ CH,

Accounts of Chemical Research

Figure 2. Potential energy surface for slow unimolecular decomposition of the isomeric cations C H +

4

9

Accounts of Chemical Research

Figure 3. Potential energy surface corresponding to no interconversion of two ions, A* and B , prior to slow unimolecular decomposition +

28

HIGH

PERFORMANCE

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SPECTROMETRY

( i v ) The b e h a v i o r o f l a b e l l e d i o n s on t h e two " h a l v e s " o f t h e s u r f a c e w i l l n o t u s u a l l y be t h e same. In p a r t i c u l a r , i s o t o p e e f f e c t s , when p r e s e n t , a r e u n l i k e l y t o be i d e n t i c a l . An e x c e l l e n t example o f t h i s k i n d o f p o t e n t i a l surface i s C H 0 . Ions g e n e r a t e d from p r e c u r s o r s h a v i n g t h e e t h e r m o i e t y ( s t r u c t u r e 29) behave i n a c o m p l e t e l y d i f f e r e n t way t o t h o s e g e n e r a t e d from 1a l k a n o l s ( 3 0 ) , 2 - a l k a n o l s (31) and compounds o f f o r m u l a ( 3 2 J , where Y i s a v a r i a b l e group. Two +

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

2

5

CH3OCH2Y

CH3CHYOH

YCH2CH2OH

CH3CH2OY

29

30

31

32

metastable decompositions o f C 2 H s O ions are observed ( 5 1 ) ; C H l o s s a t m/e 8.02 and CPU l o s s a t m/e 18.7. TEê" abundance d a t a , t o g e t h e r w i t h t h e k i n e t i c energy r e l e a s e w h i c h accompanies CHi* l o s s , a r e g i v e n i n Table I (SI). +

2

2

Table I . Precursor structure

Metastable

Decompositions o f C 2 H s O

+

ions.

m/e 8.02 m/e 18.7

k i n e t i c energy r e l e a s e ( k c a l m o l " ) o f m/e 18.7

<0.01

<3

HOCH2CH2Y

1.8±0.2

11.5±0.9

CH3CHYOH

1.9±0.1

10.1±0.5

CH3CH2OY

2.0±0.1

12.0±1.1

CH3OCH2Y

1

From t h e d a t a o f T a b l e I i t i s e v i d e n t t h a t two d i s t i n c t p o p u l a t i o n s o f i o n s , w h i c h do n o t i n t e r c o n v e r t a p p r e c i a b l y a t energies appropriate to metastable t r a n s i t i o n s , a r e b e i n g formed. Not o n l y do C H 0 i o n s formed from p r e c u r s o r s o f g e n e r a l f o r m u l a 29 undergo e x c l u s i v e methane l o s s , as opposed t o i o n s g e n e r a t e d from 30, 31 o r 32 w h i c h undergo l o s s o f methane and a c e t y l e n e , b u t a l s o t h e m e t a s t a b l e peak shapes f o r methane l o s s from t h e two t y p e s a r e d i f ferent. That f o r methane l o s s from i o n s p r o d u c e d from 29 i s g a u s s i a n , whereas methane l o s s from i o n s h a v i n g 30, 31 o r 32 t y p e p r e c u r s o r s i s f l a t - t o p p e d i n d i c a t i n g k i n e t i c energy r e l e a s e (52^5_3). Furthermore, the measured v a l u e s f o r t h e A P s f o r CHi* l o s s from t h e two +

2

f

5

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

2.

BOWEN

Unimolecular Reactions of Organic Ions

AND WILLIAMS

29

kinds o f ions, while only approximate, y i e l d values f o r the t r a n s i t i o n s t a t e e n e r g i e s w h i c h a r e d i f f e r e n t ( 5 4 ) . F i n a l l y , D l a b e l l i n g s t u d i e s (55) on i o n s p r o d u c e d from 29 (presumably s t r u c t u r e 7 J r e v e a l t h a t CH<* l o s s o c c u r s w i t h s t a t i s t i c a l s e l e c t i o n o f t h e hydro­ gen atoms w h i l e CFU l o s s from i o n s w i t h p r e c u r s o r s t r u c t u r e s 30 o r 31 (presumably s t r u c t u r e 6 i s t h e most s t a b l e form) i n v o l v e s s p e c i f i c e l i m i n a t i o n o f the h y d r o x y l h y d r o g e n , w h i c h does n o t l o s e i t s i d e n t i t y t o a s i g n i f i c a n t e x t e n t (56J ( i n t h e e n e r g y - r e l e a s i n g metastable t r a n s i t i o n ) . The above d a t a s e r v e t o i l l u s t r a t e t h e arguments i n f a v o r o f 6 and 7 r e a c t i n g o v e r p o t e n t i a l s u r f a c e s which a r e d i s t i n c t . The o v e r a l l case i s o v e r w h e l m i n g l y s t r o n g and f u r t h e r developments (57_) o f t h e p o t e n t i a l s u r f a c e a p p r o a c h c a n e x p l a i n much o f t h e d e t a i l e d c h e m i s t r y o f t h e C H 0 i o n . The e s t i m a t e d p o t e n t i a l surface i s depicted i n Figure 4, which s c h e m a t i c a l l y shows t h e d i f f e r e n t energy r e l e a s e p r o f i l e s (metastable peaks) f o r t h e two i n d e p e n d e n t d i s s o c i a t i o n s l e a d i n g t o HC=0 and CHi* (see a l s o T a b l e I ) . I t s h o u l d be n o t e d t h a t p r o t o n a t e d o x i r a n e (33) and p r o t o n a t e d a c e t a l d e h y d e (6) a r e e x p e c t e d t o i n t e r c o n v e r t p r i o r t o m e t a s t a b l e d i s s o c i a t i o n s . T h i s e x p l a i n s why l a b e l l i n g s t u d i e s r e v e a l t h a t b o t h t h e c a r b o n atoms o f i o n s o r i g i n a l l y g e n e r a t e d as 34 become e q u i v a l e n t p r i o r to metastable t r a n s i t i o n s (58)7 i a l s o why t h e deu­ t e r i u m atom a t t a c h e d t o oxygen i n 35 r e t a i n s i t s i d e n ­ t i t y (S6) w h i l e a l l carbon-bound hydrogens i n § become equivalent. +

2

5

+

a n <

*

+

+

CH CH=OH

CH CH=OD

34

35

3

33

3

Other i m p o r t a n t examples o f t h i s g e n e r a l form o f p o t e n t i a l s u r f a c e a r e C H N (22), C H 0 (20i, 5_9-61) and 0 ι » Η Ο ( 6 2 ) , where t h e m e t a s t a b l e abundance c r i ­ t e r i o n c a n be used t o c l a s s i f y t h e i o n s i n t o 3 , 4 and 5 groups r e s p e c t i v e l y , w h i c h do n o t i n t e r c o n v e r t p r i o r t o 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 s . The C H N system i s p a r t i c u l a r l y i n s t r u c t i v e i n t h a t one i o n (16) i s u n i q u e i n u n d e r g o i n g s o l e l y C Hi* l o s s . Deuterium"labelling s t u d i e s r e v e a l that t h i s i s a s p e c i f i c process which may be r a t i o n a l i z e d i n terms o f a f o u r - c e n t e r " mech­ anism (Scheme 1 ) . The m e t a s t a b l e peak f o r t h i s reaction +

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A *-

CH =NHCH CH 2

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-C H Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

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BOWEN

Unimolecular Reactions of Organic Ions

AND WILLIAMS

31

i s g a u s s i a n (22). Ions h a v i n g s t r u c t u r e s 14 and 15 a l s o undergo e t h y l e n e l o s s , b u t t h i s p r o c e s s has a~ h i g h e r a c t i v a t i o n energy t h a n i s o m e r i z a t i o n r e a c t i o n s l e a d i n g t o l o s s o f i d e n t i t y o f a l l t h e carbon-bound hydrogens o f 14 and 15 (22_) . The m e t a s t a b l e peak f o r t h i s reaction~ïs f l a t - t o p p e d t h u s i n d i c a t i n g t h a t 14 and 15 decompose o v e r a s e p a r a t e s u r f a c e from 16. T h i s ~ c o n c l u s i o n i s f u r t h e r s t r e n g t h e n e d by t h e ~ o c c u r r e n c e o f a new d i s s o c i a t i o n pathway, NH l o s s , f o r i o n s o f s t r u c t u r e 14 and 15. The t h i r d c l a s s o f i o n s , i n i t i a l l y g e n e r a t e d ~ a s 17~or 18, undergo b o t h 0 Ηι* and NH l o s s t o g e t h e r wïïh a t h i r d r e a c t i o n , H loss, in metastable t r a n s i t i o n s . F u r t h e r m o r e , t h e abundances of C Hit, NH and H l o s s e s a r e i n d e p e n d e n t , t o a f i r s t a p p r o x i m a t i o n , o f t h e p r e c u r s o r , thus i n d i c a t i n g d e c o m p o s i t i o n o v e r a common s u r f a c e . The m e t a s t a b l e peak shapes f o r t h e s e r e a c t i o n s a r e g a u s s i a n f o r C FU and NH l o s s and f l a t - t o p p e d f o r H l o s s . Clearly, i o n s o f i n i t i a l s t r u c t u r e 17 and.18 decompose o v e r a common s u r f a c e w h i c h i s d i s t i n c t "from t h o s e o v e r w h i c h 16 o r 14 and 15 d i s s o c i a t e ( 2 2 ) . The u n i m o l e c u l a r dëcompôsition~pathways and the" c o r r e s p o n d i n g m e t a s t a b l e peak shapes a r e summarized i n Scheme 1. A n o t h e r i n t e r e s t i n g example o f t h e g e n e r a l form of p o t e n t i a l energy s u r f a c e d e p i c t e d i n F i g u r e 3 i s the 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 s o f t h e C H N 0 ions i n t h e mass s p e c t r a o f some a l k y l - n i t r o b e n z e n e s ( 6 3 ) . S t a r t i n g from p r e c u r s o r s o f t h e g e n e r a l s t r u c t u r e OzNCeH^CHzR w i t h R=Br, CH o r C H , t h e m e t a s t a b l e dec o m p o s i t i o n s o f m/e 136 a r e found t o be l o s s o f NO f o r p a r a - s u b s t i t u t e d precursors while f o r the corresponding meta-isomers o n l y N 0 l o s s i s o b s e r v e d . T h i s e s t a b l i s h e s t h a t t h e i o n s formed by l o s s o f R from t h e m o l e c u l a r i o n s o f m- and £-0 NC HuCH R do n o t decompose o v e r t h e same p o t e n t i a l s u r f a c e . This i n turn leads t o the conclusion that e i t h e r or both o f the b e n z y l i c i o n s t r u c t u r e s (36 and 37) w h i c h might p l a u s i b l y be formed a t t h r e s h o l d do n o t undergo r e v e r s i b l e r i n g e x p a n s i o n t o t h e n i t r o t r o p y l i u m i o n 38. 3

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t I t i s p o s s i b l e t h a t 17 and 18 undergo a r a t e - d e t e r m i n i n g i s o m e r i z a t i o n onto the~same p o t e n t i a l s u r f a c e as t h a t o v e r w h i c h 16 decomposes. However, t h e i n t e r n a l energy o f such i o n s w i l l be much h i g h e r t h a n t h a t of i o n s g e n e r a t e d as 16 and so t h e new d e c o m p o s i t i o n c h a n n e l s , f o r l o s s o f ~ H and NH a r e a c c e s s i b l e . Nevert h e l e s s , t h i s cannot be t h e case f o r 14 and 15 because the m e t a s t a b l e peak f o r C Hi l o s s i s â~differënt shape t h u s p r e c l u d i n g d e c o m p o s i t i o n o v e r t h e same s u r f a c e as 16 b u t w i t h g r e a t l y d i f f e r e n t i n t e r n a l e n e r g i e s . 2

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38 Rate-Determining Decomposition.

Isomerization P r i o r to Unimolecular

T h i s c o r r e s p o n d s t o the g e n e r a l form o f p o t e n t i a l s u r f a c e i l l u s t r a t e d i n F i g u r e 5. Here the energy needed t o cause i s o m e r i z a t i o n o f s t r u c t u r e B to A i s more t h a n t h a t needed t o cause u n i m o l e c u l a r decompos i t i o n of B . Consequently, i o n B d i s s o c i a t e s i n preference to i s o m e r i z i n g to A . However, i o n A lies i n a p o t e n t i a l w e l l w h i c h i s so deep t h a t the l o w e s t a c t i v a t i o n energy p r o c e s s i s i s o m e r i z a t i o n t o B , w h i c h i s formed i n a h i g h l y e x c i t e d v i b r a t i o n a l l e v e l . The i o n B thus formed, t h e n d i s s o c i a t e s more r a p i d l y t h a n i t r e t u r n s t o s t r u c t u r e A , and does so w i t h a r a t e c o n s t a n t w h i c h i s much g r e a t e r t h a n t h a t (k-10 sec" ) normally a s s o c i a t e d w i t h metastable transitions. I t i s p o s s i b l e t h a t A and B may undergo t h e same r e a c t i o n s i n m e t a s t a b l e t r a n s i t i o n s , but i f t h e p o t e n t i a l s u r f a c e i s o f the g e n e r a l form d e p i c t e d i n F i g u r e 5, then f o u r c o n d i t i o n s must be s a t i s f i e d . ( i ) The m e t a s t a b l e peaks f o r any common p r o c e s s e s must be s i m i l a r . However, because o f t h e l a r g e r amount of i n t e r n a l energy p r e s e n t i n i o n s o f s t r u c t u r e B w h i c h have t h e i r o r i g i n as i s o m e r i z e d "A type i o n s , t h e m e t a s t a b l e peaks f o r d e c o m p o s i t i o n o f such i o n s a r e l i k e l y t o be broadened r e l a t i v e t o t h o s e f o r d i s s o c i a t i o n o f i o n s o r i g i n a l l y g e n e r a t e d as B . ( i i ) As d i s s o c i a t i o n o f the r e a r r a n g e d i o n s o f s t r u c t u r e B i s f a s t r e l a t i v e t o the normal time s c a l e of m e t a s t a b l e t r a n s i t i o n s , energy ceases t o be the dominant f a c t o r and " e n t r o p y e f f e c t s become i m p o r t a n t . Thus, f o r r e a r r a n g e d i o n s , s i n g l e bond-cleavage d i s s o +

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BOWEN

AND WILLIAMS

Unimolecuhr Reactions of Organic Ions

ÇH Ç H

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

2

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Accounts of Chemical Research

Figure 4. Potential energy surface and energy release profiles for slow unimolecuhr decomposition of the isomeric cations C H O* 2

s

Accounts of Chemical Research

Figure 5. Potential energy surface corresponding to rate-determining isomerization of ion A* to B* prior to unimolecular decomposition

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c i a t i o n s a r e f a v o r e d , whereas t h e r e i s d i s c r i m i n a t i o n a g a i n s t t h o s e d i s s o c i a t i o n s w h i c h have h i g h l y o r d e r e d transition states. Consequently, ions produced v i a the r a t e - d e t e r m i n i n g i s o m e r i z a t i o n a r e l i k e l y t o show a marked p r e f e r e n c e f o r s i n g l e b o n d - c l e a v a g e p r o c e s s e s ("source t y p e r e a c t i o n s ) even i f such p r o c e s s e s a r e not t h e most f a v o r a b l e e n e r g e t i c a l l y . (iii) AP measurements f o r t h e d e c o m p o s i t i o n s o f i o n s g e n e r a t e d as B , w i l l g e n e r a l l y r e v e a l d i f f e r e n t a c t i v a t i o n e n e r g i e s f o r competing p r o c e s s e s . However, s i n c e t h e r a t e - d e t e r m i n i n g s t e p s t a r t i n g from A i s the i s o m e r i z a t i o n t o B , t h e a c t i v a t i o n e n e r g i e s f o r a l l t h e e v e n t u a l d e c o m p o s i t i o n s must be t h e same and must be g r e a t e r t h a n any o f t h o s e s t a r t i n g from B . (iv) L a b e l l i n g s t u d i e s on i o n s s t a r t i n g from A may r e v e a l a lower degree o f l o s s o f i d e n t i t y o f t h e l a b e l than occurs i f the corresponding l a b e l l e d B i o n i s generated d i r e c t l y . T h i s i s because t h e r e i s l e s s time f o r i s o m e r i z a t i o n p r o c e s s e s t o cause l o s s o f i n t e g r i t y o f l a b e l l e d s p e c i e s o f h i g h i n t e r n a l energy ( r e a r r a n g e d "A type i o n s ) which d i s s o c i a t e r e l a t i v e l y rapidly. Although a l l u s i o n s t o the p o s s i b i l i t y o f ions r e a c t i n g over t h i s k i n d o f s u r f a c e were made f o r C 3 H 8 N " (22) and C H 0 (6_4) i o n s , i t was n o t u n t i l 1975 t h a t the f i r s t d e f i n i t e c a s e , i n t h e C 3 H 0 system ( 6 5 ) , was documented. Here i o n s o f m/e 59, generated~From the fragmentât i o n o f t h e m o l e c u l a r i o n s o f s u i t a b l e e t h e r s and a c e t a l s , may be a s s i g n e d s t r u c t u r e s 10 and 11 on t h e b a s i s o f α-cleavage. Ions o f s t r u c t u r e IQ undergo m a i n l y H 0 T o s s , t o g e t h e r w i t h some C ttk loss i n metastable t r a n s i t i o n s . AP measurements r e v e a l t h a t t h e t r a n s i t i o n s t a t e energy f o r H 0 l o s s i s some 5 k c a l mol" below t h a t f o r 0 Η^ l o s s . Loss o f CH =0 i s n o t o b s e r v e d i n m e t a s t a b l e t r a n s i t i o n s , even though t h e r e i s a complete CH =0 group p r e s e n t i n JQ, because the minimum energy needed t o p r o d u c e CH =0 + C Hs+ i s s i g n i f i c a n t l y g r e a t e r (9 k c a l m o l " ) t h a n t h e measured a c t i v a t i o n energy f o r C Hi* l o s s . However, i o n s gener­ a t e d i n i t i a l l y as H do undergo CH =0 l o s s , t o an a p p r e c i a b l e e x t e n t , i n m e t a s t a b l e t r a n s i t i o n s , and H 0 l o s s becomes a v e r y minor (ca 1% t o t a l m e t a s t a b l e i o n c u r r e n t from m/e 59) p r o c e s s . One r a t i o n a l i z a t i o n o f t h i s i s g i v e n Tn Scheme 2, where 11 i s c o n s i d e r e d to undergo a r a t e - d e t e r m i n i n g i s o m e r i z a t i o n t o 10 p r i o r t o m e t a s t a b l e d i s s o c i a t i o n s . The r a t e - d e t e r m i n ­ i n g s t e p i s most s i m p l y f o r m u l a t e d as a symmetry-for­ b i d d e n (66) 1 , 3 - h y d r i d e s h i f t , though o t h e r mechanisms a r e p o s s i b l e . 11

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Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

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Unimolecular Reactions of Organic Ions

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Scheme 2 H en ζ +

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The r e s u l t i n g i o n 10, formed by r a t e - d e t e r m i n i n g i s o m e r i z a t i o n o f 11 now'fias s u f f i c i e n t i n t e r n a l energy t o undergo CH =0 l o s s v i a s i m p l e bond c l e a v a g e o f t h e C-0 bond i n 10. 0 Ηι» l o s s i s a l s o p o s s i b l e , whereas H 0 l o s s , w h i c h r e q u i r e s c o n s i d e r a b l e rearrangement o f IQ p r i o r t o d i s s o c i a t i o n , i s g r e a t l y d i s f a v o r e d by "entropy" f a c t o r s . Further evidence i n favor o f the i s o m e r i z a t i o n i s found i n AP measurements f o r t h e d e c o m p o s i t i o n s o f i o n s i n i t i a l l y g e n e r a t e d as 1 1 , w h i c h a r e t h e same w i t h i n e x p e r i m e n t a l e r r o r , and c o r r e s p o n d t o an i n t e r n a l energy c o n s i d e r a b l y g r e a t e r t h a n t h a t needed t o cause d i s s o c i a t i o n o f 10. I n a d d i t i o n , t h e m e t a s t a b l e peaks f o r H 0 and C FU l o s s e s from i o n s g e n e r a t e d as 10 and 11, r e s p e c t i v e l y , a r e b r o a d e r a t h a l f h e i g h t i n ~ t h e l a t t e r case. T h i s o b s e r v a t i o n (65) t o g e t h e r w i t h Dl a b e l l i n g s t u d i e s , which r e v e a l a higher s p e c i f i c i t y f o r r e a c t i o n s s t a r t i n g from 11 t h a n J.0 (65) , a r e con­ s i s t e n t w i t h t h e h y p o t h e s i s t h a t 11 undergoes a r a t e d e t e r m i n i n g i s o m e r i z a t i o n t o 10 p r i o r t o m e t a s t a b l e transitions. The r e l e v a n t p o r t i o n o f t h e p o t e n t i a l s u r f a c e i s summarized i n F i g u r e 6. The second r e p o r t e d case o f r a t e - d e t e r m i n i n g isomerization p r i o r to unimolecular d i s s o c i a t i o n s i s a l s o i n t h e C3H70 s y s t e m , namely, p r o t o n a t e d p r o p i o n a l d e h y d e and p r o t o n a t e d acetone ( 6 7 ) . The e v i ­ dence p r e s e n t e d i s s i m i l a r t o t h a t f o r IQ and H above, and t h e r e l e v a n t p a r t o f t h e p o t e n t i a l s u r f a c e i s d e p i c t e d i n F i g u r e 7. I t i s p o s s i b l e t h a t t h i s type o f p o t e n t i a l sur­ f a c e w i l l p r o v e t o be more common t h a n h i t h e r t o i m a g i n e d as p r e v i o u s s t u d i e s o f t h e C 3 H 8 N " (22) and C3H 0 (6£) systems r e v e a l c a s e s where i s o m e r T z a t i o n may be tïïe r a t e - d e t e r m i n i n g s t e p i n d i s s o c i a t i o n o f some i o n i c s t r u c t u r e s . H a v i n g d i s c u s s e d t h e g e n e r a l shapes o f p o t e n t i a l s u r f a c e s o v e r w h i c h i o n s may be c o n s i d e r e d t o d i s s o c i a t e , i t i s i n s t r u c t i v e t o examine t h e s p e c i a l e f f e c t w h i c h t h e n a t u r e o f t h e f i n a l ( d i s s o c i a t i o n ) s t e p has upon t h e shape o f t h e m e t a s t a b l e peak f o r t h a t p r o c e s s .

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

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Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

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Figure 7. Potential energy surface for slow unimolecular decomposition of ions 8 and 9

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AND WILLIAMS

Unimolecuhr Reactions of Organic Ions

37

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

C o r r e l a t i o n o f M e t a s t a b l e Peak Shape w i t h P o t e n t i a l Energy S u r f a c e o f t h e D i s s o c i a t i o n StëpT C l e a r l y t h e r e a r e two b a s i c p o s s i b i l i t i e s ; namely that the reverse r e a c t i o n w i l l or w i l l not involve act i v a t i o n energy. These c o r r e s p o n d t o t h e p o t e n t i a l s u r f a c e s shown i n F i g u r e s 8(a) and 8 ( b ) , r e s p e c t i v e l y . In t h e former c a s e , i t i s c l e a r t h a t energy i s r e l e a s e d i n t h e d i s s o c i a t i o n ; and t h i s energy may be absorbed i n t o t h e v i b r a t i o n a l modes o f t h e p r o d u c t s o r may appear as t r a n s l a t i o n a l energy. T h i s k i n e t i c ene r g y r e l e a s e i s e v i d e n c e d by t h e b r o a d e n i n g o f t h e m e t a s t a b l e peak, w h i c h becomes f l a t - t o p p e d i n c a s e s where a r e l a t i v e l y s p e c i f i c and l a r g e amount o f energy i s i n v o l v e d . C o n v e r s e l y , i n c a s e s where t h e r e i s no r e v e r s e a c t i v a t i o n e n e r g y , l i t t l e o r no k i n e t i c energy r e l e a s e i s e x p e c t e d and t h e m e t a s t a b l e peak i s gauss i a n i n shape. Some c a s e s a r e n o t so c l e a r c u t as t o be b r a c k e t e d i n t o e i t h e r c a t e g o r y above; f o r i n s t a n c e , t h e t r a n s i t i o n s t a t e geometry may be f a i r l y f l e x i b l e , t h u s p e r m i t t i n g t h e r e l e a s e o f a range o f k i n e t i c e n e r g i e s w h i c h r e s u l t s i n t h e b r o a d e n i n g o f t h e metast a b l e peak f o r t h e p r o c e s s , a l t h o u g h i t f r e q u e n t l y remains g a u s s i a n i n shape. I n such c a s e s a v a l u e f o r ' f g k i n e t i c energy r e l e a s e may be computed from t h e peak w i d t h a t h a l f h e i g h t ( 6 8 ) . A l t e r n a t i v e l y , l o o k i n g a t the r e a c t i o n i n r e v e r s e , a g a u s s i a n m e t a s t a b l e peak c o n t a i n s t h e i n f o r m a t i o n t h a t t h e r e v e r s e r e a c t i o n can be made t o go by a l l o w i n g t h e p r o d u c t s (or p o s s i b l y t h e p r o d u c t s i n a suitably excited v i b r a t i o n a l level) to d r i f t together. A f l a t - t o p p e d peak c o r r e s p o n d s t o a d e f i n i t e energy b a r r i e r t o t h e r e v e r s e r e a c t i o n , w h i c h cannot be o v e r come by m e r e l y e x c i t i n g t h e p r o d u c t s i n t h e v i b r a t i o n al levels. R a t h e r , t h e p r o d u c t i o n and n e u t r a l must be g i v e n r e l a t i v e t r a n s l a t i o n a l energy i n o r d e r t o make the r e v e r s e r e a c t i o n go. C o n c e p t u a l l y , a f l a t topped m e t a s t a b l e peak f o r a g i v e n r e a c t i o n means t h a t t h e p r o d u c t s must be "pushed t o g e t h e r " i n o r d e r t o make t h e r e v e r s e r e a c t i o n go. One s i t u a t i o n i n w h i c h t h e p o t e n t i a l s u r f a c e i s o f t h e g e n e r a l form l i k e l y t o g i v e r i s e t o f l a t - t o p p e d m e t a s t a b l e peaks i s t h a t o f s y m m e t r y - f o r b i d d e n d i s s o c i a t i o n s (66J). Here a " c r o s s i n g " o f two m o l e c u l a r o r b i t a l energy l e v e l s o c c u r s , and upon a t t a i n i n g t h e t r a n s i t i o n s t a t e , w h i c h w i l l g e n e r a l l y be w e l l d e f i n e d g e o m e t r i c a l l y , d i s s o c i a t i o n occurs over a r e p u l s i v e potential surface. For i n s t a n c e , c o n s i d e r t h e c o n c e r t e d 1 , 2 - e l i m i n a t i o n o f H from i o n i z e d ethane (39) p r o c e e d i n g v i a a t

ie

a

v

r

a

e

2

38

HIGH

PERFORMANCE

MASS

SPECTROMETRY

planar t r a n s i t i o n state. The r e l e v a n t c o r r e l a t i o n diagram i s g i v e n i n F i g u r e 9 (69). A n a l y s i s o f t h i s d i a g r a m , l e a d s t o the c o n c l u s i o n t h a t the r e a c t i o n i s symmetry-forbidden. K i n e t i c energy r e l e a s e i s expect e d s i n c e the h i g h t r a n s i t i o n s t a t e energy i s p a r t i a l l y due t o the occupancy o f a m o l e c u l a r o r b i t a l c h a r a c t e r i z e d by mutual r e p u l s i o n between the i o n i z e d e t h y l e n e and H (see · i n F i g u r e 9 ) . E x p e r i m e n t a l l y , i o n i z e d ethane does i n d e e d l o s e H w i t h k i n e t i c energy r e l e a s e (70). A s i m i l a r a n a l y s i s f o r i o n i z e d methylamine ( 4 0 J 7 p r o t o n a t e d f o r m a l d e h y d e ( 4 1 ) , p r o t o n a t e d t h i o f o r m a l d e h y d e (42) and p r o t o n a t e d methylene i m i n e (43) l e a d s t o t h e c o n c l u s i o n t h a t t h e s e m o l e c u l e s , i f t h e y undergo c o n c e r t e d 1 , 2 - e l i m i n a t i o n s o f H , s h o u l d do so w i t h k i n e t i c energy r e l e a s e . E x p e r i m e n t a l l y , H l o s s e s are observed t o occur i n metastable t r a n s i t i o n s and i n each case the peak i s o f a f l a t - t o p p e d shape ( 7 0 ) , thus i n d i c a t i n g k i n e t i c energy r e l e a s e (52,53). THê f a c t t h a t a l l t h e s e d i s s o c i a t i o n s a r e 1,2-ëlimmat i o n s i s e s t a b l i s h e d by d e u t e r i u m l a b e l l i n g s t u d i e s (^,ΙΟ^,ΤιΟ,Τ^) , w h i c h show t h a t 2

2

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

2

2

+

CHaCHa*

CH =0H

40

41

3

39

+

CH NH Î 2

2

CH =SH 2

42

+

CH =NH 2

2

43

C H C D » l o s e s o n l y HD i n m e t a s t a b l e t r a n s i t i o n s (8,10^) and t h a t the h e t e r o a t o m d e u t e r a t e d a n a l o g u e s o f 4U t o 43 a l s o e l i m i n a t e o n l y HD i n u n i m o l e c u l a r decomposit i o n s (7_0,71) . F u r t h e r i n t e r e s t i n g a p p l i c a t i o n s o f o r b i t a l symmetry t o 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 s e x i s t (72,73) and one p a r t i c u l a r l y r e l e v a n t i n t h e p r e s e n t c o n t e x t i s t h e d e d u c t i o n t h a t H l o s s from i o n i z e d e t h y l e n e (44) o c c u r s v i a a 1 , 1 - e l i m i n a t i o n from the i o n i z e d cârbene 45. Such a p r o c e s s i s symmetry-allowed (660 and c o n s e q u e n t l y no k i n e t i c energy r e l e a s e i s o b s e r v e d to accompany H l o s s from C H i * . Were the r e a c t i o n t o o c c u r v i a a c o n c e r t e d 1 , 2 - e l i m i n a t i o n , i t would be symmetry-forbidden (66) and a f l a t - t o p p e d m e t a s t a b l e peak would be expectecT. A consequence o f the p r o p o s e d 3

3

2

2

1,2-H ^

+

CH

2

= CH * 2

2

V

ν

1,1-

*CH-CH

shift 44

f

3

•

CHECH

+ H

2

elimination 45

mechanism i s t h a t a l l t h e hydrogens i n l a b e l l e d i o n i z e d e t h y l e n e s h o u l d become e q u i v a l e n t p r i o r t o m e t a s t a b l e

Unimolecular Reactions of Organic Ions

WILLIAMS

(a)

(b)

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

transition state

reactant

reactant

Figure 8. Potential energy surfaces corresponding to dissociation step; (a) with reverse activation energy, (b) with no reverse activation energy

Figure 9. Correlation diagram for concerted, suprafacial 1,2-eUmination of H2 from ionized C H &

6

40

HIGH

PERFORMANCE

MASS

SPECTROMETRY

t r a n s i t i o n s ; hence, t h e d e c o m p o s i t i o n o f l a b e l l e d forms o f 44 must be e x p l i c a b l e i n terms o f s t a t i s t i c a l s e ­ l e c t i o n o f any hydrogen atoms t o g e t h e r w i t h an i s o t o p e e f f e c t f a v o r i n g s e l e c t i o n o f H r a t h e r t h a n D. E x p e r i ­ m e n t a l l y i t i s found (74) t h a t t h e l a b e l l i n g r e s u l t s can be i n t e r p r e t e d i n tTTis way. Moreover, t h e i s o t o p e e f f e c t s o b s e r v e d a r e such as t o s u g g e s t s t r o n g l y t h a t t h e e l i m i n a t i o n o f H i s c o n c e r t e d . T h i s i s good e v i ­ dence t h a t t h e f o r m u l a t i o n o f H l o s s from C Hif* as a c o n c e r t e d 1 , 1 - e l i m i n a t i o n from t h e i o n i z e d carbene 45 is correct. The c o r r e l a t i o n o f t h e m e t a s t a b l e peak shape t o t h e o r b i t a l symmetry o f t h e r e a c t i o n c o n c e r n e d i s o n l y one p a r t i c u l a r example o f t h e p o t e n t i a l s u r f a c e ap­ proach. I t s h o u l d be n o t e d t h a t any d i s s o c i a t i o n w h i c h occurs through a channel i n which the products a r e formed on a m u t u a l l y r e p u l s i v e p o t e n t i a l s u r f a c e c a n g i v e r i s e t o k i n e t i c energy r e l e a s e . An e l e g a n t example o f t h i s s i t u a t i o n i s found i n t h e d e c o m p o s i t i o n , v i a C Hi l o s s , o f t h e C 3 H ? 0 and C3HeN s p e c i e s 8 and 14, w h i c h may be f o r m u l a t e d as o c c u r r i n g v i a t h e mechanism o f Scheme 3. 2

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

2

2

+

2

f

+

Scheme 3 +

1,2-H

CH CH CH= ΟΗχ 3

2

1,2-H

+

3

3

2

2

^

2

^

2

shift

CH CH CH=NH

+

^CH CHCH 0Ht==^CH CH CH OH 2

shift

«- CH CHCH NH 3

2

2

+

* CH =0H

2

2

~

CH CH CH NH 2

2

2

2

C 2 H k

+ CH =NH 2

2

-C Hif 2

14

46

U s i n g t h e i s o d e s m i c i n s e r t i o n method w i t h a c o r r e c t i o n o f 10 and 3 k c a l m o l " f o r t h e d e s t a b i l i z i n g e f f e c t o f a 3- and γ - Ο Η ( o r -NH ) group (41,43) y i e l d s t h e e s t i m a t e d p o t e n t i a l s u r f a c e s shown i n F i g u r e s 10 and 11. A l s o g i v e n i n t h e s e f i g u r e s a r e t h e m e t a s t a b l e peak shapes f o r 0 Ηι» l o s s from t h e i o n s i n q u e s t i o n . I t i s i m m e d i a t e l y a p p a r e n t t h a t i n t h e oxygen system ( F i g u r e 10) energy must be c o n t i n u o u s l y p u t i n t o t h e system t o a t t a i n and f i n a l l y d i s s o c i a t e t h e r e a c t i n g c o n f i g u r a t i o n 22. C o n s e q u e n t l y , t h e m e t a s t a b l e peak f o r t h i s p r o c e s s i s e x p e c t e d t o be g a u s s i a n and narrow, as i s o b s e r v e d ( 6 7 ) . I n t h e c o r r e s p o n d i n g n i t r o g e n system ( F i g u r e l T T , t h e r e a c t i n g c o n f i g u r a t i o n 46 now 1

2

2

BOWEN

AND WILLIAMS

Unimolecular Reactions of Organic Ions

182 CH2=CH +CH =OH 2

2

CH CH CH OH 2

2

2

CH CH CH=QH Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

3

2

Journal of the American Chemical Society

Figure 10. Potential energy surface and energy release profile for C H hss starting from 8 t

k

217 ^

CH CH CH=NH 3

2

ν

CH CH CH NH 2

2

2

2

2

Journal of the American Chemical Society

Figure 11. Potential energy surface and energy release profile for C U loss starting from 14 %

k

42

HIGH

PERFORMANCE

MASS

SPECTROMETRY

a p p r o x i m a t e s t h e t r a n s i t i o n s t a t e and d i s s o c i a t e s exothermically. T h e r e f o r e , k i n e t i c energy r e l e a s e i s p o s s i b l e , and i t i s found t h a t the m e t a s t a b l e peak f o r t h i s t r a n s i t i o n i s f l a t - t o p p e d corresponding t o a r e l e a s e o f ~9 k c a l m o l " o f t r a n s l a t i o n a l energy (22). As t h e e s t i m a t e d e x o t h e r m i c i t y o f t h e d i s s o c i a t i o n o f 46 t o p r o d u c t s i s -27 k c a l m o l " , i t c a n be seen t h a t a p p r o x i m a t e l y one t h i r d o f t h e energy r e l e a s e d i s p a r t i t i o n e d i n t o t h e t r a n s l a t i o n a l mode. U s i n g t h i s f i g u r e , and c o n s t r u c t i n g analogous p o t e n t i a l s u r f a c e s f o r t h e homologues o f 8 and 14 (47 and 48 r e s p e c t i v e l y ) i n w h i c h t h e h e t e r o a t o m [X-H] group i s r e p l a c e d by an [X-CH ] group, r e s u l t s i n t h e p r e d i c t i o n s t h a t ( i ) b o t h the oxygen and n i t r o g e n c a s e s ought t o e l i m i n a t e C Hk v i a 49 and 50 r e s p e c t i v e l y (Scheme 4 ) . ( i i ) The oxygen c a s e ~ ( 4 7 ) i s o n l y r e l a t i v e l y m i l d l y e x o t h e r m i c (^11 k c a l m o l ) and so o n l y a s m a l l q u a n t i t y o f energy (^4 k c a l m o l " ) i s e x p e c t e d t o be r e l e a s e d as t r a n s l a ­ tion, ( i i i ) The n i t r o g e n analogue (48) i s e s t i m a t e d t o d i s s o c i a t e v i a 50 w i t h t h e r e l e a s e o f ^34 k c a l mol ( i . e . , ^11 k c a l m o l " as t r a n s l a t i o n ) . 1

1

3

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

2

r T

1

1

1

Scheme 4 1,2-H-shifts

+

CH CH CH=OC:H 3

2

+

+

CH CH CH 0CH3

3

2

CH =0CH

2

2

2

3

-C2Hi*

47

49 +

+

+

CH CH CH=NHCH ^ CH2CH2CH2NHCH 3

2

3

3

_

>

c R

CH =NHCH 2

3

50

48

E x p e r i m e n t a l l y , i t i s observed that ( i ) both ions o r i g i n a l l y g e n e r a t e d as 47 and 48 undergo C H loss i n m e t a s t a b l e t r a n s i t i o n s (62^7_5). ( ϋ ) The peak f o r CH l o s s from 47 i s g a u s s i a n b u t b r o a d ; a v a l u e o f ^3 k c a l mol" may be computed as t h e a v e r a g e k i n e t i c energy r e l e a s e (7_5), measured from the peak w i d t h a t h a l f h e i g h t (68). ( i i i ) The peak f o r C H l o s s from 48 i s s i m i l a r t o t h a t f o r C H^ l o s s from 14; however, the k i n e t i c energy r e l e a s e i s somewhat g r e a t e r (^11 k c a l mol" (7J5)), i n good a c c o r d w i t h t h e e x p e c t e d value. 2

2

k

1

2

2

1

k

k

2.

BOWEN

AND WILLIAMS

Unimolecular Reactions of Organic Ions

43

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

Conclusion. The c o n c e p t t h a t t h e m e t a s t a b l e d i s s o c i a t i o n s o f o r g a n i c i o n s may be c o n s i d e r e d as o c c u r r i n g o v e r an appropriate p o t e n t i a l surface i s discussed. I t s use a s s i s t s i n u n d e r s t a n d i n g phenomena such as " s c r a m b l i n g " and has a w i d e r use i n t h e s y s t e m a t i c a n a l y s i s o f unimolecular i o n i c r e a c t i o n s . In p a r t i c u l a r , conside r a t i o n o f that p o r t i o n o f the p o t e n t i a l surface which governs t h e f i n a l d i s s o c i a t i o n s t e p o f t e n p e r m i t s a b e t t e r u n d e r s t a n d i n g o f t h e shape o f t h e m e t a s t a b l e peak f o r t h a t p r o c e s s . Conversely, c o n s i d e r a t i o n o f the shape o f t h e m e t a s t a b l e peak f o r a u n i m o l e c u l a r r e a c t i o n may y i e l d v a l u a b l e m e c h a n i s t i c i n f o r m a t i o n concerning the r e a c t i o n i n question.

Abstract. Results from many studies of metastable ion decompositions i n double focussing mass spectrometers are interpreted i n terms of the potential surfaces over which gas-phase organic ions decompose. The concept of the potential surface enables the chemistry of these ions to be clearly understood. Three general types of surfaces are proposed: (1) complete e q u i l i bration of isomers prior to unimolecular decomposition, (2) no equilibration of isomers prior to unimolecular decomposition, and (3) rate-determining isomerization prior to unimolecular decomposition. Examples of each are presented and discussed. Literature Cited. 1. 2. 3. 4. 5. 6.

Cooks, R . G . , Beynon, J.H., C a p r i o l i , R.M., and Lester, G.R., "Metastable Ions", Elsevier, Amsterdam, (1973). Williams, D.H. and Howe, I., "Principles of Organic Mass Spectrometry", McGraw-Hill, London, (1972). See the relevant chapters i n "Mass Spectrometry-Specialist Periodical Reports", Vols. 1-3, The Chemical Society, London. Simm, I.G., Danby, C.J., and Eland, J.H.D., J.C.S. Chem. Comm., (1973), 832. Bowen, R.D. and Williams, D . H . , J.C.S. Perkin I I , (1976), 1479. Rosenstock, H.M., Dibeler, V . H . , and Harlee, F.N., J. Chem. Phys., (1964), 40, 591.

44

7. 8. 9. 10. 11.

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

18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.

HIGH

PERFORMANCE

MASS

SPECTROMETRY

H i l l s , L.P., Vestal, M.L. and F u t r e l l , J.H., J. Chem. Phys., (1971), 54, 3834. Löhle, U . , and Ottinger, Ch., J. Chem. Phys., (1969), 51, 3097. Vestal, M. and F u t r e l l , J.H., J. Chem. Phys., (1970), 52, 978. L i f s h i t z , C. and Sternberg, L., Int. J. Mass Spectrometry Ion Phys., (1969) 2, 303. Williams, D.H., Cooks, R . G . , and Howe, I., J. Am. Chem. Soc., (1968), 90, 6759. Beynon, J.H., Saunders, R.A. and Williams, A.E., Ind. Chem. Belge., (1964), 29, 311. Polanyi, J.H., Accounts Chem. Res., (1972), 5, 161. Carrington, T., Accounts Chem. Res., (1974), 7, 20. Davis, B . , Williams, D.H., and Yeo, A.N.H., J. Chem. Soc. (Β), (1970), 81. Yeo, A.N.H. and Williams, D.H., J. Am. Chem. Soc., (1971), 93, 395. McLafferty, F.W., Kornfeld, R., Haddon, W.F., Levsen, K . , Sakai, I., Bente, P . F . , Tsai, S.-C. and Schuddemage, H.D.R., J. Am. Chem. Soc., (1973), 95, 3886. Reyes, B.G. and Harrison A.G., Org. Mass Spectrom., (1974), 9, 221. Beauchamp, J.L. and Dunbar, R . C . , J. Am. Chem. Soc., (1970), 92, 1477. McLafferty, F.W. and Sakai, I., Org. Mass Spectrom., (1973), 7, 971. Levsen, K. and McLafferty, F.W., J. Am. Chem. Soc., (1974), 96, 139. Uccella, N.A., Howe, I., and Williams, D.H., J. Chem. Soc. (Β), (1971), 1933. Winkler, J. and McLafferty, F.W., J. Am. Chem. Soc., (1973), 95, 7533. McLafferty, F.W. and Winkler, J., J. Am. Chem. Soc., (1974), 96, 5182. Dunbar, R . C . , J. Am. Chem. Soc., (1975) 97, 1382. Bentley, T.W. and Johnstone, R.A.W., Adv. Phys. Org. Chem., (1970), 8, 197. Siegel, Α., J. Am. Chem. Soc., (1974), 96, 1251. Davidson, R.A. and S k e l l , P . S . , J. Am. Chem. Soc., (1973), 95, 6843. Lossing, F.P. and Semeluk, G.P., Canad. J. Chem. (1970), 48, 955. Lossing, F.P. and Maccoll, Α., Canad. J. Chem. (1976), 54, 990. Lossing, F . P . , Canad. J. Chem., (1971), 49, 357. Lossing, F . P . , Canad. J. Chem., (1972), 50, 3973.

2;

BOWEN

33. 34. 35. 36. 37.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch002

38.

39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52.

AND WILLIAMS

Unimolecuhr Reactions of Organic Ions

45

Lossing, F . P . , reported at the American Society for Mass Spectrometry Conference, Houston, Texas, U.S.A., (1975). Lossing, F.P. and Traeger, J.C., J. Am. Chem.Soc., (1975), 97, 1579. e.g., Wanatabe, Κ., Nakayama, J., and Mottl, J., J. Quant. Spect. Rad. Transfer, (1962), 2, 369. e.g. Refaey, K.M.A. and Chupka, W.A., J. Chem. Phys., (1968), 48, 5205. e.g., Haney, M.A. and Franklin, J.L., J. Phys. Chem., (1969), 73, 4328. For a compilation of ΔΗ values for various ions and neutrals see Franklin, J. L., D i l l a r d , J.G., Rosenstock, H.M., Herron, J.L., Draxl, Κ., and F i e l d , F . H . , "Ionization Potentials, Appearance Potentials, and Heats of Formation of Gaseous Positive Ions", National Bureau of Standards, Washington, D . C . , (1969). Beynon, J.H., Cooks, R . G . , Jennings, K.R. and Ferrer-Correia, A.J., Int. J. Mass Spectrometry Ion Phys., (1975), 18, 87. Rosenstock, H.M., Int. J. Mass Spectrometry Ion Phys., (1976), 20, 139. e.g., Radom, L., Pople, J.Α., and Schleyer, P.von R., J. Am. Chem.Soc., (1972), 94, 5935. Ref. 38, Appendix 2; see also Franklin, J.L., Ind. Eng. Chem., (1949), 41, 1070, and Franklin, J.L., J. Chem. Phys., (1953), 21, 2029. Bowen, R.D. and Williams, D . H . , Org. Mass Spectrom., 12, 475 (1977). Aue, D.H. Davidson, W.R. and Bowers, M.T., J. Am. Chem. Soc., (1976), 98, 6700. Howe, I. and McLafferty, F.W., J. Am. Chem. Soc., (1971), 93, 99. Beynon, J.H., Corn, J.E., Battinger, W.E., C a p r i o l i , R . M . , and Benkeser, R.A., Org. Mass Spectrom., (1970), 3, 1371. Holmes, J.L. and Terlouw, J.K., Org. Mass Spectrom., (1975), 10, 787. Smith, G.A. and Williams, D . H . , J. Chem. Soc. (Β), (1970), 1529. Bowen, R.C. and Williams, D . H . , Org. Mass Spectrom, 12, 453 (1977). Shaw, M.A., Westwood, R. and Williams, D . H . , J. Chem. Soc. (Β), (1970), 1773. Shannon, T.W. and McLafferty, F.W., J. Am. Chem. Soc., (1966), 88, 5021. Beynon, J.H. and Fontaine, A.E., Zeitschrift für Naturforschg, (1967), 22a, 334, and references cited therein. f

46

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53.

HIGH

PERFORMANCE

MASS

SPECTROMETRY

Beynon, J.H., Saunders, R . A . , and Williams, A.E., Zeitschrift für Naturforschg, (1965), 20a, 180. 54. Hvistendahl, G . , Bowen, R.D. and Williams, D . H . , J. Am. Chem. Soc., in press. 55. Hvistendahl, G. and Williams, D.H., J. Am. Chem. Soc., (1975) 97, 3097, (see pp. 3099 and 3100). 56. Van Raalte, D. and Harrison, A.G., Canad. J. Chem., (1963), 41, 3118. 57. Hvistendahl, G . , Bowen, R.D. and Williams, D . H . , unpublished results. 58. Harrison, A.G. and Keyes, B . G . , J. Am. Chem. Soc., (1968), 90, 5046. 59. Tsang, C.W. and Harrison, A.G., Org. Mass Spectrom., (1970), 3, 647. 60. Tsang, C.W. and Harrison, A.G., Org. Mass Spectrom., (1971), 5, 877. 61. Tsang, C.W., and Harrison, A.G., Org. Mass Spectrom., (1973), 7, 1377. 62. Mead, T . J . and Williams, D . H . , J.C.S. Perkin I I , (1972), 876. 63. Westwood, R., Williams, D.H. and Yeo, A.N.H., Org. Mass Spectrom., (1970), 3, 1485. 64. Mead, T.J. and Williams, D . H . , J. Chem. Soc. (Β), (1971), 1654. 65. Hvistendahl, G. and Williams, D . H . , J. Am. Chem. Soc., (1975), 97, 3097. 66. Woodward, R.B. and Hoffmann, R., "The Conserva­ tion of Orbital Symmetry", Verlag Chemie, Winheim/Bergstr., Germany, (1970). 67. Hvistendahl, G . , Bowen, R.D. and Williams, D. Η., J.C.S. Chem. Comm., (1976), 294. 68. T e r w i l l i g e r , D.T., Beynon, J.H. and Cooks, R . G . , Proc. Roy. Soc., (1974), 341, 135. 69. Smyth, K.C. and Shannon, T.W., J. Chem. Phys., (1969), 51, 4633. 70. Hvistendahl, G. and Williams, D . H . , J. Am. Chem. Soc., (1974), 96, 6753. 71. Beynon, J.H., Fontaine, A.E., and Lester, G.R., Int. J. Mass Spectrometry Ion Phys., (1968) 1, 1. 72. Hvistendahl, G. and Williams, D . H . , J.C.S. Perkin II, (1975), 881. 73. Williams, D. H. and Hvistendahl, G., J. Am. Chem. Soc., (1974), 96, 6755. 74. Hvistendahl, G. and Williams, D.H., J.C.S. Chem. Comm., (1975), 4. 75. Williams, D.H. and Bowen, R.D., J. Am. Chem. Soc., 99, 3192 (1977). RECEIVED December 30, 1977

3 Structures of Gas-Phase Ions from Collisional Activation Spectra* F. W. MC LAFFERTY

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

Department of Chemistry, Cornell University, Ithaca, NY 14853

"Double resonance" techniques have provided revolutionary new information for a variety of spectroscopic techniques in recent years. In mass spectrometry, double resonance has been utilized in the ion cyclotron resonance spectrometer to identify in a complex mixture of ions the precursor and product ions of a particular ion-molecule reaction. This paper concerns a technique in which a mass spectrum can be obtained of each peak in a mass spectrum; the ions representing that peak are activated by collision, causing their further decomposition to produce the "collisional activation" (CA) mass spectrum (1-3). The reverse-geometry double-focussing mass spectrometer (4) has special advantages for the measurement of such CA spectra. The sample is ionized and the resultant ions are mass analyzed in the magnetic analyzer; ions of a particular m/e value are brought into focus on a collision chamber containing a gas such as helium at ~10 torr pressure. In some ion-atom interactions part of the ion's kinetic energy is converted into internal energy without appreciable scattering of the ion. The resulting decompositions yield product ions which are separated in the electrostatic analyzer to yield the CA mass spectrum. In both formation and utility the CA spectrum resembles a normal mass spectrum; the decompositions of the collisionally activated ion follow the predictions of the quasiequilibrium theory, so that the resulting product ions are indicative of the precursor ion's structure. In addition, in most of the observed decomposition processes sufficient energy has been added by collision to make the resulting ion abundances virtually independent of the original internal energy ("temperature") of the precursor ion; the only ion energy-dependent processes are those which are involved in the decomposition of metastable ions (the MI spectrum, measured in the same manner except in the absence of the collision gas). Thus -4

Collisional Activation and Metastable Ion Characteristics. 55. For part 54, see reference 10. American Chemical © 0^12-042^^ 1155 16th St. N. W. Waehtogtoit, D. C. 20036

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

48

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both the masses and abundances of the CA spectrum, excluding peaks i n the MI spectrum, are characteristic of the precursor ion structure on a quantitative b a s i s , i n the same way that a normal mass spectrum i s a reproducible characteristic of the structure of the precursor molecule. Areas i n which CA-MS appears to be especially promising are fundamental studies of organic ion structures and reactions, MS structure determination of complex organic molecules through elucidation of the isomeric identity of fragment ions, and separation/identification of complex mixtures through MS separation of ionized molecular species which are then identified from their CA mass spectra. An excellent review of the field by Levsen and Schwarz has appeared (3), and Cooks reports on some related results (5); this article w i l l use as examples more recent work of our laboratory. CA-MS Instrumentation Most recent CA-MS studies have utilized "direct analysis of daughter ions (DADI) " (4) (also called "mass analyzed ion kinetic energy spectroscopy [MIKES]") (6) with a revers edgeometry double-focussing mass spectrometer (7) although Jennings and coworkers have recently shown there are advantages in using a normal geometry double-focussing instrument with a "linked" scan of the electrostatic and magnetic analyzers (8). Instrumentation aspects of importance include achieving purity of the precursor ion, resolution of the CA spectrum, data a c q u i s i tion and reduction, sensitivity, and quantitative reproducibility of spectra. As i s w e l l know i n normal mass spectrometry, the peaks in a unit resolution mass spectrum often contain isobaric multiplets; for example, C3H7+ and C 2 H 3 0 , both nominally m/e 43, actually differ i n mass by 37 millimass units. "Pure" precursor ions of course are desirable for CA spectra, and this can be achieved with sufficient resolving power (9); a CA-MS instrument with a double-focussing mass spectrometer before the c o l l i s i o n chamber i s under construction at Cornell as a solution to this problem (10). Even i f a l l the precursor ions have the same elemental composition, these s t i l l may contain isomeric impurities; formation of the ions using different ionizing electron energies, using different ionization methods (e.g., chemical ionization), or from different precursor molecules can be used to improve isomeric purity. A more serious problem i s the resolution achievable i n the CA spectrum. In the reversed-geometry instrument, the CA product ions are separated by the electrostatic analyzer, taking advantage of the fact that the loss i n mass on decomposition results i n a concommitant loss i n kinetic energy. However, i n the c o l l i s i o n process a small fraction of the ion's kinetic energy is converted into internal energy and, more seriously, internal +

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

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Ions from Collisional Activation Spectra

49

energy i n excess of that required for the decomposition can be released i n the reaction coordinate, appearing as a positive or negative velocity vector; this process has been extensively studied i n connection with the "flat-top" peaks produced i n metastable ion decompositions (6). This uncertainty i n the kinetic energy of a particular product ion broadens the peak, the extent of this broadening depending on the amount of energy variation relative to the total kinetic energy. Increasing the ion accelerating voltage decreases this fraction and therefore i n creases the resolution of the CA spectrum (11). A similar approach i s to use "post-acceleration" of the ions after the c o l l i s i o n chamber (12); an instrument under construction at the F O M Institute i n Amsterdam w i l l float the electrostatic analyzer and collector at as much as 40 kV, which should greatly enhance the resolution of the CA spectrum. Double-focussing mass analysis is employed i n instruments such as the spark source MS i n order to bring ions of widely varying kinetic energies but the same mass into coincident focus, and this principle w i l l be employed in the tandem double-focussing CA-MS instrument under construction at Cornell (10). The linked-scan, normal geometry double-focussing technique employed by Jennings and coworkers (8) apparently gives improved resolution for CA mass spectra; this arises because the ions produced by CA decomposition i n the field-free region before the electrostatic analyzer thus traverse most of the double-focussing path of the instrument. As already amply demonstrated i n normal MS, utilization of a dedicated computer for automated data acquisition and reduction also i s advantageous for CA-MS. The Cornell reversedgeometry CA-MS instrument was coupled to a DEC PDP-8 computer i n 1972 (7), and i n 1975 this was replaced by a PDP-11/10 dedicated computer which directs the multiple scanning of the CA spectrum through a D/A converter to the ESA (11). Special software and hardware give flexibility for selected mass scanning, averaging of the repeat scans, cathode ray tube display of the most recent and the averaged scans, comparison with previous spectra, multicomponent analysis of spectra, and so forth. Of special importance for ion structure characterization is the ±2% precision i n CA peak abundances which can be achieved with this new data system (11). In fact, this has been used to analyze ternary mixtures of isomeric C 3 H 7 S ions with ±10% accuracy based on the peak abundances of their CA spectra (13). This i s reminiscent of the quantitative analysis of light hydrocarbon mixtures using normal MS, the major incentive for the original development of the analytical mass spectrometer. In the Cornell tandem double-focussing CA-MS instrument under construction (10), we plan to have the PDP-11/45 computer also control the mass analysis of the precursor ion. The technique of "Signal Enhancement i n Real-Time" (14) w i l l be used to keep a particular precursor ion peak i n focus on the c o l l i s i o n chamber +

50

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during the continuous scan of the first magnet by an offsetting increase i n the ion accelerating voltage, during which time the CA-MS data (complete spectrum or selected ions) w i l l be obtained; the computer w i l l then direct the ion accelerating potential to focus the next precursor ion peak on the c o l l i s i o n chamber while its CA spectrum i s measured, and so forth (10), Such automated data acquisition and control for both MS sections in concert w i l l be especially advantageous for its use as a separation/identification system for complex mixtures.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

Structures of Gaseous Organic Ions The structures of a wide variety of ions have been determined by CA-MS. Table I l i s t s the elemental compositions of isomeric ions which have been studied by CA-MS at Cornell; additional studies by Levsen, Schwarz, Van de Sande, Beynon, Cooks, and their coworkers are listed i n the Levsen-Schwarz review (3). Table II shows proposed structures for 9 isomeric C3H50+ ions which give distinguishable CA spectra (there i s much better evidence for the first s i x than for the last three structures) (15). CA spectra, like normal mass spectra, can be used to characterize an ion's structure through rationalization of the decomposition products or through quantitative comparison with reference spectra of ions of established structures. This can be illustrated by studies of CgHg" isomers carried out by Dr. Claus Kôppel at Cornell recently (16). 1-

Table I. C o l l i s i o n a l Activation Studies CH

C

+ 4

, C H 3

H

+

C

+ 3

H

7 7 ' 7 8

C U 0*, 2

, C H 3

t #

C

H

+ 7

, C H *, C H 4

+

C

8

4

H

+

8 9 ' 9 11 ' +

C

H

, CgH^t, CgH^t

13 9

+

+

C H O , C H O , C H 0+, C H 0

4

2

s

3

s

3

+

6

6

n

+

6

3

+

C H 0t, C H O , C H O , C 6

+ g

g

n

+

+

l 2

1

H o \ C^H^ot g

4

C H N , C H N ; C H S , C^S" "; C ^ g C l " 2

6

3

Oligopeptides

8

2

5

+

?

3.

Ions from Collisional Activation Spectra

MCLAFFERTY

51

Table II. Possible Isomeric Structures of ΟβΕ^Ο* Ions

+ CH =CHCH=OH 2

HC=CCH OH 2

C H = C H O+= C H

+ CH CH C=0 3

2

2

2

A variety of molecules, including isotopically labeled derivatives, were used to form C 3 H g ions; their CA spectra showed that at least 13 isomers have lifetimes >10" seconds. Although many of the isomers do isomerize when formed with higher internal energies, these results contrast sharply with our previous conceptions of ready "scrambling" of hydrocarbon ions. Part of this misconception has arisen from the fact that most previous studies utilized the unimolecular decomposition products of an ion as evidence of its structure, and even the lowest a c t i ­ vation energy for ion decomposition is s t i l l higher than that for an isomerization. For example, the scrambling of isotopic labels on decomposition of the CyHj* ion from toluene indicated that this ion had the symmetrical tropylium, not the benzyl, structure (17, 18),but CA spectra show conclusively that both ions are formed and are stable for >10~ seconds (19). Similarly, the C 8 H g isomers m ethyl tropylium and a, o-, m-, and jj-methylbenzyl ions are found to be stable if formed with sufficiently low energy. However, as found for cycloheptatriene and toluene (19), isomerization does occur between the molecular ions of methylcycloheptatriene, ethylbenzene, and the xylenes (16). A number of recent studies have increased our basic knowledge of both solution and gas phase ionic reactions by direct comparison of particular reactivities (e.g., a c i d i t i e s , basicities) i n the two media (20 -22). A c l a s s i c NMR study by Olah and Porter (23) of the ionization of β-phenylethyl chloride (a, X = CI) i n superacid medium gives detailed NMR evidence for the formation of the ethylenebenzenium (ç) and oc-phenylethyl (d) cations, with the β-ethylphenyl ion (b) as the proposed intermediate (see Scheme I). Although this medium should mini­ mize solvent effects, we find that the unimolecular decomposition of a, with X as either CI or C H 3 , ions produces negligible amounts of either c or d as stable ionic products with the 10*"^ sec lifetime requirements of the CA technique. Instead, at low electron energies these precursors y i e l d ions whose CA spectra are identical to those formed by the protonation of benzocyclobutene, which thus presumably are formed originally as structure e. In contrast, ionization of β-phenylethyl bromide and iodide (a, X = Br or I) yields the ethylenebenzenium i o n , c, at low +

5

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

2

5

+

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

52 HIGH PERFORMANCE MASS SPECTROMETRY

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

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Ioris from Collisional Activation Spectra

53

electron energies . This appears to indicate that the formation of e i s favored energetically, possibly through an anchimericas sis ted reaction, but this pathway has more stringent steric requirements, so that the larger Br and I leaving groups cause the formation of c to be favored. Another problem which has been studied extensively on a theoretical as w e l l as experimental basis involves the relative energies of the possible C3H7"** isomers. Equilibrium constant measurements on ion-molecule reactions by Chong and Franklin (24) indicate the isopropyl structure to be 8 kcal/mol more stable than the protonated cyclopropane, but ion cyclotron resonance measurements (25) are consistent with complete isomerization of the latter to the former structure i n 10*" ^ seconds. Because the CA spectra of C3H7"*" ions formed by protonation of propene and of cyclopropane are identical (26), the isomerization also should be essentially complete i n 10~^seconds, indicating that the activation energy for the isomerization of protonated cyclopropane i s very low. If the transition state for this isomerization i s s i m i ­ lar to the η-propyl structure, this also indicates that its heat of formation i s surprisingly close to that of the protonated c y c l o ­ propane isomer (26). The differences i n the CA spectra of isomeric hydrocarbon ions are often relatively small, paralleling the behavior found for normal mass spectra of hydrocarbons. For example, the CA spec­ tra of sec- and tert-butyl ions are nearly the same (27). One method to increase these differences i s to form a derivative of the ions. In the case of the C 4 H g ions, simple derivatives can be formed by the reaction of the newly formed ions directly i n the MS ion source with acetyl chloride; the resulting ΟβΗ^Ο" " ions show substantial differences i n their CA spectra. The C4H9"*" ions formed from η-butyl bromide when derivatized i n this fashion give a CA spectrum which i s identical to that from sec-butyl ions, while isobutyl ions isomerize to give a 7:3 mixture of secand tert-butyl ions. Both gas phase and solution determinations show the heat of formation of tert-butyl ions to be 16 kcal/mol less than that of sec-butyl ions, so that conformational effects outweigh enthalpic factors. Obviously i t is important to the understanding of solution reactions involving organic ions to be able to separate out completely the effect of the solvent on the reaction. +

1

Applications of CA to Molecular Structure Determination Although such applications have been restricted i n the past because of instrumentation limitations, CA spectra should provide v i t a l additional information for the structure elucidation of complex molecules. The interpretation of a normal, unit resolution mass spectrum utilizes the masses of the pieces of the molecule to reconstruct the molecule's structure. Exact mass measurement of the fragments by high-resolution mass

54

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spectrometry can give the elemental compositions of these fragments, an obvious aid to putting the pieces of the molecular puzzle together correctly. As described above, the CA spectrum can provide the isomeric structure of the fragment i o n , obviously an even more valuable aid i n the interpretation process. For example, i f high-resolution measurements showed that an un­ known molecule produced a significant Οβ^Ο" " i o n , at least the nine isomeric structures of Table II should be considered as possible molecular fragments. Measuring the CA spectrum of the C 3 H 5 0 ions from the molecule should indicate the proper isomer. For example, a steroid containing a 17-α-hydroxyethyl group shows a significant C 2 H 5 C " peak i n its normal mass spectrum; the CA spectrum of this peak identifies i t as the C H 3 C H ( O H ) isomer eliminating the p o s s i b i l i t y , for example, that the steroid contains a - C H 2 O C H 3 group (2). Such applications of CA spectra have been especially useful for oligopeptide samples. The amino acid sequence i n fragment ions can be deduced from their CA spectra, and the presence of leucine be distinguished from that of isoleucine (28). 1

+

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

1

MS/CAMS As a Separation/Identification System Recognition of the usefulness of the gas chromatograph/ mass spectrometer/computer (GC/MS/COM) system for the identification and quantitation of complex unknown mixtures has led to an amazing growth i n its analytical applications i n this decade. GC/MS/COM involves separation of the mixture and identification of the individual components, with automated data reduction; other such separation/identification systems include liquid chromatography/MS/COM. Separation can also be done mass spectrometrically, characterizing the products from the decompositions of metastable ions (29) or, as we suggested i n a study on sequencing oligopeptides i n mixtures i n this fashion (30), the identification of the mass-separated ions can also be done by CAMS. Results from a surprising number of laboratories indicate a high potential for MS/CAMS as a separation/identifi­ cation system. For example, Levsen and Schulten (31) identified major components of a complex mixture produced by the pyrolysis of deoxyridonucleic a c i d , and Cooks and coworkers (5) achieved accuracies of ±20% on the quantitative analysis of a f i v e component ketone mixture. Of special note i s the 1 0 " gram sensitivity achieved i n the latter investigation. Recent studies at Cornell (9) have examined several aspects of MS/CAMS, including separation, sensitivity, mixture ionization techniques, computer identification of CA spectra, and automation. MS/CAMS appears to be especially promising i n application to complex mix­ tures for the quantitative analysis for specific components (similar to the "selected ion monitoring" i n GC/MS), and for the identification of individual components. 11

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

3.

MCLAFFERTY

55

Ions from Collisional Activation Spectra

As a separation technique, mass spectrometry has the advantage over GC of submillisecond time requirements, which would be especially advantageous for continuous analyzers. Of special importance i s the lower sample volatility requirement of MS, using direct probe introduction or special ionization methods such as field desorption or direct chemical ionization. Note that the lack of volatility restrictions on liquid chromato­ graphy i s the chief incentive for the proposed LC/MS separation/ identification systems. Resolution i n MS i s based on an entirely different principle than i n chromatography, so that it should obviously be a complementary separation technique, and a pos­ sible solution for problems i n which chromatographic resolution is inadequate. In normal mass spectrometry double-focussing instruments are employed to improve resolution, making possible the separation of isobaric multiplets. We have recently applied this (9) to improve the separation for MS/CAMS, obtaining characteristic CA spectra of each of the doublets C H 2 3 5 C l 2 and C5H12 (nominal mass 84), and also of C H C 1 C 1 and Ο Η Ο (nominal mass 86). For MS/CAMS the ionization of the sample should give a minimum number (preferably 1) of peaks for each component of a complex mixture introduced into the MS ionization chamber. Lowering the ionizing electron energy reduces the number of peaks per component and increases the relative abundance of the molecular ion, but lowers the overall sensitivity. "Soft" ionization methods such as chemical ionization often give only one peak (plus its isotopic peaks) per compound, but different reagent gases can be necessary to obtain peaks for a l l compo­ nents as the CI ionizing reagent gases (9). 3 5

2

3 7

5

1 0

Future Possibilities For C o l l i s i o n a l Activation Mass Spectra As with conventional mass spectrometry and GC/MS, the availability of CAMS systems which are convenient to use, have automated operation and data reduction, are reasonable i n price, and which show improved sensitivity and resolution, should provide, a powerful additional incentive to further applica­ tions i n a variety of areas. Improved instrumentation such as the "ZAB" reverse-geometry double-focussing mass spectrometer of VG Micromass, the "post-acceleration" reverse-geometry spec­ trometer at the FOM Institute (12), as w e l l as the tandem doublefocussing instrument under construction at Cornell (10) should aid this problem, but smaller inexpensive instruments must also become available commercially. In this regard, i t should be possible to u t i l i z e a quadrupole MS as the mass analyzer, accelerate the ions into a c o l l i s i o n region, possibly using a molecular beam of c o l l i s i o n gas as demonstrated by Moran and collaborators (32), followed by post-acceleration and separation of the CA spectrum i n an electrically isolated electrostatic analyzer (12). With no magnet, complete computer control with

56

HIGH PERFORMANCE MASS SPECTROMETRY

rapid mass response i n both the mass analysis steps should be possible. The analysis of highly complex mixtures such as biological fluids, pollutants, insect pheromones, food aromas and flavors, and pyrolysis products i s becoming of increasing importance. The sensitivity, specificity, and speed of analysis which should be possible with MS/CAMS should make it a p p l i cable to mixtures of organic compounds on a routine b a s i s , even to on-line control, for many important problems which can only be analyzed with difficulty at present.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

iterature Cited 1. McLafferty, F. W . , Bente, III, P. F., Kornfeld, R., Tsai, R . - C . , and Howe, I., J. Am. Chem. Soc., (1973), 95, 2120. 2. McLafferty, F. W . , Kornfeld, R., Haddon, W. F., Levsen, K., Sakai, I., Bente, III, P. F., Tsai, S . - C . , and Schuddemage, H. D. R., J. Am. Chem. Soc., (1973), 95, 3886. 3. Levsen, K. and Schwarz, H., Angew. Chem., Internat. Edit., (1976), 15, 509. 4. Maurer, J. H., Brunee, C., Kappus, G., Habfast, K . , Schröder, U., and Schulze, P., 19th Annual Conference on Mass Spectrometry, Atlanta, 1971, paper K-9. 5. Kruger, T. L., Litton, J. F., Kondrat, R. W., and Cooks, R. G., Anal. Chem., (1976), 48, 2113. 6. Cooks, R. G., Beynon, J. H., Caprioli, R. M., and Lester, G. R., "Metastable Ions", Elsevier, Amsterdam, 1973. 7. Wachs, T., Bente, III, P. F., and McLafferty, F. W., Int. J. Mass Spectrom. Ion Phys., (1972), 9, 333. 8. Weston, A. F., Jennings, K. R., Evans, S., and Elliot, R. M., Int. J. Mass Spectrom. Ion Phys., (1976), 20, 317. 9. McLafferty, F. W. an d Bockhoff, F. M., Anal. Chem., submitted. 10. McLafferty, F. W. in "Analytical Pyrolysis", H. L. C. Meuzelaar, Ed., Elsevier, Amsterdam, 1977. 11. Wachs, T., Van de Sande, C. C., Bente, III, P. F., Dymerski, P. P., and McLafferty, F. W., Int. J. Mass Spectrom. Ion Phys., accepted. 12. Tuithof, H. H., Int. J. Mass Spectrom. Ion Phys., submitted. 13. Van de Graaf, B. and McLafferty, F. W . , in preparation. 14. McLafferty, F. W . , Michnowicz, J. Α., Venkataraghavan, R., Rogerson, P., and Giessner, B. G., Anal. Chem., (1972), 44, 2282. 15. Dymerski, P. P. and McLafferty, F. W . , in preparation. 16. Köppel, C., Van de Sande, C. C., Nibbering, Ν. M. M., Nishishita, T., and McLafferty, F. W., J. Am. Chem. Soc., in press.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch003

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Ioris from Collisional Activation Spectra

57

17. Rylander, P. N., Meyerson, S., Grubb, H. M., J. Am. Chem. Soc., (1957), 79, 842. 18. Bursey, J. T., Bursey, M. M., and Kingston, D. G. I., Chem. Rev., (1973), 73, 191. 19. McLafferty, F. W. and Winkler, J., J. Am. Chem. Soc., (1974), 96, 5182. 20. Arnett, Ε. M., Acc. Chem. Res., (1973), 6, 404. 21. Taagepera, M., Hehre, W. J., Topsom, R. D., and Taft, R. W., J. Am. Chem. Soc., (1976), 98, 7438. 22. Farneth, W. E. and Brauman, J. I., J. Am. Chem. Soc., (1976), 98, 7891. 23. Olah, G. A. and Porter, R. D., J. Am. Chem. Soc., (1971), 93, 6877. 24. Chong, S.-L. and Franklin, J. L., J. Am. Chem. Soc., (1972), 94, 6347. 25. McAdoo, D. J., McLafferty, F. W., and Bente, III, P. F . , J. Am. Chem. Soc., (1972), 94, 2027. 26. Dymerski, P. P., Prinstein, R. M., Bente, III, P. F . , and McLafferty, F. W . , J. Am. Chem. Soc., (1976), 98, 6834. 27. Dymerski, P. P. and McLafferty, F. W . , J. Am. Chem. Soc., (1976), 98, 6070. 28. Levsen, K . , Wipf, H.-K., and McLafferty, F. W., Org. Mass Spectrom., (1974), 8, 117. 29. McLafferty, F. W. and Bryce, T. Α., Chem. Commun., (1967), 1215. 30. Wipf, H.-K., Irving, P., McCamish, M., Venkataraghavan, R., and McLafferty, F. W., J. Am. Chem. Soc., (1973), 95, 3369. 31. Levsen, K. and Schulten, H.-R., Biomed. Mass Spectrom., (1976), 3, 137. 32. Moran, T. F . , Wilcox, J. B., and Abbey, L. Ε., J. Chem. Phys., (1976), 65, 4540. Acknowledgment We are indebted to the National Institutes of Health (grant 16609) and the Army Research Office, Durham, (grant 13136-C) for generous financial support of research described i n this review. RECEIVED December 30,1977

4 Ion Chemistry via Kinetic Energy Spectrometry R. G. COOKS

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

Department of Chemistry, Purdue University, W. Lafayette, IN 47907

This paper describes studies on ion structure, reaction mechanism and thermochemistry all of which rely on the measurement of ion kinetic energy. In all experiments the ion beam undergoes modification after i t leaves the source and it is subjected to sequential analysis by magnetic and electric fields. This ensures that a particular reaction occurring in the analyzer can be selected for study. The methodology is derived from that developed for the study of metastable ions, i.e., the spontaneous delayed fragmentations of ionized molecules. In this work, measurements on metastable ions are made in conjunction with ion/molecule interactions at high relative kinetic energy occurring after ion formation and acceleration. The reactions of interest are classified as secondary processes in contrast to primary processes which occur in the ion source. According to this view, primary processes may involve complex reaction sequences, and chemical and photochemical processes may follow the primary ionization steps, but the beam is not perturbed after extraction from the ion source. Simple mass spectra are recorded. This has been the traditional source of information on ion chemistry as well as the most important route to the applications of mass spectrometry. Secondary processes on the other hand include all those in which the ions issuing from the ion source subsequently undergo measurable alterations in charge state, mass, gross structure or electronic state. Adequate characterization of these processes usually requires that two independent measurements be performed on the ion beam after i t leaves the source. Secondary processes may be spontaneous and involve emission of a photon, an electron, an atom or a molecule. Of these processes, only the latter is well-characterized, and i t represents a metastable ion dissociation. Secondary processes which are not spontaneous may occur when the ion interacts with a gas atom or molecule, an electron, a surface, a photon beam or an electromagnetic field. Reactive collisions are of no importance in the kilovolt energy range so the inelastic reactions of interest are confined to electronic transitions, charge stripping, charge ©0-8412-0422-5/78/47-070-058$10.00/0

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

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59

exchange and photoemission and the dissociations which can follow these processes. Thus, our study of chemistry w i l l be based on measurements on the processes shown i n Table I . The structure of the reactant ion i s frequently of major interest when secondary processes are studied. This structural information i s often derived by monitoring the dissociations, either spontaneous or collision-induced, of the ion i n question. This often provides direct access to molecular structure and con­ stitutes a method of product analysis f o r ion source reactions. Other methods of characterizing an ion through i t s charge changing c o l l i s i o n s or v i a simple excitation reactions w i l l also be noted below. Thermochemical measurements accomplish t h i s purpose, and ion enthalpy measurements made i n the ion source by varying the energy deposited upon ionization represent the t r a ­ d i t i o n a l source of t h i s data. Using fast ion beams k i n e t i c energy loss measurements associated with ion/molecule reactions provide analogous data. I t i s a fortunate fact that for conditions commonly f u l f i l l e d i n mass spectrometers, the heat of reaction for ion/molecule reactions i s measured to a good approximation as the k i n e t i c energy change (loss i f endothermic, gain i f exothermic) of the fast species.* The value of k i n e t i c energy measurements i n studying secondary processes i s further enhanced by the k i n e t i c energy amplification associated with the disposal of internal energy of an excited species as r e l a t i v e translational energy of i t s fragments. The range of k i n e t i c energies of the fragment ions can be 1 0 the actual center of mass energy release. This makes possible sophisticated measurements on energy p a r t i t i o n i n g as well as the characterization of the reacting ion and i n favorable cases i t s fragmentation mechanism. This measurement i s applicable to both spontaneous and collision-induced dissociations. In summary, the chief concern of t h i s paper i s the use of secondary processes to characterize ions formed i n a chemical ionization source. To f u l l y exploit the r i c h chemistry associated with low energy, gas-phase ion/molecule reactions, direct methods for characterizing the structures of product ions are needed. For t h i s purpose, we use the conjunction of a chemical ionization source as reaction vessel with the methods of ion k i n e t i c energy spec­ trometry for analysis. 5

*The target r e c o i l energy i s given by j j| g- where m i s the mass of the ion,Ν that of the target, Q i s the heat of reaction and Ε i s the reactant ion translational energy.

CO

i

α·

CO CO

w

CO

Photon-induced

C o l l i s ion-induced (Surface-induced)

m.

Autoionization

+

++

3

n

m

3

Photoexcitation

m^ + hj •+ m^ *

r

ι -> m ++ , nu + + ity +e

+

Photo i o n i zat ion

ην

m^

Photo Dissociation

+

m-j* + Ν + m-j** + Ν

+Ν

Excitation

m^

+ Ν + e"

m^

+Ν

++

m^ + Ν + m^

2

+

+ e~

+ m

+ m..

+ Ν -•m + m + Ν

mi

m^

m«

Charge exchange

Stripping

+

m^

Dissociation

+

m^

Emission

The fast analyzed species i s underlined.

INDUCED PROCESSES

SPONTANEOUS PROCESSES

Metastable Fragmentation

Table I . Reactions Studied V i a Translational Energy Measurements

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

ο

w

s ο

ο χ

Ο

4. COOKS

61

Kinetic Energy Spectrometry

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

Analysis of Mixtures by MIKES/CID By choosing an appropriate configuration for a double focusing mass spectrometer and by studying secondary fragmentations, the analysis of mixtures can readily be achieved. Q-4) The mass-analyzed ion k i n e t i c energy (MIKE) arrangement allows tor ion selection as a prelude to dissociation. Kinetic energy analysis of the fragments provides a fragmentation pattern from which the structure of the reactant ion, and hence that of the corresponding neutral molecule, can be inferred. Figure 1 summarizes the principles of this method of mixture analysis. The method i s an alternative to gas chromatography/mass spectrometry and i t has the advantage that i t employs electromagnetic rather than chromatographic separation. D i f f i c u l t i e s of v o l a t i l i t y , lengthy development times and chemical contamination or degradation associated with chromatography are avoided. This i s accomplished at the expense of a loss i n sensit i v i t y associated with measurements on secondary rather than primary ions. Although both electron impact and chemical ionization have been employed i n these analyses, chemical ionization i s preferred because i t secures the structural relationship between the neutral molecule of interest and the corresponding ion which i s actually separated and analyzed. The secondary fragmentation reaction may be spontaneous or collision-induced. The l a t t e r are much preferred since ( i ) more reactions are observed, ( i i ) the t o t a l signal due to secondary ions i s higher, t y p i c a l l y by an order of magnitude, ( i i i ) there i s a greater tendency for simple bond cleavages i n CID than i n metastable ion reactions. To i l l u s t r a t e the s e n s i t i v i t y of t h i s technique consider the scan shown i n Figure 2. This peak i s a part of the MIKE spectrum taken i n the presence of c o l l i s i o n gas, of the (M + H ) ion of p-nitrophenol which was present i n a mixture of nitrobenzenes. Of special note i n these spectra (compare r e f . l c ) i s the cleanliness of the background as contrasted to gc/ms spectra. This i s a consequence of the double f i l t e r which operates i n obtaining these spectra. The signal to noise characteristics of the peak shown i n Figure 2 are consistent with a detectability l i m i t of ca. 10~Hg for t h i s experiment. Quantitation of the procedure has not been investigated i n d e t a i l but the general considerations should be similar to those i n volved i n quantitation of gc/ms data. For highest accuracy t h i s demands use of an internal standard, preferably an i s o t o p i c a l l y labeled variant of the compound of interest. An additional consideration, i f collision-induced dissociation i s employed, i s that the pressure of the target gas must be held constant. Figure 3 demonstrates the type of accuracy which i s readily achieved, variations i n c o l l i s i o n gas pressure being the major source of error i n t h i s experiment. One of the more attractive features of t h i s method i s i t s i n s e n s i t i v i t y to the presence of large amounts of impurities. Solvent +

HIGH PERFORMANCE MASS SPECTROMETRY

(M,*H)* Ionize (M +Hf Mass (M +H)

[(Μ +Η)**]—

3

M

3

CI

m

Excite

2

3

3i

m

Energy H

32

Analyze

(M +rtf Analyze 3

m 99 Characterization

Separation

Collision Spectroscopy

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

Figure 1. Principle of mixture analysis using the reversed sector massanalyzed ion kinetic energy (MIKE) spectrometer

5xl0" g/sec n

Figure 2. Illustration of sensitivity of the MIKES mixture analysis method. The peak shown, scanned in 3 min, is a characteris­ tic fragmentation (loss of OH) of the protonated molecular ion of p-nitrophenol. 86

88

90

%E

—X— 3-methyl-2-butonon« — 0 — 2-pentonont — o — 3-ptntanont

Mole

Fraction Analytical Letters

Figure 3. Analysis of ketones in mixtures of varying composition by electron impact ionization followed by MIKES

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

4. COOKS

Kinetic Energy Spectrometry

63

may constitute the major portion of the sample without deleterious results. Indeed, the solvent could probably be used to advantage as the CI reagent gas i n some cases. These considerations suggest that the method might f i n d appropriate application i n the continuous analysis of organic reaction mixtures or effluents. Cases i n which workup must be minimized, e.g., where chromatography a l t e r s the composition of the mixture are of special interest. Results on the analysis of the mixture resulting from the methylation of 2-butanone by methyl iodide i n the presence of base are given i n Table I J. Each compound was quantitated using c h a r a c t e r i s t i c peaks i n the MIKE spectrum of i t s molecular ion (electron impact). I t i s noteworthy that the mixture included isomers which are not separated i n the mass analysis stage of the procedure. The results given are for an early and a l a t e aliquot. They indicate the progress of methylation and the s t e r i c control to which t h i s reaction i s subject. The agreement between results employing metastable ion dissociations and CID i s of the order expected i n the absence of more sophisticated internal standards. Currently, mixture analysis by CI/MIKES i s being extended to more complex compounds including natural products and pharmaceuticals. Classes of conpounds which, because of v o l a t i l i t y or thermal i n s t a b i l i t y , cannot readily be separated by gas chromatography are of special interest. For t h i s reason the MIKE spectra of barbiturates have been examined. (2) There have been continued d i f f i c u l t i e s i n the analysis of these compounds, even using the newer mass spectrometric techniques. The ethyl- and a l l y l substituted barbiturates give most d i f f i c u l t y i n analysis and we therefore chose to examine several of the most refractory isomeric and homologous barbiturates. The MIKE spectra of the (M + H ) and (M + C2H5)* ions were found to c l e a r l y distinguish them. Figure 4 compares the MIKE spectra taken i n the presence of c o l l i s i o n gas of four protonated barbiturates. Two sets of isomers and two sets of homologs are represented. The sec-butyl group of butabarbital and the sec-amyl group of pentobarbital are associated with intense fragmentation by alkene elimination. The substituents which bear fewer hydrogens on the ot-carbon show t h i s reaction to a lesser extent. The s i m i l a r i t i e s i n the spectra shown are t y p i c a l of those observed for homologous barbiturates. The current s i t u a t i o n regarding mixture analysis by MIKES i s that the technique appears to be complementary to gc/ms, being applicable i n situations i n which gc i s d i f f i c u l t . The spectra are r e a d i l y interpreted and quantitation seems not to present any new problems. As occurred i n the development of gc/ ms, i t seems l i k e l y that automation of the instrumentation w i l l be required to achieve i t s f u l l potential which should include continuous monitoring c a p a b i l i t i e s . The somewhat lower sensit i v i t y compared with gc/ms should not often preclude i t s use, and the potential to analyze i n v o l a t i l e and thermally unstable b i o l o g i c a l compounds i s a most a t t r a c t i v e compensatory feature. +

HIGH PERFORMANCE MASS

SPECTROMETRY

Table I I . Analysis of Reaction Mixtures from the Methylation of Butanone

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

Early

Late

+

M*

Unimol

Unimol + CID

72

0.15

0.15

86

0.18

0.20

86

0.17

0.16

100

0.35

0.35

100

0.02

0.02

114

0.09

114

128

Unimol

Unimol + CID

0.04

0.04

0.10

0.88

0.92

0.03

0.02

0.08

0.02

—

-

0.01

0.01

4. COOKS

Kinetic Energy Spectrometry

65

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

Fragmentation Mechanisms and Metastable Ions i n Chemical Ionization Chemical ionization allows ready access to types o f ions which cannot be generated by electron impact. There has, however, been r e l a t i v e l y l i t t l e attention given the fragmentation mechanisms of these ions. This has been a consequence o f the emphasis accorded the determination of molecular weights by CI and the resulting efforts to minimize fragmentation. When secondary reactions are studied, fragmentations are naturally highlighted and i t has been observed that metastable ions i n CI often have i n t e n s i t i e s comparable to those observed i n EI. The study of metastable ions i n CI reveals the existence of a fragmentation mechanism i n which a neutral alkane molecule i s eliminated from onium type ions. For example, protonated t-butyl ethyl ether fragments by eliminating a butane molecule (1) while H CH.

Œ CH=ÔH + C H 3

4

CD

10

CH / I 3 CH. the trimethyloxonium ion losses methane. The reaction has also been observed i n halonium and ammonium ions. In a l l cases i t probably occurs v i a a four-centered mechanism (see below). I t i s sometimes observed i n competition with a l k y l r a d i c a l loss and alkene molecule elimination. The reaction i s quite general, since i t also occurs i n odd-electron ions. (3) Thus i t has been observed from the molecular ions of ketones and amines. Figure 5 compares the fragmentations of the molecular ion and the (M + H ) ion of diisopropyl ketone. The s i m i l a r i t y i n behavior o f the odd and even electron ions i n undergoing loss of an alkane molecule i s remarkable. Alkane loss has long been known i n the mass spectra of alkanes themselves, but, except for an isolated observation on ketones (4), the reaction has u n t i l recently gone unnoticed. I t now seems~that i t constitutes an important general fragmentat i o n mechanism which p a r a l l e l s the well-known alkene eliminat i o n (McLafferty rearrangement) i n the types of ions i n which i t occurs and i n i t s importance as a favored process at low internal energy. The four centered mechanism has been e x p l i c i t l y demonstrated f o r diisopropyl ketone by deuterium labeling. +

C H

C

3^ / \ ^ C

Œ

3" / H

C H

C

D

x

X

CH

3 3

>

H-C-D C^

+ 0=C=C Χ

3

(

Ή

X

3

3

66

HIGH PERFORMANCE MASS SPECTROMETRY

(M*H)

Butabarb (s-Bu)

+

' 212

Pentobarb (s-Am!

(M*H) 226

-132

-J

(M+H)

Butethal (n-Bu)

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

212

Amobarb (i-Am)

(M+H) 226

ι r Figure 4. MIKE spectra taken in presence of target gas of the proto­ nated barbiturates indicated. The stable ion beam, (M + H)* is recorded at an attenuation of JO . 3

|<M*H)+|

Figure 5. MIKE spectra showing spontaneous alkane elimination from both the molecular ion and the protonated molecule for diisopropyl ketone

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

4.

COOKS

67

Kinetic Energy Spectrometry

Studies i n other cases are i n hand. A tentative generalization i s that the reaction i s f a c i l i t a t e d by positive charge density on the heteroatom or functionalized carbon. The study of metastable ions i n CI not only provides informat i o n on fragmentation mechanisms but i t i s a valuable source o f information on the internal energies of ions extracted from the source. I f c o l l i s i o n s relax the ions below the activation energy for the lowest energy fragmentation then no metastable ions w i l l be observed. Experiments i n which an inert bath gas i s admitted to the CI source and metastable ion abundances are followed are p a r t i c u l a r l y attractive as a new method of studying energy transfer i n ion/molecule c o l l i s i o n s . In a related type of experiment a correlation has been observed between the presence of metastable ions i n CI and the activation energy f o r the lowest energy fragmentation. (5) Thus, C3H5 " ions which require 2-3 eV of internal energy to undergo H loss show essentially no metastable peak even when generated by a variety of ion/molecule reactions. The process can, however, be induced by c o l l i s i o n and the k i n e t i c energy release i s then 0.47 eV i n good agreement with the value of 0.43 eV found f o r collision-induced dissociation of C3H5"" ions generated by electron impact. Figure 6 which i s adapted from ref. 6 shows these results as compared to the metastable dissociations of the same ions. The l a t t e r occur v i a two competitive reactions to give a composite metastable peak. On c o l l i s i o n , only the higher activation energy, higher frequency factçr reaction i s observed. In contrast to the behavior of C^Hr , the molecular ions of substituted nitrobenzenes which can undergo NO* loss a t considerably lower internal energies, show abundant metastable peaks. These reactions correspond e n t i r e l y to those observed for the same ions generated by electron impact, both sets of ions showing composite metastable peaks with the same k i n e t i c energy releases. Figure 7 i l l u s t r a t e s the composite metastable peaks associated with NO' loss from the molecular ions of pchloro and p-hydroxy nitrobenzene. The contrasting behavior o f the nitrocompounds and CJir can be interpreted i n terms of the e f f i c i e n c i e s of quenching of the states responsible f o r fragmentation on the time scale associated with metastable ions. 4

2

1

Isotope Labeling and the MIKE Spectrometer I t would be d i f f i c u l t to overestimate the importance that labeled compounds have had i n the elucidation of gas-phase ion chemistry. Frequently the synthesis of pure compounds, highly incorporated at s p e c i f i c s i t e s , has been the challenging and time consuming step i n such work. The MIKE spectrometer relaxes the requirements for both chemical and isotopic purity and so f a c i l i tates t h i s type of endeavor. (7) Quite simply, mass selection acts as a f i n a l stage of chemical and isotopic p u r i f i c a t i o n i n the synthesis. Subsequent to mass-analysis, either metastable or c o l l i s i o n -

68

HIGH PERFORMANCE MASS

SPECTROMETRY

ENERGY RELEASE

Threshold for (A)-

CID

m* E (A)"0.5eV rev

Thresholdfor(B)-

0 27eV EI CH=C-CH2+H

0 43eV;0-47eV EI CI

2

12.0 -

E (B)«l.2eV rtv

CALCULATED BARRIER _

I OOeV EI

not observed

PR0PENYL+

ο CH Ç«CH

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

2

2

Figure 6. Thermochemistry of the reactions C H * -» C H * + H (6). Also shown are the measured kinetic energy releases for the unimolecular (m*) and collision-induced dissociations (CID) when the ion is generated by electron impact (EI) and chemical ionization (CI). 3

5

3

S

2

a)pOH

80 %e

Figure 7. Composite metastable peaks for NO- loss from the molecular ions of the substituted nitrobenzenes indicated. The molecular ions were formed in the CI source by charge exchange with argon ions, were mass selected, and their energy spectra were plotted.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

4.

COOKS

Kinetic Energy Spectrometry

69

induced dissociations may be studied depending upon whether react­ ing ions of higher or lower internal energy are of interest. These points are i l l u s t r a t e d by the elimination of propane from the diisopropyl ketone molecular ion. (Id) The acidic hydrogens on the α-carbons are readily exchanged with i n base. The p a r t i a l l y incorporated compound obtained by a single exchange step serves for analysis by the MIKES technique as i l l u s t r a t e d i n Figure 8. This shows part of the MIKE spectrum of the à^compound (401 of the ketone sample) compared to that of the unlabeled compound. Alkane elimination i s seen to involve loss of both labeled hydrogen atoms. Indeed, informative results are obtained on both the cL-ketone and the cL -ketone which can be selected independently for study. Experiments run i n the presence of target gas show, i n addition, collision-induced dissociation by loss of an a l k y l radical. The MIKE spectra of the labeled compounds confirm this and show that no hydrogen isomerization i n volving the methyl groups occurs. As a variation on the above approach i n which the MIKES i s used to purify a crude labeled compound, the synthesis i t s e l f can be carried out i n the CI source. Thus, using simple labeled reagents the ion of interest can be synthesized, purified and i t s reactions characterized, a l l within the mass spectrometer. Proton A f f i n i t i e s using Metastable Ions Metastable ions, because they refer to species which^have_^ just enough energy to react at a rate of approximately 10 sec , provide a source of thermochemical data on reaction thresholds. A long standing generalization i s that i f competitive fragmentations from the same ion both give r i s e to metastable peaks, the reactions must have similar activation energies. I f i n addition, the reactions are of similar type so that their frequency factors are comparable, then the relative magnitudes of their activation energies can be expected to determine the relative metastable peak heights. Thus, comparison of a kinetic quantity, the relative rates of two reactions from a given ion, allows the determination of a thermochemical quantity, the relative free energies of activation. In the cases of interest here, a direct correlation with enthalpy of activation i s expected because of the detailed s i m i l a r i t y i n the competitive reactions examined. Furthermore, this correlation should extend to the enthalpies of reaction provided reverse activation energies are negligible or similar. Thus, the r e l a t i v e metastable ion abundance should correlate with the relative product enthalpies. Figure 9 i l l u s t r a t e s the basis of the method. We have applied (8) these concepts to the competitive metastable ion dissociations of proton bound dimers, Β ΗΒ . These reactions Ί

+

B HB

2

B]HB

2

1

+

+ Β Η +B χ

+

+ Bi + B H 2

2

+

?

(2) (3)

70

HIGH PERFORMANCE MASS SPECTROMETRY

Analytical Chemistry

70 71 72 Mass

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

Figure 8. Partial MIKE spectra (no collision gas) of the molecular ions of unlabeled and labeled ketones mass selected from a partially incoroprated sample

Figure 9. (a) Rate constant vs. internal energy curves for competitive reactions of different activation energy but simihr frequency factor. When the internal energy is high enough for the higher energy process to occur fast enough to be observed as a metastable ion, the lower energy process is going faster still, and it dominates the spectrum at all internal energies; (b) the same situation illustrated by the very different state densities for the competitive fragmentations at an internal energy in excess of both activation energies.

4. COOKS

71

Kinetic Energy Spectrometry

are p a r t i c u l a r l y appropriate for t h i s treatment since they are simple bond cleavages, presumably involving steeply r i s i n g rate constant vs internal energy curves. Furthermore reverse activation energies are l i k e l y to be small. The difference i n product enthalpies for the competitive reactions (2) and (3) i s +

Δ(ΔΗ ) = AHfC^H*) + ΔΗ (Β ) - AH (B ) - ΔΗ (Β Η ) £

£

2

£

]L

£

2

(4)

but the proton a f f i n i t y PA i s the negative of the enthalpy change on addition of a proton, +

+

ΡΑ(Β ) = ΔΗ (Β ) + ΔΗ (Η ) - ΔΗ (Β^Η ) Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

χ

£

1

£

£

(5)

hence substituting i n (4) we have, Δ (AH ) - ΡΑ(Β ) - PA(B ) £

χ

(6)

2

Thus, the more abundant metastable peak for reactions (2) and (3) should indicate the base of greater proton a f f i n i t y . The order­ ing of proton a f f i n i t i e s should be independent of the internal energy d i s t r i b u t i o n of the reactant ion B^HB^"" although the meta­ stable ion abundance r a t i o w i l l depend on t h i s factor. We leave for elsewhere an attempt to develop t h i s quantitative r e l a t i o n ­ ship further; here we present results on the r e l a t i v e ordering of proton a f f i n i t i e s by t h i s new method. A mixture of 3-aminopentane and 2-aminobutane introduced into the CI source v i a a methane gas stream gave the mass spectrum shown as Figure 10. The ions at m/e 88 and 74 are due to pro­ tonated amines, those at 114, 128 and 142 appear to be immonium ions formed by transamination of the (M - H ) ions and those at 147, 161 and 175 are the proton bound dimers. The MIKE spectrum of the asymmetrical dimer m/e 161 i s shown i n Figure 11. As expected from data taken by equilibrium studies (9), 3-amino­ pentane has the larger proton a f f i n i t y (the difference i s 1 kcal mole-1). The method i s expected to be sensitive to small differences i n proton a f f i n i t y as the schematic i l l u s t r a t i o n of Figure 9 shows. This s e n s i t i v i t y i s i l l u s t r a t e d by a comparison of s-butylamine and pyridine which have been found by i c r (10) t o have v i r t u a l l y identical proton a f f i n i t i e s . Figure 12 i s a slow scan through part of the MIKE spectrum of the proton bound dimer of these two bases. Protonated pyridine i s formed i n higher abundance suggesting that pyridine has the greater proton a f f i n i t y , probably by 0.1 to 0.2 kcal mole-1. These results were obtained without correcting for c o l l e c t i o n and detector e f f i c i e n c i e s . This can be done by studying labeled ions i f isotope effects can be ignored. The dimer of pyridine and dr-pyridine provides a case i n point, results for i t being shown i n Figure 13. This type of experiment can also be designed for the determination of isotope effects on proton a f f i n i t i e s . 1

+

161

2

147

4

142

128 114

JUL

88

74

>

M

>

o

M

o

Ο

Figure 10. CI (CH^) mass spectrum of a mixture of 3-aminopentane and 2-aminobutane showing formation of proton boundQ dimers

_JL_

175

2

NH + >-NH + CH

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

COOKS

Kinetic Energy Spectrometry

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

(tIOOO)

1 60

40 %E

Figure 11. MIKE spectrum (no collision gas) of the proton bound dimer formed from 2-aminobutane and 3-aminopentane. The stronger base gives the large metastable peak for formation of the BH+ ion.

48

'

50

'

52

%F

Figure 12. Part of the MIKE spectrum of the s-butylamine/ pyridine proton bound dimer illustrating a case in which the metastable peaks for Reactions 2 and 3 differ in height by less than a factor of two. The proton affinity difference in this case is estimated to be 0.1 to 0.2 kcal mol' . 1

74

HIGH PERFORMANCE MASS SPECTROMETRY

As a f i n a l i l l u s t r a t i o n of the s e n s i t i v i t y of the MIKES approach i n investigating ion chemistry, Figure 14 shows a p a r t i a l MIKE spectrum of a C - labeled pyridine/s-BuNH2 dimer formed using only unenriched compounds. These species were selected from the complicated mixture of ions present i n the ion source. The doubly labeled ion represents only I I of the protonated dimer ion current. Nevertheless, i t s metastable reactions can r e a d i l y be studied the l a b e l pattern shown i n part (b) being that associated with pyridine and agreeing with the s t a t i s t i c a l l y required r a t i o of 3:10:5 for 80 :81 :82 . Work currently i n hand has shown that the method can be extended to bases belonging to other functional groups, and a ladder of b a s i c i t i e s i s being established. Collision-induced dissociation, although less sensitive to small differences i n proton a f f i n i t i e s than are metastable ion reactions, has been found to give corresponding r e s u l t s . The k i n e t i c energy releases for some of these reactions have been measured, and the small values recorded are consistent with the proposed n e g l i g i b l e effect of reverse a c t i v a t i o n energy. I 3

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

+

+

+

Ion Structure Determinations In keeping with the importance of determining ion structures, there has been a great deal of emphasis placed on t h i s subject i n recent years. Measurements of metastable ion characteristics, especially k i n e t i c energy release, ion enthalpies, and c o l l i s i o n a l activation (collision-induced dissociation) spectra have been most valuable i n t h i s regard. Our recent work i n t h i s area has f a l l e n into two categories, (a) the application of established methodology to investigate the structures of ions generated by chemical ionization, (b) the testing of new methods for characterizing ions. Examples from each topic are covered i n turn below. The combination of a chemical i o n i z a t i o n source with a MIKE spectrometer allows ions formed by CI to be independently characterized. This i s r e a d i l y done by mass-selection, followed by collision-induced dissociation. The r e s u l t i n g MIKE spectrum w i l l contain metastable peaks as w e l l as those due to CID. Figure 15 shows a set of these spectra for the ethylated nitrobenzenes indicated.(11) A s t r i k i n g feature of the spectr| i s the occurrence of major reactions common to a l l four (M + C-Hr) ions. The reactions correspond to loss of C H., C X O aild CJlrONO. The l a t t e r two processes can occur as simple Bond cleavages only i f the n i t r o group i s ethylated. ,As a further test of t h i s structure, the corresponding protonated molecules were examined i n the same way. Major reactions now observed were loss of HO" and MXJT, supporting the conclusion that the n i t r o group i s more basic than the r i n g or the para substituent. A characteristic of r i n g a l k y l a t i o n or protonation i s the loss of the substituent as a free r a d i c a l . Thus, one can contrast the absence of CI* loss i n the spectrum of ethylated 2

4. COOKS

Kinetic Energy Spectrometry

Py....Ht...Py (d ) e

W )PyH* 9

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

PyH

%Ε

Figure 13. Metastable peaks for the formation of labeled and un­ labeled pyridinium ions from a partially labeled dimer. Collection and detection efficiencies can be estimated from this data if second­ ary isotope affects are assumed negligible.

(Py...H ..NH Bu )-*C +

l

t

t

ι βι •

51

52

53

%E

Figure 14. Illustration of the selectivity and sensi­ tivity of the MIKES tech­ nique for studying ion thermochemistry. The doubly labeled ion stud­ ied was selected from the naturally occumng mix­ ture.

75

HIGH PERFORMANCE MASS SPECTROMETRY

o)pNO

.197* t

-28 -45

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

50

200 I77

150

100

+

b)pCN

J

L 150

100

50

186

c)pCI

50

150

100

186

d)pOH

50

100

150

Figure 15. MIKE spectra taken in the presence of collision gas of the (M + Ety ions of the substituted nitrobenzenes indicated. The abscissae of the spectra are calibrated in terms of ion mass. The stable ion beams have been divided by approximately 10 . s

4. COOKS

Kinetic Energy Spectrometry

77

£-chloronitrobenzene (Figure 15c) with the spectra of protonated p-chlorophenol, ethylated p-chlorobenzoic acid and ethylated pchlorobenzonitrile. Loss of CI* i n these compounds gives peaks which are 53%, 50%, and 3% of the most abundant fragment ions, respectively. In these and other cases there i s also evidence for a mixture of ring and substituent alkylated ions. We turn now to the testing of newer methods of characterizing ions. Those which employ the same instrumentation and methods as CID and metastable ion reactions are most attractive. Thus, charge stripping (7) provides a case i n point, the cross section

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

+ N+ m^* + Ν + e-

(7)

for the reaction being readily measured r e l a t i v e to that f o r an ion chosen to serve as an internal standard. This procedure was adopted i n comparing the isomeric C;$HgN ions generated from t butylamine and diethylamine. The l a t t e r showed a peak due to charge stripping which was more than an order of magnitude more intense than the former. I t seems probable that t h i s difference i s due less to differences i n the cross section f o r stripping (a process with a large energy loss which should be r e l a t i v e l y i n ­ sensitive to structural variation) than i t i s due to differences i n the s t a b i l i t y of the nascent doubly charged ions. Stripping at k i l o v o l t energies i s a v e r t i c a l process, the doubly charged ion being generated with the same structure as i t s singly charged precursor. Thus, the greater extent of fragmentation of the more highly branched C3HgN ion generated from t-butylamine i s the expected result. Although t h i s method of characterizing ions r e l i e s on a single parameter, i t i s of some interest as a means of sampling singly charged ions of lower average internal energy than i s the case f o r collision-induced dissociation.(12) A consequence i s that comparisons between stripping and CID sEould aid i n uncovering isomerizations occurring below the threshold for fragmentation. As a second example of newer methods of characterizing ions, we s h a l l consider measurements of k i n e t i c energy loss f o r collision-induced dissociations. Kinetic energy releases can be measured from the same data so we consider them together. As an example, H loss from a l k y l cations can be considered. Analogies i n structure and fragmentation mechanism of C2H3 , C?H C1 , C H3 , C H5 , and C H are inferred from the fact that these ions when generated from a variety of precursors give the energy losses and k i n e t i c energy releases shown i n Table I I I . The methyl cation shows contrasting behavior i n both i t s k i n e t i c energy loss and i t s energy release. +

++

2

+

2

+

+

3

+

3

+

4

3

78

HIGH PERFORMANCE MASS

SPECTROMETRY

Table III. Energy Releases and Losses for A l k y l Ions

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

Ion

Energy Loss (eV)

Energy Release (meV)

10.3±1.6

330±15

9.4±1.4

339t31

11.3±0.5

334±4

11.0

334

10±1

296±17

6.4±0.9

83±4

Conclusion Ion chemistry and i t s analytical applications have been treated here with a focus on particular instrumentation and types of measurements. The combination of chemical ionization with the mass-analyzed ion k i n e t i c energy (MIKE) technique i s valuable i n determining the structures of ions generated by low energy ion/molecule reactions, i n the analysis o f complex mixtures without p r i o r separation and i n mechanistic studies employing labeled compounds. The usefulness of k i l o v o l t energy ion/molecule reactions as a surprisingly subtle probe of ion properties i s shown. The compatibility of these and metastable ion reactions i n terms of instrumentation and the complementary information they supply i s noteworthy. Wider use of charge changing c o l l i s i o n s as well as collision-induced dissociation for organic ions seems appropriate. The range of inquiry which can be based on the rather simple measurement of ion k i n e t i c energy remains a constant source of pleasure t o t h i s research group. Acknowledgement This work has been supported by the National Science Foundation and done i n collaboration with T. L. Kruger, V. M. Franchetti, J . F. L i t t o n , R. W. Kondrat, C. S. Hsu, R. Flammang, E. Soltero-Rigau and D. Cameron.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch004

4. COOKS

Kinetic Energy Spectrometry

79

Abstract Secondary reactions including spontaneous and collision­ -induced dissociation and charge changing collisions, have been studied by the methods of ion kinetic energy spectrometry. Emphasis is on ions generated by chemical ionization which are mass-selected before reaction and energy analyzed after. Appli­ cations to the analysis of mixtures without chromatographic separation are demonstrated. Ion structure determinations are made on CI generated ions. Kinetic energy release and loss measurements are used to characterize ions. Studies on labeled compounds employing partially labeled material are shown to be possible so facilitating mechanistic investigations. Alkane elimination is shown to be a general low energy fragmentation occurring in both odd- and even-electron ions. The occurrence of metastable ion dissociations in chemical ionization experiments has been explored and these reactions form the basis for a new and sensitive method of ordering proton affinities in the gas phase. Literature Cited 1. Smith, D.H., Djerassi, C., Maurer, K.H., and Rapp, U . , J . Am. Chem. Soc., (1974), 96, 3482. 2. Schlunegger, U.P., Angew. Chem., Int. Ed. Engl., (1975), 14, 679. 3. Kruger, T.L., Litton, J.F., and Cooks, R.G., Anal. Chem., (1976), 9, 533. 4. Kruger, T.L., Litton, J.F., Kondrat, R.W., and Cooks, R.G., Anal. Chem., (1976), 48, 2113. 5. Levsen, Κ., and Schulten, H.R., Biomed. Mass Spectrom., (1976), 3, 137. 6. Soltero-Rigau, E., Kruger, T.L., and Cooks, R.G., Anal. Chem., (1977), 49, 435. 7. Litton, J.F., Kruger, T.L., and Cooks, R.G., J . Am. Chem. Soc., (1976), 98, 2011. 8. Cooks, R.G., Yeo, A.N.H., and Williams, D.H., Org. Mass Spectrom., (1969), 2, 985. 9. Cameron, D., Clark, J.E., Kruger, T.L., and Cooks, R.G., Org. Mass Spectrom., in press. 10. Holmes, J . L . , Osborne, A.D., and Weese, G.M., Org. Mass Spectrom., (1975), 10, 867. 11. Beynon, J.H., Brothers, D.F., and Cooks, R.G., Anal. Chem., (1974), 46, 1299. 12. Cooks, R.G., and Kruger, T.L., J. Am. Chem. Soc., (1977), 99, 1279. 13. Aue, D.H., Webb, H.M., and Bowers, M.T., J . Am. Chem. Soc., (1972), 94, 4726. 14. Kruger, T.L., Flammang, R., Litton, J.F., and Cooks, R.G., Tetrahedron Letters, (1976), 4555. 15. Cooks, R.G., Beynon, J.H., and Litton, J.F., Org. Mass Spectrom., (1975), 10, 503. RECEIVED December 30, 1977

5 Field Ionization Kinetic Studies of Gas-Phase Ion Chemistry N. M. M. NIBBERING

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

Laboratory for Organic Chemistry, University of Amsterdam, Amsterdam, The Netherlands

In the last few years the method of Field Ionization Kinetics (FIK) has been developed rapidly by several groups (1). The technique has proved to be successful in providing detailed information on the mechanisms of decompositions of ions in the gas phase (1,2). This information has been d i f f i c u l t or even impossible to obtain from conventional electron impact (EI) studies. Although the underlying theory of the FIK method has been described extensively i n detail (1,3), i t w i l l be repeated here i n a very simple way. If, for example, a 10 μm conditioned wire emitter (4) at potential V (- 8 kV) is positioned approximately 1.5 mm from a grounded and slotted cathode, gas phase molecules may be ionized in the strong e l e c t r i c f i e l d at a very narrow region close to the emitter. To a good approximation, the potential is equal to the emitter potential V at this point (Figure 1). Suppose that the ions, formed by either direct ionization or unimolecular decomposition close to the emitter, are stable for ≥ 1 0 sec. They w i l l acquire a kinetic energy eV (Turing acceleration from the emitter to the cathode and w i l l pass the e l e c t r i c sector of a double focussing mass spectrometer, set to transmit ions with a kinetic energy eV . Consequently, they w i l l be mass analyzed at their correct m/e-values. In this way a f i e l d ionization (FI) spectrum is obtained, containing peaks corresponding to the ions generated very near to the emitter, i . e . , wijhin approximately 1 0 sec. Fragment ions, m , generated by expulsion of (M-m) from M ions between the emitter and cathode at potent i a l V (Figure 1) are not transmitted through the e l e c t r i c sector, because they have insufficient kinetic 0

0

-5

0

0

- 1 1

+

+

x

©0-8412-0422-5/78/47-070-080$05.00/0

5.

81

Field Ionization Kinetic Studies

NiBBERiNG

energy (em/M ( V Q - V ^ ) + eVy) t o be f o c u s s e d by t h i s s e c t o r . However, t h e s e i o n s can be t r a n s m i t t e d t h r o u g h the e l e c t r i c s e c t o r by i n c r e a s i n g the e m i t t e r p o t e n ­ t i a l , V Q , by an amount A V , such t h a t the k i n e t i c energy of the fragment i o n s , m , i s g i v e n by e q u a t i o n (1) (3a). +

e V

0

=

ΤΓ

( V

0

+

Δ Υ

* V

+

e V

X

Thus i t i s p o s s i b l e t o m o n i t o r a t a f i x e d e l e c t r i c s e c ­ t o r v o l t a g e the abundance o f m i o n s as a f u n c t i o n o f the e m i t t e r p o t e n t i a l V Q + A V ( 3 a ) . A scan o f the e m i t t e r p o t e n t i a l , a c h i e v e d by i n c r e a s i n g A V , a l l o w s one t o v i e w the d e c o m p o s i t i o n s o f i o n s M o c c u r r i n g a t e v e r - i n c r e a s i n g d i s t a n c e s from the e m i t t e r . Of c o u r s e , these i n c r e a s e d d i s t a n c e s correspond to longer l i f e ­ t i m e s (5) o f the p a r e n t i o n , M . E x p r e s s i n g the abun­ dance o f m i o n s due t o l o s s o f (M-m) as a f u n c t i o n o f time f o l l o w i n g FI o f M, the FIK c u r v e o f m i s ob­ t a i n e d ( F i g u r e 2 ) . The time r a n g e , c o v e r e d c o n t i n u ­ o u s l y by the FIK method, i s a p p r o x i m a t e l y 1 0 " to 10" s e c . A d d i t i o n a l p o i n t s a t lçnger t i m e s can be o b t a i n e d from d e c o m p o s i t i o n s o f M i o n s i n the f i r s t and second f i e l d f r e e r e g i o n s , which a r e a l s o a c c e s s i b l e by the c o n v e n t i o n a l EI t e c h n i q u e ( F i g u r e 1 ) . The s t r e n g t h o f the FIK method i s shown t o f u l l advantage, i f i t i s used i n c o m b i n a t i o n w i t h a double f o c u s s i n g mass s p e c t r o m e t e r and w i t h i s o t o p i c l a b e l l i n g , f o r the e l u c i d a t i o n o f mechanisms o f gas-phase ion decomposition processes at 1 0 " t o 10' sec. (3a). The f i r s t and a l r e a d y c l a s s i c a l example o f such mecFP a n i s t i c s t u d i e s has been the FIK s t u d y on c y c l o h e x e n e 3,3,6,6-dit ( 6 ) . S i n c e then many m e c h a n i s t i c FIK s t u d i e s Kave "appeared i n the l i t e r a t u r e , t o w h i c h the reader i s r e f e r r e d ( l c , 2 , 7 ) . In our l a b o r a t o r y , tïïe FIK method i n c o m b i n a t i o n w i t h d e u t e r i u m l a b e l l i n g has been a p p l i e d t o gas phase d e c o m p o s i t i o n s o f the m o l e c u l a r i o n s o f 2-phenoxyethyl c h l o r i d e and o f 3 - p h e n y l p r o p a n a l , as w i l l be d i s c u s s e d below. In t h i s way, we i n t e n d t o show the a p p l i c a t i o n of t h i s p o w e r f u l t e c h n i q u e f o r i n v e s t i g a t i o n o f gasphase i o n i c d e c o m p o s i t i o n s .

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

+

+

+

1 1

9

1 1

7

FIK Study on 2-Phenoxyethyl

Chloride (8).

A p r e v i o u s EI s t u d y o f 2-phenoxyethyl

chloride,

C 6 H 5 O C H 2 C H 2 C I , i n combination w i t h deuterium l a b e l l i n g has shown, t h a t the m o l e c u l a r i o n s l o s e i n a p p r o x i 1

m a t e l y e q u a l amounts «C^Cl and

2

•CH C1 ( 9 ) . 2

T h i s must

82

HIGH PERFORMANCE MASS SPECTROMETRY

slotted cathode emitter

/

J

electric sector set to transmit ions with a kinetic energy eV magnetic sector

v

x

Q

1 field free region

,'

detector

st

2 field free region

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

nd

Figure 1. Double-focusing field ionization mass spectrometer (not drawn to scale)

Figure 2. FIK curve of ions m*

(right) *Advances in Mass Spectrometry Figure 3. FI spectra of 2-phenoxyethyl chloride and of its 1,1-d«- and 2,2,-d analogs. The left ordinate scale refers to the intensities of ions with m/e < 130; the right ordinate scale to those of ions with m/e > 130. f

5.

83

Field Ionization Kinetic Studies

NiBBERiNG

94

63

.O-CH2-CH2-CI

COT

1

?

6

ri» 80 60

107

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

107

Lo

121

121 20

15 20

I lift 60

40

I ill.J

100

80

120

160

15 20

0-CD,-CH,-CI

65

158

I·/·

HOO 0.84 80 0.64

M 158

94

—95

60

0.44

M 158

—•'94 109

40

123 109

0.24

123

I-20 15 20

liiiji 40

60

-lilt— 80

100

ϊ ί ! 0 13θ/J\lI50

160

84

HIGH P E R F O R M A N C E MASS

SPECTROMETRY

a r i s e from a n e a r l y c o m p l e t e l y e q u i l i b r a t e d p o s i t i o n a l i n t e r c h a n g e o f t h e phenoxy group and t h e c h l o r i n e atom i n t h e m o l e c u l a r i o n s p r i o r t o l o s s o f a CH C1 r a d i c a l . We have a d d r e s s e d o u r s e l v e s t o t h e q u e s t i o n o f whether FIK c o u l d show t h e time dependence o f t h i s p o s i t i o n a l i n t e r c h a n g e . Of c o u r s e , normal e l e c t r o n - i m p a c t ( E I ) mass s p e c t r o m e t e r s p r e s e n t an i n t e g r a t e d view o f i o n c h e m i s t r y from t h e time o f f o r m a t i o n t o ^ 1 0 " s e c , and, t h e r e f o r e , t h i s i n f o r m a t i o n i s n o t o b t a i n a b l e on t h e s e instruments. The F I s p e c t r a o f 2-phenoxyethyl c h l o r i d e and o f the 1,1-d - and 2,2,-d analogues a r e g i v e n i n F i g u r e 3 without c o r r e c t i o n f o r c o n t r i b u t i o n s of n a t u r a l isotopes and o f i s o t o p i c i m p u r i t i e s . They show t h a t a t 2

6

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

2

2

1 1

10 s e c , t h e o r i g i n a l - C r ^ C l group i s e l i m i n a t e d from the m o l e c u l a r i o n s w i t h o u t s u b s t a n t i a l i n t e r f e r e n c e by the p o s i t i o n a l i n t e r c h a n g e p r o c e s s . To f o l l o w t h e p o s i t i o n a l i n t e r c h a n g e i n t h e m o l e c u l a r i o n s as a f u n c t i o n o f t j m e , F I K measurements were p e r f o r m e d on the (M-CH C1) and (M-CD C1) i o n s g e n e r a t e d from t h e 1 , l - d - and 2,2-d m o l e c u l a r i o n s . Thç measured abundances o f t h e (M-CH C1) and (M-CD C1) i o n s a r e e x p r e s s e d i n p e r c e n t a g e s o f t h e i r sum as a f u n c t i o n o f time and t h e s e r e s u l t s a r e g i v e n i n F i g u r e s 4a and 4b f o r t h e 1 , l - d - and 2,2-d compounds, r e s p e c t i v e l y . I t i s v e r y c l e a r from these f i g u r e s , t h a t a t s h o r t e r times t h e p o s i t i o n a l i n t e r c h a n g e o f t h e phenoxy group and t h e c h l o r i n e atom cannot compete w i t h t h e e l i m i n a t i o n o f -CD C1 (-CH C1) from t h e 1,1d2 - ( 2 , 2 - d ) m o l e c u l a r i o n s , b u t i t competes much more e f f e c t i v e l y a t l o n g e r times (~ 1 0 " sec) c o r r e s p o n d i n g t o m o l e c u l a r i o n s o f lower i n t e r n a l energy. This observation i n d i c a t e s that the p o s i t i o n a l interchange o c c u r s i n t h e gas phase m o l e c u l a r i o n s o f 2-phenoxye t h y l c h l o r i d e , and t h a t i t i s a p r o c e s s h a v i n g a lower f r e q u e n c y f a c t o r and lower a c t i v a t i o n energy than t h e e l i m i n a t i o n o f -CH C1 v i a a s i m p l e c l e a v a g e . Note a l s o from F i g u r e 4 t h a t t h e t i m e - r e s o l v e d p o s i t i o n a l i n t e r change reaches a t l e a s t a h i g h e r p e r c e n t a g e o f e q u i l i b r a t i o n (87-931) than can be deduced from p r e v i o u s E I r e s u l t s (851) ( 9 ) , w h i c h r e p r e s e n t o n l y an i n t e g r a t e d v a l u e o v e r t h e time range up t o ~ 10 s e c . 2

2

2

2

2

2

2

2

2

2

2

1 0

2

6

FIK Study on 3 - P h e n y l p r o p a n a l The

(10).

e l i m i n a t i o n s o f C H 0 and o f C r U 0 from t h e 3 2 1 m o l e c u l a r i o n s o f 3 - p h e n y l p r o p a n a l , C H CH CH CHO upon e l e c t r o n impact have been s t u d i e d p r e v i o u s l y by D- and C-13 l a b e l i n g (11,12). In s p i t e o f the extensive 2

2

3

6

5

2

2

NiBBERiNG

Field Ionization Kinetic Studies

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

mVe 107

n

-11.0

-11.0

/el09

-10.5

-10.0

-9.5

logt

-10.5

logt Advances in Mass Spectrometry

Figure 4. Intensities of m/e 107 and m/e 109 expressed in percentage of their sum as a function of time for the l,l-d - and 2,2-d -2-phenoxyethyl chlorides [(a) and (b), respectively]. The dashed lines refer to the percentage of equilibrated positional interchange of the phenoxy group and the chlorine atom. 2

2

86

HIGH PERFORMANCE MASS SPECTROMETRY

hydrogen r a n d o m i z a t i o n i n t h e m o l e c u l a r i o n s p r i o r t o o r d u r i n g f r a g m e n t a t i o n , i t has been s u g g e s t e d t h a t a hydrogen atom from p o s i t i o n 2 m i g r a t e s t o t h e p h e n y l r i n g d u r i n g t h e e l i m i n a t i o n s o f C H 0 and o f C 3 H 4 O ( 1 1 ) . T h i s h y p o t h e s i s c a n be t e s t e d w i t h t h e F I K method. I n F i g u r e 5 t h e E I spectrum and t h e F I s p e c t r a o f 3 - p h e n y l p r o p a n a l a t an unheated and h e a t e d e m i t t e r have been r e p r o d u c e d . I t i s s e e n , t h a t t h e i o n s m/e 92 and m/e 78, g e n e r a t e d by e l i m i n a t i o n s o f C H 0 and CaHitO from t h e m o l e c u l a r i o n s r e s p e c t i v e l y , a r e p r e s e n t i n t h e F I s p e c t r a . The F I s p e c t r a o f 3phenylpropanals, l a b e l l e d with deuterium i n the 1 p o s i t i o n ( 1 - d i ) , the 2 p o s i t i o n , (2,2-d ), the 3 p o s i t i o n ( 3 , 3 - d ) and i n t h e p h e n y l r i n g (0-ds) show t h a t t h e i o n s m/e 92 and m/e 78 r e t a i n t h e hydrogen atom from p o s i t i o n 1 t o tïïe e x t e n t o f a p p r o x i m a t e l y 90% (10.)· C o n t r a r y t o c o n c l u s i o n s from p r e v i o u s E I r e s u l t s (11) we now c o n c l u d e t h a t a hydrogen atom from p o s i t i o n 1 and n o t from p o s i t i o n 2 m i g r a t e s t o the p h e n y l r i n g d u r i n g t h e e l i m i n a t i o n s o f C H 0 and o f C r U 0 , a t l e a s t w i t h i n 1 0 " s e c . The e l i m i n a t i o n o f C H 0 o c c u r s by a 1,5 hydrogen m i g r a t i o n , i^.e. , t h e w e l l - k n o w n M c L a f f e r t y r e a r r a n g e m e n t , whereas the second e l i m i n a t i o n might p r o c e e d v i a a 1,5and/or a 1,4-hydrogen s h i f t (Scheme 1 ) . 2

2

2

2

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

2

2

2

2

1 1

3

2

2

Scheme 1

0

0 The e l i m i n a t i o n o f C3rU0 g i v e s an i s o l a t e d peak a t m/e 78 i n t h e F I spectrum ( F i g u r e 5 ) , so t h a t t h i s r e a c t i o n c a n be r e a d i l y s t u d i e d by F I K making u s e o f the v a r i o u s d e u t e r a t e d 3 - p h e n y l p r o p a n a l s . This i s not t r u e f o r t h e e l i m i n a t i o n o f C H 0 because t h i s r e a c t i o n i s s u b j e c t t o i n t e r f e r e n c e by t h e s i m p l e c l e a v a g e o f t h e C - C bond i n t h e d e u t e r a t e d 3phenylpropanals which occurs w i t h randomization o f hydrogen atoms (cf_. peaks a t m/e 91 and 92 i n t h e F I spectra, given i n Figure 5). F I K c u r v e s have been measured f o r t h e [M-C3H D 0 (x+y=4)] i o n s from t h e v a r i o u s d e u t e r a t e d ^ 2

2

+

3

2

5.

NiBBERiNG

87

Field Ionization Kinetic Studies

3 - p h e n y l p r o p a n a l s . E x p r e s s i n g t h e measured abundances o f t h e s e i o n s from d e u t e r a t e d 3 - p h e n y l p r o p a n a l i n p e r c e n t a g e s o f t h e i r sum as a f u n c t i o n o f time i n t h e g r a p h s , p r e s e n t e d i n F i g u r e 6, t h e f o l l o w i n g i n t e r e s t i n g r e s u l t s are obtained. i ) The hydrogen atom o r i g i n a l l y a t p o s i t i o n 1 i s p r e d o m i n a n t l y t r a n s f e r r e d t o g i v e CerU** ions at short i o n l i f e t i m e s . i i ) T r a n s f e r o f t h e hydrogen atoms from p o s i t i o n 3 t o y i e l d t h e C H * i o n s becomes more i m p o r t a n t a t l o n g e r t i m e s (note t h e i n c r e a s e o f m/e 80, i _ . e. C n^O * , with increasing time). 6

6

+

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

s

2

i i i ) The hydrogen atoms from p o s i t i o n 2 a r e n o t i n v o l v e d i n the p r o d u c t i o n o f C H ions i n t h e measured time range. + e

6

6

i v ) One o f t h e o r i g i n a l p h e n y l r i n g hydrogen atoms i s i n c r e a s i n g l y r e t a i n e d i n t h e n e u t r a l e l i m i n a t e d CatUO m o i e t y a t l o n g e r t i m e s , a l b e i t to a small extent. The f o l l o w i n g e x p l a n a t i o n i s proposed f o r t h e s e results. I n t h e measured time range o f 1 0 " to 1 0 " * s e c , two s p e c i f i c hydrogen exchange p r o c e s s e s i n the molecular ions o f 3-phenylpropanal occur p r i o r t o o r d u r i n g t h e f o r m a t i o n o f t h e C H * i o n s . The most i m p o r t a n t hydrogen exchange p r o c e s s t a k e s p l a c e between t h e hydrogen atoms from p o s i t i o n s 1 and 3, as d e p i c t e d i n Scheme 2. 1 0 , 3

9

5

+

6

6

Scheme 2

b

a

d

c

c KrÇ 6

etc.

HIGH PERFORMANCE MASS V. too

y. 100

PhCH CH CH0 2

SPECTROMETRY

2

El 78 (a)

50

50

65 0

Ί

1

Ί

115 _iL.

Τ

133

ο too

PhCH CH CHO

1.25

2

2

Fi (b)

OJ75

50 025

67

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

0

I

I

I

Γ

Ί

2

too

2

133

I high emitter temperature! (c)

3.0

1.0

0

Γ

syo PhCH CH CHO FI

50

615·(134*921

0

—ι )

I 110

100

90

70

130 m/e

120

Journal of the American Chemical Society

Figure 5. EI and FI spectra of 3-phenylpropanal [(b) unheated emitter, (c) heated emitter]. In the FI spectra the left ordinate scale refers to the intensities of ions with m/e < 134; the right ordinate scale to those of ions with m/e > 134. %

.

100

»

1

1

1

1

1

• 1 _

80

60

£3~ 2CH CDO CH

Q-CD CH2CHO

2

2

40

m/e 7$^ 20 — 1

1 I I

I

I

'

m/f80^-«-

I I

100 m/#78

"

~*~—*—--*^£n/f83

80

60

{3* 2 °2CH0 CH

C

^-CH CH CHO 2

2

AO m/e 82

20

-

m/e 79 • 103

, 1 , , , < 1 10.0 9.5 10.3

,1 10.0

9.5

Journal of the American Chemical Society

Figure 6. Intensities of the (M-C H D O fx + y = 4)Υ' ions expressed in percentage of their sum as a function of time for 3-phenylpropanals, deuterated in the 1, 2, and 3 positions ana in the phenyl ring as indicated s

x

y

5.

NiBBERiNG

Field Ionization Kinetic Studies

89

I t s h o u l d be n o t e d t h a t the hydrogen atom a b s t r a c t i o n from p o s i t i o n 3 by t h e r a d i c a l s i t e a t the oxygen atom i n t h e r e a c t i o n a b ( o r the e q u i v a l e n t p r o t o n a b s t r a c t i o n from p o s i t i o n 3 by the l o n e p a i r o f e l e c ­ t r o n s a t the oxygen atom, i f the charge r e s i d e s i n i t i a l l y i n the p h e n y l r i n g ) has been o b s e r v e d p r e v i o u s l y i n the m o l e c u l a r i o n s o f e t h y l 3-phenylpropionate (13). The o t h e r hydrogen exchange p r o c e s s a t s h o r t t i m e s i s b e s t e x p l a i n e d by an exchange between the hydrogen atoms from the p h e n y l r i n g and p o s i t i o n 1, as r a t i o n a l i z e d i n Scheme 3. Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

Scheme 3

A s i m i l a r exchange p r o c e s s , as p r e s e n t e d i n Scheme 3, has been o b s e r v e d i n the m o l e c u l a r i o n s o f 3-phenylp r o p y l bromide ( 1 4 ) . I t f u r t h e r s u p p o r t s the i d e a t h a t the e l i m i n a t i o n o f C2H2O v i a a M c L a f f e r t y r e a r ­ rangement ( v i d e supra) o c c u r s s t e p w i s e , w h i c h i s now w e l l a c c e p t e d (15). I n any e v e n t , the o p e r a t i o n o f b o t h schemes 2 and 3 a c c o u n t s f o r the i n c o r p o r a t i o n of the two hydrogen atoms from p o s i t i o n 3 i n the ΟβΗβ i o n s a t l o n g e r t i m e s ( v i d e s u p r a ) . T h i s FIK s t u d y does n o t show any a c t i v e p a r t i c i p a t i o n o f the hydrogen atoms from p o s i t i o n 2 i n the hydrogen exchange p r o c e s s e s p r i o r t o o r d u r i n g the f o r m a t i o n o f the 0βΗ ' i o n s . I t i s o f i n t e r e s t t o note t h a t such exchanges have been o b s e r v e d f o r m e t a s t a b l e decompo­ s i t i o n s i n the f i r s t f i e l d f r e e r e g i o n f o r i o n s g e n e r a t e d by E I (11_). T h i s s u g g e s t s t h a t an exchange between the hydrogen atoms a t p o s i t i o n 2 and, f o r example, t h e p h e n y l r i n g can o n l y compete w i t h the exchange p r o c e s s e s g i v e n i n schemes 2 and 3 f o r m o l e c u l a r i o n s o f l o w e r i n t e r n a l energy, i - e . t h o s e decomposing i n the f i r s t f i e l d f r e e r e g i o n . U n f o r ­ t u n a t e l y , t h i s p r o p o s a l c o u l d not be t e s t e d because of t h e absence o f a m e t a s t a b l e peak f o r the e l i ­ m i n a t i o n o f C3Hi»0 from the m o l e c u l a r i o n s o f 3p h e n y l p r o p a n a l under F I c o n d i t i o n s . The mechanism f o r the C H« 0 e l i m i n a t i o n r e q u i r e s f u r t h e r comment. The C H * i o n s , r e s u l t i n g from t h i s +

6

+

6

6

3

+

90

HIGH PERFORMANCE MASS SPECTROMETRY

e l i m i n a t i o n , appear t o o r i g i n a t e from the m o l e c u l a r i o n s and from the (M-28) * i o n s , as shown by appro­ p r i a t e m e t a s t a b l e d e c o m p o s i t i o n s i n the f i r s t f i e l d f r e e r e g i o n under EI c o n d i t i o n s . T h e r e f o r e , i t may be c o n c l u d e d t h a t t h e C H * i o n s are g e n e r a t e d by suc­ c e s s i v e hydrogen m i g r a t i o n from p o s i t i o n 1 t o the p h e n y l r i n g , c a r b o n monoxide l o s s i n a slow and r a t e d e t e r m i n i n g s t e p and a f a s t e l i m i n a t i o n o f e t h y l e n e , as i n d i c a t e d i n scheme 1. F i n a l l y , some comments s h o u l d be made on c i n n a m y l a l c o h o l , which has been s t u d i e d e x t e n s i v e l y by EI i n c o m b i n a t i o n w i t h D- and C - l a b e l l i n g (16>,17). This compound, an isomer o f 3 - p h e n y l p r o p a n a l , behaves q u i t e d i f f e r e n t l y upon E I , a l t h o u g h i t s m o l e c u l a r i o n s e l i m i ­ n a t e C H 0 and C 3 H 4 O as w e l l (16^,17). FI s p e c t r a o f c i n n a m y l a l c o h o l a t an unheated ancPheated e m i t t e r a r e g i v e n i n F i g u r e 7. C l e a r l y these s p e c t r a are d i f ­ f e r e n t from the FI s p e c t r a o f 3 - p h e n y l p r o p a n a l ( F i g u r e 5 ) . However, peaks a t m/e 92 and m/e 78 a r e o b s e r v e d , e s p e c i a l l y a t h i g h e r emTtter t e m p e r a t u r e , a l t h o u g h t h e i r abundances were too low t o o b t a i n r e l i a b l e FIK results. N e v e r t h e l e s s , i t may be c o n c l u d e d t h a t s m a l l f r a c t i o n o f the m o l e c u l a r i o n s o f c i n n a m y l a l c o h o l may have i s o m e r i s e d t o 3 - p h e n y l p r o p a n a l , p o s s i b l y as follows : +

6

6

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

1 3

2

2

C H CH=CHCH OH 6

5

2

ί

, +

*

+

C H CH-CH CH=OH*>C H CH CH CHo' * 6

5

2

£

6

5

2

2

h

Note, t h a t i o n g i s i d e n t i c a l t o i o n b i n Scheme 2. I t i s i n t e r e s t i n g Tn t h i s r e s p e c t t h a t tEe r a t i o o f i n t e n ­ s i t i e s o f the m e t a s t a b l e peaks i n the f i r s t f i e l d f r e e r e g i o n f o r t h e l o s s o f C 2 H 2 O and C3Hi*0 upon EI a r e ^150 f o r c i n n a m y l a l c o h o l and ^200 f o r 3 - p h e n y l p r o p a n a l . T h i s would mean t h a t i n c i n n a m y l a l c o h o l t h e e l i m i n a ­ t i o n o f C 3 H 4 O w h i c h r e q u i r e s a h i g h e r a c t i v a t i o n energy, can compete more e f f e c t i v e l y w i t h the l o s s o f C 2 H 2 O than i n 3-phenylpropanal, i f t h e i r decompositions i n t h e same t i m e window are c o n s i d e r e d . Ions h seem, t h e r e f o r e t o be s l i g h t l y more e x c i t e d t h a n t h o s e d i r e c t l y g e n e r a t e d from 3 - p h e n y l p r o p a n a l . T h i s can be e x p l a i n e d , i f the i s o m e r i z a t i o n of cinnamyl a l c o h o l p r o c e e d s t h r o u g h a s l o w s t e p , presumably f -> to e v e n t u a l l y g i v e a r e l a t i v e l y h i g h e r e x c i t e d 3-phenyl­ p r o p a n a l i o n . The e l i m i n a t i o n s o f C 2 H 2 O and o f CaH^O can t h e n compete more e f f e c t i v e l y w i t h each o t h e r i n the f i r s t f i e l d f r e e r e g i o n . A s i m i l a r phenomenon has been d e s c r i b e d r e c e n t l y . Fast unimolecular d i s -

5.

NiBBERiNG

91

Field Ionization Kinetic Studies

" PhCH=CHCH OH 2

FI

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

- ία)

I

L

l

l

1

I

1

ι

I

1

- PhCH=CHCH OH 2

_

133

FI (high emitter temperature)

(b) 1I,

" . . . . ι . , 60

70

.ii 80

90

, .1 , 1 100

110

LJ 120

ι

130

I m/e

Journal of the American Chemical Society

Figure 7. FI spectra of cinnamylalcohol at an unheated (a) and heated (h) emitter. The left ordinate scale refers to the intensities of ions with m/e < 134; the right ordinate scale to those of ions with m/e > 134.

92

HIGH PERFORMANCE MASS SPECTROMETRY

s o c i a t i o n s o f the (M-methyl) i o n from m e t h y l i s o p r o p y l e t h e r i n t h e m e t a s t a b l e r e g i o n are a t t r i b u t e d t o a r a t e d e t e r m i n i n g i s o m e r i z a t i o n o f t h i s i o n t o the (M-methyl) s t r u c t u r e from d i e t h y l e t h e r (18J).

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

Conclusions. The r e s u l t s , o b t a i n e d from FIK f o r the systems d e s c r i b e d , show t h a t t h i s method i s e x t r e m e l y v a l u a b l e f o r o b t a i n i n g a deeper i n s i g h t i n t r u e gas-phase i o n d e c o m p o s i t i o n s and i n the l o n g - s t a n d i n g p r o b l e m o f s c r a m b l i n g o f hydrogen atoms. T h i s l a t t e r phenomenon appears t o c o n s i s t o f a s e r i e s o f s p e c i f i c hydrogen exchange p r o c e s s e s , as n o t e d p r e v i o u s l y by o t h e r a u t h o r s (2a). Experimental. E x p e r i m e n t a l d e t a i l s w i l l be d e s c r i b e d f u l l y e l s e where (8,10) and the most i m p o r t a n t c o n d i t i o n s are o n l y given here. The FIK e x p e r i m e n t s were p e r f o r m e d on a V a r i a n MAT 711 double f o c u s s i n g mass s p e c t r o m e t e r (Mattauch-Herzog geometry) equipped w i t h a c o m m e r c i a l l y combined EI/FI/FD s o u r c e . Data a c q u i s i t i o n and d a t a p r o c e s s i n g were a c h i e v e d w i t h the V a r i a n S p e c t r o System 100 on l i n e and s p e c i a l computer programmes, w r i t t e n f o r t h e FIK e x p e r i m e n t s , were used ( 1 9 ) . F u r t h e r exp e r i m e n t a l c o n d i t i o n s f o r 2-phenoxyetEyl c h l o r i d e were: I n l e t system: r e f e r e n c e i n l e t system a t 130°C Ion s o u r c e t e m p e r a t u r e : 100°C Emitter Current: S mA Analyzer pressure: 6x10" Torr Source p r e s s u r e : 5 x 1 0 " T o r r Mass r e s o l u t i o n (10% v a l l e y d i f i n i t i o n ) : 1200 Energy r e s o l u t i o n ( a t an a c c e l e r a t i n g v o l t a g e o f 8453 Volts): 1.4* V o l t a g e a t f o c u s s i n g e l e c t r o d e : ±6 kV. The e x p e r i m e n t a l c o n d i t i o n s employed f o r t h e 3p h e n y l p r o p a n a l s t u d i e s were: I n l e t system: c o o l e d d i r e c t i n s e r t i o n probe at -5 t o -10°C Ion s o u r c e t e m p e r a t u r e : 98°C E m i t t e r c u r r e n t : 0 mA Analyzer pressure: 6x10" Torr Source p r e s s u r e : 7x10" Torr Mass r e s o l u t i o n (101 v a l l e y d e f i n i t i o n ) : 500 Energy r e s o l u t i o n ( a t an a c c e l e r a t i n g v o l t a g e o f 8400 Volts): II V o l t a g e a t f o c u s s i n g e l e c t r o d e : ±6 kV. 9

6

9

6

5.

NiBBERiNG

Field Ionization Kinetic Studies

93

For b o t h s t u d i e s a c t i v a t e d t u n g s t e n w i r e e m i t t e r s o f 10 \xm w i t h an average n e e d l e l e n g t h o f 10 ym were used and p o s i t i o n e d 1.45 mm from t h e grounded s l o t t e d c a t h o d e .

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

Acknowledgement. The a u t h o r i s e x t r e m e l y g r a t e f u l t o Drs. J. v a n der G r e e f and Mr. F. A. P i n k s e , who, w i t h g r e a t enthu­ s i a s m , have d e v e l o p e d t h e F I K method i n h i s l a b o r a t o r y . He f u r t h e r acknowledges t h e c o n t r i b u t i o n s o f Drs. C. B. T h e i s s l i n g and Dr. P. W o l k o f f C h r i s t e n s e n i n t h e c h e m i c a l f i e l d and t h e c o n t r i b u t i o n o f Dr. C. W. F. K o r t who d e v e l o p e d t h e s o f t w a r e f o r FIK. F i n a l l y , he w o u l d l i k e t o thank P r o f . H. D. Beckey and h i s group o f the U n i v e r s i t y o f Bonn f o r s t i m u l a t i n g d i s c u s s i o n s and the g i f t o f some w e l l - a c t i v a t e d e m i t t e r s .

Abstract. Field Ionization Kinetics has provided a clear i n ­ sight into the positional interchange of the phenoxy group and halogen atom in the molecular ions of 2-phen­ oxyethyl chloride and into the various hydrogen ex­ change processes i n the molecular ions of 3-phenyl­ propanal prior to or during fragmentation. This information could not be obtained from previous elec­ tron impact studies. Literature Cited. 1.

2.

a. Beckey, H. D . , Field Ionisation Mass Spectro­ etry, (1971), Akademie-Verlag, Berlin and Pergamon Press, Oxford, b. Robertson, A. J. B . , i n "Mass Spectrometry", Maccoll, A. (Ed.), Int. Rev. Sci., Physical Chemistry Ser. One, V o l . 5, Butterworths, London and University Park Press, Baltimore, (1972), p. 103. c) Derrick, P. J., i n "Mass Spectrometry", Maccoll, A. (Ed.), Int. Rev. Sci., Physical Chemistry Ser. Two, V o l . 5, Butterworths, London and Boston, Mass., (1975), p. 1. a. Derrick, P. J. and Burlingame, A. L., Acc. Chem. Res., (1974) 7, 328. b. McMaster, Β. N., Johnstone, R. A. W. (Ed.), i n Mass Spectrometry (Specialist Periodical Reports), The Chemical Society, London, (1975), V o l . 3, p. 33. c. Burlingame, A. L., Kimble, B. J., and Derrick, P. J., Anal. Chem., (1976) 48, 368R.

94

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch005

3.

HIGH PERFORMANCE MASS

SPECTROMETRY

a. Falick, Α. Μ., Derrick, P. J., and Burlingame, A. L., Int. J . Mass Spectrom. Ion Phys., (1973) 12, 101. b. Beckey, H. D. Hey, Η., Levsen, K. and Tenschert, G., Int. J . Mass Spectrom. Ion Phys., (1969) 2, 101. 4. Schulten, H.-R. and Beckey, H. D., Org. Mass Spectrom., (1972), 6, 885. 5. Falick, Α. Μ., Int. J . Mass Spectrom. Ion Phys., (1974) 14, 313. 6. Derrick, P. J., Falick, A. M. and Burlingame, A. L., J . Am. Chem. Soc., (1972) 94, 6794. 7. Borchers, F . , Levsen, K. and Beckey, H. D., Int. J. Mass Spectrom. Ion Phys., (1976) 21, 125. 8. Greef, J . van der, Theissling, C. B . , and Nibbering, Ν. Μ. Μ., 7th International Mass Spectrometry Conference, Florence, I t a l y , 1976, Paper No. 168; will appear in Advan. Mass Spectrom. 7 Daly, N. (Ed.). 9. Theissling, C. Β . , Nibbering, Ν. Μ. Μ., and Boer, Th.J. de, Advan. Mass Spectrom., (1971) 5, 642. 10. Christensen, P. Wolkoff, Greef, J . van der, and Nibbering, N. M. M. J. Am. Chem. Soc. (submitted) 11. Venema, Α., Nibbering, Ν. M. M . , and Boer, Th.J. de, Org. Mass Spectrom., (1970) 3, 583. 12. Venema, A. and Nibbering, Ν. Μ. Μ., Org. Mass Spectrom., (1974) 9, 628. 13. Resink, J . J., Venema, Α., and Nibbering, Ν. M. M. Org. Mass Spectrom., (1974) 9, 1055. 14. Nibbering, Ν. M. M. and Boer, Th.J. de, Tetrahedron, (1968) 24, 1427. 15. Kingston, D. G. I., Bursey, J. T., and Bursey, M. M . , Chem. Rev., (1974) 74, 215. 16. Schwarz, H . , Köppel, C. and Bohlmann, F . , Org. Mass Spectrom., (1973) 7, 881. 17. Köppel, C. and Schwarz, Η., Org. Mass Spectrom., (1976) 11, 101. 18. Hvistendahl, G. and Williams, D. H . , J. Am. Chem. Soc., (1975) 97, 3097. 19. Greef, J . van der, Pinkse, F. Α., Kort, C. W. F. and Nibbering, Ν. Μ. Μ., Int. J . Mass Spectrom. Ion Phys., i n press. RECEIVED December 30, 1977

6 Organic Trace Analysis Using Direct Probe Sample Introduction and High Resolution Mass Spectrometry WILLIAM F. HADDON

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

Western Regional Research Center, U.S. Department of Agriculture, Albany, CA 94710

Many interesting problems in organic trace analysis are inaccessible to combined gas chromatographymass spectrometry (GC/MS). For example, a recent treatise on the analysis of organic pollutants in water points out that between 80 and 90 percent of the extractable organic compounds in polluted water f a i l , even after derivitization, to pass through a gas chromatographic column (1). One approach for introducing less volatile compounds into the mass spectrometer in a highly purified state is the use of a liquid chromatograph coupled directly to the mass spectrometer (2,3,4). However, as an alternative to utilizing chromatographic separation prior to analysis, we can consider the mass spectrometer itself as an analytical instrument which is capable in itself of performing highly efficient separations, based, for example, on mass or energy differences of generated ions or on selective ionization, as well as precise identification and quantitation, based on reference mass spectra obtained separately on known compounds. This use of a mass spectrometer for combined separation-identification functions might be called "mass spectrometer-mass spectrometer" (MS/MS) analysis, with the direct probe serving as the vehicle for sample introduction. A number of laboratories have reported results using this approach, and the methods used to achieve selectivity in complex mixtures have included field ionization (5), chemical ionization (6,7), negative chemical ionization (8,9), collisional activation (10), mass-analyzed ion kinetic energy (11), and high resolution electron ionization (EI) (12-15) techniques. This report describes the use of the high resolution EI method in which particular ions are monitored as a function of temperature as the components of interest volatilize ©0-8412-0422-5/78/47-070-097$10.00/0

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

98

HIGH PERFORMANCE MASS SPECTROMETRY

from t h e d i r e c t i n t r o d u c t i o n p r o b e . The term h i g h r e s o l u t i o n s e l e c t e d i o n m o n i t o r i n g (SIM) i s used t o d e s c r i b e t h i s type o f experiment ( 1 6 ) , and the i o n abundance p r o f i l e r e c o r d e d as a f u n c t i o n o f t e m p e r a t u r e i s c a l l e d an e x a c t mass fragmentogram. In many o r g a n i c t r a c e a n a l y s i s p r o b l e m s , the p r e p a r a t i o n o f h i g h l y p u r i f i e d samples amenable t o low r e s o l u t i o n mass s p e c t r a l i d e n t i f i c a t i o n r e q u i r e s ex­ tensive e f f o r t . Employing i n c r e a s e d mass r e s o l u t i o n t o a c h i e v e h i g h e r s e l e c t i v i t y can reduce the e x t e n t o f sample p u r i f i c a t i o n s i g n i f i c a n t l y i n many c a s e s , and r e c e n t examples o f GC-high r e s o l u t i o n SIM f o r b o t h b i o f l u i d a n a l y s i s (17,18) and e n v i r o n m e n t a l m o n i t o r i n g (19) a r e i l l u s t r a t i v e . In many l a b o r a t o r i e s concerned w i t h a n a l y z i n g p a r t i c u l a r components o f complex m i x t u r e s , the s a v i n g s i n t h e c o s t o f sample p r e p a r a t i o n made p o s s i b l e by the a v a i l a b i l i t y o f h i g h r e s o l u t i o n SIM c a p a b i l i t y may j u s t i f y the h i g h e r i n i t i a l c o s t o f a s u i t a b l e h i g h r e s o l u t i o n mass s p e c t r o m e t e r . Furthermore, s m a l l r a d i u s ( 6 - i n c h o r l e s s ) m a g n e t i c s e c t o r mass s p e c t r o ­ meters h a v i n g b o t h the f a s t scan r a t e s r e q u i r e d by GC/MS a p p l i c a t i o n s and the c a p a b i l i t y f o r h i g h r e s o ­ l u t i o n (10-20,000) o p e r a t i o n w i t h good s e n s i t i v i t y a r e becoming a v a i l a b l e c o m m e r c i a l l y . On a t l e a s t one s m a l l r a d i u s i n s t r u m e n t o f t h i s t y p e , image c u r v a t u r e c o r ­ r e c t o r s have been employed t o enhance the h i g h r e s o ­ l u t i o n p e r f o r m a n c e , and f u r t h e r improvements i n r e s o ­ l u t i o n and s e n s i t i v i t y f o r these s m a l l r a d i u s i n s t r u ­ ments w i l l u n d o u b t e d l y be f o r t h c o m i n g . Two examples d e s c r i b e d below from the f i e l d s o f c l i n i c a l and f o o d c h e m i s t r y i l l u s t r a t e the u t i l i t y o f t h e h i g h r e s o l u t i o n d i r e c t probe method f o r t r a c e analysis. In a d d i t i o n , p e s t i c i d e s i n human t i s s u e have been measured a t h i g h r e s o l u t i o n on a p h o t o - p l a t e equipped mass s p e c t r o m e t e r (Γ5), and s i m i l a r h i g h r e s o l u t i o n methods have been employed t o measure p e s t i ­ c i d e s i n f o o d samples (9) and b i o f l u i d s (8) u s i n g n e g a t i v e c h e m i c a l i o n i z a t i o n , and t o q u a n t i t a t e drug m e t a b o l i t e s r a p i d l y i n b l o o d plasma (7.) u s i n g c h e m i c a l i o n i z a t i o n mass s p e c t r o m e t r y . These papers c o n t a i n e x c e l l e n t d e s c r i p t i o n s o f the p r a c t i c a l problems o f p r e p a r i n g samples and q u a n t i t a t i n g the r e s u l t s . Experimental H i g h r e s o l u t i o n SIM o p e r a t i o n can be a c h i e v e d on a m a g n e t i c s e c t o r mass s p e c t r o m e t e r by i n c o r p o r a t i n g a s w i t c h e d v o l t a g e d i v i d e r c i r c u i t , or by employing c o m p u t e r - d r i v e n power s u p p l i e s .

6. HADDON

99

Organic Trace Analysis

The o v e r - a l l e l e c t r o n i c s t a b i l i t y n e c e s s a r y f o r q u a n t i t a t i v e work depends on t h e p r e c i s i o n r e q u i r e d and on t h e mass r e s o l u t i o n s e l e c t e d f o r t h e a n a l y s i s . These s t a b i l i t y r e q u i r e m e n t s c a n be d e r i v e d from t h e G a u s s i a n c u r v e o f F i g u r e 1, w h i c h r e p r e s e n t s a mass s p e c t r a l peak. The 10 p e r c e n t v a l l e y d e f i n i t i o n o f mass s p e c t r o m e t e r r e s o l u t i o n c o r r e s p o n d s t o t h e o r d i ­ n a t e v a l u e a t a d i s t a n c e 2.44 σ from t h e c e n t e r o f t h e peak (5 p e r c e n t o f maximum h e i g h t f o r a s i n g l e p e a k ) , where σ i s t h e s t a n d a r d d e v i a t i o n o f t h e c u r v e . The o v e r - a l l i n s t r u m e n t s t a b i l i t y , S, i n p a r t s p e r m i l l i o n (ppm) f o r a p a r t i c u l a r a n a l y s i s i s 6

S = (a /2.44)(10 /R) U) where σ i s the number o f s t a n d a r d d e v i a t i o n s t o t h e o r d i n a t e a t t h e r e q u i r e d p e r c e n t a c c u r a c y , and R i s t h e mass r e s o l u t i o n (Μ/ΔΜ, 10 p e r c e n t v a l l e y d e f i n i t i o n )

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

x

T a b l e I . Mass S p e c t r o m e t e r S t a b i l i t y i n P a r t s p e r M i l l i o n Necessary f o r Q u a n t i t a t i v e High R e s o l u t i o n S e l e c t e d Ion M o n i t o r i n g . Resolution

Desired Q u a n t i t a t i v e Accuracy

(Percent):

99

95

90

80

16.

45.

61.

89.

9.8

27.

36.

53.

10,000

4.9

13.

18.

26.

15,000

3.3

9.0

12.

18.

20,000

2.4

6.7

9.2

2.7

3.6

3,000 5,000

50,000

.98

C a l c u l a t e d from Eq. 1. 'Μ/ΔΜ based on 10 p e r c e n t v a l l e y

13. 5.

definition.

T a b l e I l i s t s t y p i c a l c a l c u l a t e d v a l u e s o f S. These v a l u e s show t h a t q u a n t i t a t i v e p r e c i s i o n o f 90 p e r c e n t o r g r e a t e r s h o u l d be e a s i l y a c h i e v e d on most commercial mass s p e c t r o m e t e r s w h i c h have been d e s i g n e d f o r a c ­ c u r a t e mass measurement a p p l i c a t i o n s . When o n l y one o r two peaks need t o be m o n i t o r e d , t h e c i r c u i t r y o f an e x i s t i n g peak matcher c a n be modi­ f i e d t o m o n i t o r b o t h peaks by s w i t c h i n g between peak t o p s . (2,19) On one w i d e l y used commercial h i g h r e s o ­ l u t i o n i n s t r u m e n t , t h i s i s done by d i s c o n n e c t i n g t h e peak matcher scan c o i l s ( 2 ) . A l t e r n a t i v e l y , r e p e t i t i v e

100

HIGH PERFORMANCE MASS SPECTROMETRY

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

s c a n s o v e r narrow mass ranges can be u t i l i z e d , but a t reduced s e n s i t i v i t y . An advantage o f t h i s l a t t e r dynamic method o f r e c o r d i n g d a t a i s t h a t the peak p r o f i l e information i s continuously a v a i l a b l e during the e x p e r i m e n t . An i n c r e a s e beyond two c h a n n e l s can be a c h i e v e d w i t h o u t a computer system by i n c o r p o r a t i n g a s w i t c h a b l e v o l t a g e d i v i d e r c i r c u i t (13) (20) ( 2 1 ) . I t i s imp o r t a n t f o r a c i r c u i t o f t h i s type to employ samplea n d - h o l d a m p l i f i e r s f o r each c h a n n e l t o p r o v i d e cont i n u o u s o u t p u t s i g n a l s s u i t a b l e f o r d r i v i n g an o s c i l l o g r a p h i c or m u l t i p l e pen r e c o r d e r . Computer-Controlled Power S u p p l i e s f o r H i g h R e s o l u t i o n SIM. A d e d i c a t e d computer can p e r f o r m b o t h d a t a c o l l e c t i o n and i n s t r u m e n t c o n t r o l f u n c t i o n s f o r h i g h r e s o l u t i o n SIM when used i n c o n j u n c t i o n w i t h a programmable power s u p p l y f o r the mass s p e c t r o m e t e r a c c e l e r a t i n g and e l e c t r i c s e c t o r v o l t a g e s . The computer p r o v i d e s some a d d i t i o n a l b e n e f i t s over a h a r d - w i r e d system: The number o f mass c h a n n e l s can be l a r g e and can be changed d u r i n g the a n a l y s i s ; the f r a c t i o n o f t i m e a t a p a r t i c u l a r mass v a l u e can be v a r i e d a c c o r d i n g t o the e x p e c t e d abundance o f the peak; and the s y s t e m , when s u i t a b l y programmed, can sweep s h o r t mass r e g i o n s t o p r o v i d e peak p r o f i l e i n f o r m a t i o n w h i c h can be used b o t h t o a s c e r t a i n the degree o f i n t e r f e r e n c e from i s o b a r i c i o n s near the e l e m e n t a l c o m p o s i t i o n o f i n t e r e s t , and t o make a u t o m a t i c p e r i o d i c a d j u s t m e n t s o f the a c c e l e r a t i n g v o l t a g e t o compensate f o r d r i f t i n voltages. F i g u r e 2 shows the programmed power s u p p l y c i r c u i t r y u s e d i n our l a b o r a t o r y f o r h i g h r e s o l u t i o n SIM on a CEC 21-110A d o u b l e - f o c u s s i n g mass s p e c t r o m e t e r . Many o f the e l e c t r o n i c and programming d e t a i l s , i n c l u d i n g c h o i c e o f s u i t a b l e power s u p p l y u n i t s , a r e from the Washington U n i v e r s i t y system o f Holmes f221 f o r low r e s o l u t i o n SIM. In the USDA system a s i n g l e programmer (D/A c o n v e r t e r ) w i t h a 1 - v o l t o u t p u t d r i v e s a p a i r o f power s u p p l i e s i n s e r i e s , one w i t h a v o l t a g e g a i n o f 100 (KEPCO OPS-2000, Kepco, I n c . , F l u s h i n g , N.Y.) f o l l o w e d by a second w i t h a g a i n of -1 (KEPCO NTC2000). These power s u p p l i e s d i r e c t l y r e p l a c e the e l e c t r i c s e c t o r s u p p l y f o r m e r l y used w i t h the i n s t r u ment. The 21-110 r e q u i r e s p l u s and minus 375 v o l t s f o r n o m i n a l 8 kv. o p e r a t i o n . We d e r i v e a f i x e d p o r t i o n o f t h i s v o l t a g e from the i n t e r n a l r e f e r e n c e s u p p l y o f the OPS-2000 t h r o u g h R and R , and a v a r i a b l e p o r t i o n from the D/A c o n v e r t e r (DATEL DAC-169, 16 b i t p r e c i s i o n , D a t e l Systems, I n c . , Canton, Ma.) t h r o u g h R i . The 2

3

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

6. HADDON

101

Organic Trace Analysis

KEPCO

NTC-2000

100 (EA+E.)

0 to +1000V

INV (IN) E (0 to +1V or 0 to +10V) A

SPC-16 D/A

CONVERTER INTERFACE 16-BIT LATCH

LOGIC SIGNALS

DATEL DAC-169 16 BIT D/A CONVERTER

-100 EA +EI] 0 to -1000V

Rl

NULL

WNr-

KEPCO OPS-2000

10KÛ

R2

10KÛ

+6.2V REF

Figure 2. Programmed power supply interface for CEC 21-110 mass spectrometer

102

HIGH PERFORMANCE MASS SPECTROMETRY

s e t t i n g o f R d e t e r m i n e s the f r a c t i o n o f f i x e d v o l t a g e a c c o r d i n g to the r e q u i r e m e n t s o f mass range and p r e c i s i o n . For a t e n p e r c e n t mass r a n g e , each d i g i t a l s t e p o f the programmed v o l t a g e c o r r e s p o n d s t o a 1.5 ppm change i n mass. The r e l a t i o n s h i p between mass and v o l t a g e o u t p u t f o r programmed a c c e l e r a t i n g v o l t a g e o p e r a t i o n i s 3

where m i s the mass i n f o c u s a t the c o l l e c t o r w i t h the D/A c o n v e r t e r a t 0 v o l t s , or d i g i t a l b i t s e t t i n g , r e q u i r e d t o ' ? o c u s mass m. ~Eq. 2 i s d e r i v e d from the mass s p e c t r o m e t e r e q u a t i o n by w r i t i n g a c c e l e r a t i n g v o l t a g e as a sum o f the a c c e l e r a t i n g v o l t a g e a t m p l u s the added v o l t a g e from the D/A c o n v e r t e r and a p p l i e s to b o t h s i n g l e and d o u b l e focussing sector instruments. F i g u r e 3 shows t h a t a l i n e a r r e l a t i o n s h i p i s o b t a i n e d f o r Eq. 2 f o r the 21110 mass s p e c t r o m e t e r m o d i f i e d as i n F i g u r e 2 over the mass range 293-331. V a l u e s of D/A c o n v e r t e r v o l t a g e w h i c h f o c u s p a r t i c u l a r e x a c t masses can be d e t e r m i n e d by l o c a t i n g i n t e r n a l r e f e r e n c e p e a k s , t y p i c a l l y d e r i v e d from p e r f l u o r o k e r o s e n e (PFK), and u t i l i z i n g them t o d e r i v e the s l o p e and i n t e r c e p t by l e a s t squares f i t to Eq. 2. A l t e r n a t i v e l y , the s p e c t r o m e t e r can be s e t to the c e n t e r o f a known peak, w h i c h g i v e s m directly, and k can be c a l c u l a t e d by m a n u a l l y l o c a t i n g one or more a d d i t i o n a l r e f e r e n c e peaks as V j j / a i s v a r i e d . The computer can be programmed to a d j u s t the app l i e d a c c e l e r a t i n g v o l t a g e d u r i n g an e x p e r i m e n t t o compensate f o r i n s t a b i l i t i e s i n the mass s p e c t r o m e t e r by sweeping a s i n g l e r e f e r e n c e peak p e r i o d i c a l l y , and c h a n g i n g the v o l t a g e a t each m/e a c o n s t a n t amount t o c o r r e c t f o r s h i f t s i n peak c e n t r o i d , a l t h o u g h t h e r e a r e s m a l l e r r o r s i n t h i s p r o c e d u r e because mass and v o l t a g e a r e not l i n e a r l y r e l a t e d (Eq. 2 ) . Feedback c o n t r o l o f t h i s type a l l o w s the use o f l e s s e x p e n s i v e power supp l i e s , w h i c h o f t e n have e x c e l l e n t s h o r t term s t a b i l i t y but p o o r e r l o n g term or t e m p e r a t u r e s t a b i l i t y (2_2) . M i c r o p r o c e s s o r - b a s e d SIM modules are becoming a v a i l a b l e , and one c o m m e r c i a l system s u i t a b l e f o r h i g h r e s o l u t i o n measurement i n c l u d e s a peak s t a b i l i z i n g c a p a b i l i t y and the f a c i l i t y f o r m o n i t o r i n g up to 8 m/ev a l u e s ( 2 3 ) . As w i t h a l l SIM c i r c u i t s l i m i t e d t o peak s w i t c h i n g , the one drawback r e l a t i v e to a computerbased system i s t h a t peak p r o f i l e i n f o r m a t i o n i s not e a s i l y o b t a i n e d . A s o l u t i o n to t h i s p r o b l e m i s to devote t h r e e c h a n n e l s o f the peak s e l e c t o r t o the same peak, one a t the c e n t e r , and two a t the 10 p e r c e n t

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

0

0

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3.6 3.4 -

y/ 293 299 / #

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#

3.3 -

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/

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0.8

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VD/A, VOLTS

Figure 3. Mass-voltage relationship for programmed accelerating voltage operation of 21110 mass spectrometer. M = m/e value focused at collector. V = voltage output of D/A converter. D/A

104

HIGH PERFORMANCE MASS SPECTROMETRY

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

i n t e n s i t y p o i n t s on the h i g h and low mass s i d e o f the peak. Three e x a c t mass fragmentograms c o i n c i d e n t i n t i m e ( t e m p e r a t u r e ) and h a v i n g 1:10:1 i n t e n s i t y r a t i o s c o n f i r m the absence o f i n t e r f e r i n g i s o b a r i c i o n s d u r i n g the a n a l y s i s ( 2 4 ) . Applications Aflatoxin Analysis. I n our l a b o r a t o r y we have measured s m a l l amounts o f a f l a t o x i n s i n foods and f e e d s , and i n the b i o f l u i d s o f e x p e r i m e n t a l a n i m a l s (25-27). A f l a t o x i n s are metab­ o l i t e s o f the mold A s p e r g i l l u s F l a v u s , and one o f the metabolites, a f l a t o x i n B i , i s of p a r t i c u l a r i n t e r e s t because i t i s a n a t u r a l l y o c c u r r i n g c a r c i n o g e n w h i c h i s sometimes p r e s e n t a t up to s e v e r a l p a r t s - p e r - b i l l i o n (ppb) i n some a g r i c u l t u r a l p r o d u c t s (28-30). The s t r u c t u r e s and p a r t i a l EI mass s p e c t r a o f s i x a f l a ­ t o x i n s are shown i n F i g u r e 4, and the mass s p e c t r a o f about 50 a d d i t i o n a l m y c o t o x i n s a r e a v a i l a b l e e l s e w h e r e (3JL). P u r i f i c a t i o n and subsequent t r a n s f e r o f a f l a ­ t o x i n s i n t o the mass s p e c t r o m e t e r i s d i f f i c u l t because the compounds a r e u n s t a b l e when h i g h l y p u r i f i e d , bond s t r o n g l y t o g l a s s s u r f a c e s , and cannot be s e p a r a t e d by gas chromatography. These f a c t o r s r e s t r i c t the use o f low r e s o l u t i o n mass s p e c t r a l a n a l y s i s f o r s t r u c t u r a l l y s p e c i f i c v e r i f i c a t i o n or q u a n t i t a t i o n of a f l a t o x i n s . The use o f h i g h r e s o l u t i o n SIM on p a r t i a l l y p u r i f i e d a f l a t o x i n c o n t a i n i n g m i x t u r e s i n t r o d u c e d v i a the d i r e c t probe s i g n i f i c a n t l y l o w e r s the l i m i t s o f d e t e c t i o n f o r mass s p e c t r a l a n a l y s i s o f t h e s e compounds, and has the a d d i t i o n a l advantage t h a t p r i o r i s o l a t i o n p r o c e d u r e s can be s i m p l i f i e d (12) . By u s i n g h i g h r e s o l u t i o n SIM we have d e t e c t e d a f l a t o x i n s B i and Mi i n e x p e r i m e n t a l m i l k samples a t 19 and 140 ppb, r e s p e c t i v e l y . An a n a l y t i c a l e x t r a c t i o n scheme f o r o b t a i n i n g p a r t i a l l y p u r i f i e d a f l a t o x i n s from f r e e z e - d r i e d m i l k and s u i t a b l e f o r use i n c o n j u n c t i o n w i t h h i g h r e s o l u t i o n mass s p e c t r a l a n a l y s i s i s shown i n F i g u r e 5. E x t r a c t A c o n t a i n s a l l o f the a f l a t o x i n s . In e x t r a c t s Β and C, w h i c h are more h i g h l y p u r i f i e d , a f l a t o x i n s B i and Mi a r e p a r t i a l l y s e p a r a t e d because of d i f f e r e n c e s i n p a r t i t i o n c o e f f i c i e n t s i n the e x t r a c t i o n s o l v e n t s (32). H i g h r e s o l u t i o n SIM d a t a f o r e x t r a c t s A and C a r e shown i n F i g u r e s 6 and 7. These d a t a o f i n t e n s i t y vvs. mass r e p r e s e n t scans o v e r 0.3 amu f o r each a p p r o p r i a t e i n t e g r a l m/e a t mass r e s o l u t i o n o f 7,000. The m i d d l e s c a n f o r e x t r a c t A ( F i g . 6 ) , w h i c h was r e c o r d e d a t the t e m p e r a t u r e o f maximum r a t e o f v o l a t i l i z a t i o n o f the a f l a t o x i n s , shows the Mi m o l e c u l a r i o n a t m/e 328, the

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M-16 i o n o f Mi and m o l e c u l a r i o n o f B i (same e l e m e n t a l c o m p o s i t i o n , C i H i 0 ) a t m/e 312, and the M-29 i o n o f Mi a t m/e 299. The abundance r a t i o [M] ·/[M-29] agrees w i t h i n e x p e r i m e n t a l e r r o r w i t h t h e r a t i o o f t h e s e peaks i n t h e r e f e r e n c e low r e s o l u t i o n mass spectrum o f a f l a t o x i n Mi shown i n F i g u r e 4 and c o n f i r m s t h e absence o f i n t e r f e r e n c e a t a r e s o l u t i o n o f 7000 f o r this particular extract. Figure 7 gives equivalent d a t a f o r e x t r a c t C o b t a i n e d from t h e same sample o f f r e e z e - d r i e d m i l k . The a d d i t i o n a l peak a t m/e 314 i s from 12 ng a f l a t o x i n B , added as an i n t e r n a l s t a n d a r d . The abundance r a t i o s between a f l a t o x i n i o n s a t m/e 312 and 328 i n t h e s e scans r e f l e c t t h e d e c r e a s e d amount o f a f l a t o x i n B f o r e x t r a c t C w h i c h r e s u l t e d from s o l v e n t p a r t i t i o n i n g during extraction. Thus f o r e x t r a c t A ( F i g . 6) t h e i n t e n s i t y r a t i o o f C i H i 0 t o C i H i 0 i s 0.32, compared t o 0.06 f o r pure Mi (see F i g . 4 e ) , but f o r e x t r a c t C ( F i g . 7) t h e r a t i o i s 0.092, w h i c h i n d i c a t e s l e s s a f l a t o x i n B , as e x p e c t e d . The methodo l o g y t o q u a n t i t a t e t h e compounds i s c u r r e n t l y b e i n g developed. A n o t a b l e f e a t u r e o f t h e d i r e c t probe method f o r a f l a t o x i n a n a l y s i s i s an enhancement o f s e n s i t i v i t y w h i c h o c c u r s when p a r t i a l l y p u r i f i e d samples o f a f l a t o x i n a r e r u n on t h e mass s p e c t r o m e t e r , r e l a t i v e t o measurements on h i g h l y p u r i f i e d samples. Apparently, t h i s i s because b o n d i n g t o t h e s u r f a c e o f t h e sample c o n t a i n e r s i s s u b s t a n t i a l l y reduced i n a complex mixt u r e f o r t h e s e compounds. The d a t a o f F i g u r e 8 i l l u s t r a t e t h i s enhancement o f s e n s i t i v i t y f o r a f l a t o x i n B i added t o an e x t r a c t o f p o o l e d human u r i n e s . The c u r v e s o f F i g . 8 a r e e x a c t mass fragmentograms, r e c o r d e d d u r i n g r a p i d t e m p e r a t u r e programming o f t h e d i r e c t probe from about 50°C t o 250°C, w i t h the mass s p e c t r o m e t e r tuned t o the m o l e c u l a r i o n o f B , m/e 312.0635, a t 7000 r e s o l u t i o n . A c o m p a r i s o n o f t h e response o b t a i n e d i n c u r v e A o f F i g . 8 f o r 1.3 ng p u r e B i w i t h t h a t o f c u r v e D, o b t a i n e d from 0.03 ng B i added t o the u r i n e e x t r a c t , i l l u s t r a t e t h e 1 0 0 - f o l d enhancement o f s e n s i t i v i t y f o r d e t e c t i n g a f l a t o x i n s B i i n a complex m i x t u r e . The s e n s i t i v i t y enhancement i s somewhat g r e a t e r f o r a f l a t o x i n M i , f o r w h i c h n e g l i g i b l e response i s o b t a i n e d f o r 30 ng o f p u r i f i e d compound, compared t o a s i g n a l t o background r a t i o o f b e t t e r than 100 f o r 13 ng i n t r o d u c e d i n a m i x t u r e , as shown i n F i g s . 6 and 7. Q u a n t i t a t i v e H i g h R e s o l u t i o n SIM f o r A n a l y z i n g P u r i n e s i n B l o o d and T i s s u e . Q u a n t i t a t i v e d i r e c t probe measurements a t t h e 2100 ppm l e v e l f o r f i v e p u r i n e components o f human b l o o d 7

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Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

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Figure 4a, b, c. 70 eV mass spectra of aflatoxins

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

HADDON

Organic Trace Analysis

200

240

210

320

360

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M/E

200

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M/E American Chemical Society

Figure 4d, e, /. 70 eV mass spectra of aflatoxins

108

HIGH PERFORMANCE MASS SPECTROMETRY

FREEZE DRIED MILK

1:1 MeOH-H0 2

Residue (discard)

primary extract

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

3 vol. CHC1, Combined CHCI3 extracts (Extract A)

MeOH-H0 phase 2

(discard)

evaporate residue re-dissolve in 1:1 MeOH-H0 2

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(discard) Association of Official Analytical Chemists, Inc.

Figure 5. Analytical extraction of aflatoxins B and M from freeze-dried milk t

t

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Organic Trace Analysis

, 104 MV

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

2800 MV

, 171 MV

65 MV

U 649 MV.

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5 6 1

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Figure 6. High resolution SIM scans of intensity in millivolts (mV) vs. mass for 13 ng aflatoxin M and 1.7 ng aflatoxin B in 100fig dried milk extract A. Direct introduction probe temperature increases from A to C. t

t

HIGH PERFORMANCE MASS SPECTROMETRY

512 MV

217 MV

157 MV

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

M,

- 5 MV

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299

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MASS Association of Official Analytical Chemists, Inc.

Figure 7. High resolution SIM scans of intensity in millivolts (mV) vs. mass for extract C. 12.4 ng aflatoxin B (mass 314) added as internal standard. Direct probe temperature increases from A to B. 2

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

6. HADDON

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111

and t i s s u e have been r e p o r t e d by Snedden and P a r k e r u s i n g h i g h r e s o l u t i o n SIM (13) ( 3 3 ) . The h i g h r e s o l u t i o n mass s p e c t r a l a n a l y s i s f o r t h e p u r i n e s p r o v i d e d q u a n t i t a t i v e measurement o f h y p o x a n t h i n e ( I ) , x a n t h i n e ( I I ) , u r i c a c i d ( I I I ) , a l l o p u r i n o l (IV) and p u r i n o l (V) (see F i g u r e 9 ) , w h i c h a r e i m p o r t a n t i n t h e s t u d y and t r e a t m e n t o f gout. The use o f h i g h r e s o l u t i o n mass s p e c t r o m e t r y made p o s s i b l e a c c u r a t e a n a l y s i s a t t h e s e l e v e l s w i t h o u t p r e - p u r i f i c a t i o n o f t h e samples. More r e c e n t l y t h e same group has used h i g h r e s o l u t i o n mass s p e c t r o m e t r y t o q u a n t i t a t e o e s t r o g e n and p r o g e s t e r o n e i n human o v a r i a n t i s s u e a t 10-50 ppm, a g a i n u s i n g p r o c e d u r e s t h a t r e q u i r e no c h e m i c a l s e p a r a t i o n o r d e r i v i t i z a t i o n p r i o r t o mass s p e c t r a l a n a l y s i s ( 1 4 ) . To i n s u r e t h a t t h e i r method i s v a l i d , t h e a u t h o r s r e c o r d e d a h i g h r e s o l u t i o n spectrum o f t h e m i x t u r e t o be a n a l y z e d a t t h e chosen r e s o l u t i o n , i n t h i s case 20,000, and compared t h e abundances o f c h a r a c t e r i s t i c mass peaks i n t h e e x p e r i m e n t a l sample w i t h those i n t h e h i g h r e s o l u t i o n r e f e r e n c e spectrum o f t h e pure compound. F i g u r e 10 i l l u s t r a t e s t h e e x c e l l e n t agreement o b t a i n e d a t f i v e o f t h e s i x masses examined f o r I I I i n human muscle t i s s u e . S i m i l a r experiments w i t h the o t h e r p u r i n e s o f F i g u r e 9 y i e l d e d a s e t o f masses a p p r o p r i a t e f o r a n a l y z i n g I-V t o g e t h e r . I n t e g r a t i n g t h e s e l e c t e d i o n p r o f i l e s ( e x a c t mass fragmentograms) a t f i v e masses as a f u n c t i o n o f temp e r a t u r e gave a s e t o f r e l a t i v e peak a r e a s . These peak a r e a s were r e l a t e d t o t h e r e l a t i v e amounts o f I-V u s i n g a s e t o f f i v e l i n e a r s i m u l t a n e o u s e q u a t i o n s and r e sponse c o e f f i c i e n t s d e v e l o p e d from runs on p u r i f i e d compounds, a c c o r d i n g t o e s t a b l i s h e d p r o c e d u r e s o f q u a n t i t a t i v e mass s p e c t r o m e t r y ( 3 4 ) . The i n t r o d u c t i o n o f a c c u r a t e l y weighed (mg amounts) samples f a c i l i t a t e d the c a l c u l a t i o n o f a b s o l u t e c o n c e n t r a t i o n s . An e v a l u a t i o n o f t h e s e n s i t i v i t y and measurement e r r o r f o r t h e a n a l y s i s r e v e a l s t h a t d i f f e r e n t methods o f sample p r e p a r a t i o n g i v e d i f f e r e n t q u a n t i t a t i v e p r e cision. F i g . 11 shows t h a t t h e b e s t r e s u l t s were o b t a i n e d u s i n g powdered samples o f d e s s i c a t e d b l o o d and muscle t i s s u e . D e p o s i t i n g t h e samples on t h e d i r e c t probe s u r f a c e ( g o l d ) by e v a p o r a t i o n o f an aqueous s o l u t i o n gave s i g n i f i c a n t l y lower p r e c i s i o n f o r a g i v e n sample amount, a p p a r e n t l y because o f i n t e r a c t i o n s between t h e sample and t h e s u r f a c e o f t h e probe f o r t h e more p o l a r compounds. When a l e s s p o l a r s u b s t a n c e , c a f f e i n e , was a n a l y z e d , t h e r e was no dependence o f p r e c i s i o n on t h e method o f p r e p a r i n g t h e sample, as shown i n F i g . 11.

112

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HIGH PERFORMANCE MASS SPECTROMETRY

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t

100 T

TIME, SEC. Association of Official Analytical Chemists, Inc.

Figure 8. Exact mass fragmentogram for C H 0 (aflatoxin Bi molecular ion, m/e 312.0635): A, 1.65 ng B from reference solution; B, blank, extract B; C, urine extract plus 0.13 ng B ; D, urine extract plus 0.030 ng B . î7

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Figure 9. Structures of purines analyzed by high resolution SIM: I, hypoxanthine; II, xanthine; III, uric acid; IV, allopurinol; and V, oxipurinol.

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American Chemical Society

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90

Figure 10. Partial high resolution mass spectrum of substances evaporated from human muscle, showing peaks attributable to uric acid. ( a) Relative intensities of uric acid peaks from muscle; (b) relative intensities of sam peaks from uric acid; (c) nominal mass of multiplet.

25

loi

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American Chemical Society

Figure 11. Dependence of analytical precision of high resolution SIM results on concentration and diluent for caffeine, hypoxanthine, xanthine, and uric acid in solution and solid mixtures

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Discussion The mass s p e c t r o m e t e r i s w e l l s u i t e d t o t r a c e a n a l y s i s o f the t y p e d i s c u s s e d h e r e f o r two r e a s o n s : The p r o c e s s o f i o n p r o d u c t i o n by the mass s p e c t r o m e t e r i s g e n e r a l l y l i n e a r o v e r many o r d e r s o f magnitude o f sample c o n c e n t r a t i o n ; and the s e l e c t i v i t y o f the method can be e x t r e m e l y g r e a t when e i t h e r h i g h mass r e s o l u ­ t i o n , a s e l e c t i v e i o n i z a t i o n method, or a c o m b i n a t i o n of t h e s e a r e employed t o e f f e c t s e p a r a t i o n between d i f f e r e n t components o f m i x t u r e s . The wide dynamic range n e c e s s a r y f o r q u a n t i t a t i o n i s w e l l accomodated by electron multiplier detection. Photoplate detection w i l l be g e n e r a l l y l e s s s u i t a b l e f o r t r a c e a n a l y s i s problems o f t h i s n a t u r e because of extensive blackening of the p h o t o g r a p h i c p l a t e near i n t e n s e l i n e s , and nonl i n e a r i t y of response. The a f l a t o x i n s a r e f a v o r a b l y a n a l y z e d by h i g h r e s o l u t i o n SIM i n complex m i x t u r e s i n p a r t because o f t h e i r low r a t i o o f hydrogen t o c a r b o n , w h i c h l e a d s t o an e x a c t mass v a l u e below the masses o f o t h e r sub­ stances, p r i m a r i l y l i p i d s , t y p i c a l l y present i n food e x t r a c t s . Many o t h e r e n v i r o n m e n t a l p o l l u t a n t s i n ­ c l u d i n g h a l o g e n a t e d p e s t i c i d e s and many o f the common m y c o t o x i n s (35.) have comparable o r g r e a t e r mass d e f e c t s and s h o u l d be amenable t o a n a l y s i s by t h i s method. We have f r e q u e n t l y o b s e r v e d peaks below the e x a c t mass p o s i t i o n s o f the a f l a t o x i n s , as shown f o r the scans a t m/e 299 and 312 o f F i g u r e 6. These peaks may a r i s e from h a l o g e n a t e d p e s t i c i d e c o n t a m i n a n t s . High reso­ l u t i o n SIM may be a v a l u a b l e complement t o GC/MS and t o n e g a t i v e c h e m i c a l i o n i z a t i o n t e c h n i q u e s (8_,_9) f o r such compounds. Surface e f f e c t s . I n t e r a c t i o n s w i t h the s u r f a c e o f cont a i n e r s used t o i n t r o d u c e samples v i a the d i r e c t probe can a f f e c t d e t e c t i o n l i m i t s a d v e r s e l y , and an under­ s t a n d i n g o f s u r f a c e e f f e c t s appears to be i m p o r t a n t f o r f u l l y u t i l i z i n g the method i n t r a c e a n a l y s i s . In a d e t a i l e d s t u d y o f s u r f a c e i n t e r a c t i o n s f o r s m a l l pep­ t i d e s , Friedman (36-38) d e s c r i b e s the r a t e o f v o l a t i ­ l i z a t i o n (dn/dt) o f a pure compound from a s u r f a c e by the e q u a t i o n

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%

H

= N Ae" o

E / R T

(3)

where N i s the number o f sample m o l e c u l e s i n i t i a l l y on the s u r f a c e , A i s a f r e q u e n c y f a c t o r , and the exponen­ t i a l term e ~ ' g i v e s the f r a c t i o n o f m o l e c u l e s a t t e m p e r a t u r e Τ w i t h s u f f i c i e n t energy t o overcome s u r ­ face bonding. Ε i s the a c t i v a t i o n energy f o r removing 0

E

R T

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a m o l e c u l e from the s u r f a c e . A h i g h r a t e o f v o l a t i l i z a t i o n i s r e a l i z e d by i n c r e a s i n g N , f o r example by d i s p e r s i n g the sample by e v a p o r a t i o n from s o l u t i o n and by r e d u c i n g E, by u s i n g an i n e r t d i r e c t probe s u r f a c e . The enhanced s e n s i t i v i t y f o r a f l a t o x i n s i n mixt u r e s t h a t we o b s e r v e i s c o n s i s t e n t w i t h Friedman's model f o r s u r f a c e v o l a t i l i z a t i o n . Apparently other compounds c o d e p o s i t e d from s o l u t i o n a l o n g w i t h the a f l a t o x i n s e i t h e r occupy a c t i v e s i t e s on the sample tubes p r e f e r e n t i a l l y , o r s h i e l d the a f l a t o x i n s from them, r e s u l t i n g i n more e f f i c i e n t v o l a t i l i z a t i o n a r i s i n g from a r e d u c t i o n i n E. The c u r v e s o f measurement e r r o r f o r the p u r i n e s ( F i g . 1 1 ) , w h i c h i n d i c a t e lower p r e c i s i o n f o r more p o l a r compounds, a r e s u g g e s t i v e o f s u r f a c e i n t e r a c t i o n s ^ but the i n t e r p r e t a t i o n i s l e s s o b v i o u s , because d i s p e r s i n g the compounds over the g o l d s u r f a c e o f the sample probe a c t u a l l y l o w e r e d the p r e c i s i o n o f the a n a l y s i s . The p r e s e n c e o f h i g h concent r a t i o n s of i n o r g a n i c s a l t s probably accounts f o r t h i s e f f e c t f o r the p u r i n e s . I n Friedman's s t u d y o f s m a l l peptide v o l a t i l i z a t i o n , traces of i n o r g a n i c s a l t s l o w e r e d the r a t e o f v o l a t i l i z a t i o n s u b s t a n t i a l l y a t a given temperature (38). The s u r f a c e e f f e c t p r o b l e m i s an i m p o r t a n t a r e a f o r f u r t h e r study. I t has been s u g g e s t e d r e c e n t l y t h a t a r e d u c t i o n i n s u r f a c e b o n d i n g e x p l a i n s the s p e c t r a o b t a i n e d from " n o n - v o l a t i l e " compounds a b s o r b e d on a c t i v a t e d (surface-prepared) tungsten emitter wires u s i n g f i e l d d e s o r p t i o n mass s p e c t r o m e t r y (39,40.). M i n i m i z i n g s u r f a c e i n t e r a c t i o n s appears p r o m i s i n g as a g e n e r a l method t o enhance s e n s i t i v i t y f o r mass s p e c t r a l a n a l y s i s of l e s s v o l a t i l e substances. Of c o u r s e , i t i s i m p o r t a n t t o r e c o g n i z e t h a t the c h e m i c a l i n s t a b i l i t y o f a p a r t i c u l a r s u b s t a n c e may be s i g n i f i c a n t l y d e c r e a s e d r e l a t i v e t o i t s s t a b i l i t y i n a s o l u t i o n or s o l i d sample m a t r i x ; f o r example, a f l a t o x i n s d i s p e r s e d on a s u r f a c e show g r e a t l y enhanced r e a c t i v i t y to UV l i g h t . Ion Source C o n t a m i n a t i o n . C o n t a m i n a t i o n o f the i o n s o u r c e , w h i c h may o c c u r r a p i d l y i n some c a s e s , can a p p r e c i a b l y r e d u c e the s e n s i t i v i t y o f the method. T h i s f a c t o r must be weighed w i t h the advantages o f u s i n g the d i r e c t probe when a l t e r n a t i v e GC/MS p r o c e d u r e s a r e a p p l i c a b l e . The r a p i d i t y o f s o u r c e c o n t a m i n a t i o n v a r i e s w i d e l y i n the few examples r e p o r t e d . Snedden and P a r k e r e x p e r i e n c e d l e s s t h a n 20 per c e n t d e c l i n e i n s e n s i t i v i t y i n s i x months o f p u r i n e a n a l y s i s ( 1 3 J . C o n v e r s e l y , Dougherty (8.) found t h a t s e n s i t i v i t y f o r p o l y c h l o r i n a t e d b i p h e n y l (PCB) d e t e c t i o n was s e v e r e l y r e d u c e d a f t e r r u n n i n g t e n samples o f u n p u r i f i e d human u r i n e e x t r a c t . M i n i m a l s o l v e n t e x t r a c t i o n and column 0

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chromatography p r i o r t o d i r e c t probe a n a l y s i s s o l v e d t h i s p r o b l e m , as i t has i n our l a b o r a t o r y f o r a f l a t o x i n a n a l y s i s . Other approaches t o r e d u c i n g i o n source c o n t a m i n a t i o n may be a p p l i c a b l e i n some c a s e s . F o r example, i t s h o u l d be p o s s i b l e t o m e c h a n i c a l l y v e n t t h e v o l a t i l i z e d sample away from t h e i o n i z a t i o n chamber u n t i l t h e temperature o f v o l a t i l i z a t i o n f o r t h e compounds o f i n t e r e s t i s reached (see F i g . 8 ) , t h e r e b y reducing the q u a n t i t y o f m a t e r i a l which enters the i o n source. Chemical B i n d i n g E f f e c t s . The c h e m i c a l s t a t e o f t h e sample c a n a f f e c t i t s v o l a t i l i t y . A comparison o f the q u a n t i t a t i v e mass s p e c t r a l measurements f o r u r i c a c i d i n b l o o d plasma w i t h t h e c o n c e n t r a t i o n v a l u e s o b t a i n e d by e n z y m a t i c a n a l y s i s s u g g e s t s t h a t t h e mass s p e c t r o meter d e t e c t s o n l y t h e u r i c a c i d w h i c h i s bound l o o s e l y t o b l o o d p r o t e i n s , and n o t t h e u r i c a c i d i n s o l u t i o n , w h i c h may e x i s t p r i m a r i l y as t h e sodium s a l t . These d a t a , w h i c h must be c o n s i d e r e d p r e l i m i n a r y , suggest t h a t mass s p e c t r a l a n a l y s i s , when p e r f o r m e d w i t h o u t p r i o r sample t r e a t m e n t , may i n d i c a t e i n d i r e c t l y t h e e x t e n t o f c h e m i c a l b i n d i n g f o r s m a l l m o l e c u l e s i n some cases. Conclusions High r e s o l u t i o n s e l e c t e d i o n m o n i t o r i n g measurements on samples i n t r o d u c e d on t h e d i r e c t probe c a n p r o v i d e a c c u r a t e and h i g h l y s p e c i f i c q u a l i t a t i v e and q u a n t i t a t i v e i n f o r m a t i o n about compounds p r e s e n t i n t r a c e amounts. T h i s m i x t u r e a n a l y s i s method i s app l i c a b l e t o some compounds w h i c h cannot be s e p a r a t e d by gas chromatography because o f low v o l a t i l i t y o r chemical instability. The h i g h e s t s e n s i t i v i t i e s a r e obt a i n e d f o r s u b s t a n c e s h a v i n g l a r g e mass d e f e c t s and t h i s embraces a number o f c l a s s e s o f compounds, i n c l u d i n g h a l o g e n a t e d p e s t i c i d e s and m y c o t o x i n s , w h i c h a r e o f p a r t i c u l a r i n t e r e s t i n e n v i r o n m e n t a l and f o o d c h e m i s t r y . M a g n e t i c s e c t o r mass s p e c t r o m e t e r s h a v i n g s u f f i c i e n t e l e c t r o n i c s t a b i l i t y f o r a c c u r a t e mass measurement c a n be m o d i f i e d f o r a c c u r a t e q u a n t i t a t i v e h i g h r e s o l u t i o n s e l e c t e d i o n m o n i t o r i n g measurements.

References 1. Keith, L.H., in Identification and Analysis of Organic Pollutants in Water, L.H. Keith, ed. (Ann Arbor Science Publishers, Ann Arbor) 1976, p. iii. 2. McFadden, W.H., Schwartz, H.L. and Evans, S., J. Chromatogr. (1976) 122, 389.

118

3. 4. 5. 6. 7. 8. Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch006

9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27.

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Arpino, P.J., Dawkins, B . J . , and McLafferty, F.W., J. Chromatogr. Sci. (1974) 12, 574. Carroll, D.I., Dzidic, I., Stillwell, R.N., Haegele, K.D. and Horning, E.C., Anal. Chem. (1975) 47, 2369. Sphon, J.Α., Dreifuss, P.A. and Schulten, H.R., J. Assoc. Official Anal. Chemists, (1977) 60, 73. Hunt, D.F. and Ryan III, J.F., Anal. Chem., (1972) 44, 1306. Weinkam, R.J., Rowland, M. and Meffin, P . J . , Biomed. Mass Spectrom. (1977) 4, 42. Dougherty, R.C. and Piotrowska, K., Proc. Nat'l. Acad. Sci. USA, (1976) 73, 1777. Dougherty, R.C. and Piotrowska, K., J. Assoc. Official Anal. Chemists, (1976) 59, 1023. Levson, K. and Schulten, H.R., Biomed. Mass Spec­ trom. (1976) 3, 137. Soltero-Rigau, E. Kruger, K.L. and Cooks, R.G., Anal. Chem. (1977) 49, 435. Haddon, W.F., Masri, M.S., Randall, V.G., Elsken, R.H., and Meneghelli, B . J . , J. Assoc. Official Anal. Chemists (1977) 60, 107. Snedden, W. and Parker, R.B., Anal. Chem. (1971) 43, 1651. Snedden, W. and Parker, R.B., Biomed. Mass Spec­ trom. (1976) 3, 275. Hutzinger, O., Jamieson, W.D., and Safe, S., Nature (London) (1974) 252, 698. Fenselau, C., Anal. Chem. (1977) 49, 563A. Millington, D.S., Buoy, M.E., Brooks, G., Harper, M.E. and Griffiths, Κ., Biomed. Mass Spectrom. (1975) 2, 219. Millington, D.S., J. Steroid Biochem. (1975) 6, 239. Evans, K.P., Mathias, Α., Mellor, Ν., Silvester, R. and Williams, A.E., Anal. Chem. (1975) 47, 821. Gallegos, E . J . , Anal. Chem. (1975) 47, 1150. Hammar, C.G., and Hessling, R., Anal. Chem. (1971) 43, 298. Holmes, W.F., Holland, W.H., Shore, B.L., Bier, D.M. and Sherman, W.R., Anal. Chem. (1973) 45, 2063. Vacuum Generators, Ltd., Altrincham, Cheshire, England. Millington, D.S., personal communication. Haddon, W.F., Wiley, M. and Waiss, A.C., Anal. Chem. (1971) 43, 268. Masri, M.S., J. Am. Oil Chem. Soc. (1970) 47, 61. Masri, M.S., Haddon, W.F., Lundin, R.E., and Hseih, D.P.H., J. Agric. Food Chem. (1974) 22, 512.

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28. Wilson, B.J. and Hayes, A.W. in Toxicants Oc­ curring in Foods, National Academy of Sciences, Washington, D.C., pp. 372-423 (1973). 29. Heildelberger, C., Annu. Rev. Biochem. (1975) 44, 79. 30. Ong, T.M., Mutat. Res. (1975) 32, 35. 31. Aflatoxin Mass Spectral Data Bank, Pohland, A.E. and Sphon, J.Α., ed., U.S. Food and Drug Adm., Bureau of Foods, Division of Chem. and Phys., Washington, D.C. 32. Masri, M.S., Page, J.R., and Garcia, V.G., J . Assoc. Official Anal. Chemists (1969) 52, 641. 33. Parker, R.B., Snedden, W., and Watts, R.W.E., Biochem. J . (1969) 115, 103. 34. Kiser, Introduction to Mass Spectrometry and Its Applications, Prentice-Hall, Inc., Englewood Cliffs (1965), p. 216. 35. Kingston, D.G.I., J. Assoc. Official Anal. Chemists (1976) 59, 1016. 36. Beuhler, R . J . , Flanigan, E., Greene, L . J . and Friedman, L . , Biochem. and Biophys. Res. Commun. (1972) 46, 1082. 37. Beuhler, R.J., Flanigan, E., Greene, L . J . and Friedman, L . , Biochem. (1974) 13, 5061. 38. Beuhler, R.J., Flanigan, Ε., Greene, L . J . and Friedman, L . , J . Am. Chem. Soc. (1974) 96, 3990. 39. Soltman, B., Sweeley, C.C. and Holland, J.F., Anal. Chem. (1977) 49, 1164. 40. Hunt, D.F., Shabanowitz, J . and Botz, F.K., Anal. Chem. (1977) 49, 1160. RECEIVED December 30, 1977

7 Introduction to Gas Chromatography/High Resolution Mass Spectrometry B. J. KIMBLE

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

University of California-Berkeley, Berkeley, CA 94720

The combination of a gas chromatograph (GC), a mass spectrometer (MS) and an on-line computer is now well-established as an exceptionally powerful and versatile tool for identifying and quantitating the components present in organic mixtures. As with any successful technique, many improvements have been incorporated in recent years in order to provide the maximum amount of information that can be derived from a GC/MS analysis. Significant developments include the use of: a) glass capillary columns (1-3), for minimized surface effects and increased chromatographic resolution; b) direct interfacing of capillary columns to the mass spectrometer ion source (4-7), to reduce sample losses in a molecular separator and to preserve chromatographic resolution by elimi nating large-volume connectors; c) high pressure ionization methods (e.g., chemical ionization, 8-14), to provide complementary in formation to assist in the interpretation of electron impact spectra; d) improved computer techniques, for automated data acquisition, data handling (15-17), spectrum recognition (18-23) and interpretation (24-26). An a d d i t i o n a l approach f o r t h e improved u t i l i t y o f t h e GC/MS t e c h n i q u e would be t o d e t e r m i n e t h e r e c o r d ed mass v a l u e s i n each spectrum w i t h s u f f i c i e n t a c c u r a c y t o be a b l e t o compute t h e e x a c t e l e m e n t a l comp o s i t i o n o f each o f t h e i o n s p e c i e s c o n t r i b u t i n g t o t h e spectrum (27) . Such an achievement would p r o v i d e t h e maximum amount o f s t r u c t u r a l i n f o r m a t i o n t h a t c a n be d i r e c t l y d e r i v e d from a mass spectrum — i . e . , a d a t a ©0-8412-0422-5/78/47-070-120$10.00/0

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s e t c o m p r i s e d o f e x a c t e l e m e n t a l c o m p o s i t i o n s and t h e i r r e l a t i v e abundances. The r o u t i n e a v a i l a b i l i t y o f e l e m e n t a l c o m p o s i t i o n s p e c t r a from a GC/MS a n a l y s i s would s u b s t a n t i a l l y a s s i s t t h e i n t e r p r e t e r / a n a l y s t i n s e v e r a l ways, a l l o f w h i c h d e r i v e from t h e i n c r e a s e d s t r u c t u r a l s p e c i f i c i t y i n h e r e n t i n such d a t a . I n t h e case o f mass s p e c t r a which a r e , i n f a c t , interprétable by a t r a i n e d spect r o m e t r i s t , exact elemental composition i n f o r m a t i o n would e l i m i n a t e t h e guesswork i n v o l v e d i n r e l a t i n g mass v a l u e s and mass d i f f e r e n c e s t o s t r u c t u r a l u n i t s , and t h u s , would r e s u l t i n more r a p i d and r e l i a b l e i n t e r pretations. T h i s i s p a r t i c u l a r l y t r u e when t h e r e c o r d e d spectrum r e s u l t s from t h e c o - e l u t i o n o f two o r more components, and t h e i n t e r p r e t i v e p r o c e s s has t o i n c l u d e t h e c o r r e c t assignment o f masses i n t o t h e i r appropriate "sub-spectra". Elemental composition i n f o r m a t i o n would a l s o f a c i l i t a t e t h e l o c a t i o n and q u a n t i t a t i o n o f s p e c i f i c components i n m i x t u r e s , s i n c e the i n t e n s i t i e s f o r a p a r t i c u l a r e l e m e n t a l c o m p o s i t i o n c o u l d be p l o t t e d as a f u n c t i o n o f scan number; such an e l e m e n t a l c o m p o s i t i o n chromatogram would c o n s t i t u t e a more s p e c i f i c s t r u c t u r a l i n d i c a t o r t h a n do n o m i n a l mass chromatograms. Of p a r t i c u l a r u t i l i t y , e l e m e n t a l c o m p o s i t i o n s p e c t r a would p r o v i d e d i r e c t s t r u c t u r a l i n f o r m a t i o n i n t h e case o f " h a r d - t o - i n t e r p r e t " s p e c t r a o f t r u l y unknown components — t h a t i s , when l i t t l e o r no c h e m i c a l information i s a v a i l a b l e to a s s i s t i n the i n t e r p r e t a t i o n . A l s o , unexpected compounds c a n a r i s e i n a v a r i e t y o f s i t u a t i o n s as a r t i f a c t s o r c o n t a m i n a n t s , o r due t o i n a d e q u a t e f r a c t i o n a t i o n and/or d e r i v a t i z a t i o n p r o c e d u r e s , e t c . ; and o f c o u r s e , " d i f f i c u l t " s p e c t r a occur p a r t i c u l a r l y i n analyses o f mixtures c o n t a i n i n g s e v e r a l hundred components. W i t h t o d a y s i n c r e a s i n g need t o s t u d y more and more c o m p l i c a t e d samples ( p a r t i c u l a r l y e n v i r o n m e n t a l m i x t u r e s such as sewage e f f l u e n t s , and samples f o r w h i c h m i n i m a l s e p a r a t i o n and f r a c t i o n a t i o n steps are d e s i r e d ) , i t i s t h i s aspect o f complex m i x t u r e a n a l y s i s t h a t would p a r t i c u l a r l y benef i t from t h e a v a i l a b i l i t y o f e l e m e n t a l c o m p o s i t i o n spectra. To d a t e , t h e concept o f e l e m e n t a l c o m p o s i t i o n assignments i n GC/MS a n a l y s e s has been e x p l o r e d i n a v a r i e t y o f ways, and a p p l i c a t i o n s o f t h e t e c h n i q u e seem l i k e l y t o i n c r e a s e as s u i t a b l e commercial i n s t r u m e n t a t i o n becomes more w i d e l y a v a i l a b l e . U n f o r t u n a t e l y , a somewhat ambiguous t e r m i n o l o g y has a l r e a d y e v o l v e d conc e r n i n g use o f t h e p h r a s e s " a c c u r a t e mass measurement" and, i n p a r t i c u l a r , " h i g h r e s o l u t i o n " . In general, 1

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122

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t h e s e terms a r e used t o c o n t r a s t w i t h t h e measurement o f n o m i n a l masses ( e . g . , m/e 100 o r 101) and i n s t r u m e n t o p e r a t i o n a t n o m i n a l mass r e s o l u t i o n ( e . g . , Μ/ΔΜ < 1,000); however, i t s h o u l d be r e c o g n i z e d t h a t i n p r a c t i c e t h e s o - c a l l e d a c c u r a t e mass measurements may n o t be p a r t i c u l a r l y " a c c u r a t e " , n o r t h e mass r e s o l u t i o n p a r t i c u l a r l y " h i g h " . F o r s i m p l i c i t y , t h e acronyms GC/LRMS and GC/HRMS w i l l be used here t o denote GC/MS a n a l y s e s i n v o l v i n g t h e c o n t i n u o u s r e c o r d i n g o f complete mass s p e c t r a a t n o m i n a l (low) r e s o l u t i o n and h i g h e r mass r e s o l u t i o n s r e s p e c t i v e l y . I t s h o u l d a l s o be n o t e d t h a t t h e terms " a c c u r a t e mass measurement" and " h i g h r e s o l u t i o n " a r e n o t synonymous; t h i s may be i l l u s t r a t e d by summarizing t h e approaches t h a t have been r e p o r t e d i n the l i t e r a t u r e concerning the use o f elemental c o m p o s i t i o n i n f o r m a t i o n i n GC/MS a n a l y s e s . E l e m e n t a l c o m p o s i t i o n m o n i t o r i n g o f GC e f f l u e n t s . I n t h i s approach, t h e o b j e c t i v e i s t o u t i l i z e t h e mass s p e c t r o m e t e r as a h i g h l y s t r u c t u r a l l y s p e c i f i c GC d e t e c t o r f o r q u a n t i t a t i v e s t u d i e s , p a r t i c u l a r l y when the compound o f i n t e r e s t i s p r e s e n t i n a h i g h l y complex m i x t u r e (28-35). The mass s p e c t r o m e t e r i s o p e r a t e d a t some i n c r e a s e d mass r e s o l u t i o n ( e . g . , 10,000) w i t h a s i n g l e a c c u r a t e mass ( c h a r a c t e r i s t i c o f t h e components o f i n t e r e s t ) f o c u s s e d c o n t i n u o u s l y on t h e d e t e c t o r . The i n c r e a s e d mass r e s o l u t i o n aims t o reduce t h e i n t e r ­ f e r e n c e s from o t h e r i o n s h a v i n g t h e same n o m i n a l mass but o f a d i f f e r e n t e l e m e n t a l c o m p o s i t i o n , thus en­ h a n c i n g compound s p e c i f i c i t y w i t h r e s p e c t t o c o - e l u t i n g components from t h e gas chromatograph, i n s t r u m e n t back­ ground, column b l e e d , e t c . E l e m e n t a l c o m p o s i t i o n assignments from s p e c t r a r e ­ c o r d e d a t n o m i n a l mass r e s o l u t i o n . Here, t h e masses o f the r e c o r d e d peaks i n each spectrum a r e d e t e r m i n e d w i t h g r e a t e r t h a n n o m i n a l mass a c c u r a c y , and e l e m e n t a l c o m p o s i t i o n s a r e computed from t h e mass measurements (36; see a l s o 37, 3 8 ) . However, as t h e mass r e s o l u t i o n i s n o t i n c r e a s e ? , problems a r i s e i f t h e nominal mass r e s u l t s from i o n s o f more t h a n one e l e m e n t a l compo­ sition i . e . , i f t h e peak i s a c t u a l l y an u n r e s o l v e d doublet or m u l t i p l e t . This disadvantage represents a p a r t i c u l a r problem i n t h e a n a l y s i s o f complex m i x t u r e s when t h e components o f t h e m i x t u r e may n o t be chromat o g r a p h i c a l l y r e s o l v e d , and more c o m p l i c a t e d s p e c t r a a r e o f t e n produced. The u s e o f a double-beam mass s p e c t r o m e t e r f o r GC/MS a n a l y s e s (39^-41) i n which a mass c a l i b r a n t and t h e sample a r e a n a l y s e d s e p a r a t e l y but s i m u l t a n e o u s l y u s i n g two s e p a r a t e i o n s o u r c e s , a

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common mass a n a l y z e r and two s e p a r a t e d e t e c t o r s s h o u l d improve mass measurement a c c u r a c y b u t does n o t s o l v e the problem o f inadequate r e s o l u t i o n o f doublet o r m u l t i p l e t masses i n t h e sample s p e c t r a . A n o t h e r t e c h n i q u e , w h i c h u t i l i z e s a q u a d r u p o l e mass s p e c t r o ­ meter t o " s i m u l t a n e o u s l y p r o d u c e p o s i t i v e and n e g a t i v e i o n s p e c t r a , may a l s o be d e v e l o p e d f o r a c c u r a t e mass measurement i n GC/MS s t u d i e s (£2).

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

1 1

E l e m e n t a l c o m p o s i t i o n assignment from s p e c t r a r e c o r d e d a t i n c r e a s e d mass r e s o l u t i o n . I n t h i s c a s e , t h e aim i s t o c o n t i n u o u s l y r e c o r d complete mass s p e c t r a t h r o u g h o u t a c h r o m a t o g r a p h i c a n a l y s i s a t a s u f f i c i e n t l y h i g h mass r e s o l u t i o n t o e l i m i n a t e u n r e s o l v e d peaks and w i t h s u f ­ f i c i e n t mass measurement a c c u r a c y t o e x a c t l y d e t e r m i n e a l l o f t h e e l e m e n t a l c o m p o s i t i o n s p r e s e n t i n each spec­ trum. I n p r i n c i p l e , t h i s GC/HRMS method c a n be under­ t a k e n u s i n g mass s p e c t r o m e t e r s equipped f o r e i t h e r p h o t o p l a t e d e t e c t i o n (43-45) o r e l e c t r i c a l d e t e c t i o n (44-51, see a l s o 5 2 ) . I n p r a c t i c e , however, i t i s t h e l a t t e r method (which p a r a l l e l s n o m i n a l mass GC/MS o p e r a t i o n ) w h i c h has t h e p o t e n t i a l f o r p r o v i d i n g t h e maximum f l e x i b i l i t y and speed i n terms o f c o m p u t e r i z e d o p e r a t i o n , r e p e t i t i v e spectrum a c q u i s i t i o n , l a r g e spectrum c a p a c i t y , and t h e g e n e r a t i o n o f t o t a l i o n i z a ­ t i o n and mass chromatograms. I t i s t h i s GC/HRMS approach u t i l i z i n g magnetic s c a n n i n g and e l e c t r i c a l d e t e c t i o n w h i c h w i l l be d i s ­ c u s s e d more f u l l y h e r e . I t i s not intended t o describe d e t a i l s o f i n s t r u m e n t d e s i g n and s e t - u p p r o c e d u r e s , b u t r a t h e r t o present f o r the chemist/user the p r i n c i p a l p a r a m e t e r s i n v o l v e d , and t h e i r r e q u i r e m e n t s , l i m i t a ­ t i o n s and i n t e r - r e l a t i o n s h i p s ; i t i s t h i s knowledge t h a t becomes i m p o r t a n t i n p r a c t i c a l terms f o r t h e e f f e c t i v e and e f f i c i e n t i n t e r p r e t a t i o n o f GC/HRMS d a t a . Background The p r i m a r y parameters o f i n t e r e s t i n o b t a i n i n g e l e m e n t a l c o m p o s i t i o n s p e c t r a a r e mass measurement a c c u r a c y (a measure o f a b i l i t y t o a c c u r a t e l y d e t e r m i n e the t r u e mass) and dynamic mass r e s o l u t i o n ( t h e degree t o w h i c h masses c a n be r e s o l v e d under magnetic s c a n n i n g conditions). I n v e s t i g a t i o n o f t h e s e parameters de­ pends, o f c o u r s e , on t h e s p e c i f i c mode o f s p e c t r o m e t e r and computer o p e r a t i o n ; t h e d i s c u s s i o n h e r e i s based on d e v e l o p m e n t a l GC/HRMS s t u d i e s u n d e r t a k e n u s i n g a modi­ f i e d ΑΕΙ MS-902 d o u b l e - f o c u s s i n g mass s p e c t r o m e t e r t o g e t h e r w i t h o n - l i n e , r e a l - t i m e d a t a a c q u i s i t i o n and r e d u c t i o n (47-49, 5 3 ) .

124

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Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

I n o u t l i n e , a spectrum i s produced by exponen­ t i a l l y s c a n n i n g over the mass range from h i g h mass t o low mass. The r e s u l t i n g a n a l o g s i g n a l from the de­ t e c t o r a m p l i f i e r i s d i g i t i z e d a t e q u a l time i n t e r v a l s and the d i g i t a l v a l u e s f o r each peak d e t e c t e d above a c o n s t a n t p r e s e t t h r e s h o l d v a l u e a r e saved f o r a n a l y s i s , t o g e t h e r w i t h the a b s o l u t e time o f o c c u r r e n c e o f t h e peak w i t h r e s p e c t t o the s t a r t o f the scan (54). The d i g i t a l v a l u e s f o r each peak d e f i n e the peak p r o f i l e , from w h i c h the peak i n t e n s i t y i s d e t e r m i n e d from i t s a r e a (5J5, the sum o f t h e d i g i t a l v a l u e s f o r t h a t peak) and the peak p o s i t i o n i n time i s d e t e r m i n e d from t h e t i m e computed f o r the peak c e n t e r - o f - g r a v i t y o r cent r o i d (54). Mass/time f u n c t i o n . In the i d e a l c a s e , t h e r e f o r e , t h e mass (M) o f any peak i s an e x p o n e n t i a l f u n c t i o n o f t h e e l a p s e d time ( t ) from the s t a r t o f the s c a n ( F i g u r e 1 ) . That i s , M « "

t / T

(1)

e

,f

where τ i s t h e t i m e c o n s t a n t " o f the e x p o n e n t i a l f u n c ­ t i o n , i . e . , t h e time t a k e n t o scan between any mass, M , and the mass M /e (where e=2.718). At the s t a r t o f the s c a n , t = 0 and M i s e q u a l t o the maximum mass value, M , so t h a t e q u a t i o n (1) becomes x

x

m a x

M = M

max

e"

t / x v

(2) J

S c a n r a t e . The s c a n r a t e i n t h e commonly quoted u n i t s o f seconds/mass decade (a mass decade c o v e r s the range Μ t o M /10) can be d e r i v e d from t h i s e q u a t i o n by con­ s i d e r i n g t h e t i m e d i f f e r e n c e ( t - t i ) f o r two masses Mi and Mi/10: χ

x

2

M

>

M

e

• max "

t l / T

a n d

M

'

-

M

max

β

'*

ΐ Λ

These e q u a t i o n s combine t o g i v e t -ti

= τ l o g 10 = τ (3) G 10 where τ i s the time t o scan one mass decade, i . e . , the s c a n r a t e i n seconds/decade. 2

1 0

R e s o l u t i o n . As n o r m a l l y d e f i n e d , the mass r e s o l u t i o n , R, a t 10% v a l l e y s e p a r a t i o n o f two e q u a l mass peaks i s g i v e n by

7.

KIMBLE

Gas Chromatography/High R

125

Resolution Mass Spectrometry

= Μ/ΔΜ

(4)

where M i s t h e n o m i n a l mass and ΔΜ i s t h e a c c u r a t e mass d i f f e r e n c e f o r t h e two mass peaks ( F i g u r e 2 ) . The time d i f f e r e n c e , A t , between t h e maxima o f t h e s e two peaks can be d e t e r m i n e d from t h e r a t e o f change o f mass w i t h time (from e q u a t i o n 2) g i v i n g -M d

M

= —5**

. '

t / T

e

·dt

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

which approximates t o τ f o r s m a l l v a l u e s o f ΔΜ and A t . (2) g i v e s AM -At M ~T~

D i v i d i n g by e q u a t i o n

and u s i n g e q u a t i o n ( 4 ) , t h i s reduces t o At = " I

(5)

From symmetry c o n s i d e r a t i o n s , t h e time d i f f e r e n c e , A t , between t h e peak maxima i s e q u a l t o t h e time t a k e n t o scan a c r o s s one o f t h e s e peaks between t h e p o i n t s w h i c h a r e a t 5% o f t h e maximum peak h e i g h t ( F i g u r e 2 ) . Thus, i f τ and At a r e known, then t h e r e s o l u t i o n c a n be c a l c u l a t e d f o r each s i n g l e peak t h r o u g h o u t t h e mass range. A l s o , e q u a t i o n ( 5 ) shows t h a t f o r c o n s t a n t mass r e s o l u t i o n , R , and s c a n r a t e τ (=τ l o g 1 0 ) , t h e w i d t h s o f a l l s i n g l e t peaks measured a t 5 1 o f r h e i r maximum h e i g h t s h o u l d be c o n s t a n t . E q u a t i o n s 3 and 5 , combined t o g i v e 1 0

t =

- T

1

0

/ R

log

e

10 ,

(6)

p e r m i t v a r i o u s i n s t r u m e n t parameters t o be c a l c u l a t e d and compared w i t h e x p e r i m e n t a l r e s u l t s . F o r example, f o r a c o n s t a n t r e s o l u t i o n (10% v a l l e y ) o f 10,000 and a s c a n r a t e o f 6 seconds/decade, t h e p e a k w i d t h f o r a l l masses a t t h e i r 5% l e v e l s i s g i v e n by At =

s e c = 260.6 ysec ΙΟ* χ 2.3026

PERFORMANCE

MASS

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

HIGH

ρ _ M . M _ " M -M, ΔΜ ~ 2

Τ

At

Figure 2. Mass resolution (10% valley defi­ nition)

SPECTROMETRY

7.

KIMBLE

Gas Chromatography/High

Resolution Mass Spectrometry

127

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

For a d i g i t i z a t i o n r a t e o f 50 kHz, t h e d a t a p o i n t s a r e s e p a r a t e d i n time u n i t s o f 1/50,000 s e c o r 20 y s e c , so t h a t i n t h i s example, t h e w i d t h s o f a l l s i n g l e t peaks s h o u l d be d e f i n e d by 260/20 = 13 d a t a p o i n t s between t h e i r 5% l e v e l s . Mass measurement a c c u r a c y . I t i s t h e a b i l i t y t o mea­ sure masses i n a spectrum w i t h h i g h a c c u r a c y t h a t i s the b a s i s f o r d e t e r m i n i n g t h e c o r r e c t e l e m e n t a l com­ p o s i t i o n s . As p e r f e c t l y e x a c t mass measurements cannot be a c h i e v e d i n p r a c t i c e , t h e approach used t o g e n e r a t e a h i g h r e s o l u t i o n spectrum i s t o compute, f o r each measured mass, a l i s t o f p o s s i b l e e l e m e n t a l compo­ s i t i o n s (56) whose a c c u r a t e masses f a l l w i t h i n a s m a l l mass "wincfow" around each measured mass. I n o r d e r t o r e s t r i c t t h e e l e m e n t a l c o m p o s i t i o n l i s t i n g t o somewhat manageable p r o p o r t i o n s , t h e u s e r i s r e q u i r e d t o s e l e c t the t y p e s and maximum numbers o f each element t h a t he c o n s i d e r s r e l e v a n t on c h e m i c a l grounds. He i s a l s o r e q u i r e d t o i n p u t t h e " w i d t h " o f t h e mass window t o be used f o r t h e c a l c u l a t i o n s i . e . , t h e measured mass ± 6ppm, o r a mass window o f 26. The v a l u e o f 6 must be chosen c a r e f u l l y so t h a t the c o r r e c t e l e m e n t a l c o m p o s i t i o n f o r a p a r t i c u l a r measured mass i s i n c l u d e d i n t h e l i s t o f p o s s i b i l i t i e s . I f t h e chosen v a l u e o f 6 i s t o o s m a l l , t h e n t h e c o r r e c t c o m p o s i t i o n may n o t be l i s t e d ; however, i f t h e chosen v a l u e o f δ i s s i g n i f i c a n t l y l a r g e r than necessary, then the r e s u l t i n g l i s t o f c o m p o s i t i o n s r a p i d l y becomes t o o u n w i e l d y t o e v a l u a t e . The s e l e c t i o n o f t h e a p p r o p r i a t e v a l u e o f 6 f o r any p a r t i c u l a r s e t o f i n s t r u m e n t oper­ a t i n g parameters depends d i r e c t l y on a knowledge o f t h e mass measurement a c c u r a c y d e t e r m i n e d e x p e r i m e n t a l l y under t h o s e c o n d i t i o n s . The a t t a i n m e n t o f h i g h mass measurement a c c u r a c y i s dependent upon many f a c t o r s (57-60) such as adequate d e f i n i t i o n o f a c t u a l peak shapes, tTïë absence o f abnormal peakshapes, d e f i n i t i o n o f t h e a c t u a l mass/time f u n c t i o n , s o f t w a r e a l g o r i t h m s f o r mass c a l c u l a t i o n , and mass r e s o l u t i o n . The dependency on mass r e s o l u t i o n r e l a t e s t o t h e p r e s e n c e o f u n r e s o l v e d peak d o u b l e t s o r m u l t i p l e t s ( F i g u r e 3 ) ; f o r these peakshapes, t h e p o s i t i o n o f t h e c e n t e r - o f - g r a v i t y o f t h e o v e r a l l peak p r o f i l e i s i n a c c u r a t e , r e s u l t i n g i n i n a c c u r a t e mass measurements f o r t h e i o n s p e c i e s a c t u a l l y p r e s e n t . I n g e n e r a l , improved mass measurements c a n be o b t a i n e d by a v e r a g i n g t h e measurements from s e v e r a l s p e c t r a ( 6 1 , 6 2 ) . T h i s p r o c e s s r e d u c e s t h e e f f e c t o f t h e random e r r o r s a s s o c i a t e d w i t h a c c u r a t e mass d e t e r m i n a t i o n s , and, t h u s , a s m a l l e r mass window c a n be used i n t h e

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generation o f p o s s i b l e elemental compositions f o r averaged mass measurements. S t a t i s t i c a l l y , the mass measurement a c c u r a c y would be e x p e c t e d t o be improved by a f a c t o r o f /n where η i s t h e number o f measurements averaged f o r a p a r t i c u l a r a c c u r a t e mass.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

P r a c t i c a l C o n s i d e r a t i o n s and t h e E v a l u a t i o n o f Instrument Performance? GC and f a s t - s c a n n i n g HRMS. I n p r a c t i c a l t e r m s , t h e a b i l i t y t o d e t e r m i n e a c c u r a t e mass measurements f o r s p e c t r a r e c o r d e d from c h r o m a t o g r a p h i c e f f l u e n t s c e n t e r s on the performance o f t h e f a s t - s c a n n i n g h i g h r e s o l u t i o n mass s p e c t r o m e t e r and i t s d a t a system (57, 63^-67). As f o r GC/LRMS, t h e gas chromatograph and GC/MS i n t e r f a c e may be o f v a r i o u s d e s i g n s p r o v i d e d t h a t : a) the i n c r e a s e d p r e s s u r e i n t h e i o n s o u r c e due t o the c a r r i e r gas p e r m i t s o p e r a t i o n o f the mass spectrometer ; b) each c h r o m a t o g r a p h i c peak i s o f s u f f i c i e n t d u r a t i o n so t h a t s p e c t r a w i l l be r e c o r d e d f o r each component; c) a s u f f i c i e n t amount o f each component i s i n t r o ­ duced v i a t h e GC i n l e t system i n t o t h e i o n s o u r c e so t h a t r e c o g n i z a b l e s p e c t r a c a n be recorded. As t h e s e d e s i g n c o n s i d e r a t i o n s have been t h e s u b j e c t o f many p u b l i c a t i o n s ( e . g . , 6 8 ) , o n l y the most i m p o r t a n t a s p e c t s f o r GC/HRMS w i l lïïe"d i s c u s s e d f u r t h e r h e r e . The main parameters f o r GC/HRMS o p e r a t i o n a r e summarized i n T a b l e 1; many o f t h e s e p a r a m e t e r s , o f c o u r s e , a l s o p e r t a i n t o GC/LRMS a n a l y s e s , b u t they become somewhat more c r i t i c a l f o r t h e c o n c o m i t a n t measurement o f a c c u r a t e masses under f a s t - s c a n n i n g h i g h r e s o l u t i o n c o n d i t i o n s . The t a b l e a l s o i n d i c a t e s t h e p r i m a r y optimum r e q u i r e m e n t s f o r each parameter. F o r s e v e r a l o f these, there are c o n f l i c t i n g requirements due t o t h e i n t e r - r e l a t i o n s h i p s t h a t e x i s t between t h e d i f f e r e n t p a r a m e t e r s , and t h e a c t u a l v a l u e s u t i l i z e d f o r a n a l y s e s w i l l n e c e s s a r i l y be a s e t o f v a l u e s t h a t a c h i e v e t h e optimum compromise. Scan c y c l e t i m e . The o v e r a l l c y c l e time f o r r e c o r d i n g a s i n g l e spectrum i s a f u n c t i o n o f the s c a n r a t e , t h e mass r a n g e , and t h e time r e q u i r e d t o r e s e t the magnetic f i e l d between t h e minimum and maximum mass v a l u e s . As d e s c r i b e d above, t h e t h e o r e t i c a l s c a n r a t e , τ , i s a c o n s t a n t and i s d i r e c t l y p r o p o r t i o n a l t o t h e time c o n s t a n t o f t h e e x p o n e n t i a l f u n c t i o n , τ. I n p r a c t i c e , 1 0

7.

KIMBLE

Gas Chromatography/High Resolution Mass Spectrometry

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

T a b l e 1,

129

P r i m a r y C o n s i d e r a t i o n s f o r GC/HRMS

Parameter

Requirement

mass measurement accuracy

maximize t o l i m i t number o f p o s s i b l e e l e m e n t a l comp o s i t i o n s generated

dynamic mass resolution

maximize t o reduce number o f u n r e s o l v e d p e a k s , hence i n c r e a s e mass measurement accuracy minimize t o increase sensitivity

sensitivity

maximize t o reduce sample quantity requirements

scan t i m e ( f u n c t i o n of mass range and s c a n r a t e )

m i n i m i z e scan time t o p r e s e r v e chromatographic r e s o l u t i o n i n t o t a l i o n i z a t i o n and mass chromatograms maximize mass range f o r u s e f u l information maximize s c a n r a t e (sec/decade) for increased s e n s i t i v i t y and mass measurement accuracy

magnet r e s e t t i m e

m i n i m i z e t o reduce "wasted" t i m e and p r e s e r v e chromatographic resolution i n t o t a l i o n i z a t i o n and mass chromatograms

GC peak e l u t i o n time

m i n i m i z e f o r h i g h e r chromatographic r e s o l u t i o n maximize w i t h r e s p e c t t o s c a n c y c l e time ( i . e . , s c a n time + magnet r e s e t time) to ensure s u f f i c i e n t time f o r r e c o r d i n g mass s p e c t r a

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the mass/time f u n c t i o n i s n o t p e r f e c t o v e r t h e whole mass range; t h a t i s , τ i s n o t c o n s t a n t b u t v a r i e s w i t h mass as i l l u s t r a t e d i n F i g u r e 4. The use o f an i n t e r ­ n a l mass s t a n d a r d such as p e r f l u o r o k e r o s i n e ( P F K ) , w h i c h c o n t r i b u t e s peaks o f known a c c u r a t e mass t h r o u g h ­ out t h e mass r a n g e , p r o v i d e s a means f o r d e t e r m i n i n g the a c t u a l mass/time f u n c t i o n over s m a l l s e c t i o n s o f the mass range. Thus, a v a l u e o f τ can be a s s i g n e d t o each o f t h e c a l i b r a t i o n masses, and from each o f t h e s e v a l u e s t h e measured s c a n r a t e , τ , i n seconds/decade can be c a l c u l a t e d from e q u a t i o n 3. The v a r i a t i o n o b s e r v e d f o r a n o m i n a l s c a n r a t e o f 6 seconds/decade f o l l o w s t h e p r o f i l e f o r τ shown i n F i g u r e 4, and ranges between about 6.5 seconds/decade a t m/e 580 and 5.5 seconds/decade a t m/e 80; t h e a c t u a l o v e r a l l s c a n t i m e between m/e 800 and m/e 65 i s about 7.2 seconds (48, 49). I t s h o u l d be n o t e d t h a t t h e upper s e c t i o n oF~~the mass range (~ m/e 800-650) i s n o t e a s i l y u s a b l e f o r ac­ c u r a t e mass a s s i g n m e n t s due t o t h e low i n t e n s i t y o f t h e PFK c a l i b r a t i o n masses i n t h i s r e g i o n , and t h e r a p i d r a t e o f change o f τ i n t h i s r e g i o n p r e c l u d e s a c c u r a t e e x t r a p o l a t i o n o f τ above t h e h i g h e s t r e l i a b l e c a l i ­ b r a t i o n mass. The t i m e t a k e n t o r e t u r n t o t h e i n i t i a l maximum mass v a l u e f o r t h e n e x t scan ( t h e magnet r e s e t t i m e ) s h o u l d , o f c o u r s e , be m i n i m i z e d as f a r as p o s s i b l e t o r e d u c e "wasted" t i m e and m i n i m i z e t h e o v e r a l l scan c y c l e t i m e . As r e p o r t e d p r e v i o u s l y (£8), magnet c i r ­ c u i t m o d i f i c a t i o n s u n d e r t a k e n on a MS-902 mass spec­ t r o m e t e r have p e r m i t t e d t h i s t i m e t o be r e d u c e d t o 2.4 seconds w h i l s t m a i n t a i n i n g mass c a l i b r a t i o n up t o - m/e 650 f o r t h e subsequent s c a n . W i t h t h e s e i n s t r u m e n t p a r a m e t e r s , t h e r e f o r e , t h e o v e r a l l scan c y c l e t i m e ( i . e . , s c a n t i m e + magnet r e s e t time) i s j u s t under 10 seconds.

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

1 0

GC peak e i u t i o n t i m e . The v a l u e f o r t h e o v e r a l l scan c y c l e t i m e i s i m p o r t a n t f o r t h e a d j u s t m e n t o f t h e gas c h r o m a t o g r a p h i c o p e r a t i n g parameters ( e . g . , f l o w r a t e , column t e m p e r a t u r e and programming r a t e ) . In order to e n s u r e t h a t mass s p e c t r a can be r e c o r d e d f o r any GC peak, t h e t i m e f o r e i u t i o n o f a peak has t o be a d j u s t e d so t h a t i t i s a t l e a s t t w i c e t h e scan c y c l e t i m e . As i l l u s t r a t e d i n F i g u r e 5, t h e minimum f a c t o r o f two d e r i v e s from t h e unknown time r e l a t i o n s h i p between t h e s t a r t o f a s c a n and t h e commencement o f e i u t i o n o f a GC peak. I t i s n e c e s s a r y , t h e r e f o r e , i n t h i s c a s e , t o ensure t h a t a l l c h r o m a t o g r a p h i c peaks e l u t e i n t o t h e mass s p e c t r o m e t e r i o n s o u r c e over a time p e r i o d o f a t

KIMBLE

Gas Chromatography/High

Resolution Mass Spectrometry

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

Mass A

Centroid of Mass A

Figure 3. Effect of inadequate mass resolution on mass measurement ac­ curacy

Figure 4. The variation of τ as a function of mass

Figure 5. The extreme relationships between scan cycle time and GC peak eiution time; scan cycle time equals one-half of the GC peak eiution time

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Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

l e a s t 20 seconds so t h a t a t l e a s t one u s a b l e spectrum can be r e c o r d e d . The u s e o f a GC peak e i u t i o n time o f j u s t t w i c e the scan c y c l e time r e s u l t s i n mass chromatograms which show a v a r i e t y o f p r o f i l e s from t h e same GC peak ( s e e F i g u r e 6 ) . S i m i l a r f e a t u r e s may a l s o be seen w i t h t o t a l i o n i z a t i o n chromatograms, which c a n c o m p l i c a t e the matching o f such o u t p u t w i t h gas chromatograms r e c o r d e d by a flame i o n i z a t i o n d e t e c t o r ; q u a n t i t a t i v e comparisons a r e a l s o more d i f f i c u l t t o u n d e r t a k e w i t h such v a r i a t i o n s i n peak h e i g h t s . The scan c y c l e t i m e , t h e r e f o r e , d i r e c t l y l i m i t s t h e o v e r a l l gas chromato­ g r a p h i c performance t h a t c a n be u t i l i z e d e f f e c t i v e l y . Mass measurement a c c u r a c y . The a b i l i t y t o a c c u r a t e l y measure masses under GC/HRMS c o n d i t i o n s i s , o f c o u r s e , the o b j e c t o f t h e e x e r c i s e . However, i t i s t h e i n t r o ­ d u c t i o n o f t h e sample v i a a gas chromatograph t h a t p r e s e n t s major problems f o r d e t e r m i n i n g a c c u r a t e mas­ s e s . Because o f t h e s h o r t r e s i d e n c e time o f each component i n t h e i o n s o u r c e , a w e l l - d e f i n e d peak p r o ­ f i l e f o r each mass has t o be d e t e r m i n e d i n a v e r y s h o r t time (~ 260 psec a t a s c a n r a t e o f 6 seconds/decade and a r e s o l u t i o n o f 10,000). A l s o , o n l y one o r two r e a ­ s o n a b l y i n t e n s e s p e c t r a c a n be e x p e c t e d t o be r e c o r d e d from each component. T h i s v i r t u a l l y e l i m i n a t e s t h e a b i l i t y t o average the measured masses t o improve a c c u r a c y , and, t h e r e f o r e , i t i s n e c e s s a r y t h a t h i g h a c c u r a c y measurements s h o u l d be r e l i a b l y produced f o r each i n d i v i d u a l spectrum. The l a r g e volume o f d a t a g e n e r a t e d from a GC/HRMS a n a l y s i s a l s o demands a h i g h degree o f r e l i a b i l i t y as d e t a i l e d i n v e s t i g a t i o n s i n t o anomalous f e a t u r e s a r e e x t r e m e l y time-consuming. I n a d d i t i o n t o t h e g e n e r a t i o n o f e l e m e n t a l com­ p o s i t i o n l i s t i n g s f o r measured a c c u r a t e masses, a d e t a i l e d knowledge o f a t t a i n a b l e mass measurement a c c u r a c y i s a l s o i m p o r t a n t f o r GC/HRMS s t u d i e s i n o r d e r t o g e n e r a t e a c c u r a t e mass chromatograms ( o r e l e m e n t a l c o m p o s i t i o n chromatograms) t o l o c a t e t h e e i u t i o n times o f s p e c i f i c components o r compound c l a s s e s f o r f u r t h e r d e t a i l e d s t u d y (£7). I n t h i s c a s e , the u s e r s e l e c t s the e l e m e n t a l c o m p o s i t i o n o f i n t e r e s t and t h e c o r ­ r e s p o n d i n g a c c u r a t e mass i s c a l c u l a t e d . An a p p r o p r i a t e mass window (δ) i s s p e c i f i e d and, f o r each spectrum, the i n t e n s i t y o f t h e a c c u r a t e mass which i s l o c a t e d w i t h i n t h i s s p e c i f i e d mass window around t h e c a l c u l a t e d mass, i s saved. The i n t e n s i t i e s p l o t t e d as a f u n c t i o n o f s c a n number c o n s t i t u t e t h e e l e m e n t a l c o m p o s i t i o n o r a c c u r a t e mass chromatogram. Here a g a i n , s e l e c t i o n o f t h e s i z e o f the mass window depends on knowledge o f t h e

Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0070.ch007

7.

KIMBLE

Gas Chromatography/High

Resolution Mass Spectrometry

133

mass measurement a c c u r a c y ; t h e c h o i c e i s c r i t i c a l t o ensure t h a t t h e c o r r e c t masses a r e l o c a t e d b u t t h a t " e x t r a n e o u s " masses a r e e x c l u d e d as f a r as p o s s i b l e . M e n t i o n s h o u l d a l s o be made o f t h e g e n e r a t i o n o f nomin a l mass s p e c t r a and chromatograms from a c c u r a t e mass data. Here t h e i n t e n s i t i e s o f a l l a c c u r a t e masses t h a t f a l l w i t h i n t h e mass range between (X.0000-0.4000) amu and (X.0000+0.6000) amu a r e summed t o g i v e t h e i n t e n s i t y o f n o m i n a l mass X. The mass measurement a c c u r a c y becomes i m p o r t a n t f o r t h e a c c u r a t e masses t h a t may l i e c l o s e t o t h e l i m i t s o f t h i s r a n g e , and cons i d e r a t i o n s h o u l d be g i v e n t o t h e c o n v e n t i o n s used f o r d e f i n i n g t h e n o m i n a l mass o f an i o n ( 6 9 ) . In v i e w o f a l l t h e s e b a s i c c o n s i d e r a t i o n s , i t i s e s s e n t i a l t h a t a d e t a i l e d e v a l u a t i o n o f a c c u r a t e mass measurement c a p a b i l i t y s h o u l d be u n d e r t a k e n f o r a g i v e n s e t o f o p e r a t i n g parameters t o ensure r e l i a b l e s i n g l e scan s p e c t r a and a c c u r a t e mass chromatograms. The p r a c t i c a l d e t e r m i n a t i o n o f mass measurement accuracy i s undertaken f o r a p a r t i c u l a r s e t o f i n s t r u ment o p e r a t i n g p a r a m e t e r s by r e c o r d i n g a number o f s p e c t r a o f a s e l e c t e d compound whose p r i n c i p a l masses are u n i q u e l y known. Because o f t h e c o n t i n u o u s v a r i a t i o n i n sample f l o w r a t e w h i c h r e s u l t s from samples i n t r o d u c e d v i a a gas chromatograph, t h e b a s i c e v a l u a t i o n i s made under GC/HRMS o p e r a t i n g c o n d i t i o n s ( i . e . , w i t h normal c a r r i e r gas f l o w r a t e , column temp e r a t u r e , e t c . ) , but w i t h i n t r o d u c t i o n o f the e v a l u a t i o n compound v i a a b a t c h i n l e t system a t c o n s t a n t sample f l o w r a t e . A c t u a l GC/HRMS e v a l u a t i o n c a n t h e n be checked by i n t r o d u c i n g a known compound v i a t h e gas c h r o m a t o g r a p h i c i n l e t and v e r i f y i n g t h a t t h e r e s u l t i n g mass measurements a r e c o n s i s t e n t w i t h t h e b a s i c e v a l u a t i o n f o r s i m i l a r masses o f s i m i l a r i n t e n s i t i e s . The compound s e l e c t e d f o r e v a l u a t i o n o f mass measurement a c c u r a c y s h o u l d produce i o n masses t h a t a r e s i n g l e t peaks w e l l - s e p a r a t e d from o t h e r masses a t t h e o p e r a t i n g mass r e s o l u t i o n . I d e a l l y , t h e y s h o u l d a l s o a d e q u a t e l y c o v e r t h e mass range o f i n t e r e s t , and s h o u l d be o f a p p r o x i m a t e l y t h e same r e l a t i v e i n t e n s i t i e s t o p e r m i t e v a l u a t i o n o f mass measurement a c c u r a c y as a f u n c t i o n o f b o t h mass and i n t e n s i t y . In p r a c t i c e , a compromise has t o be made w i t h r e s p e c t t o t h e s e l a t t e r r e q u i r e m e n t s , and a v a r i e t y o f compounds f o r t h i s purpose have been r e p o r t e d i n t h e l i t e r a t u r e ( e . g . , p e r c h l o r o b u t a d i e n e , £1, and h e p t a c o s a f l u o r o t r i b u t y l amine, 48,49). E v a l u a t i o n o f t h e measurements o b t a i n e d f o r t h e s e l e c t e d masses from s e v e r a l scans can be u n d e r t a k e n by a v a r i e t y o f r e l a t e d methods. One approach (61)

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described the production o f a histogram which p l o t s the p e r c e n t a g e o f t h e t o t a l number o f mass measurements as a f u n c t i o n o f t h e i r mass measurement e r r o r s (the d i f ­ f e r e n c e between t h e measured mass and t h e t r u e mass). T h i s method, however, s u f f e r s from t h e drawback t h a t o n l y a l i m i t e d number o f scans were e v a l u a t e d , and t h e r e s u l t i n g h i s t o g r a m was g e n e r a t e d from c o m p o s i t e e r r o r measurements from i o n s o f d i f f e r i n g masses and a l s o differing relative intensities. As GC/HRMS a n a l y s e s n e c e s s a r i l y i n v o l v e t h e p r o ­ d u c t i o n o f l a r g e numbers o f s p e c t r a and r e q u i r e a c o r r e s p o n d i n g computer c a p a b i l i t y , a more d e t a i l e d s t a t i s t i c a l e v a l u a t i o n c a n be u n d e r t a k e n i f a l a r g e number ( e . g . , > 100) o f s p e c t r a a r e r e c o r d e d and e v a l ­ uated automatically. I n t h i s approach (7£), f o r each s e l e c t e d a c c u r a t e mass, M , t o be e v a l u a t e d , t h e mea­ s u r e d mass i s l o c a t e d i n each spectrum w i t h i n an e s ­ t i m a t e d mass window around t h e t r u e mass, Mt. F o r each v a l u e o f M , s e v e r a l p a r a m e t e r s a r e c a l c u l a t e d from a l l of the recorded s p e c t r a : a) The number o f s p e c t r a (N) f o r w h i c h t h e measured mass was found w i t h i n t h e mass window. (The e s t i m a t e d mass window s h o u l d be chosen so t h a t i t r e p r e s e n t s t h e a b s o l u t e maximum mass measure ment e r r o r t h a n c a n be t o l e r a t e d f o r s p e c t r a l interpretation e.g., ±20 ppm. Thus, f o r a l l v a l u e s o f Μ^, Ν s h o u l d c o r r e s p o n d t o t h e number o f s p e c t r a r e c o r d e d ; i . e . , a l l o f t h e measure ments w i l l be w i t h i n 20 ppm o f t h e i r t r u e v a l ­ ue) . b) The mean mass e r r o r , E. ( T h i s may be p o s i t i v e or n e g a t i v e w i t h r e s p e c t t o M t ) . c) The s t a n d a r d d e v i a t i o n o f t h e mass measurement e r r o r s (σ ppm). d) The s t a n d a r d d e v i a t i o n o f t h e mean mass e r r o r (o = σ//Ν). e) Mean peak i n t e n s i t y . f ) S t a n d a r d d e v i a t i o n o f t h e i n t e n s i t y measure­ ments. (For a d d i t i o n a l e v a l u a t i o n o f i n s t r u m e n t p e r f o r m a n c e , mean and s t a n d a r d d e v i a t i o n v a l u e s a r e a l s o c a l c u l a t e d f o r a v a r i e t y o f o t h e r p a r a m e t e r s a s s o c i a t e d w i t h each s e l e c t e d mass; t h e s e i n c l u d e τ, W. , W., , R, as ex­ p l a i n e d below). * These v a l u e s p e r m i t a more d e t a i l e d e v a l u a t i o n o f the r e l a t i v e e f f e c t s o f t h e s y s t e m a t i c and random e r r o r s a s s o c i a t e d w i t h mass measurement a c c u r a c y . I n the absence o f s y s t e m a t i c e r r o r s , t h e mean e r r o r Ε s h o u l d approach zero ( i . e . , t h e mean measured mass s h o u l d e q u a l t h e t r u e mass), and t h e r e i s a 99.78% t

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chance t h a t t h e mean mass w i l l be w i t h i n 3 o o f t h e t r u e v a l u e . A l s o , f o r a normal d i s t r i b u t i o n , 99.78% o f t h e measurements f o r each mass s h o u l d f a l l w i t h i n 3σ o f the mean measured v a l u e , i . e . , v i r t u a l l y a l l o f t h e measurements s h o u l d f a l l w i t h i n a s p r e a d o f 6σ ppm. A s u i t a b l e c h o i c e f o r d e t e r m i n i n g t h e mass window (2δ) f o r e l e m e n t a l c o m p o s i t i o n l i s t i n g s and chromatograms would r e s u l t , t h e r e f o r e , from u s i n g a δ v a l u e e q u a l t o the sum o f t h e maximum v a l u e o f 3σ f o r t h e masses c o n s i d e r e d , and t h e maximum a b s o l u t e v a l u e o f Ε f o r t h e same masses (see F i g u r e 7 ) . The use o f t h e 3σ v a l u e s ( c o r r e s p o n d i n g t o 99.78% of t h e measurements f o r a normal d i s t r i b u t i o n ) r a t h e r t h a n 2σ v a l u e s (95% o f t h e measurements) becomes im­ p o r t a n t f o r GC/HRMS a n a l y s e s because t h e l a r g e number of s p e c t r a ( s e v e r a l hundred, each p o s s i b l y c o n t a i n i n g s e v e r a l hundred a c c u r a t e m a s s e s ) , t h a t a r e g e n e r a l l y r e c o r d e d n e c e s s i t a t e s a h i g h degree o f r e l i a b i l i t y as w e l l as a c c u r a c y . I n g e n e r a l , t h e number o f e l e m e n t a l c o m p o s i t i o n s computed f o r a t y p i c a l measured mass (M) becomes unmanageable f o r a mass window l a r g e r t h a n about M ± 15 ppm, p a r t i c u l a r l y f o r more complex mole­ c u l e s t h a t may c o n t a i n many t y p e s o f atoms ( e . g . , C, C , H, N, 0, S i , F ) . Large mass measurement e r r o r s are a l s o p r o b l e m a t i c f o r the g e n e r a t i o n o f elemental c o m p o s i t i o n chromatograms s i n c e t h e mass measurement d i s t r i b u t i o n (spread) may o v e r l a p w i t h t h e d i s t r i b u t i o n of measured masses f o r a n o t h e r e l e m e n t a l c o m p o s i t i o n p r e s e n t i n some o f t h e s p e c t r a . Thus, i n t e n s i t i e s o f e x t r a n e o u s masses may be i n c l u d e d i n t h e f i n a l o u t p u t even though t h e " c o r r e c t " mass window has been s e l e c ­ ted, and t h i s would r e s u l t i n one o r more a r t i f a c t peaks i n t h e e l e m e n t a l c o m p o s i t i o n chromatogram. I n p r a c t i c a l terms f o r s p e c t r a l i n t e r p r e t a t i o n , i t i s a l s o i m p o r t a n t t o know t h e minimum a b s o l u t e mass i n t e n s i t y v a l u e f o r w h i c h t h e d e s i r e d mass measurement a c c u r a c y can be a s s u r e d ; d a t a o u t p u t c o n t a i n i n g l o w e r i n t e n s i t y v a l u e s c a n t h e n be e v a l u a t e d w i t h a p p r o p r i a t e c a u t i o n . F i n a l l y , i t i s i m p o r t a n t t o remember t h a t t h e c o n s i d e r a t i o n o f mass measurement a c c u r a c y r e l a t e s o n l y to w e l l - d e f i n e d normal peak shapes. Any s i g n i f i c a n t d i s t o r t i o n o f such peak shapes, such as u n r e s o l v e d d o u b l e t s , s h o u l d be r e c o g n i z e d and t h e e f f e c t on mass measurement a c c u r a c y t a k e n i n t o a c c o u n t .

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1 3

Sensitivity. I n GC/HRMS, an e v a l u a t i o n o f o v e r a l l s y s ­ tem s e n s i t i v i t y must c o n s i d e r n o t o n l y t h e d e t e c t i o n o f s p e c i f i e d masses from a g i v e n q u a n t i t y o f a component i n j e c t e d i n t o t h e gas chromatograph (as f o r GC/LRMS), but a l s o t h e mass measurement a c c u r a c y t h a t c a n be

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Mass Chromatoçram

30 NUMBER

Figure 6. Representation of an accurate mass chromatogram for equal GC peak shapes; scan cycle time equals one-half of the GC peak eiution time

Figure 7. The evaluation of mass measurement accuracy; M = true mass, M = mean measured mass, Ε = mean error, σ = standard deviation of the measured masses. t

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o b t a i n e d f o r t h e s e masses. T h i s more s t r i n g e n t c r i ­ t e r i o n r e s u l t s i n somewhat l e s s s e n s i t i v i t y compared t o d e t e c t i n g t h e p r e s e n c e o f a p a r t i c u l a r mass, s i n c e t h e peak p r o f i l e s must be s u f f i c i e n t l y w e l l - d e f i n e d t h a t the peak c e n t e r - o f - g r a v i t y o r c e n t r o i d can be a c c u ­ r a t e l y and r e l i a b l y d e t e r m i n e d . S e v e r a l d i s c u s s i o n s have appeared i n t h e l i t e r a ­ t u r e c o n c e r n i n g the t h e o r e t i c a l a s p e c t s o f s e n s i t i v i t y and mass measurement a c c u r a c y (57_, 7 1 ) . B a s i c a l l y , t h e l i m i t i n g f a c t o r concerns the s t a t i s t i c s a s s o c i a t e d w i t h the i o n a r r i v a l times a t the d e t e c t o r , and t h i s d e t e r ­ mines how w e l l the r e s u l t i n g d i g i t i z e d peakshape i s d e f i n e d ; t h e f r e q u e n c y o f d i g i t i z a t i o n o r the number o f d a t a p o i n t s / m a s s peak i s a l s o a c o n s i d e r a t i o n here ( 7 2 ) . I t has been p r e d i c t e d (71) t h a t f o r a mass r e s o l u t i o n o f 10,000, mass measurement a c c u r a c i e s w i t h i n 10 ppm ( = 3σ, o r 99.78% c o n f i d e n c e l e v e l ) s h o u l d be a c h i e v e d w i t h 30 i o n s / p e a k , and w i t h i n 17 ppm (=3σ) f o r 10 i o n s / p e a k . E s t i m a t e s made from a c t u a l mass measure­ ments (73) i n d i c a t e t h a t 10-15 i o n s / p e a k a r e r e q u i r e d t o g i v e a mass measurement a c c u r a c y o f 30 ppm (=3σ). The r e l a t i o n s h i p between t h e a b s o l u t e peak i n t e n s i t y , I (the sum o f t h e d i g i t a l v a l u e s f o r a peak p r o f i l e ) , and the number o f i o n s , N, c o m p r i s i n g t h a t peak may be d e t e r m i n e d (61) from the e q u a t i o n I . Ν "

r

ÎRef

where G i s t h e g a i n o f t h e m u l t i p l i e r the primary v a r i a b l e under normal o p e r a t i n g c o n d i t i o n s . (the other parameters a r e : R = input r e s i s t a n c e of the m u l t i p l i e r a m p l i f i e r i n ohms, e = charge on an e l e c t r o n i n cou­ lombs, f = f r e q u e n c y o f d i g i t i z a t i o n i n s e c " , ν = v o l t a g e i n c r e m e n t r e p r e s e n t e d by one b i n a r y " b i t " on the A/D c o n v e r t e r i n v o l t s ) . As w i t h GC/LRMS, i t i s i m p o r t a n t t h a t t h e o v e r a l l s e n s i t i v i t y i s d e t e r m i n e d f o r a s e l e c t e d component i n t r o d u c e d t h r o u g h t h e gas chromatograph, p a r t i c u l a r l y t o t a k e i n t o a c c o u n t any l o s s e s t h a t may o c c u r when using a molecular separator i n t e r f a c e . I t i s also n e c e s s a r y f o r GC/HRMS t h a t one o r more i o n masses ( e . g . , basepeak and/or m o l e c u l a r i o n , e t c . ) a r e s e ­ l e c t e d i n o r d e r t o s p e c i f y the mass measurement ac­ c u r a c y t h a t can be o b t a i n e d from an i n j e c t i o n o f a g i v e n amount o f the compound. In a d d i t i o n , the l i m i t e d number o f h i g h r e s o l u t i o n s p e c t r a t h a t can be r e c o r d e d f o r any p a r t i c u l a r GC peak under GC/HRMS c o n d i t i o n s a l s o has t o be c o n s i d e r e d . In t h e l i m i t i n g c a s e , when 1

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the scan c y c l e time ( e . g . , -10 seconds) i s about oneh a l f o f t h e GC peak e i u t i o n t i m e , t h e maximum r e c o r d e d i n t e n s i t y f o r any mass may be e x p e c t e d t o v a r y by a f a c t o r o f about two (see F i g u r e 6 ) , depending on t h e time o f s t a r t i n g a scan i n r e l a t i o n t o t h e time when the GC peak b e g i n s t o e l u t e a r e l a t i o n s h i p which i s unknown i n p r a c t i c e . F o r an i n j e c t i o n o f Ν ng o f t h e s e l e c t e d component, t h e maximum sample f l o w r a t e a t t h e top o f t h e GC peak c o r r e s p o n d s t o about N/10 ng/sec f o r a GC peak e i u t i o n time o f 20 seconds. Measured mass i n t e n s i t i e s , t h e r e f o r e , w i l l be p r o p o r t i o n a l t o sample f l o w r a t e s between about N/20 and N/10 ng/sec. I f the v a r i a t i o n o f mass measurement a c c u r a c y w i t h r e s p e c t t o a range o f measured i n t e n s i t i e s has been d e t e r m i n e d under t h e same c o n d i t i o n s , t h e n an assessment can be made f o r t h e mass measurement a c c u r a c y e x p e c t e d f o r s e l e c t e d masses r e c o r d e d from an i n j e c t i o n o f Ν ng under a g i v e n s e t o f e x p e r i m e n t a l c o n d i t i o n s ( i . e . , s c a n r a t e , mass r e s o l u t i o n , m u l t i p l i e r g a i n , e t c . ) . Dynamic mass r e s o l u t i o n . A knowledge o f t h e a c t u a l mass r e s o l u t i o n o f each r e c o r d e d peak i s an i m p o r t a n t measure o f t h e o v e r a l l p e r f o r m a n c e o f a f a s t - s c a n n i n g h i g h r e s o l u t i o n mass s p e c t r o m e t e r , and d i r e c t l y r e l a t e s t o t h e a b i l i t y t o a c c u r a t e l y measure masses. A l s o , i t i s f r e q u e n t l y n e c e s s a r y t o be a b l e t o d e t e r m i n e whether o r n o t c e r t a i n mass d o u b l e t s would be e x p e c t e d t o be r e s o l v e d under t h e i n s t r u m e n t c o n d i t i o n s used. As d