Advances in Dendritic Macromolecules, Volume 2

ADVANCES IN DENDRlTlC MACROMOLECULES

Volume 2

1995

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ADVANCES IN DENDRITIC MACROMOLECULES Editor: G E O R G E R. N E W K O M E Department of Chemistry University of South Florida Tampa, Florida

VOLUME 2

1995

@) Greenwich, Connecticut

JAI PRESS INC. London, England

Copyright O 1995 by l A l PRESS INC. 55 Old Post Road, No. 2 Greenwich, Connecticut 06836 ]A/ PRESS L TD. The Courtyard 28 High Street Hampton Hill, Middlesex TW12 1PD England All rights reserved. No part of this publication may be reproduced, stored on a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, filming, recording, or otherwise, without prior permission in writing from the publisher.

ISBN: 1-55938-939-7 Manufactured in the United States of America

CONTENTS

LIST OF CONTRIBUTORS PREFACE George R. Newkome THE CONVERGENT-GROWTHAPPROACH TO DENDRlTlC MACROMOLECULES Craig 1. Hawker and Karen L. Wooley CASCADE MOLECULES: BUILDING BLOCKS, MULTIPLE FUNCTIONALIZATION, COMPLEXING UNITS, PHOTOSWITCHING Rolf Moors and Fritz Vijgtle IONIC DENDRIMERS AND RELATED MATERIALS Robert Engel SILICON-BASED STARS, DENDRIMERS, AND HYPERBRANCHED POLYMERS Lon 1.Mathias and Terrell W. Carothers HIGHLY BRANCHED AROMATIC POLYMERS: THEIR PREPARATION AND APPLICATIONS Young H. Kim DENDRlTlC BOLAAMPHIPHILES AND RELATED MOLECULES Gregory H. Escamilla lNDEX

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LIST OF CONTRIBUTORS

Terrell W. Carothers

Department of Polymer Science University of Southern Mississippi Hattiesburg, Mississippi

Robert Engel

Department of Chemistry and Biochemistry Queens College of the City University of New York Flushing, New York

Gregory H. Escamilla

Department of Chemistry University of South Florida Tampa, Florida

Craig J. Hawker

IBM Research Division Almaden Research Center San Jose, California

Young H. Kim

DuPont Central Research and Development Experimental Station Wilmington, Delaware

Lon J. Mathias

Department of Polymer Science University of Southern Mississippi Hattiesburg, Mississippi

Rolf Moors

Institut fur Organische Chemie und Biochemie Universitat Bonn Bonn, Germany

Fritz Vogtle

Institut fur Organische Chemie und Biochemie Universitat Bonn Bonn, Germany

VII

LIST OF CONTRIBUTORS Karen L Wooley

Department of Chemistry Washington University St. Louis, Missouri

PREFACE

As recently illustrated by Professor Vogtle in a highlight (Angew. Chem., Int. Ed. Engl. 1994, 55, 2413) concerning dendritic chemistry, annual publications in this field are increasing at an incredible rate. As the combinations of building blocks and cores proliferate, the diversity of the resultant macromolecules will continue to expand our knowledge of new unnatural molecules with specific composition. This review series was organized to cover the synthetic, as well as chemical, aspects of this expanding field: the chemistry to and supramolecular chemistry of dendritic or cascade supermolecular compounds. Since one-step procedures to the related hyperbranched polymer are close cousins to the dendritic family, reviews have also been incorporated. In Chapter 1, Hawker and Wooley delineate the convergent growth approach to dendrimers, then relate their three-dimensional architectures to different block polymers. In Chapter 2, Moors and Vogtle describe Professor Vogtle's initial cascade molecules via the repetitive strategy, then expand his original concepts of its application by others, and lastly delineate the synthesis of a new series of tosylamide cascades. They also demonstrate the utility of his original Michael addition/reduction procedure by its application to differ cores. Chapter 3, composed by Professor Engel, describes ionic dendrimers which incorporated an internal transition metal center as well as his work based on ammonium and phosphonium centers. In Chapter 4, Mathias and Carothers review recent studies on silicon-based dendrimers and hyperbranched polymers. Chapter 5, by Kim, describes the preparation

IX

X

PREFACE

and utility of hyperbranched aromatic polymers. Lastly in Chapter 6, Escamilla reviews the historical as well as recent examples of ionic and nonionic bolaamphiphiles. I personally wish to thank these authors for their contributions to this volume and for their continuing contributions to this field. Future volumes in this series will highlight the work of others in the field of cascade/dendritic macromolecules. George R. Newkome Editor

THE CONVERGENT-GROWTH APPROACH TO DENDRITIC MACROMOLECULES

Craig J. Hawker and Karen L. Wooley

I. II. III. IV. V. VI. Vn. VIII.

ABSTRACT 2 INTRODUCTION . 2 DEVELOPMENT OF THE CONVERGENT-GROWTH APPROACH . . . 4 CHARACTERIZATION 10 CONTROL OF SURFACE FUNCTIONALITY 14 DENDRITIC BLOCK COPOLYMERS 21 HYBRID LINEAR-DENDRITIC BLOCK COPOLYMERS 29 PHYSICAL PROPERTIES OF DENDRITIC MACROMOLECULES . . . 3 3 FUTURE DIRECTIONS 36 ACKNOWLEDGMENTS 37 REFERENCES 37

Advances in Dendritic Macromolecules Volume 2, pages 1-39. Copyright © 1995 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-9397

1

2

CRAIG J. HAWKER and KAREN L. WOOLEY

ABSTRACT The developing field of dendritic macromolecules has been characterized by two different, but complementary, synthetic strategies: the divergent-growth and convergent-growth approaches. The fundamental aspects of the convergent-growth approach are examined and described with the synthesis of dendritic polyether macromolecules based on 3,5-dihydroxybenzyl alcohol as the monomer unit. Using this series of dendritic polyether macromolecules, the techniques and methods for characterization of molecules, prepared by the convergent-growth approach, are demonstrated. Examples of the control of chain ends, internal building blocks, and the synthetic utility of the focal-point group are provided by the preparation of a number of unique macromolecular architectures. Finally, the physical properties of these three-dimensional macromolecules are compared with traditional linear polymers.

I. INTRODUCTION Analogous to the term dendrite, a noun describing an object resembling a tree in properties, growth, structure, or appearance, dendritic macromolecules are three-dimensional polymers with treelike, highly branched structures. It is now generally accepted that dendritic macromolecules are more accurately defined as systems possessing "perfectly" branched structures, characterized by large numbers of chain ends, all emanating from a central core, with at least one branch junction at each monomer unit. Dendritic macromolecules, which have also been termed cascade, arborol, starburst, or fractal structures,* are a fundamentally new class of polymers. They have received a considerable amount of interest recently with a large number of reviews and papers appearing in the literature detailing various aspects of their synthesis, characterization, and properties. Hyperbranched macromolecules^-^ are a related class of materials, also treelike and globular in nature, but less highly branched and significantly less regular than the dendritic systems and, while also interesting, are beyond the scope of this chapter. Initially, one may question the relevance of such exotic structures, and also the justification for devoting large amounts of time, resources and effort to their preparation and study. The answer to this question is related to one of the fundamental roles of science in today's society, namely, continued technological advancement, in part, driven by the production of new materials with enhanced and/or novel properties and by the more complete understanding of structure-property relationships for materials

The Convergent-Growth Approach

3

in use today."^ In view of these goals, the preparation and study of dendritic macromolecules and other two- and three-dimensional structures are becoming increasingly important.^ This has led to several instances where the microstructure of the polymers has affected the physical and chemical properties of the bulk material. Further characterization of physical properties and the development of a basic understanding of the relationship between microscopic structure and the overall microscopic and macroscopic properties of materials are currently of great potential and interest. These factors, coupled with the large degree of control possible over macromolecular architecture, demonstrate the significance of studying dendritic macromolecules. A number of excellent reviews on dendritic macromolecules has appeared. ^'^ This introduction, therefore, will cover only the basic aspects of dendritic macromolecules. For a more concise treatment, the reader is directed to the above reviews. Prior to 1990, the synthesis of dendritic macromolecules had been accomplished by a single methodology termed the divergent-growth or starburst approach. This synthetic strategy was pioneered by two independent groups of researchers headed by George Newkome^ and Donald Tomalia.^ Their seminal synthetic efforts, both published in 1985, but preceded by a number of theoretical treatments^^^ can be considered the first true attempts to prepare high molecular weight, regularly branched, dendritic macromolecules. A characteristic of the divergent-growth approach is that growth begins at a central polyfunctional core. Reaction of the core molecule with polyfunctional monomer units or building blocks then leads to the next generation compound with a concomitant increase in the number of chain-end functional groups. Deprotection or chemical transformation of these functional groups leads to the original reactive functionalities. This two-step process has been repeated to give larger dendritic macromolecules (Scheme 1), with growth continuing to generation 10. A fundamental aspect of the divergent-growth approach is the rapid increase in the number of chain-end functional groups. Associated with this is the increase in the number of reactions required to functionalize the chain ends fully. Incomplete reaction of these rapidly increasing terminal groups leads to failure sequences or imperfections in the next generation. These potential difficulties and the lack of control over the number and placement of functionalities at the chain ends led us to reevaluate the synthetic approach to dendritic macromolecules.

CRAIG J. HAWKER and KAREN L. WOOLEY

CLVJL-CL

c.

CL ) C-~C6re~C—\^L :cf—c

C—Core—C I C

CL

C

CL

C = coupling site R = reactive group C^ = latent coupling site R—^L = monomer unit CL

'

T

4—C—Core—C

^

(

c ^:X< ^^c

X

c

Xc

c

X ^ R_f^,

c

c

c

c ^c

e—C—^C—^C C—Core C C^

C

°Xc c

.c

c.

c

CL

x= c

= < ! > ' Scheme 1.

11. DEVELOPMENT OF THE CONVERGENT-GROWTH APPROACH While the divergent-growth approach allowed an entry into the field of dendritic macromolecules and its use continues to produce novel and fascinating structures, the need existed to develop a complementary approach to synthesize dendritic macromolecules. To develop an alternate strategy, we decided to apply the disconnection method in organic

The Convergent-Growth

X

Approach

X. .X

X

C / 4 C—^C—(^ + C

C-^—C—Core—C—^C )-cC c C (

X

X

3 CC = coupling site R = reactive group CL, = latent coupling site

R R-Core-R

.

<^=

R

Cu-f

X

CL—(-R = monomer unit R

Scheme 2.

synthesis to the preparation of dendritic macromolecules. Because of the symmetrical nature of dendrimers, disconnection leads to the chain ends outlined in Scheme 2. It was expected that this new approach would provide enhanced control over the synthesis by producing a variety of macromolecular architectures, thus expanding the field of dendritic macromolecules. In essence, this new strategy is opposite to the divergent-growth approach, and was termed the convergent-growth approach to dendritic macromolecules.^^ Growth begins at the chain ends. Repetition of a two-step growth and activation process leads to larger dendritic fragments, the final reaction being attachment to a polyfunctional core. In contrast to the divergent approach, generation growth involves only two coupling reactions and a single activation reaction throughout the synthesis. The possibility of side and/or incomplete reactions is thereby reduced, and the low number of reactions, also, leads to a greater degree of control over both the chain ends and, to a certain extent, the interior structure of the macromolecule. The convergent-growth approach is, also, characterized by the continu-

6

CRAIG J. HAWKER and KAREN L. WOOLEY

ous presence of a single reactive functionality at the focal point, which can be exploited to give a variety of novel macromolecular architectures. To demonstrate this new methodology, the synthesis of a series of dendritic polyether macromolecules based on 3,5-dihydroxybenzyl alcohol (1) as the monomer unit or building block was attempted. ^"^ The criteria, which determined the selection of building block and repeat linkage, were the chemical stability of the resultant polyether as well as the high yields that can be obtained for the formation of benzyl ethers. For brevity, the various dendritic macromolecules will be named using the following notation [G-JC]-/, in which [G-x] refers to generation (G) number, or the number of layers of building blocks (x = 0,1,2,...), and / refers to the single functionality located at the focal point. After coupling to a core molecule, the designation is [G-Jc]„-[C] where n represents the number of dendritic fragments of generation x coupled to the core (C). A systematic nomenclature for dendritic macromolecules, however, has recently been introduced.^^ The general family name for the above molecules based on 3,5-dihydroxybenzyl alcohol as the monomer unit and l,l,l-tris(4'-hydroxyphenyl)ethane as the core molecule is Z-cascade: [3-1,1,1]: (5-(2-/7-phenyl-2-oxaethyl)-1,3-phenylene): (5 -(2oxaethyl)-1,3-phenylene)^"^: (2-oxaethyl)benzene. In this two step growth and activation process, generation growth involved a WilUamson reaction of a benzyUc bromide with a diphenolic compound, in this case the monomer unit 1. Activation was effected through conversion of a benzylic alcohol to a benzylic bromide by reaction with carbon tetrabromide and triphenyl phosphine (PPh3). As with all multistep syntheses, it was essential to optimize the yield and efficiency of each reaction. For the alkylation step, the optimum conditions involved refluxing a mixture of the monomer unit 1 with 2.05 equivalents of the benzylic bromide in the presence of potassium carbonate and 18-crown-6 in acetone. Vigorous stirring was essential to effect a high rate of conversion. The first step was reaction of 1 with the known benzylic bromide 2, actually the first-generation bromide [G-1]Br, in refluxing acetone for 48 hours with added K2CO3 and 18-c-6 giving the second generation alcohol 3, [G-2]-0H in 91% yield. This was followed by bromination of the second-generation alcohol, where the optimum conditions were treatment with 1.25 equivalents of carbon tetrabromide/triphenyl phosphine in tetrahydrofuran (THF) at room temperature for about 15 minutes. Longer reaction times lead to de-

The Convergent-Growth Approach

7

creases in yield, presumably due to cleavage of the benzyl ether groups. Using these conditions, 3 was converted to the desired second-generation bromide 4, [G-2]-Br, in reproducible yields of over 90%. Comparing structures of 4 and 2, it can be seen that this two-step procedure leads to an increase of one generation layer, or generation number, and an approximate doubling of molecular weight, while the single reactive functional group at the focal point is maintained. As shown in Scheme 3, repetition of this two-step procedure then leads to larger dendritic fragments. The purified yield for each step remains above 90% up to generation 4. Above generation 4, the yield of both the coupling step and the bromination step decreased on going to generation 5 and, subsequently, to generation 6. This decrease in yield required larger excesses of CBr4 and PPh3 to force the bromination step to completion. Having obtained pure, monodisperse dendritic fragments, the final step was coupling to a polyfiinctional core. The only requirements for this reaction are that the chemistry is compatible with the functional groups already present in the dendritic fragment. In the above series, the first core investigated was l,l,l-tris(4'-hydroxyphenyl)ethane (5), which allowed use of the same Williamson coupling chemistry employed in building the fragments. Altemate chemistry may, also, be used to couple to the core. A variety of different cores has been employed, ranging from polyphenolic dendrimers^^^ to functionalized fuUerenes.^^ Reaction of 3.1 equivalents of the fourth-generation bromide, [G-4]-Br 6, with one equivalent of the core molecule 5 in the presence of K2CO3 and 18crown-6 gave the desired trialkylated dendritic macromolecule, [G-4]3[C] 7, in 84% yield after purification by flash chromatography (Scheme 4). In a similar fashion, trialkylated dendritic macromolecules were prepared for each generation from G = 0 to G = 6. Again yields were high for generations 0 to 4 (84-91 %) decreasing to 76% for G = 5 and to 51% for G = 6. These results, coupled with the yields obtained in the preparation of the dendritic fragments, suggest that after generation 4, steric congestion increases around the single functional group at the focal point, thereby, reducing its reactivity. This is not unreasonable since [G-6]3-[C] is a highly-branched macromolecule of nominal molecular formula C2687H2304O3gi and molecular weight 40,689 with eight layers of aromatic rings. It does, however, illustrate a major limitation of the convergent-growth approach: as the macromolecules increase in size, growth is retarded through a combination of "masking" of the function-

O

2 [G-2>OH

CBr4 PPh,

4 (G-2>er

^?

o

o ^

^

^

^ . ^ 0

^ ° ^

o li o Scheme 3.

The Convergent-Growth Approach OH

[G-4]-Br

+

^

JO

Vo^«

^t:H D

w

Scheme 4.

ality at the focal point by the growing globular dendritic macromolecule and "masking" of the phenolic groups in the core by the large dendritic fragments already attached. Both of these effects would lead to lower reactivity. A number of variations in the convergent-growth approach have been made to alleviate this problem. ^^^^

10

CRAIG J. HAWKER and KAREN L. WOOLEY

III. CHARACTERIZATION Accurate characterization of the products obtained is one facet of all of the syntheses of dendritic macromolecules, whether by the convergentor divergent-growth approaches, that demands particular attention. This is especially important since the molecules are large and complex. For synthetic polymers or biomolecules of similar molecular weight, structural determination is a major and sophisticated undertaking and, in many cases, the amount of detail that can be obtained is limited. Due to the symmetrical nature of the dendritic systems studied, accurate structural determination is possible. The essentially opposed growth strategies of the convergent versus divergent approaches result in different considerations that must be addressed in characterizing the products prepared by the convergent growth approach. It was found that many standard techniques were of only limited usefulness. The infrared spectrum, for example, is quickly overwhelmed by the dominant functional groups of the building blocks. Peaks due to changes in the functionality at the focal point are not observable. Similarly, as molecular weight increases, determination of molecular weight by mass spectrometry becomes progressively more difficult since current ionization techniques do not give molecular ions above about 2000 amu for the polyethers described previously. Elemental analysis, also, did not prove accurate enough to detect the subtle changes occurring in the molecular structure with generation growth or activation of the focalpoint group. However, a number of techniques proved to be invaluable in characterizing dendritic macromolecules prepared by the convergent-growth approach. Of primary importance was ^H and ^^C nuclear magnetic resonance (NMR) spectroscopy which allowed observation not only of the unique functionality at the focal point but also of a varying amount of distinction between the protons present in the various layers of the dendritic macromolecule. Figure 1, for example, shows the 300 MHz ^H NMR spectrum of the third generation bromide, [G-3]-Br 8, revealing distinct sets of resonances which can be correlated with the structure expected from the synthetic strategy. The resonances for the chain-end phenyl rings occur at 7.25-7.45 ppm while the resonances for the aromatic protons of the monomer units occur in the region from 6.50-6.70 ppm. A large amount of fine structure can

The Convergent-Growth Approach

11

.^,

cry 8.50

I 8.00

7.50

7.00

6.50

6.00 ppm

5.50

5.00

4.50

4.00

3.50

Figure 1. 300-MHz ^H NMR spectrum of third generation bromide [G-3]-Br.

be observed for this set of resonances and three triplets are observed in the ratio 1:2:4 which correlates with that expected for the three distinctly different layers of building blocks present in 8. Fine detail relating to the structure is, also, seen in the resonances for the benzylic protons at 4.90-5.10 ppm. The most important resonance in the spectrum is the small singlet at 4.40 ppm arising from the unique bromomethyl group at the focal point. This resonance proved to be a useful tag in following the reaction sequence, since, on generation growth, a hydroxymethyl group is obtained (4.60 ppm), the resonance of which is easily distinguishable from the bromomethyl resonance. Similarly, attachment to the polyfunctional core introduced a different functionality at the focal point which gave rise to discrete resonances in the ^H NMR spectrum. Also, integration of this resonance due to the benzylic protons of the focal-point group

12

CRAIG j . HAWKER and KAREN L. WOOLEY

and comparison with the integration values for the other resonances in the spectrum allowed confirmation of the generation number. Complementary information was obtained from examination of the ^^C NMR spectra of the various compounds. The different functional groups at the focal points gave rise to different resonances and the different layers of building blocks could be discemed. From NMR spectroscopy alone, therefore, a large amount of information was obtained supporting the proposed structure. These results combined with the information obtained from other spectroscopic and chromatographic techniques, described below, provided an accurate structural determination of the dendritic macromolecules obtained. One of the unique features of dendritic macromoleules is that they have the potential to be discrete molecules of specified size, shape, and molecular weight. Therefore, determinating the purity of the products obtained was a key issue. In this case, the change in polarity of the dendritic fragments on going from a hydroxymethyl group at the focal point to a bromomethyl group was sufficiently large enough to allow purification at each step of the synthesis by flash chromatography, while also allowing the purity of the products to be routinely checked by thin layer chromatography and, more recently, by high pressure liquid chromatography (HPLC). Due to the near doubling of molecular weight at each generation-growth step, size-exclusion chromatography (SEC) proved to be extremely valuable, and was able to detect lower molecular weight impurities at levels as low as 0.5%. This is demonstrated in Figure 2, which shows an overlay of SEC traces for the various dendritic fragments from generation 0 to generation 6. Only very sUght broadening is observed from [G-0]-Br, or benzyl bromide (nominal mol. wt. = 171), to [G-6]-Br (nominal mol. wt. = 13,542) and the dramatic changes in retention volume from one generation to the next are readily apparent. As molecular weight increased, there was essentially no difference between the nominal molecular weight and the molecular weight determined by low-angle laser light scattering. However, there was a difference when these values were compared to the polystyrene-equivalent molecular weights obtained from conventional Gel Permeation Chromatography (GPC), and that difference increased as the molecular weight increased. For example, [G-6]3-[C] has a nominal molecular weight of 40,689 and a LALLS M^ of 38,500 ± 1900 but shows a GPC polystyrene-equivalent M^ of only 15,400. This behavior is due to the increase

13

The Convergent-Growth Approach [G-«]-Br with/] =

6 5 4

3

2

1

[G-0]-Br M.W. = 171

[G-6]-Br M.W. = 13 542

20

40

60

Relention Volume (mlj Figure 2. Overlay of SEC traces for the dendritic bromides from [G-0] to [G-6] with nominal molecular weights shown.

in radius by a constant monomeric distance (resulting in a cubic increase in volume), while the molecular weight effectively doubles with each generation-growth step (resulting in an exponential increase in molecular weight). At higher molecular weights, the monomeric radial increase, and hence volume increase, is quite small compared with the mass increase. These findings suggest that above a critical molecular weight, dendritic macromolecules are much more compact than normal linear polymers. This behavior has also been observed in other dendritic systems.^^ While polydispersity has relatively little meaning when applied to dendritic macromolecules, values for all of the samples were less than 1.02, and the peak width was considerably less than that for narrow molecular weight polystyrene standards of comparable molecular weight.

14

CRAIG J. HAWKER and KAREN L. WOOLEY

The combination of standard techniques described above has also been used by other authors^^-^ to determine accurately the structure of dendritic systems prepared by the convergent-growth approach. Imperfections may be detected, and reactions can be easily monitored for product purity. Therefore, by following a predetermined synthetic strategy, molecules of discrete size and molecular weight can be prepared. In the following text, the characterization techniques described above, will be extended to determine and confirm the structure of more complex dendritic macromolecules such as surface-functionaUzed and other block copolymers.

IV. CONTROL OF SURFACE FUNCTIONALITY Since the convergent-growth approach begins at the chain ends and proceeds via a limited number of reactions, a unique opportunity existed to control accurately the number and, to a certain extent, the placement of functional groups at the chain ends. The methodology employed to accomplish this relied on the stepwise alkylation of the monomer unit and/or the core molecule. Controlling the points in the synthesis where stepwise alkylation is performed allows the preparation of dendritic macromolecules with 1,2, 3 , . . . or /? functional groups at the chain ends. To demonstrate this, the synthesis of the two extreme cases, namely, a dendritic macromolecule with a single functionality at the chain ends"^ and one where a segment of the periphery is fully functionaUzed,-- was attempted. The polyether chemistry developed above was used, and it was initially found that a variety of functional groups, such as ester, nitrile, or halide, were stable under the reaction conditions used to construct the macromolecule. For the monofunctionalized case, the monomer unit, initially 3,5-dihydroxybenzaldehyde (9), was alkylated in a stepwise manner by benzyl bromide followed by 4-bromomethylbenzonitrile (10) to give, after manipulation of the focal point group, the first-generation benzylic bromide 11. As can be seen, the dendritic fragment 11 has only one of the two chain-end phenyl rings substituted by a cyano group. Repetition of this stepwise alkylation of the monomer unit 1 with a monofunctional fragment and an unsubstituted fragment at each stage of the generation growth then leads to the fourth-generation fragment, NC-[G-4]-Br 12, in which only one of the terminal 16 phenyl rings carries a cyano group.

The Convergent-Growth Approach

HO

HO

15

-

.

n,

^^^_^^0

o

jr^^'.^.

CNK&-
13. Scheme 5.

Alkylation of the triphenolic core molecule 5, in a stepwise fashion, with two equivalents of the unfunctionalized fourth-generation bromide, [G4]-Br 6, followed by one equivalent of 12 gives a dendritic macromolecule, NC-[G-4]-[C]-[G-4]2 13, in which only a single cyano group is present at the chain ends (Scheme 5).

=—•

5

stepwise alkyiatjon of core

°

Bri6-{G-4]-Br J £

Bf

-^ BTA

IS

Scheme 6.

16

The Convergent-Growth Approach

17

For the preparation of the second extreme case, the standard convergent-growth approach is begun with the desired functionaUzed chain ends, and growth is continued in the usual manner. For example, alkylation of the monomer unit 1 with 4-bromobenzyl bromide (14) leads to the fourth-generation dendritic fragment, Bri5-[G-4]-Br 15, in which all sixteen of the terminal phenyl rings carry a bromine substituent. It is at this stage that stepwise alkylation is introduced. As shown in Scheme 6, alkylation of the core 5 with two equivalents of [G-4]-Br 6, followed by one equivalent of the fully functionaUzed fragment, Bri6-[G-4]-Br 15, gives the dendritic macromolecule, Bri6-[G-4]-[C]-[G-4]2 16. The periphery of 16 is unusual since one area is totally devoid of functional groups whereas the other has every terminal phenyl ring bearing a bromine substituent. Also, by synthetic choice, the areas are of unequal size with twice as many terminal phenyl rings unfunctionalized as there are functionalized rings. Characterization of surface-functionalized dendritic macromolecules was achieved by the same methods and techniques as described previously. However, further information could be obtained from the ^H and ^^C NMR, and in the cyano case, from the infrared spectra. By observation of the unique resonances for the functionality itself or the phenyl ring to which it is attached, the number of functional groups at the chain ends could be quantified. For example, the ^H NMR spectrum of 13 shows an ABq (7.46 and 7.61 ppm) at lower field to the resonance for the terminal phenyl rings (7.30-7.40 ppm). This unique and distinct set of resonances is due to a p-cyano-substituted phenyl ring. By comparing integration values, it was confirmed that only one of the exterior 48 phenyl rings carries a cyano substituent. Similar results were obtained for the brominated derivative 16. Having demonstrated the ability to prepare the two extreme cases of surface functionalization, we were confident that our synthetic strategy and the concept of accurately controlling the number and placement of functionality at the chain ends of dendritic macromolecules were viable. Therefore, by a combination of stepwise monomer alkylation and stepwise core alkylation, dendritic macromolecules can be prepared with any number of functionalities at the chain ends. The only requirement governing the choice of the chain-end functionality is that it be compatible with the chemistry employed for growth.

CRAIG J. HAWKER and KAREN L. WOOLEY

18

JQl..^

-^•^.-4::^

CN,e-ICMHCHG-5]

Figure 3.

Dipolar dendritic macromolecule, CN^^-[G-4]-[C]-[G-5], 17.

Using the methodology developed above to control surface functionalization, we have prepared a number of tailor-made dendritic macromolecules to examine specific properties. Recently, the preparation and characterization of strongly dipolar dendritic macromolecules have been reported.^^ These molecules are designed to obtain large dipole moments through the specific placement of different functionalities at opposed regions of the dendritic chain ends. This is achieved by preparing dendritic fragments which are fully substituted with either electron-withdrawing cyano groups or electron-donating benzyloxy groups. Coupling of these fragments to a linear difunctional core in a stepwise fashion gave dendrimers such as 17 in which the electron-withdrawing cyano groups are segmentally opposed by the electron-donating benzyloxy groups (Figure 3). It was found that the dipole moments of these functionalized dendrimers were much larger than those found for the corresponding symmetrical structures, and this difference increased with increasing molecular weight. Also, as the molecular weight increased, the relationship between dipole moment and molecular weight departed signifi-

The Convergent-Growth Approach

19

20 '

161

o

E o = o "o a

I

4 i • • 3000

6000

Symmetrical Dendrimers Dipolar Dendrimers

9000

-r 12000

15000

Molecular Weight

Figure 4. Plot of dipole moment versus molecular weight for series of symmetrical and dipolar dendritic macromolecules.

cantly from linearity (Figure 4). This behavior can be attributed to the increasingly globular nature of the dendrimers which affects the vector addition of the numerous dipole moments. Conversely, if a functionalized starting molecule is employed in the convergent-growth approach, but, in this case, with no stepwise growth steps, a final structure is obtained in which every chain end carries a functional group. This strategy has been employed in the synthesis of a unique class of materials called dendritic micelles or Micellanes™. Such covalently bound unimolecular micelles were first introduced by Newkome.^"^ Unlike Newkome's purely aliphatic hydrocarbon Micellanes™, we decided to synthesize similar compounds containing aromatic rings and ether linkages.-^^ It was hoped that stacking interactions would be observed with certain electron-deficient small molecules due to the presence of electron-rich aromatic rings in the intemal structure of the dendritic micelle. Therefore starting from methyl 4-bromomethylbenzoate (18) and 3,5-dihydroxybenzyl alcohol (1), dendritic macromolecules, such as 19, which are fully terminated with methyl esters, were

20

CRAIG J. HAWKER and KAREN L. WOOLEY HO

^°^^""^,> CHjO

^ /

Approach

((CH302C)iHG^])r[C] IS Hydrolysis KOH/H2O

0 OK*

K*cro

Figure 5. Preparation and structure of dendritic micelles, ((K02C)i5-[G4])2-[C], 20.

prepared by use of the convergent-growth approach described above. Hydrolysis of 19 then leads to a water soluble derivative 20 which has a hydrophobic aromatic polyether core surrounded by a hydrophilic carboxylate layer (Figure 5). The analogy with traditional micelles is readily apparent. There is, however, one unique and critical difference. The structure is static and does not vary with concentration. Therefore, there is no critical micelle concentration and no distortion at high concentration.

The Convergent-Growth Approach

21

The dendritic micelle 20 was found to solvate hydrophobic molecules, such as pyrene, and a dramatic increase in the saturation concentration of hydrophobic molecules in water was observed. This increase was of a magnitude similar to that observed for traditional micelles derived from sodium dodecyl sulfate (SDS). However, unlike SDS micelles, 20 demonstrated solubihzing ability at concentrations as low as 5 x 10"^ M. This is consistent with its covalently bound static structure, and allowed the development of a novel, recyclable solubilization and extraction system. It was also found that a relationship existed between the solubilizing power of 20 and the electron density of the hydrophobic polycycUc aromatic molecule. This suggests that more sophisticated molecular recognition may be possible for the correctly designed system. The appUcation of such systems in areas such as drug delivery, catalysis, and artificial enzymes has great potential. Further property studies of dendritic micelle systems have been reported by Newkome.^^

V. DENDRITIC BLOCK COPOLYMERS If the structure of either 16 or 17 is examined, it becomes apparent that both can be considered as examples of block copolymers, since areas or blocks of the periphery are substituted with different chain ends. This raises the unique question as to the types of three-dimensional architectures that may be considered block copolymers. We have identified three different types of architectures that can be considered block copolymers for purely dendritic macromolecules and have termed them, dendritic surface-block (e.g., 16 and 17), dendritic segment-block, and dendritic layer-block copolymers. The three different architectures are represented schematically in Figure 6. As their name implies, dendritic segmentblock copolymers are characterized by different segments or fragments emanating radially from a central core, while dendritic layer-block copolymers have concentric layers of different chemistry around the central core. Since the preparation of the latter two block copolymers relies on different chemistries, the convergent growth approach was extended to the synthesis of dendritic aromatic polyesters based on 3,5-dihydroxybenzoic acid as the building block.^^ The combination of this chemistry in a controlled and systematic way with the polyether chemistry, discussed above, would then lead to either segment- or layer-block copolymers depending on the sequence of addition steps.

CRAIG I. HAWKER and KAREN L. WOOLEY

22 X X

Surface-block

Segment-block

Layer-block

Figure 6. Schematic representation of three different architectures that can be considered dendritic block copolymers.

The synthesis of the segment-block copolymers depends on the preparation of different dendritic fragments which are then coupled either to the monomer unit or to the core molecule in a stepwise fashion to give the desired product. For example the modified monomer unit, trichloroethyl 3,5-dihydroxybenzoate (21) is monoalkylated under standard conditions with the second-generation ether 4 to give the monophenolic 22. Switching to ester chemistry, esterification of 22 with the ester fragment 23 using DCC/DPTS as coupling agents afforded the third-generation dendrimer 24. As defined by the synthetic blueprint, 24 has both an ester block and an ether block attached to the same unique monomer unit at the focal point (Scheme 7). Coupling to the trifunctional core molecule 5 leads to a dendritic segment-block copolymer 25 which has a nominal molecular weight of 5370 amu. Since there is free rotation around all of the branching points in this molecule, there are a number of possible conformations which would lead to different degrees of mixing for the blocks. However, due to constraints arising from the branching sequence, a structural isomer is not allowed where all three polyester blocks are adjacent (Scheme 8).^^ While different chemistries are also employed in the synthesis of dendritic layer-block copolymers, the dendritic fragments used in the construction of these molecules are all the same and the block copolymer is formed through the addition of different monomer units in discrete steps of the synthesis to create layers. Many of the initial examples of

23

The Convergent-Growth Approach

il

10

fen" cc^

0-., €^V

/ - ^

OCH,

K2CO3 I8-C-6

b
^

€> o

4L.

^

"^ OCHjCO,

0^°pr^o 22

Scheme 7.

dendritic macromolecules prepared by Newkome^^ and Tomalia^ can be considered dendritic layer-block copolymers since, by the choice of chemistry used in the growth sequence, altemating layers of functional groups are obtained. Dendritic layer-block copolymers have the potential for great use in the areas of catalysis and molecular recognition where active sites are incorporated into the internal structure of the macromolecule. It was decided, therefore, to explore the synthesis of such molecules

1 \~° H

Zn/HOAc ^

y-'

om,eo,

O^ »HO

/ ^ DCC DPTS

9 ^ ^^ Q

:

^

°

^

^

o ^ ^ ^

2£

6i ^ Scheme 8. 24

^

The Con vergent-Growth Approach

25

0^

fen 6

Or-. f

. ^ . Br

"W"" f

OCHjCCI,

K2CO3

J [G-2>Br

0^ Scheme 9.

by the convergent-growth approach. There have been two reported examples of dendritic layer-block copolymers prepared by the convergent-growth approach. ^^'^^ One of the examples^^ incorporated both ether and ester chemistry into the structure, as described below. Starting with ether chemistry, the dendritic fragment 4 was prepared from benzyl bromide and the monomer unit, 3,5-dihydroxybenzyl alcohol 1. Changing the monomer unit to trichloroethyl 3,5-dihydroxybenzoate (21) allowed use of the same ether chemistry in constructing the third-generation compound 26, but permitted a change to ester formation in subsequent generation-growth steps (Scheme 9). Deprotection of 26, followed by generation growth and coupling to the triphenolic core 5 using DCC/DPTS chemistry, then gave 27. This dendritic layer-block copolymer 27 is characterized by two inner concentric layers of hydrolyzable ester-functional groups surrounded by three outer concentric layers of ether-functional groups (Scheme 10).^^ The concept of having layers of reactive functionalities or sites in the interior of dendritic macromolecules has been elegantly demonstrated recently by Newkome's group.^^ The synthesis of dendritic micelles, containing layers of triple bonds to which metal clusters can be attached.

1. Zn/HOAc 2. & DCC, DPTS

Scheme 10.

26

The Con vergent-Growth Approach

27

can be considered the first example of purposefully constructing dendrimers resembling more complex catalytic or enzymatic systems. Application of dendritic structures to this area of research has great potential, since the synthetic methodologies for constructing dendritic macromolecules are mature enough to allow control over the size and shape of the molecule, the number of active sites, the solubility of the overall molecule, and the nature of the interior. It was this last point that raised the important questions whetherthe interior of dendritic molecules exists as a unique and controllable microenvironment and how solvent affects groups located internally. To investigate these questions further, a solvatochromic probe was covalently attached to the focal point of a series of sizes of dendritic molecules, e.g., 28. The solvatochromic molecule was chosen to be a derivative of 4-(iV,A^-dimethylamino)-l-nitrobenzene and the chemistry used for coupling is outlined in Scheme Investigation by UV-Vis spectroscopy of a series of dendritic molecules from generation 0 to 6, containing the solvatochromic chromophore at their focal point, did indeed demonstrate that the probe was sensitive to changes in both the solvent and the size of the attached dendrimer. In solvents of medium to low polarity, the absorption maximum increased from generation 0 to generation 6. For example, in CCI4 the X^^ underwent a bathochromic shift from 366 nm for G = 0 to 383 nm for G = 6 (Figure 7). The relationship between X^^ and generation number was not linear and a marked discontinuity was observed between generation 3 and 4, correlating with a shape change from an extended to a more globular structure. Other evidence for such a conformational transition has been presented.^^ These results confirm that the influence of the building blocks of the dendrimer on the microenvironment of the solvatochromic probe increases as the size of the dendrimer increases, with an accompanying decrease in effects due to solvent. The interior of a dendritic macromolecule is, therefore, a unique microenvironment, the polarity of which can be manipulated by the size of the dendrimer, the nature of the intemal building blocks, and by the bulk solvent. The resemblance to the controlled microenvironments of some enzyme-active sites is tantalizing offering a number of unique opportunities and applications.

^

fe^4 V ^ , o-^:^

•oor^^o

^^^A 'teC

^

(0 X Z H

^^a)66®'

"

I

ffi

in

6

28

I

The Convergent-Growth Approach

29

ayu"

• • • E

• 380-

•

E E

5

•

c o o <

•

•

3

•

• 370-

• •

11

360-

1"

1

•

toluene as solvent

•

CCI4 as solvent

1

1

1

1

Generation Number Figure 7. Plot of absorption maximum (nm) versus generation number with CCI4 and toluene as solvent.

VI. HYBRID LINEAR-DENDRITIC BLOCK COPOLYMERS From the discussion above, there are a number of different macromolecular architectures that can be termed dendritic block copolymers. However, it is also possible to envisage unique architectures that are a combination of globular dendritic and linear fragments. The convergentgrowth approach was especially suited for the synthesis of these materials, since the single functionaUty at the focal point offered a well-defined point of attachment for the linear polymer chain. Again, a number of different architectures are possible depending on whether the dendrimer molecule is incorporated into the main chain, or the side chain, of the hybrid structure. Examples of the latter were prepared by the copolymerization of dendritic macromonomers with small monomer units.^^ In this case, the dendritic macromonomer is prepared by reaction of a dendritic fragment containing a hydroxymethyl group at the focal point

orA A 6 6

Scheme 12.

30

The Con vergent-Growth Approach

with p-chloromethyl styrene in the presence of sodium hydride. The introduction of the styrene unit at the focal point was observed and quantified as described above, since, once again, a group with distinctive resonances at the focal point was introduced. A series of macromonomers, such as 29, were prepared using this chemistry, and their copolymerization with styrene under standard free-radical conditions was investigated. The resultant hybrid copolymers were shown to have the expected structure, where the globular dendritic fragments are attached to a linear polystyrene backbone. Significantly, the feed ratios and the product ratios were approximately the same for all of the copolymerization studies, and even at macromonomer molecular weights of 6805 (G = 5), only a small decrease in incorporation was observed with increasing size of the dendritic macromonomer. This suggests that steric crowding around the styrene unit at the focal point is not great enough to affect its reactivity significantly with the relatively bulky, growing polymer chain. Other polymerizable groups, such as methacrylate, have been introduced at the focal point, greatly broadening the range of hybrid copolymers that can be prepared.^ Similar structures may also be prepared by polymer modification. The ability of the focal-point group to react with the terminal functionality of polymer chains was crucial to the syntheses of two other examples of hybrid linear-dendritic block copolymers. These incorporated the dendrimer into the backbone of the copolymer by reaction of either a monofunctional or a difunctional linear polymer with a dendritic fragment containing the appropriate functional group at its focal point. This resulted in either a sperm-like structure, where a linear segment is terminated by a single globular dendritic fragment, or a barbell-like structure in which the linear segment is terminated at both ends by a globular dendritic fragment. A number of different methodologies and chemistries have been explored for the production of such systems, and the choice is limited only by the stability of both blocks to the chemistry employed in their coupling. For example, termination of bis-ended living polystyrene with dendritic polyether fragments, containing bromomethyl groups at the focal point, leads to a barbell-like dendritic polyether-polystyrene-dendritic polyether triblock copolymer.^^ Perhaps the best studied of the above systems has been the reaction of mono or difunctional polyethylene glycols with dendritic polyether fragments, with a single bromomethyl group at the focal point (Scheme 13).^^

31

oA,.

<

i 5 Z

(0

O X LU

6

i i»

V^O'

U^-K-* ^ •^^

I

fcWH5

')

<\\ y^o o^'"^

^

er*^

32

The Convergent-Growth Approach

33

Interestingly, there was again no retardation to reaction as either the linear polyethylene glycol chain or the dendritic fragment increased in molecular weight. In fact, there was an increase in the rate of reaction.^^ This further demonstrates the relative accessibility and reactivity of the focal-point group. PreUminary investigation of the physical properties of these unusual hybrid barbell- and sperm-Uke copolymers, such as 30, has shown that they exhibit unusual solubility behavior and are able to form micelles in solvents in which only one block is selectively soluble. In the solid state, phase separation has been shown to occur after the linear polyethylene glycol block has reached a critical molecular weight.^^ Vll. PHYSICAL PROPERTIES OF DENDRITIC MACROMOLECULES One of the principal reasons for studying dendritic macromolecules is to investigate the new and improved properties resulting from the unique three-dimensional architecture of these materials. Thisfieldof study has lagged significantly behind the synthetic endeavors, since the majority of papers has been devoted to the synthesis and characterization of dendritic macromolecules. However, the proportion of work studying physical properties is growing and is likely to become a key area of research in years to come. The completed investigations of physical properties have provided a number of interesting and unusual findings which suggest even more exciting results to come. Low viscosity and apparent lack of chain entanglement, make dendritic macromolecules of particular interest with potential commercial use as viscosity modifiers. For a series of dendritic polyether macromolecules based on 3,5-dihydroxybenzyl alcohol as the monomer unit, intrinsic viscosity as a function of molecular weight has been studied by size-exclusion chromatography coupled with viscometry.^^ The intrinsic viscosity of normal linear polymers increases with increasing molecular weight. For dendritic macromolecules, however, a fundamentally different relationship is observed. As shown in Figure 8, intrinsic viscosity initially increases with molecular weight, followed by a clear maximum and then a decrease in viscosity as the molecular weight is increased. This unique behavior is consistent with that expected for spherical architecture. As mentioned previously, a cubic increase in volume occurs

34

CRAIG J. HAWKER and KAREN L. WOOLEY

0.055 H

•

IG-X]3-[C]

•

[G-X]-OH

0.025

Generation Number (X) Figure 8. Intrinsic viscosity of dendritic macromolecules in THF as a function of generation number.

resulting in an exponential increase in mass as the generation number increases. As the generation number increases for perfectly spherical dendritic macromolecules, the ratio of the change in volume to the change in mass is initially greater than 1. At a critical point, however, the ratio becomes less than 1 and continues to decrease. This changeover point correlates with the maximum between generation 3 and generation 4, and, coupled with the discontinuity observed for the solvatochromic dendrimers, provides further support for a shape transition at this point. Theoretical treatments by Lescanec and Muthukumai^^ have, also, predicted this behavior suggesting that a density maximum occurs at the center of the dendrimer. This is in direct contrast to a model by de Gennes^^ which suggests a density maximum at the surface. The answer to this question no doubt lies in the synthesis of appropriately labeled or functionalized dendritic macromolecules for which the position of the terminal groups can be accurately determined.

The Convergent-Growth Approach

35

320

o

3101

3 03 Urn

0)

300

a E 0) C

290

o '35 c (0

(0 (0

280 270

5 260 2.5

4.5

Figure 9. Variation of glass transition temperature as a function of log molecular weight.

For all of the dendritic macromolecules discussed above, a recurring observation was the significantly increased solubility of these materials when compared with linear polymers of the same or similar structure. While other authors have also reported"*^ this phenomenon, the reason for it is not understood now. A recent study"^^ has suggested that it may be due to a combination of effectsfromthe amorphous and nonentangled nature of these highly branched materials coupled with the extremely large numbers of chain ends. One physical property that is identical for dendritic and linear macromolecules is the variation of glass-transition temperature with molecular weight."^^ The trend of glass-transition temperature reaching a maximum with increasing molecular weight was characteristic for a number of dendritic systems. This is shown in Figure 9 for dendritic polyethers based on 3,5-dihydroxybenzyl alcohol. The glass-transition temperature is independent of the nature of the group at the focal point and the functionaUty of the core molecule. Surprisingly, the glass-transition behavior can be described for these macromolecular systems, containing large numbers of chain ends, by a modified version of the chain-end.

36

CRAIG J. HAWKER and KAREN L. WOOLEY

free-volume theory. However, a strong dependence on the nature of the chain-end functional groups, as well as the internal building blocks, was noted. A significant recent finding has been the observation of two glass-transition temperatures for a dendritic surface-block copolymer based on 3,5-dihydroxybenzyl alcohol which has one half of the chain ends functionalized with carboxylic acid groups and the other half devoid of functionality.^^ This is thefirstexample of phase separation in purely dendritic block copolymers, though individual phase transitions have been observed for hybrid linear-dendritic systems. It has been recently shown"^ that dendritic fragments with a hydroxymethyl group at the focal point form stable monolayers on the surface of water. The JC-A isotherms showed a strong dependence on the molecular weight of the dendrimer and the compression rate. The latter is due to the characteristic ability of dendritic macromolecules to occlude solvent molecules.

Vm. FUTURE DIRECTIONS The work presented above, coupled with the results from other authors, has demonstrated that the convergent-growth approach to dendritic macromolecules is a viable synthetic methodology. It is complementary to the divergent-growth approach, and both of these techniques have been used to prepare a wide variety of molecular architectures not previously synthesized. The authors believe that the synthetic area is far from mature. Other architectures are possible, the fertile field of hybrid copolymers has barely been touched, and perhaps the most promising aspect of all is the synthesis of tailor-made dendritic macromolecules. These specifically engineered molecules will be used to study specific properties, to simulate and improve on known biological systems, and to prepare materials for advanced technological applications. A prime example is dendritic micelles which mimic three-dimensional biological systems, but have a number of discemible advantages. A large amount of work is still needed to understand fully the fundamental physical properties of these unique systems. The number of reports in this area is growing steadily and, as these materials become more readily available, many exciting findings will no doubt appear. These findings, coupled with a growing body of theoretical data, will

The Convergent-Growth Approach

37

then be used to define more accurately the synthetic targets to be prepared by either the convergent- or divergent-growth approaches. Finally, it is hoped that the authors have highlighted a recurring theme in dendritic macromolecules. The high degree of control coupled with the wide range of building block and terminal groups that can be employed to synthesize these compounds allows a multitude of different systems to be prepared. Truly, one can envisage as many different molecules as there are trees. ACKNOWLEDGMENTS The authors are deeply indebted to the guidance, support, and wisdom of Professor Jean M. J. Frechet throughout all of the studies described. We would also like to thank the members of the Frechet research group and other workers whose names appear in the reference list. Finally, gratitude is directed to Professor George Newkome and Dr. Donald Tomalia, whose early work and perseverance have laid the foundation for others to follow, and have made the task easier. With thanks, we acknowledge financial support from the National Science Foundation, Australian Research Council, IBM Corporation, and the Eastman Kodak Company. REFERENCES 1. Newkome, G. R.; Moorefield, C. N. In Advances in Dendritic Macromolecules; Newkome, G. R., Ed; JAI Press: Greenwich, CT, 1994; Chapter 1. 2. (a) Kim, Y. H.; Webster, O. W. Macromolecules 1992, 25, 5561; (b) Kim, Y. Adv. Mater. 1992,4,764. 3. Hawker, C. J.; Lee, R.; Frechet, J. M. J. J. Am. Chem. Soc. 1991, 775,4583. 4. Bikales,N.M.Pofym.y. 1989,79,11. 5. Odian, G. Principles of Polymerization, 3rd ed.; Wiley-Interscience: New York, 1991. 6. Tomalia, D. A.; Naylor, A. M.; Goddard III, W. A. Angew. Chem. Int. Ed. Engl. 1990,29, 138. 7. Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985,50,2004. 8. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G; Martin, S.; Roeck, J.; Ryder, J.; Smith, R Polym. J. 1985, 7 7,117. 9. Burchard, W.; Kajaiwara, K.; Nerger, D. J. Polym. ScL, Polym. Phys. Ed 1982,20, 157. 10. De Gennes, P. G.; Hervet, H. J. J. Phys. Lett. 1983,44, 351. 11. Maciejewski, M. J. Macromol. ScL, Chem. 1982, A17,689. 12. Flory, R J. J. Am. Chem. Soc. 1952, 74, 111 8.

38

CRAIG J. HAWKER and KAREN L. WOOLEY

13. Hawker, C. J.; Frechet, J. M. J. J. Chem. Soc, Chem. Commm. 1990, 1010. 14. Hgwker, C. J.; Fr^chet, J. M. J. J. Am. Chem, Soc. 1990,772, 7638. 15. Newkome, G. R.; Baker, G. R.; Young, J. K.; Traynham, J. G. / Polym. ScL, Polym. Chem. Ed. 1993,31 641. 16. (a) Wooley, K. W.; Hawker, C. J.; Frechet, J. M. J. J. Am. Chem. Soc. 1991, 775, 4252; (b) Wooley, K. W.; Hawker, C. J.; Frechet, J. M. J. Submitted for publication. 17. Wooley, K. W; Hawker, C. J.; Frechet, J. M. J.; Wudl, F; Srdanov, S.; Shi, S.; Li, C,; Kao, M. J. Am. Chem. Soc. 1993, 775, 9836. 18. Tomalia, D. A.; Hedstrand, D. M.; Wilson, L. R. In Encyclopedia of Polymer Science and Engineering, 2nd ed.; Wiley: New York, 1990; pp 69-75. 19. (a) Miller, T. M.; Neenan, T. X. Chem. Mater 1990,2,349; (b) MUler, T. M.; Kwock, E. W; Neenan, T. X. Macromolecules 1992, 25, 3143. 20. (a) Zhang, J.; Moore, J. S.; Xu, Z.; Aguirra, R. A. J. Am. Chem. Soc. 1992, 77^, 2273; (b) Morikawa, A.; Kakimoto, M.; Imai, Y Macromolecules 1992, 25, 3247. 21. Hawker, C. J.; Frechet, J. M. J. Macromolecules 1990, 23,4726. 22. Wooley, K. L.; Hawker, C. J.; Frechet, J. M. J. J. Chem. Soc, Perkin Trans. 11991, 1059. 23. Wooley, K. L.; Hawker, C. J.; Fr6chet, J. M. J. J. Am. Chem. Soc. 1993,775,11496. 24. Newkome, G. R.; Moorefield, C. N.; Baker, G. R.; Johnson, A. L.; Behera, R. K. Angew. Chem. Int. Ed. Engl. 1991,30, 1176. 25. Hawker, C. J.; Wooley, K. L.; Frechet, J. M. J. J. Chem. Soc, Perkin Trans. 11993, 1287. 26. (a) Newkome, G. R.; Young, J. K.; Baker, G. R.; Potter, R. L.; Audoly, L.; Cooper, D.; Weis, C. D.; Morris, K.; Johnson Jr., C. S. Macromolecules 1993,26, 2394; (b) Newkome, G. R.; Moorefield, C. N.; Baker, G. R.; Saunders, M. J.; Grossman, S. H. Angew. Chem. Int. Ed. Engl. 1991,30, 1178. 27. Hawker, C. J.; Frechet, J. M. J. J. Chem. Soc, Perkin Trans. 11992, 2459. 28. Hawker, C. J.; Frechet, J. M. J. /. Am. Chem. Soc 1992,114, 8405. 29. Newkome, G. R.; Lin, X. Macromolecules 1991, 24, 1443. 30. Newkome, G. R.; Moorefield, C. N. Polym. Prep. 1993,34, 75. 31. Hawker, C. J.; Wooley, K. L.; Frechet, J. M. J. J. Am. Chem. Soc 1993, 775,4375. 32. (a) Moreno-Bondi, M. C ; Orellana, G.; Turro, N. J.; Tomalia, D. A. Macromolecules 1990,23,912; (b) Naylor, A. M.; Goddard, W A.; Kiefer, G. E.; Tomalia, D. A. J. Am. Chem. Soc 1989, 777, 2339. 33. Hawker, C. J.; Frechet, J. M. J. Polymer 1992,33, 1507. 34. Wooley, K. L.; Frechet, J. M. J. Unpublished results. 35. Gitsov, I.; Wooley, K. L.; Hawker, C. J.; Frechet, J. M. J. Polym. Prep. 1991, 32, 631. 36. Gitsov, L; Wooley, K. L.; Frechet, J. M. J. Angew. Chem. Int. Ed Engl. 1992, 31, 1200. 37. Gitsov, L; Wooley, K. L.; Hawker, C. J.; Ivanova, P T; Frdchet, J. M. J. Macrvmolecules 1993,26,5621. 38. Gitsov, L; Frechet, J. M. J. Unpublished results. 39. Mourey, T. H.; Turner, S. R.; Rubenstein, M.; Frechet, J. M. J.; Hawker, C. J.; Wooley, K. L. Macromolecules 1992,25, 2401.

The Convergent-Growth Approach

39

40. Lescanec, R. L.; Muthukumar, M. Macromolecules 1990, 25, 2280. 41. Miller, T. M.; Neenan, T. X.; Zayas, R.; Bair, H. E. J. Am, Chem. Soc. 1992,114, 1018. 42. Wooley, K. L.; Fr^chet, J. M. J.; Hawker, C. J. Polymer J. 1994,26,187. 43. Wooley, K. L.; Hawker, C. J.; Pochan, J. M.; Fr6chet, J. M. J. Macromolecules 1993, 26,1514. 44. Saville, R M.; White, J. W; Hawker, C. J,; Wooley, K. L.; Fr6chet, J. M. J. 7. Phys. Chem. 1993,97, 293.

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CASCADE MOLECULES: BUILDING BLOCKS, MULTIPLE FUNCTIONALIZATION, COMPLEXING UNITS, PHOTOSWITCHING

Rolf Moors and Fritz VogtIe

ABSTRACT I. INTRODUCTION A. Repetitive Synthesis II. TOSYLAMIDE CASCADES A. Divergent Synthetic Strategy B. Convergent Synthetic Strategy III. POLYAMINE DENDRIMERS A. Tris(2-aminoethyl)amine as Core Unit B. Pentaethylenehexamine as Core Unit C. Cyclam and Hexacyclene as Core Units

Advances in Dendritic Macromolecules Volume 2, pages 41-71. Copyright © 1995 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-939-7

41

42 42 42 46 46 53 56 56 58 59

42

ROLF MOORS and FRITZ VOGTLE

rV. SALEN UNITS AND MULTIPLE COBALT COMPLEXES . . . A. Salen Units B. Multiple Cobalt Complexes V. PHOTOSWrrCHING DENDRIMERS VI. CHIRAL CASCADE MOLECULES VII. MISCELLANEOUS RESEARCH DIRECTIONS AND FUTURE DEVELOPMENTS ACKNOWLEDGMENTS REFERENCES

61 61 63 64 66 69 70 70

ABSTRACT Dendrimers, with bulky arene units repeating up to the third generation, were synthesized by using repetitive convergent and divergent strategies. By employing different multidirectional core units, the procedure is generalized. The first X-ray structure of a first-generation cascade molecule is presented, and its photoswitching azobenzene derivate demonstrates reversible (£)/(Z)-isomerization. The pursuit of our cascadelike polyamine synthesis, developed in 1978,^ is achieved with an improved reduction method. The resulting amines are converted into imines that can complex transition metals. Crown compounds based on "Hexacyclen" and "Cyclam" as core units represent another type of potential complexing dendrimer. New perspectives for the synthesis of chiral cascades are presented.

I.

INTRODUCTION

In 1978, we reported the repetitive synthesis of noncyclic and cyclic (so called "nonskid chainlike") polyaza compounds, which were the first examples of cascade molecules^ (Scheme 1). Since that time, dendrimers have gained widespread attention in organic, as well as in inorganic^'^ and physical chemistry."* In 1992, De Gennes received the Nobel prize in physics for his studies on chaos Sind fractals. His results are relevant for the molecular design of cascade polymers especially in their threedimensional growth. A. Repetitive Synthesis

Repetitive strategy is a fundamental principle for the synthesis of dendrimers, that was first coined, to the best of our knowledge in our seminal cascade paper. ^ It implies a repetitious sequence of the same reaction steps, as initially demonstrated in the synthesis of linear polyamines,^ by sequential Michael addition, followed by a facile nitrile reduction (Scheme 1). The preparation of Newkome's arborols^ is an-

Cascade Molecules

43 CN

NHo H2N'^^ -^

NC ^

H2C=CH-CN

/ .^ N N ^^ \

•

1

NaBH4/Co(ll) •

? 2

NC

NC>. NHo 1

/'^v.'^CN

-CN

HoN-

•

.N ^NH2

HoN

3

U. 4 Scheme 1. The first examples of cascade molecules by Vogtie et al.

other example that makes use of this strategy in dendrimer chemistry (Scheme 2). This strategy has been of basic importance not only in the field of cascade molecules. In 1978, Vogel et al. synthesized methano-bridged annulene derivates by a repetitive synthetic strategy^ (Scheme 3). The repetitive steps (initial Wittig reaction followed by reduction of the resulting ester groups to the aldehyde) led him to a new class of aromatic compounds. Another example of a repetitive methodology is the stereoregular Diels-Alder oligomerization procedure reported in 1992 by Stoddart et al.^ (Scheme 4). With this molecular "LEGO" strategy, he built several cycloacenes by periodical repetition of the same procedures. One common example of repetitive synthetic strategy comes from the field of natural products. The preparation of oligo- and polypeptides is a repeating sequence of protection and activation of the reactants, followed by the addition of a new amino acid. In 1963, one of the highlights in repetitive synthesis was the automation of peptide production by Merrifield^ (Figure 1). In the literature, authors often speak of a "protein machine" since it is now possible to build up peptides mechanically without the preparative help of a chemist.

1) LDA.

^0CH2Ph "^

Br J

^-OCHoPh ^ - 0CH2Ph

2) H2. Pd/C

Br

Br

0CH2Ph 0CH2Ph

Scheme 2. The repetitive synthesis of Newkome's arborols. 44

Cascade Molecules

45 0 (H5C2)2P^C02C2H5 /

.CHO ft I

I

+

•^^t^HO

Wittig—reaction

(H5C2)2P'^C02C2H5

^

10

11

12

Scheme 3. Annulene derivatives prepared in a repetitive manner by Vogel.

Nature is able to do the same thing through biochemical mechanisms. The way, in which oligo- and polypeptides are built by microorganisms with the help of coenzymes, does not differ principally from that which we use for the synthesis of dendrimers. It also is a circle of retuming reaction steps with the intention of building proteins resulting in biopolymers.

5l< ^ (lO^-^T^ Bdxcxibl: 13

14

" H

^ A

14

15

"

H

H

^

15 CH2CI2, 9-10 kbar. 55-60 °C. 24 h

16 Scheme 4. Stoddart's molecular "Lego".

46

ROLF MOORS and FRITZ VOGTLE

Ksiyrenej

«~^>-CHo-

OOCRHCHNH - OCRHCHN - Boc

I HBr/CF3C00H

W^l^

< ; £ 2 ^ C H 2 - OOCRHCHNH - OCRHCHNH2

Figure 1. Merrifield synthesis of peptides.

IL TOSYLAMIDE CASCADES

Since dendrimers have gained widespread attention in organic chemistry, we reentered the "cascade arena" and planned a new synthetic concept, based on the divergent as well as the convergent strategy succesfully applied by Denkewalter,^ Newkome,"^'^^ Tomalia,^^ Masamune,^ and others. We turned to the synthesis of monodisperse dendritic molecules using large and bulky repeating units.^^"^^ A. Divergent Synthetic Strategy

As monomeric building blocks for a divergent strategy, we used several benzylic bromides (17-21) and the isophthalate 22 because each could

Cascade Molecules

47 Br

Br

TsNH

22 Scheme 5. Starting materials for tosylamide cascades.

be prepared in simple steps from commercially available starting materials (Scheme 5). The reaction sequence always started with the substitution of the bromide by the amine in a mixture of A^,Af-dimethylformamide (DMF) and K2CO3, with first-generation yields of about 80% in all cases. One of the problems in the synthesis of dendrimers is to obtain single crystals, but our recent efforts have been rewarded with the hexaester 23a by recrystallization from acetonitrile.^^'^^'^'* The X-ray structure (Figure 2) shows that the molecule adopts a configuration, in which two of the three isophthaloyl groups point in the same direction, while the remaining one points in the opposite direction. The molecules are packed in an octopuslike manner where the tosyl and isophthaloyl groups of adjacent molecules interlock like tentacles to

Figure 2, X-ray structure of the first-generation dendrimer 23a.

figure 3. X-ray structure of the first-generation dendrimer 23a showing the disordered solvent molecules. 48

Cascade Molecules

49

create differently sized cavities occupied alternately by acetonitrile and imperfectly with water"* (Figure 3). The next step in the reaction sequence began with the reduction of the ester groups with LiAlH4 in tetrahydrofuran (THF). After quenching the reaction mixture with acetic anhydride, the resulting acetate was cleaved with KOH to give the corresponding polyol. This was treated with a mixture of PBrj in CHCI3 to give the bromide 23c. At this step, the analogous reaction cycle starts again (Scheme 6). Schemes 7 a-c show the dendritic molecules that resulted from this divergent strategy. ^^"^^ In this way, the third-generation dendrimer 27 (Scheme 7c) with 24 ester groups was prepared. Not only is its molecular mass of 6910.6 Da huge for a dendrimer in the third generation, but also the size of this molecule grows rapidly as the number of generations increases. Within a small number of generations, we were able to build dendrimers that reach nanoscale dimensions and architectures.^"*'^^

A Br

+ 3

'

V^

22

HNTs

Br

NTs

Br

r ^

J TsN

"* A,

23

17 X = CO2CH3

— •

X = CH2OH

23a

23b

— •

X = CH2Br

23c

H3C02C\^';^^^C02CH3 +

6 HNTs

22

Scheme 6. Reaction scheme for the synthesis of tosylamide cascades.

Ts ^NY^C02CH3

J

CO2CH3

H3CO2C

CO2CH3

H3CO2C CO2CH3 H3CO2C

N Y N " ^ N ^"^^^^^^^CO2CH3

TsN^

H3CO2C " ^

CO2CH3

H3CO2C ^'^•*^^C02CH3

Scheme 7a. Obtained dendrimers.

50

u +^ A

NTs NTs

23 TsN

X.^.I'JC 26

X

X"^^"NTs

NTs

k p ^ X'^-^^NTs

A

r"'

A.

^"

"-A•crsA'^« TsN,^^^5s,,^-s^,A^V TsN X « CO2CH3

27 Scheme 7b. Obtained dendrimers.

51

C02CH3

C02CH3

A

A

H 3CO2C ^'^V:!*^ N ^ Y V ^ N ^^^^s^ CO2CH3 Ts IL J Ts Ts p ^ Ts N ^^'v^'^'xx N Y

H3CO2C Y ^

CO2CH3

^ CO2CH3 CO2CH3

28 CO2CH3 H3C02CY^C02CH3

k ^

H3CO2C j ^

J

^

TsN^^^^C02CH3

f S T fi^ Ts ^^^^YV^^^'^^Y^C02CH3

H3C02C^^^*^N^"Y'^Y^^^ ^^

\ ^

^^^^^ H3C02CY^NTS ^ ^

k^

^ ^ 'U^

CO2CH3

^NTs A ,

H3C02C''^^^C02CH3

H3CO2C

H3C02C'^^«^^C02CH3

jT^

H 3CO2C ^ ^ ^ CO2CH3

Scheme 7c. Obtained dendrimers.

52

29

Cascade Molecules

53

B. Convergent Synthetic Strategy Benzene Derivatives as Core Units

Using convergent methods, we also tried to work out an altenative route that would lead us to the same type of dendrimers.^^ As starting material, we used 3,5-bis(bromomethyl)nitrobenzene (31) that reacted under similiar conditions with the isophthalate (22) to yield the first generation of our new building block. The reduction of the nitro group in about 90% yield was easily achieved with hydrazine hydrate/Raney nickel in ethanol. The final tosylation led us to a new convergent molecule 34, that was reacted in DMF/K2CO3 with hexabromide (21)^^ to give the oligoester (35) in good yields (Scheme 8 a and b). This example shows that highly branched and bulky nanoscale dendrimers can be built up with good yields by both convergent and divergent methods. With the new reactive building block, 34, we were able to synthesize the second-generation cascade molecules in a single-step reaction from most of the benzylic bromides mentioned in Section H. A. NO2

K2CO3/DMF

+ 22 ^^ 3 1

^^

j'°2

P^^gy.-Ni

l ^ ^ H3C02CY''^NTS

N2H5OH/C2H5OH

TSNY"^C02CH3

V 32 V H3CO2C

CO2CH3

TsCI/Pyr. H3C02CY''^NTS

\

TSNY^^C02CH3

HNTs H3CO2C

CO2CH3 H3C02CY<5yNTs

V H3CO2C

34

V'

TSNY'^C02CH3

CO2CH3

Scheme 8a. Convergent synthetic strategy and the second-generation dendrimer obtained.

ROLF MOORS and FRITZ VOGTLE

54 Br

Br

34 +

H3CO2C Y " ^ CO2CH3 H3C02Css^.'^C02CH3

V

K^

CO2CH3 H3C02CY^N

H3CO2C

-

"^^

--

H3CO2C H3C02CY''**SS^N"'"S

H3CO2C

,^^.

H3CO2C Y \

N s X k i ^

TH3C02C-f<>r' J H3CO2C ILJH3C02CY^^ H3CO2C

T^

U2^"3

35 "^"^ Scheme 8b. Convergent synthetic strategy and the second-generation dendrimer obtained.

Hexacyclene as Core Unit

Wheras Shinkai et al. showed the possibility of synthesizing a type of dendrimer containing crown units as covalently bonded elements in the periphery/^'^^ we obtained the first dendrimer with an aza crown as the core unit.^^ Again we synthesized it by a new convergent strategy. Starting with commercially available materials, our convergent building block 42 was the result of a six-step synthesis shown in Scheme 9. The

Cascade Molecules

55

H3C02C'V'W'^°2CH3

^_ H3C02Cv^^^C02CH3 ^"^ • IIJ NQOCH3

36 ^ ' ^

^7 HO

H3C02Cv.^-..:^C02CH3

^

O 38

T

LiAIH4^

Br

^

i J

^^^3

Br

Br OH

^Br3_

3 9 ^0CH3 ^ ^T T

oo

R

R

H3C02CY-!^C02CH3

"^ ^ CO2CH3 Ts

H3CO2C

Ts ^ V

/-'^-^

t>-K ^ H3C02C'^

JL N

N

H3CO2C

Ts

^N

N

H3CO2C

Scheme 9.

,C02CH3

i ^

Ts

L P

7

^°^7^4o2CH3 ^

H3CO2C'

HjCOjC^

TsN

CO2CH3

J

^rl?r Ts Ts

l i j

CO2CH3 CO2CH3 ~^CO,CH,

T»^ - ^ 1 ^ _ ^ Ts CO2CH3 H3CO2C CO2CH3TS CO2CH3 ^^loors. Vbgtie.

Another convergent strategy for the preparation of crown

dendrimers.

final substitution of hexacyclene (43) at all nitrogen atoms gave a 31% yield of aza crown (44) after column chromatography. The ability of 44 to complex is the subject of future investigation in the same way as we try to transfer the concept of using aza crowns as core units in other types of cascade molecules (described in Section III.B.).

56

ROLF MOORS and FRITZ VOCTLE

III. POLYAMINE DENDRIMERS A. Tris(2-aminoethyl)amine as Core Unit Since polyamines are industrially available compounds, we returned to our first successful cacade synthesis in 1978^ where we produced dendritic oligoamines. It seemed attractive to pursue this synthesis with new preparative and analytical methods, which then were limited. As starting materials, we selected the commercially available tris(2-aminoethyl)amine (TREN) due to its inherently branched structure. The synthesis was accomplished in a manner identical to that conducted 16 years ago, affording a 90% yield of the first-generation dendrimer 46 by reaction of TREN with acrylonitrile and catalytic amounts of acetic acid (Scheme 10). To enhance the generality of the reduction stage, we tried to find a new and more efficient method. Common reduction reagents, like LiAlH4 or NaBH4, led to cleavage of side arms or decomposition of the molecule. We, therefore, had to find a mild and selective agent, reactive enough to lead the reduction to the amine, but not destructive to the polyamine skeleton. As a commercially available reagent that fulfills these conditions, we utilized diisobutylaluminumhydride (DIB AH). After the nitrile was refluxed for 24 hours in a IM solution of DIB AH in hexane, the resulting amine was isolated as an oily, colorless product. The next reaction sequence was treating it with acrylonitrile giving us the secondgeneration dendrimer (48) with twelve nitrile groups (Scheme 11). In contrast to the parallel works of Mulhaupt^^ and Meijer et al.,^* the advantage of our method is that we are able to reduce these oligonitrile systems on a laboratory scale without using high hydrogen pressures or

NC ^CN H2N — N ^ k

H2C = CH-CN^ H3CC02H,24h

NH2

NC^-^N — N ^ ^ ^ k yNv

46 Scheme 10. Synthesis of the first-generation nitrile.

Cascade Molecules

57

NC NN

"^CN

DIBAH,24h

1

hexane/THF

NC

CN

46

Scheme 11. Synthesis of the second-generation nitrileviaa new reduction method.

autoclaves. To test the efficiency of this reduction method and to generalize the procedure further, we used the system of benzylamine/acrylonitrile^ to build up a dendrimer. Without any preparative problem, we synthesized the third generation. The reduction of the nitrile always gave the amine in nearly quantitative yield (Scheme 12). We are constructing the fourth generation 54 by using the same repetitive method but this project is still underway.

ROLF MOORS and FRITZ VOCTLE

58

CN

^

NH2

"CN

^

H2C = CH-CN

DIBAH.24h

^

H3CC02H.24h

hexane/THF 89%

50

49

CN

NH2

/

N-x^CN \ H3CC02H,24h

CN

\^

1)DIBAH

f^

2)C3H3N CM

51

<> N-^ N

CN CN

52 CN CNNC^

CN

H -N

NCCN

53

^N^-^CN

s

't^CN ^CN CN

\ /r^ J

J'

CN

XN

r^'

CN

CN .CN

/^{

2)C3H3N 1)DIBAH

CN -CN

-N^"--^^N-

u

54

(in work)

CN

(

\^

CN

NC

Scheme 12. Benzylamine as core unit.

B. Pentaethylenehexamine as Core Unit In contrast to the three-dimensional growth of the TREN dendrimer 48, we thought it would be interesting to synthesize a linear "polymer dendrimer" based on pentaethylenehexamine. We lised the same strategy described in Section III. A. The primary Michael addition of acrylonitrile yielded the octanitrile 56 without any problems. Similarly, the DIBAH reduction led to the amine 57 (Scheme 13). Contrary to all expectations, the addition of acrylonitrile failed at this step. In the mass spectra, we

Cascade Molecules

59

^ / \ H / \ A H/N H2NVN^N%NA^NA,NH2

H2C=CH-CN H3CC02H.24h""

55 NC

NC

NC DIBAH,24h

NC^^

^ N^^NTVN " V N A ^ N ' X ^ N ""

CN

CN

^CN

1 hexane/THF 78%

CN

56 H2N

H2N

'A ,

HoN-

A \/

H2N

' A V

A ^1

'A ^

/—-^^^2 ^1

H2C=CH-CN

//

H-iCC0oH,24h// H3CC02H,24h i

57 NH2

NH2

NH2

U 0 U .CN •N

^CN NC NC

58

s"! ("( n

NC

CN

NC

CN

NC

CN

Scheme 13. Pentaethylenehexamine as core unit.

found fragments where only some hydrogens of the amine molecule were substituted by acrylonitrile sidearms, indicating that steric overcrowding may be one of the reasons why the molecule failed to react uniformly. C. Cyclam and Hexacyclene as Core Units

As shown in Section II.B., it was possible to use an aza crown as the core of a new type of dendrimer. So we tried to combine our new stategy in synthesizing TREN cascades with the experience we collected in synthesizing our crown dendrimer (44). We selected cyclam (59), as the

60

ROLF MOORS and FRITZ VOGTLE

f ^ l^N

NC, N!^

L

H9C=CH-CN

J

^N

^

N;:

H3CCO2H

KJ

^r ^ ^N

NC^

59

^

^CN

N^S,

L

J

^N

N:;

k^

hexane/THF

CN

60 .N

N^

-N

N;*

^

H9C = C H - C N H3CCO2H

61 NC

^CN

NC NC'

CN

62 Scheme 14. "Cyclam" as core unit.

aza crown core, which we treated with four equivalents of acrylonitrile. The formation of the tetranitrile proceeded without any difficulties and was followed by a successful DEBAH reduction. Repetition of the Michael addition easily lead us to the second-generation dendrimer (62, Scheme 14). In the same way, we tried to obtain the second generation of a hexacyclene dendrimer 65. One of the problems occurring in this divergent synthesis was the low solubility of the first-generation hexanitrile in THF. As a consequence, the reduction yielded only 32% of the desired hexamine 64. The subsequent addition of acrylonitrile led to the dodecanitrile (65, Scheme 15), the only compound of this type unstable in oxygen! It decomposed after several hours yielding an oily, black liquid. Experiments are in progress to generate information about the complexing behavior of these crown dendrimers. One of the interesting aspects will be the influence of the "dendritic surrounding" on the selectivity of the aza crown.

Cascade Molecules

61 CN XN

!^N I ^N H'l k/Nv H

N^J, HoC=CH-CN I • N""^ ',H H3CCO2H ^ NC'

^N Nv, I I ^N N^ ^ k ^ N ^

43

Nc

DIBAH.24h • hexane/THF CN

63

/NH2

^N

N>.

H2C=CH-CN^

"N N''^ H2N...--^k^N^^—-^NH2

HoN-"

H3CCO2H

64 NC

CN

If ^N^

NC

/

NC^^'^

^

C

NCNC^

—sl^

'

^CN ^

"^^CH

1 J

NC

CN

CN

Scheme 15. "Hexacyclene" as core unit. IV. SALEN UNITS A N D MULTIPLE COBALT COMPLEXES A. Salen Units^^

To prove that all side arms of the dendrimer were reduced to the amine by our DIBAH reduction method and to demonstrate the possibility of synthesizing new, functionaUzed (in this case complexing, Section IV.B) dendrimers, we attempted a Schiff base formation. ^^ On account of the stability of salicyl imines and their cation-complexing abilities, we chose to react salicylic aldehyde with amine 47.

OH

A

^

N

OH

CHO toluene/20OC

^|

f^^

^'

'^ OH

X

66

I^

Ho^k

"^ U

N\

N

N

"°-0 C 67 Scheme 16. The dendritic imine of TREN.

,^^v^OH

n HO

HOv

II

N

n

HO.

OC

70

N

N

"v..

V N

'"'^-^OH

N<s

H o X ^ UJ 68

i^

r

69 Scheme 17. Linear and crown imines. 62

Cascade Molecules

63

The reaction was accomplished in toluene, and water was removed by adding anhydrous Na2S04^^ (Scheme 16). The reaction between amine 47 and 1-hydroxybenzaldehyde (66) in toluene proceeded smoothly at room temperature. Elemental analysis, mass, and NMR spectra showed without doubt that the amine 47 reacted six times, giving a 70% yield of the pure orange colored hexaimine 67. The analogous reaction was tried with the linear octamine 57 and the first-generation amine of the cyclam dendrimer 61. Again, this reaction afforded the corresponding imines in good yields (Scheme 17; 68 and 69), opening the way to new, exciting ligands, which are available for the preparation of multiple-metal complexes. B. Multiple Cobalt Complexes

It is well known that Salen is a useful ligand for complexing transition-metal cations, especially Co(n) (Scheme 18:70). So far most studies have been aimed at the ability of Co(n) Salen to complex oxygen reversibly, its electrochemical behavior, and especially its catalytic activity.^"^ Since the new ligands are "multiple Salen systems," we supposed that the oxygen-complexing and electrochemical properties are also multiplicative. Thus we will be able to complex two, three, or four Co(n) cations with one ligand molecule. To prepare our cobalt complexes, we again chose the first-generation TREN dendrimer 67. The preparation of the triple cobalt complex 71 was done analogously to that described by West^^ (Scheme 19). As a result of this reaction, we isolated a violet product with a peak at 1284.3 by fast atomic bombardment mass spectrometry (FABMS). The mass of the molecular ion indicated the incorporation of three cobalt atoms. This result was confirmed by elemental analysis. We tried examining the oxygen-complexing ability of our salen-type complex 71, but

70 Scheme 18. Cobalt salen.

64

ROLF MOORS and FRITZ VOGTLE

Co(H3CC00 2 ^ ^ /

H5C2OH

^. \ ^v,\

7 >

\ /

\/

'••6 a°' 71 Scheme 19. A dendritic triple salen complex.

its stability in air was rather high, contrasted with the simple Co Salen that decomposed in solution after several hours under conditions for oxygen fixation. Qualitative cyclovoltammograms in DMF showed that there is more than one reversible redox element in the molecule. More detailed studies will be the subject of future developments by the same method that we used to synthesize the cobalt complexes of the multiple Salen Ugands 68 and 69 in Scheme 17. V. PHOTOSWITCHING DENDRIMERS In our efforts to obtain functional dendrimers, we envisioned preparing a phot05witching type of cascade molecule that undergoes reversible (£)/(Z)-isomerization depending on the wavelength under which it was irradiated. To achieve our plan, we chose the benzylic bromide 23c and 3-(tosylamino)azobenzene (72) as the photoactive molecule (Scheme 20). The reaction provided a 40% yield of the first-photos witching dendrimer 73.^^ Irradiation experiments on 73 (all £) at 313 nm led to the photostationary equiUbrium (PSE) I (Figure 4) where most of the azobenzene units were switched to the (Z)-configuration. Irradiation at 436 nm led to the equilibrium PSE II (Figure 4), where the reisomerized (£)-form was dominant. It was difficult to prove how many of the azobenzene units isomerized after irradiation. Thus 73 can be used only for qualitative statements. But

Scheme 20. The first-photoswitching dendrimer. extinction

ii

1.2 1.0 0.8 0.6 0.4-

y \^^^^ ^

0.2 1—1—1

300

400

1^

500

wavelength [nm]

Figure 4. UV-VIS spectrum of the photoswitchable dendrimer 73. 65

ROLF MOORS and FRITZ VOGTLE

66

these experiments show that it is possible to build up dendrimers able to change their molecular parameters (e.g., size, complexing abilities, reactivity) dependent of the wavelength. Vl. CHIRAL CASCADE MOLECULES The synthesis of chiral dendrimers by using commercially available chiral core units is another attractive field of research in dendrimer chemistry. As Newkome et al.^^ and Seebach et al.^^ have shown, this is an efficient method for preparing such molecules. We tried to transfer our synthetic strategy, developed for oligoamines, to accommodate chiral core units. The commercially available enantiomers of 1,2diphenyl-l,2-diaminoethane (74a and 74b) looked like optimal precursors for chiral dendrimers (Scheme 21).

Michaal-addition

75b

75a ODIBAH-radiiction 2)lHcha9l-ouidititon

76a

>.

n

NC

CN

1.. CN

J

NC

.N

n

NC

76b

CN

Scheme 21. Chiral building blocks as core units in the synthesis of cascade molecules.

Cascade Molecules

67

Vs. />

Brj/Fe

^v • ^

1) n-BuLi 2) B(0CH3)3

V. • v ^

CH2CI2/CCI4

^j^yV--

3) NaOH/H202

77

78

/NH2

^NH2

NN

> -

-

,

u M

/^

M

Na2S04

s H2N

toluene

7f*

47 NH2

81:R=

S R

81 R

Scheme 22. Chiral dendritic imines with cyclophane periphery.

Preparation of the first-generation dendrimer appeared to yield chiral 75a,b without any problems. The CD spectra for both enantiomers showed the expected Cotton effects, but the mass spectra did not exhibit correct molecular peaks. As we found out by NMR spectoscropy, a mixture of stereochemically pure, once- and twice-substituted products was formed. The mass spectra showed peaks at half the mass of the molecular ion, but they do not arise from the tetranitriles 75a,b as predicted, but resulted from decomposition of the chiral amines 74a,b probably due to steric crowding.

ROLF MOORS and FRITZ VOGTLE

68

Another possibility that may lead us to chiral dendrimers lies in the axial chirality of substituted [2.2]/7-cyclophanes. The salicylaldehydecontaining cyclophane (80) of this type was presented by Belokon et al.^^ In contrast to the experiments mentioned above, we tried to bring elements of chirality into the periphery of the molecule by connecting it through an imine bridge (Section IV.A.). The synthesis of 4-hydroxy[2.2]/7-cyclophane (79), via the bromide^^ and the final formyla-

DIBAH.24h 83

hexane/THF 89%

CN

^^2 H2C = CH-CN ^

[I J

34

\

CN

H3CC02H.24h ^ X ^

f^

1)DIBAH

'2)C^H^

'NN

CN

OCH3 ethe'Tcleavage

85 CN

f

N-..^CN

J

CN CN

85a Scheme 23.

Ideas for a "dendritic toolbox."

Cascade Molecules

69

tion, yielded the racemic aldehyde 80 (see Scheme 22). The preparation of the hexaimine 81 has, thus far, failed, but further experiments are in progress. VII. MISCELLANEOUS RESEARCH DIRECTIONS AND FUTURE DEVELOPMENTS With the intention of producing a cascadeUke building block that we can connect with various core units, we have planned the convergent synthetic strategy shown in Scheme 23. With the first-generation nitrile 83, we are testing methods of cleaving the ether bridge in order to obtain the phenol 83a, which will react in a Williamson synthesis with most benzylic bromides. After the solution of this problem, we will be able to produce higher generation dendrimers. Thus it should be no problem to build up a "dendritic toolbox" containing the convergent building blocks we need. As we mentioned in Section II.A., it is quite difficult to obtain single crystals of cascade molecules. Therefore, we prepared different derivatives with the expectation of creating enhanced crystallization properties. Two of these derivatives are shown in Scheme 24.^^ The hexatosylate 86 was synthesized in a mixture of chloroform and pyridine with 4-toluenesulfonylchloride, but, in contrast to most other similar reactions, the yield was low (2%).

/NHTs TsHNv

s

s R TsHN

87

N\ R

NHTs

8 7 : .=

H o ^

OH

N"^CH3

Scheme 24.

Functionalized dendrimers.

70

ROLF MOORS and FRITZ VOGTLE

The synthetic strategy for producing the interesting pyridoxal derivative 87 followed the same procedures that we have tested (Section IV.A.) yielding the "hexakis-provitamin,B6" The accumulation of potentially biochemically active compounds or building units connected to a dendritic skeleton may lead to a new group of drugs capable of acting at low dosages with higher efficiency. In the same way, colors or other industrial products may be enhanced or modified by multiplying active centers or groups.^^ ACKNOWLEDGMENTS We thank the co-workers Dr. R. Guther, Dr. R. Hoss, F. Ott, W. Schmidt and G. Harder for NMR spectra, Dr. M. Bauer and U. Wolff for the irradiation experiments and UV-VIS spectra, Dr. G. Eckhardt and Dr. S. Schuth for the mass spectra. Prof. Dr. E. Steckhan and R. Wendt for cyclovoltammograms, and W. Josten and H.-B. Mekelburger for some drawings.

REFERENCES 1. Buhleier, E.; Wehner, W.; Vogtle, F Synthesis 1978, 155. 2. Rengan, K.; Engel, R. J. Chem. Soc, Chem. Commun. 1990, 1084. 3. Uchida, H.; Kabe, Y; Yoshino, K.; Kawamata, A.; Tsumuraya, T.; Masamune, S. J. Am. Chem. Soc. 1990, 772, 7077. 4. De Gennes, R G.; Hervet, H. J. Phys. Lett. (Paris) 1983, 44, 351. 5. Newkome, G. R.; Moorefield, C, N.; Baker, G. R.; Johnson, A. L.; Behera, R. K. Angew. Chem. 1991,102,1205-1201; Angew. Chem., Int. Ed. Engl. 1991,50,1176. "Arboror' is a synonym introduced by G. R. Newkome and resulting from merging "Arbor" (Latin: tree) and alcohol. It is the expression for the treelike structures and the alcohol functionalities in these cascade molecules. 6. Wagemann, W.; lyoda, M.; Deger, H. M.; Sombroek, J.; Vogel, E. Angew. Chem. 1978, 90, 988; Angew. Chem., Int. Ed. Engl. 1978, 77, 956; Vogel, E.; Will, S.; Schulze-Tilling, A.; Neumann, L.; Lex, J.; Bill, E.; Trautwein, A. X.; Wieghardt, K. Angew. Chem. 1994, 106, 111; Angew. Chem., Int. Ed Engl. 1994, 33, 731; Lausmann, M.; Zimmer, L; Lex, J.; Leueken, H.; Wieghardt, K.; Vogel, E. Angew. Chem. 1994,106, 776; Angew. Chem.. Int. Ed Engl. 1994,33, 736. 7. Ashton, R R.; Brown, G. R.; Isaacs, N. S.; Giuffrida, D.; Kohnke, F. H.; Mathias, J. P.; Slawin, A. M. Z.; Smith, D. R.; Stoddart, J. F; Williams, D. J. J. Am. Chem. Soc. 1992,114, 6330. 8. Okuda, T. A^a/wrw/s5.1968,55, 209. 9. Denkewalter, R.; Kole, J.; Lukasavage, W J. U.S. Patent 4289872, 1985; Chem. Abstr. 1985, 7^2, 79324q. 10. Newkome, G. R; Zhong-qi, Y; Baker, G. R.; Gupta, V. K.; Russo, R S.; Saunders, M. J. J. Am. Chem. Soc. 1986,108, 849; Newkome, G. R.; Baker, G. R.; Saunders,

Cascade Molecules

11.

12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

25. 26. 27. 28.

29. 30. 31.

71

M. J.; Russo, P. S.; Gupta, V. K.; Zhong-qi, Y; Miller, J. E.; Bouillion, K. J. Chem. Soc, Chem Commun. 1986, 752; Newkome, G. R.; Nayak, A.; Behara, R. K.; Moorefield, C. N.; Baker, G. R. J. Org. Chem. 1992,57, 358. Tomalia, D. A.; Baker, H.; Dewald, J. R.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, R Polym. J. 1985, 77,117; Tomalia, D. A.; Baker, H.; Dewald, J. R.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, R Macromolecules 1986, 79,2466; Padias, B. A.; Hall, H. K., Jr.; Tomalia, D. A.; McConnell, J. R. J. Org. Chem. 1987, 52, 5305; Tomalia, D. A.; Hedstrand, D. M.; Ferritto, M. S. Macromolecules 1991,24, 1435. Mekelburger, H.-B.; Rissanen, K.; Vogtle, F. Chem. Ben 1993,126,1161. Mekelburger, H.-B.; Vogtle, R Supramolec. Chem. 1993, 7,187. Mekelburger, H.-B.; Jaworek, W.; Vogtle, F Angew. Chem., Int. Ed. Engl. 1992, J7, 1571. Kadei, K.; Moors, R.; Vogtle, F Chem. Ben 1994, 727. In press. Whitesides, G. M.; Mathias, J. R; Seto, C. T. Science 1991,254,1312. Vogtle, F ; Gross, J.; Seel, C ; Nieger, M. Angew. Chem. 1992,104, 1112; Angew. Chem., Int. Ed. Engl. 1992,31,1069. Nagasaki, T; Ukon, M.; Arimori, S.; Shinkai, S. J. Chem. Soc, Chem. Commun. 1992, 698. Nagasaki, T; Kimura, O.; Ukon, M.; Arimori, S.; Hamachi, I.; Shinkai, S. J. Chem. Soc, Perkin Trans. 11994, 75. Womer, C ; Mulhaupt, R. Angew. Chem. 1993, 705,1367; Angew. Chem., Int. Ed. Engl. 1993,31, 1306. de Brabander-van den Berg, E. M. M.; Meijer, E. W. Angew. Chem. 1993, 705, 1310, Angew. Chem., Int. Ed. Engl. 1993,31,1308. Tietze, L. F ; Eicher, T. Reaktionen und Synthesen. Thieme, Stuttgart, 1981, Vol. 58, p. 69. Salen is the acronym for A^,yV'-bis(salicylidene)ethylenediamine. Hammerschmidt, R. F ; Broman, R. F J. Electroanal. Chem. 1979, 99, 103; Kapturkiewicz, A.; Behr, B. Inorg. Chim. Acta 1983,69,247; Eichhom, E.; Rieker, R.; Speiser, B. Angew. Chem. 1992,104,1246. V^QSUB.O.J. Chem. Soc 1954, 395. Newkome, G. R.; Lin, X.; Weis, C. D. Tetrahedron Asymmetry 1991, 2,957. Lapierre, J. M.; Skobridis, K.; Seebach, D. Helv. Chim. Acta 1993, 76, 2419. Rozenberg, V.; Kharitonov, V.; Antonov, D.; Sergeeva, E.; Aleshkin, A.; Ikonnikov, N.; Orlova, S.; Belokon, Y. Angew. Chem. 1994,106,106; Angew. Chem., Int. Ed. Engl. 1994,33,91. Reich, H. J.; Cram, D. J. J. Am. Chem. Soc 1969, 91, 106; Krohn, K.; Rieger, H.; Hopf, H.; Barrett, D.; Jones, P G.; Doring, D. Chem. Ben 1990, 72i, 1729. Moors, R. Ph. D. Thesis, University of Bonn, 1994. Roy, R.; Zanini, D.; Meunier, S. J.; Romanowska, A. J. Chem. Soc, Chem. Commun. 1993,1869.

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IONIC DENDRIMERS AND RELATED MATERIALS

Robert Engel

I. INTRODUCTION A. The Structural Concept of Dendrimers B. The Structural Types of Charged Dendrimers 11. DENDRIMERS CONTAINING COMPLEXED TRANSmON-METALIONS A. A Rationale for Preparation and Investigation B. Multinuclear Dendrimers Based on Bipyridylpyrazine Bridging Ligands C. Multinuclear Linear Metal Arrays with Other Bridging Ligands III. AMMONIUM- AND PHOSPHONIUM-CENTERED DENDRIMERS IV. SURFACE-CHARGED DENDRIMERS V. IONIC MOLECULAR TRAINS AND CATENANES NOTES REFERENCES Advances in Dendritic Macromolecules Volume 2, pages 73-99. Copyright © 1995 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-939-7

73

74 74 75 76 76 76 84 87 93 94 96 96

74

ROBERT ENGEL

I.

INTRODUCTION

A. The Structural Concept of Dendrimers Beginning with the discovery that atoms bind to form molecules with discrete atomic ratios and with regular geometric forms, molecular topology has been a topic of fascination for chemists. They have been stimulated continually to new levels of accomplishment by contemplating the architectural possibilities for covalently bound atoms, such as the potential existence of enantiomeric and diastereoisomeric species bearing stereogenic tetrahedral and trigonal bipyramidal sites, or the nonbonded yet definitively associated components of catenanes, and the preparation of representative examples expressing these topological characteristics. In recent years, a particular topic of architectural interest has been the design and construction of dendrimeric molecules. Dendrimeric molecules, also known as cascade molecules or Starburst* molecules, represent an architectural class of macromolecules different from both ordinary polymers of the linear or cross-linked classes and biopolymers of the carbohydrate or peptide classes. The construction of cascade molecules in a systematic divergent manner has its origins in the preparation of a series of branched polyamines more than a decade ago.^"^ Starting from a primary amine, each of the available hydrogens on nitrogen was replaced by an alkyl group

R--NH2 I

H2C=CHCN "

CH2CH2CN

reduction

R-N CH2CH2CN Do

H2C=CHCN -*

Do'

CH2CH2CH2N(CH2CH2CN)2 R-N 'CH2CH2CH2N(CH2CH2CN)2 Di

reduction

CH2CH2CH2NH2 R-N^ ^CH2CH2CH2NH2

CH2CH2CH2N(CH2CH2CH2NH2)2 • R-N^ 'CH2CH2CH2N(CH2CH2CH2NH2)2 Di'

Scheme 1.

Ionic Dendrimers

75

through a Michael-type addition using acrylonitrile. Reduction of the two new terminal cyano groups to primary amino groups provided new sites for extension in two directions each, as illustrated in Scheme 1. As the name implies, dendrimers have incorporated into their structures a regular branching aspect which is not present in typical polymeric materials. A general notation system has been developed^ to describe these branched systems. Referring to Scheme 1, the initiator core I (the primary amine) possesses a branching capability (A^^) of 2 (two arms may be attached with capability for continuing reaction). Initial elaboration of the initiator core produces the dendrimer (DQ and DQ') of generation zero (GQ). The termini of H^ possess a branching capability {N^ of 2, and continued elaboration yields the first-generation (Gj) dendrimer Di(andD/). The characteristic of regular and repetitive branching within a molecular species has caught the attention of chemists in recent years to imagine a wide range of macromolecular structures and to consider the potential of such species for numerous applications. Although initial efforts in the design and preparation of dendrimers were concemed with structures which may be categorized as classically neutral/organic, and work continues at an increasing pace with such materials, the preparation and investigation of dendrimers bearing charged sites within their structures have begun. It is with the efforts to date in this latter area that this review is concemed, along with the preparation and investigation of charged structures technically not dendrimeric in nature, but closely associated. B. The Structural Types of Charged Dendrimers The variety of charged dendrimeric species, which has been investigated, can be divided according to the location and nature of the charged site within the dendrimer structure. A major category of structure, which has invited attention owing to its potential for applications in several areas of endeavor, is that in which transition-metal ions are regularly associated with branched polydentate ligands. Such species allow the incorporation of large numbers of transition-metal ions into discrete molecules, which have the potential to exhibit intriguing electrochemical and photophysical characteristics. More in line with classical organic structures are the dendrimers which incorporate cationic ammonium or phosphonium sites within the cova-

76

ROBERT ENGEL

lent structure of the dendrimerand those dendrimers bearing anionic sites at the termini of the branches, i.e., at the surface of the elaborated dendrimer. These materials are synthesized using ordinary organic chemical techniques and can be prepared as definitive structures capable of purification and characterization. Several areas of application are evident for such materials. Finally, there has emerged a series of structures, similar in nature to the catenanes, in which cationic ammonium sites are present within the components. These materials hold potential as building blocks for supramolecular species with a variety of novel characteristics and applications. II. DENDRIMERS CONTAINING COMPLEXED TRANSITION-METAL IONS A. A Rationale for Preparation and Investigation

Early recognition of the photoinduced redox characteristics of ruthenium(II) complexes of the bidentate ligand 2,2'-bipyridine^ has piqued the curiosity of physical and inorganic chemists, leading to the investigation of the numerous structural and photophysical aspects of the parent and structurally related species.^^^ One major effort in this regard has been the attempt to investigate such complexes containing several ruthenium(II) sites held in particular spatial arrays^*'^^ and in matrices other than classical aqueous solution, such as near the surface of porous Vycor glass.^^"^^ An intriguing extension of this effort has been the incorporation of ruthenium(II) sites in dendrimeric species and the investigation of the characteristics thereof. B. Multinuclear Dendrimers Based on Bipyridylpyrazine Bridging Ligands

The construction of dendrimers bearii^g transition-metal ion sites, as with the synthesis of any other dendrimeric species, requires the initial development of a building component capable of branching and/or extending a core unit. WJiile conceptually any simple bridging ligand could serve for the construction of dendrimers using a transition-metal center with an octahedral array of ligands, bridging bidentate ligands are desired for stability. A particul^ly useful bidentate ligand building

Ionic Dendrimers

77 —1 2+

component for transition-metal ion dendrimers is to be found in 2,3bis(2-pyridyl)pyrazine (1) (DPP), the preparation of which was first reported by Goodwin and Lions.^^ This tetranitrogen compound bears a critical structural feature, allowing it to serve simultaneously as a bidentate ligand for two associated transition-metal ions. The ligand 1 was, in fact, used, prior to the construction and investigation of transition-metal dendrimers, as a coordinating agent for "monomeric" ruthenium(n) species 2^^ and 3.^^ The use of 1 as a bridging ligand for the preparation and subsequent spectroscopic and electrochemical investigation of diruthenium(n) complexes, such as 4,^^'^^ anticipated its use for dendrimer construction.

78

ROBERT ENGEL 8+

5 M= Os 6 M = Ru

Extension beyond the dimetallic stage for complexes constructed using 1 was accomplished with both a ruthenium(II)^^ and an osmium(II) core in octahedral coordination.^^ The peripheral metal sites in each complex (5 and 6) were occupied by ruthenium(n) species, each peripheral site capped by a pair of 2,2'-bipyridyl ligands. (In all of the preparations noted here, the bridges of the multinuclear complexes were formed by simple displacement of monodentate chloride or pyridine ligands by the bridging species which was bidentate in nature toward each metal center.) In addition to 2,2'-bipyridyl, o-phenanthroline (7) and 2,2':6',2''-terpyridine (8) were used.

79

Ionic Dendrimers

10 4+

C 11

N

N=\

N

N—^ 12

A source of potential difficulty in evaluating the electrochemical and photophysical characteristics of the transition-metal-centered dendrimers is the presence of stereogenic centers undefined in their nature. While the potential difficulties for interpreting their characteristics are assumed to be relatively minor, detailed knowledge of their structures is severely hindered by the lack of definition in this matter. Although the resolution into their enantiomeric forms of octahedral metal complexes bearing bidentate ligands was accomplished at an early stage,^^ the application of such materials for the preparation even of dinuclear complexes was greatly delayed.^^ Only recently has the preparation of a particular stereoisomer of a diruthenium complex been accompUshed by the resolution of the bis-o-phenanthroline complex (9). The subsequent use of the optically active material in a stereoselective reaction with 2,5-bis(2-pyridyl)pyrazine (10) yielded the dinuclear com-

80

ROBERT ENGEL

plex 11 directly in approximately 90% optical purity. Higher optical purities are obtained upon recrystallization.^^ The selection of bridging and nonbridging bidentate ligands was wisely made in this study such that each of the two possible modes of adding the bridging ligand would yield the same adduct enantiomer. Optically active diruthenium complexes have been prepared as well through the use of 2,2'-bipyrimidyl (12), as the bridging bidentate ligand.^^ Using the same fundamental approach as has been noted for the preparation of dinuclear complexes, larger transition-metal ion-centered dendrimers have been constructed. In addition to the tetranuclear species already noted,^^'^^ mono-, di- and triruthenium centered species have been prepared using the substituted tris(2,2'-bipyridyl) bridging ligand 13. Ruthenium(n) has been complexed to each of the bidentate sites on the arms of 13, each ruthenium capped with two additional 2,2'-bipyridyl ligands.^^ Each of these complexes, in particular the triruthenium species 14, is capable of further elaboration to higher generations of dendrimer structure by the introduction of potential bridging capping ligands on the peripheral metal sites, although this has not to date been reported. Although high-efficiency electronic energy transfer has been observed between uncoordinated arms of the monoruthenium complex of ligand 13 and the metal site, no evidence has been found of spectroscopic, photophysical or electrochemical interaction between metal sites of 14.^^ Studies have also been made of the process of energy transfer within complexes of 13 bearing ruthenium(II) and osmium(n) centers.^^ The conformation of 14 is assumed to be that shown, with maximal distance between the charged metal sites. Molecular modeling studies might be of some use in considering the relationships of the possible conformations. Of course, the investigated material, 14, is a mixture of two diastereoisomeric pairs of enantiomers, the ratio of diastereoisomeric forms unknown. Although the metal bridging sections of 14 do not appear to allow interaction of the metal sites, it is rather different with complexes related to the tetrametallic species 5 and 6 noted earUer. Not only does energy transfer occur among the metallic sites, but such transfer can be channeled in particular directions by the judicious choice of bridging and capping ligands. Noting that the bridging ligand 2,5-bis(2pyridyl)pyrazine (10) is more easily reduced than the isomeric bridging ligand 2,3-bis(2-pyridyl)pyrazine (1), and that the capping ligand 2,2'-

C02CH2CH3

CH3CH202C

C02CH2CH3 13

CO2CH2CH3

CH3CH2O2C

bpy = 2,2'-bipyriciyl

14

81

6+

82

ROBERT ENCEL CL2

15

15

BLn = Bridging Ligand CLn = Capping Ligand 17

bipyridyl (15) is less readily reduced than the capping ligand 2,2'-biquinolyl (16), particular placement of osmium(II) and ruthenium(n) sites with bridging and capping ligands allows preselecting the site of energy absorption and the paths of energy transfer within complexes of the general type shown schematically as IIP Further elaborated dendrimers based on ruthenium(II) and osmium(n) metallic centers, using disubstituted pyrazines as bridging ligands, have been constructed bearing four,^"^ six,^^'^^ and ten^''^^ metal ions. The photophysical characteristics of these materials have been investigated, and intense absorptions have been found both in the ultraviolet region, attributable to ligand-centered transitions, and in the visible region, attributable to metal-to-ligand charge-transfer transitions. The complexes also exhibit luminescence derived from the lowest metal-to-ligand charge-transfer excited state. Transmission of energy between metal sites within a given complex is in accord with the concepts found for the smaller tetrametallic species.^^ The electrochemical behavior of the entire range of complexes has also been investigated and dependencies upon the specific metals and ligands present in the several types of positions have been noted.^"^'^^'^^ Most recently, a dendrimer bearing a total of 22 ruthenium(n) sites, three generations of dendritic layers with each branching ruthenium(n) site bidirectional about a tridirectional core ruthenium(II) site, has been prepared using 2,3-bis(2-pyridyl)pyrazine (1) as the bridging ligand and 2,2'-bipyridyl (15) as the termini-capping ligands.^^ The neutral complex salt includes a total of 44 associated hexafluorophosphate anions, and

84

ROBERT ENCEL

exhibits photophysical and electrochemical behavior in accord with that noted for lower generation materials. The preparation and characteristics of this and related materials have recently been reviewed.^^ It should be noted that all of the dendrimeric materials described above, bearing more than two metallic centers, have been prepared using a ruthenium(n) complex that is a mixture of diastereoisomers.^^ Although the original material is composed of 92% of one diastereoisomer, the elaboration to each successive generation introduces additional stereogenie centers resulting in an extremely complex mixture of isomers of unknown proportion. It is assumed that this fact is relatively unimportant for the photophysical and electrochemical characteristics of the materials. However, it would be of interest to note any differences in characteristics for those diastereoisomers whose through space distances of metallic centers differ greatly although their through bond (through ligand) distances are the same. One intriguing system, 18, which avoids any stereochemical ambiguities and incorporates 12 ruthenium(II) sites into thefirst-generationlevel of an arborol, has recently been reported.^^ Building on a previously reported nonionic cascade molecule base,^^ tridentate tripyridyl coordinating sites were added for coordination with ruthenium(II). These were capped with an additional tridentate tripyridyl ligand bearing a triply branching arm suitable for continued dendrimer elaboration. Ruthenium(II) has also been used in the construction of a bidirectional core species 19 using the capping ligands of 18.^^ The ligands, involved in coordination with transition-metal ions in these dendrimeric species, bring to mind potential metal-complexing agents in the aza crown series. Although the aza crowns by themselves are not charged, their potential in metal-ion binding for the construction of charged dendrimers is evident. Of particular interest are those recently synthesized in which up to nine azacrown units are joined in dendrimeric fashion as a "crowned" arborol.^^ The construction of this material allows for elaboration to higher dendrimer generations incorporating additional azacrown units and greater metal ion binding potential. C. Multinuclear Linear Metal Arrays with Other Bridging Ligands

Stereochemical questions concerning the structures of previously noted polymetallic complexes, using dipyridylpyrazine bridging ligands.

Ionic Dendrimers

85

21

20

22

can be obviated through the use of substituted tridentate ligands related to 2,2':6^2"-terpyridine (8). Substitution of a second tridentate coordination function at the 4-position of the central ring generates a bridging ligand which allows the construction of a rigid linear "string" of coordinated metalUc centers. Two such ligands, 20 and 21, have been synthesized and used for the construction of short "strings" of ruthenium(II) centers, examples of which are shown as 22 and 23.^^^^ The construction of a dendrimeric structure, rather than a Unear one, requires a point of branching on the connecting ligand. This is provided with the connecting ligand l,3,5-tris(2,2':6,2''-terpyridin-4'-yl)benzene

86

ROBERT ENGEL

24

^24) 34-36 w^iiie iQ (jate 24 has been used only as a core structure connecting a total of three ruthenium(II) centers, it holds the potential to serve for the construction of much larger dendrimeric arrays of metalcentered complexes. A variety of ruthenium(II) complexes has been prepared using 20, 21 and 24 that bear electron-donating or electronwithdrawing substituents on the capping ligands.^^^^ Electrochemical activity and absorption spectra havebeen measured for these complexes. Linear multinuclear structures have also been constructed using cyano bridging. The bridge differs from those previously mentioned in that it is monodentate with regard to each of the metal centers involved.^^ In these complexes again involving ruthenium(n), unlike the structures previously noted, the two metal centers, linked by a particular bridge, are necessarily bound differently to that bridge, one through carbon and the other through nitrogen. This allows investigation of differential oxidation of the sites and the processes of energy transfer between metal centers. The capping ligand in each instance is a nonbridging cyano ligand, as shown in 25. Photophysical investigations demonstrated that the transfer of energy between the metal centers is very efficient in these complexes. Judicious choice of nonbridging ligands allows the transfer of energy in a controlled direction.^^ Construction of short chains, bearing a rhenium center at one end, has also been accomplished, as with 26. Monolayer coverage of a TiOj surface with the polyruthenium(n) and ruthenium/rhenium complexes has been investigated for constructing semiconductor materials which would convert hght energy into electrical current.^^

87

Ionic Dendrimers 2+

2PF6-

25 2+

"jy 26

ill. AMMONIUM- AND PHOSPHONIUM-CENTERED DENDRIMERS Dendrimers, wherein amino-linked nitrogen serves as the core and/or branch points of the elaborated structures, have been available for some time."^'^^^^ More recently, dendrimers have been constructed in which nitrogen is present in a quatemary ammonium ion form at both core and

ROBERT ENGEL

88

R-X .

-CH2OCH3

+ R _ p . ^.

X^CH20CH3

27 4X" (CH3)3SiI

27 -CH2OCH3 3

/3

Scheme 2.

branch sites, as well as dendrimers in which phosphorus is present in the form of quaternary phosphonium ions. These species have been synthesized in a standard, specific approach for the defined addition of successive generations. Dendrimers, in which phosphonium ion sites were incorporated, were prepared by using tri(p-methoxymethyl)phenylphosphine (27) for the construction of both the core and branch points, as shown in Scheme 2 42-45 Alkylation or arylation of the parent 27 yielded the core for the dendrimer. Subsequent generations were introduced by repetitive sequences of two reactions, the one-step facile deblocking of the benzyUc ether linkages with concomitant formation of the reactive benzylic iodide, followed by dendrimer elaboration by reaction with 27. In this manner "balloon" dendrimers of the type shown as 28 were generated with a variety of alkyl groups as the "tail", along with "star" type dendrimers, 29. These materials exhibited significant solubility in a wide

R-P-

C H 2 - P 4 { / - C H 2 - P -

13X-

-CH2OCH3

28

CH2-P4/V-CH2-P-

17 X-

-CH2OCH3 3 J

29

Ionic Dendrimers

89

H2O2 27

.

Q^p. ; ^ > - C H 2 0 C H 3

(CH3)3SiI

27

Cl3SiH >-CH20CH3

3X-

;s^^^-CH2P-K^CH20CH3

3X-

0=P- i.

j)-CH2P-K.

30 NaAuCU

31

ClAu-P- ^ ^ ^ - C H 2 P 4 Y / - C H 2 0 C H 3

ax-

Scheme 3.

range of organic as well as aqueous media through the fourth generation. They also showed distinctive signals in the ^^P NMR spectrum for each generation of phosphonium ion site. Dendrimers, bearing cores other than the phosphonium ion type, have been generated from the same fundamental building block, 27. Oxidation of 27 leads readily to the corresponding phosphine oxide upon which elaboration of the phosphonium ion dendrimer structure can be accomplished using the same sequence of reactions as the elaboration to form 28 or 29. The resultant phosphine oxide/phosphonium ion dendrimer 30 is capable of undergoing reduction at the core to generate a phosphine/phosphonium ion dendrimer 31 which exhibits normal phosphine chemistry at the core site, including complexation with metal ions, as shown in Scheme 3."^'"^^ Further, the phosphonium ion core of the "star" tetraarylphosphonium ion is subject to the addition of a fifth aryl group at phosphorus to generate a pentaarylphosphorane 32. This material can be elaborated to higher generations of phosphorane/phos-

90

ROBERT ENGEL CH2OCH3

CH2OCH3

CH3OCH2

CH2OCH3

CH2OCH3 32

-^CHa^Q

5X-

33

phonium ion dendrimer using the same sequence of reactions previously noted. The phosphorane/phosphonium ion dendrimer 33 is unique in that is bears a pentadirectional monoatomic core site, albeit an electrically neutral one. Nitrogen holds the potential to serve in much the same capacity as does phosphorus for constructing ionic dendrimers. The use of triethanolamine as the fundamental building block for ammonium ion based dendrimers has been explored."^^ Alkylation of triethanolamine with a variety of haloalkanes (Scheme 4) provides cores for "balloon" and "star" ionic dendrimers with a wide range of physical characteristics."^^"*^ For example, although the core structures for the octadecyl alkylated 34d and 2-hydroxyethyl alkylated 34a species are widely different in their melting points, 34d being significantly lower in melting point than 34a, the differently alkylated materials vary relatively little in their melting

91

Ionic Dendrimers N(CH2CH20H)3 + R-X

—•

R-N(CH2CH20H)3 X34a-d

TsCl N(CH2CH20H)4

+ X- N(CH2CH20H)3 N(CH2CH20Ts)4 .

^ + 3 ^ N[CH2CH2N(CH2CH20H)4]4

34a

35a

R-N(CH2CH20H)3

X- TsCl

+ XR-N(CH2CH20Ts)3

N(CH2CH20H)3

4XR-N[CH2CH2N(CH2CH20H)3]3

34b-d

35a

35b-d* • TsCl

2. N(CH2CH20H)

+ + + 17 XN{CH2CH2N[CH2CH2N(CH2CH20H)3]3}4

l.TsCl 2. N(CH2CH20H)

36a

+ + + + 65 XN(CH2CH2N{CH2CH2N[CH2CH2N(CH2CH20H)3]3}3)4 37a

^^^'^

l.TsCl + + + 13 x* 2. N(CH2CH20H)' R-N{CH2CH2N[CH2CH2N(CH2CH20H)3]3}3

.TsCl 2. N(CH2CH20H)

36b-d

+ + ' + + 40 XR-N(CH2CH2N{CH2CH2N[CH2CH2N(CH2CH20H)3]3}3)3 37b-d

a R = CH2CH2OH b R = CH3 cR = CH2C6H5 d R = Ci8H37

Scheme 4.

points at the third generation of elaboration, 37d and STa."*^ Further, although the hydroxyl-terminated dendrimers exhibit high aqueous solubility with relatively low solubiUty in organic media other than low molecular weight alcohols, alkylated, chlorinated or acylated species, such as 38, exhibit significant organic solubility at the termini with severely decreased aqueous solubility."^^ Apparently, solubiUties of the ionic dendrimers can be programmed on the basis of the termini (surface) exposed to the solvent. + + + / = \ N{CH2CH2N[CH2CH2N(CH2CH202C--^ /—CU^ 38

17X)3]3}4

92

ROBERT ENGEL /—\ 39 •'^

l.HOCHzCHjCl

rT\+y\

2.TsCl 3.Dabco(39)

^

^

+/

\+/\

"^ ^ / ^^^. 4TsO

+/~Z\ ^

I.HOCH2CH2CI ^

2.TsCl 3. Dabco (39)

8TsO' 40

Scheme 5.

Nominally linear arrays of poly ammonium ion systems have also been produced using a repetitive sequence of alkylation/tosylation/displacement based on a bicyclic diamino structure, l,4-diazabicyclo[2.2.2]octane (Dabco*) (39)."*^ Using this approach, "strings", such as 40, can be prepared as shown in Scheme 5. Ammonium ion dendrimers of both the "balloon" and "string" types have been constructed as attachments to polymer chains which are insoluble in both organic and aqueous media.'*^'*^ Using triethanolamine or Dabco, the pendant benzylic chloride sites along the backbone of a Merrifield peptide resin have been alkylated. Elaboration of the resultant ionic dendrimer core sites, using the approaches noted previously, produces polymers bearing high concentrations of covalently bound positively charged sites with relatively free floating anions readily available for exchange. Rapid and reversible exchange of monoanions and dianions is possible with these materials, indicating that the anions are not strongly intercalated within the arms of the dendrimers. This is in accord with molecular modeling studies"^^ of triethanolamine ammonium dendrimers which indicate that halide ions are energetically in more favorable positions near the surface (termini) of the structure than intercalated among the arms, although they would be closer to the cationic sites in the latter situation. The Merrifield resin-based polyammonium ion species are closely related to a series of polyphosphonium ion materials reported to be biocidal toward several strains of bacteria."^^'^^ These materials were not elaborated about the phosphonium ion sites, but rather were produced by the polymerizing or copolymerizingp-vinylbenzyltributylphosphonium salts. The antibacterial activity of such materials, resultingfi*ombinding

Ionic Dendrimers

93

to the cell surface, holds promise for further applications of the cationic dendrimers. IV. SURFACE-CHARGED DENDRIMERS Surface-charged dendrimers are those in which charges are located only at the termini of the elaborated branches, while the core and branch system are uncharged. In general, the species of this category, which have been constructed, have involved anionic sites, specifically carboxylate anions, at the termini of the branches. Dendrimers described as "unimolecular micelles"^^'^^ have been constructed for which the terminal functional group may be varied among several possibilities including amino, carboxylate ester, and carboxylate anion.^^'^"^ These dendrimers have been prepared by a sequence of reactions involving ammonia as the core site and primary amino groups as the branch points, each undergoing Michael-type addition reactions with acrylate esters for elaboration of the branching structure. Extension of the individual chains to introduce a new branch point (primary amino site) is accomplished by ester-amide conversion. Termini of carboxylate anions are generated either by basic hydrolysis of terminal ester linkages after elaboration by a Michael-type addition reaction, or by basic hydrolysis of terminal ester groups formed by alkylation of primary amino sites with methyl chloroacetate. These sequences are illustrated in Scheme 6. The investigation of the physical characteristics of such dendrimers bearing terminal carboxylate groups has constituted an extremely active area of endeavor and continues to be such. Several studies concerned with defining the size and shape of dendrimers, constructed as noted in Scheme 6, have been reported,'^'*^'^^'^^ as have investigations of the conditions of crowding at the reactive termini which prevent complete reactivity for continued elaboration. Using measurements of hydrodynamic volumes, it is noted that the dendrimers expand in three dimensions such that they maintain a constant terminal-group surface area while the number of branch points and linker units accumulates in each succeeding generation.^^ Investigations of the photophysics of dendrimers bearing anionic surfaces interacting with octahedral ruthenium(II) complexes have yielded data indicating that the nature of binding depends on the degree of elaboration of the dendrimer. For

94

ROBERT ENCEL l.H,C=CHC02CH3 ^ =>

:NH3

:N(CH2CHoCONHCHoCH'>NH2)3

repea.reagen. sequence n times •

2. H2NCH2CH2NH2 l.H2C=CHC02CH3^,.,^— :N(

NHCH2CH2C02Na)3

2. NaOH :N(

NH2)3

1. CICH2CO2CH3

(n+i) generation :N(

NHCH2C02Na)3

dendrimers elaborated to only relatively few generations, the ruthenium(II) complex species associate at a greater distance from the dendrimer surface than they do with higher generation species.^^"^^ Finally, anionic surface dendrimers have been constructed as "balloons" attached along a Merrifield resin backbone."^^ Using an elaboration method based on the diethyl malonate and triethyl methanetricarboxylate procedures previously described,^^ dendrimers bearing double and triple branching hydrocarbon arms were prepared with carboxylate termini. These dendrimers are insoluble in all ordinary solvents and serve as high-capacity cation-exchange materials. V. IONIC MOLECULAR TRAINS AND CATENANES More than thirty years ago,^^ the first intentional preparation of a catenane provided significant imaginative impetus for further adventures in the realm of chemical topology. While catenanes themselves are not branched species, as is implied by the terms dendrimers or cascade molecules, they are materials which incorporate some of the most interesting of supramolecular effects.^^ Recently, using the tetracationic cyclophane 41 as a fundamental building block, several [2]- and [3]catenanes bearing charged rings have been synthesized.^^^"^ Examples of these materials are shown as 42 and 43. In addition to their synthesis and characterization, the ordering of the aromaticringsof the linked (but not covalently bound) rings, relative to each other in the catenane structures, has been investigated using a variety of techniques. It is anticipated that the investigation of the self-assembling characteristics of the components of these materials will

Ionic Dendrimers

95

42

41

8PF.

43

lead to a much clearer understanding of supramolecular self-assembling processes in general. A structurally intriguing material has also been reported recently in which networks of interlocking rings, incorporating manganese(n), copper(II), and pyridinium sites, are constructed to provide a molecularbased magnetJ^ Net electronic spin is provided by pendant nitrosyl functionaUties as well as the metal sites, resulting in a material which behaves as a magnet below 22.5 K. The capability for extending the interlocking rings to great distances in three dimensions and incorporating further electronic spin entities holds promise for constructing even better molecular magnetic systems using supramolecular concepts. Finally, note should be made of a series of catenanes employing rings which are essentially azacrowns.^^^^ While these catenanes are not by themselves charged, they can be constructed with coordinated metal ions, such as copper(I), to produce polycationic species, which exhibit intriguing physical characteristics.

96

ROBERT ENGEL

NOTES *STARBURST is a registered trademark of The Dow Chemical Company. ^Dabco is a registered trademark of Air Products and Chemicals, Inc.

REFERENCES 1. Buhleier, E.; Wehner, W.; V5gtle, F. Synthesis 1978,155. 2. Vogtle, R; Weber, E. Angew. Chem., Int. Ed. Engl. 1979,18,753. 3. Mekelburger, H.-B.; Jaworek, W.; Vogtie, F. Angew. Chem., Int. Ed. Engl. 1992, J7,1571. 4. Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III. Angew. Chem., Int. Ed. Engl. 1990,29,138, and references therein. 5. Gafney, H. D.; Adamson, A. W. J. Am. Chem. Soc. 1972,94, 8238. 6. Bock, C. R.; Meyer, T. J.; Whitten, D. G. J. Am. Chem. Soc. 191A, 96, Al 10. 7. Navon, G.; Sutin, N. Inorg. Chem. 1974,13, 2159. 8. Kalyanasundaram, K. Coord. Chem. Rev. 1982,46,159. 9. Creutz, C ; Sutin, N. Inorg. Chem. 1976, 75, 496. 10. Brewer, K. J.; Murphy, W. R., Jr.; Spurlin, S. R.; Petersen, J. D. Inorg. Chem. 1986, 25, 882. 11. Braunstein, C, H.; Baker, A. D.; Strekas, T. C ; Gafney, H. D. Inorg. Chem. 1984, 23, 857. 12. Murphy, W. R., Jr.; Brewer, K. J.; Gettliffe, G.; Petersen, J. D. Inorg. Chem. 1989, 28,81. 13. Kennelly, T; Gafney, H. D.; Braun, M. J. Am. Chem. Soc. 1985,107,4431. 14. Shi, W.; Gafney, H. D. J. Am. Chem. Soc. 1987,109, 1582. 15. Fuchs, Y; Lofters, S.; Dieter, T.; Shi, W.; Morgan, R.; Strekas, T. C ; Gafney, H. D.; Baker, A. D. J. Am. Chem. Soc. 1987,109, 2691. 16. Shi, W.; Gafney, H. D. 7. Phys. Chem. 1988, 92, 2329. 17. Goodwin, H. A.; Lions, F J. Am. Chem. Soc. 1959,81, 6415. 18. Campagna, S.; Denti, G.; Sabatino, L.; Serroni, S.; Ciano, M.; Balzani, V. J. Chem. Soc, Chem. Commun. 1989,1500. 19. Bailar, J. C , Jr. Coord. Chem. Rev. 1990,100,1, and references therein. 20. Hua, X.; von Zelewsky, A. Inorg. Chem. 1991,30, 3796. 21. De Cola, L.; Belser, P; Ebmeyer, F; Barigelletti, F; Vogtle, F; von Zelewsky, A.; Balzani, V. Inorg. Chem. 1990,29,495. 22. De Cola, L.; Barigelletti, F; Balzani, V.; Belser, P; von Zelewsky, A.; Seel, C ; Frank, M.; Vogtle, F Coord Chem. Rev 1991, 111, 255. 23. Denti, G.; Serroni, S.; Campagna, S.; Ricevuto, V; Balzani, V. Coord. Chem. Rev. 1991, 111, 227. 24. Denti, G.; Campagna, S.; Sabatino, L.; Serroni, S.; Ciano, M.; Balzani, V. Inorg. Chem. 1990,29,4750. 25. Campagna, S.; Denti, G.; Serroni, S.; Ciano, M.; Balzani, V. Inorg. Chem. 1991, 30, 3728.

Ionic Dendrimers

97

26. Denti, G.; Serroni, S.; Campagna, S.; Ricevuto, V.; Juris, A.; Ciano, M.; Balzani, V. Inorg, Chim. Acta 1992,198-200, 507. 27. Serroni, S.; Denti, G.; Campagna, S.; Ciano, M.; Balzani, V. J. Chem. Soc, Chem. Commun, 1991,944. 28. Denti, G.; Campagna, S.; Serroni, S.; Ciano, M.; Balzani, V. J. Am. Chem. Soc. 1992,114, 2944. 29. Serroni, S.; Denti, G.; Campagna, S.; Juris, A.; Ciano, M.; Balzani, V. Angew. Chem., Int. Ed. Engl. 1992,31,1493. 30. Dagani, R. Chem. Eng. News 1993, 71(5), 28. 31. Newkome, G. R.; Cardullo, R; Constable, E. C; Moorefield, C. N.; CargillThompson, A. M. W. J. Chem. Soc, Chem. Commun. 1993,925. 32. Newkome, G. R.; Lin, X. Macromolecules 1991,24, 1443. 33. Nagasaki, T; Ukon, M.; Arimori, S.; Shinkai, S. J. Chem. Soc, Chem. Commun. 1992, 608. 34. Constable, E. C; Cargill-Thompson, A. M. W. J. Chem. Soc, Chem. Commun. 1992, 617. 35. Constable, E. C; Cargill-Thompson, A. M. W. /. Chem. Soc, Dalton Trans. 1992, 3467. 36. Collin, J.-R; Lain^, R; Launay, J.-R; Sauvage, J.-R; Sour, A. J. Chem. Soc, Chem. Commun. 1993,434. 37. Bignozzi, C. A.; Roffia, S.; Chiorboli, C; Davila, J.; Indelli, M. T.; Scandola, P. Inorg. Chem. 1989,28,4350. 38. Bignozzi, C. A.; Argazzi, R.; Chiorboli, C; Roffia, S,; Scandola, F. Coord. Chem. Rev. 1991,111,261. 39. Tomalia, D. A.; Hall, M.; Hedstrand, D. M. J. Am. Chem. Soc 1987,109,1601. 40. Hall, H. K., Jr.; Polls, D. W. Polymer Bull. 1987,17,409. 41. Naylor, A. M.; Goddard, W. A., Ill; Kiefer, G. E.; Tomalia, D.A.J, Am. Chem. Soc 1989, 111, 2339. 42. Rengan, K.; Engel, R. / Chem. Soc, Chem. Commun. 1990, 1084. 43. Rengan, K.; Engel, R. J. Chem. Soc, Perkin Trans. 11991,987. 44. Engel, R.; Rengan, K.; Chan, C.-s. Phosphorus, Sulfur, and Silicon 1993, 77, 221. 45. Engel, R.; Rengan, K.; Chan, C.-s. Heteroatom Chem. 1993,4, 181. 46. Rengan, K.; Engel, R. J. Chem. Soc, Chem. Commun. 1992, 757. 47. Engel, R. Polymer News 1992,17, 301. 48. Torres, N.; Cherestes, A.; Engel, R. Unpublished results of this laboratory. 49. Kanazawa, A.; Ikeda; T; Endo, T. J. Polym. Sci. Part A - Polym. Chem. 1993, 31, 1441. 50. Kanazawa, A.; Ikeda, T; Endo, T J. Polym. Sci. Part A - Polym. Chem. 1993,31, 1467. 51. Newkome, G. R.; Moorefield, C. N.; Baker, G. R.; Saunders, M. J.; Grossman, S. H. Angew. Chem., Int. Ed. Engl. 1991,30,1178. 52. Hawker, C. J.; Wooley, K. L.; Pr6chet, J. M. J. J. Chem. Soc, Perkin Trans. 11993, 1287. 53. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, R Polym. J. 1985,17,117.

98

ROBERT ENGEL

54. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, R Macwmokcules 1986, 79, 2466. 55. Tomalia, D. A.; Hall, M.; Hedstrand, D. M. J. Am. Chem. Soc, 1987,109,1601. 56. Tomalia, D. A.; Berry, V.; Hall, M.; Hedstrand, D. M. Macwmokcules 1987, 20, 1164. 57. Moreno-Bondi, M.; Orellana, G.; Turro, N. J.; Tomalia, D. A. Macwmokcules 1990,25,910. 58. Caminati, G.; Turro, N. J.; Tomalia, D. A. J, Am. Chem. Soc. 1990, 772, 8515. 59. Turro, N. J.; Barton, J. K.; Tomalia, D. A. Ace. Chem. Res. 1991,24, 332. 60. Gopidas, K. R.; Leheny, A. R.; Caminati, G.; Turro, N. J.; Tomalia, D. A. J. Am. Chem. Soc. 1991, 775, 7335. 61. Newkome, G. R.; Yao, Z.-q.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985, 50, 2003. 62. Wasserman, E. J. Am. Chem. Soc. 1960,82,4433. 63. Lehn, J. M. Angew. Chem., Int. Ed. Engl. 1988,27, 91. 64. Odell, B.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. R; Williams, D. J. Angew. Chem., Int. Ed. Engl 1988,27,1547. 65. Ashton, R R.; Odell, B.; Reddington, M. V.; Slawin, A. M. Z.; Stoddart, J. R; Williams, D. J. Angew. Chem., Int. Ed Engl. 1988,27,1550. 66. Ashton, R R.; Goodnow, T. T; Kaifer, A. E.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. R; Vicent, C ; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1989,28,1396. 67. Brown, C. L.; Philp, D.; Stoddart, J. R Synlett 1991,459. 68. Brown, C. L.; Philp, D.; Stoddart, J. R Synlett 1991,462. 69. Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. P.; Vicent, C ; Williams, D. J. J. Chem. Soc, Chem. Commun. 1991,630. 70. Ashton, R R.; Brown, C. L.; Chrystal, E. J. T; Goodnow, T T; Kaifer, A. E.; Parry, K. R; Philp, D.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. R; Williams, D. J. J. Chem. Soc, Chem. Commun. 1991, 634. 71. Anelli, R L.; Ashton, R R.; Spencer, N.; Slawin, A. M. Z.; Stoddart, J. P.; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1991,30,1036. 72. Ashton, R R.; Brown, C. L.; Chrystal,E. J. T;Goodnow, T. T; Kaifer, A. E.; Parry, K. R; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. R; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1991,30,1039. 73. Ashton, R R.; Brown, C. L.; Chrystal, E. J. T; Parry, K. R; Pietraszkiewicz, M.; Spencer, N.; Stoddart, J. R Angew. Chem., Int. Ed. Engl. 1991,30, 1042. 74. Anelli, R L ; Ashton, R R.; Ballardini, R.; Balzani, V.; Delgado, M.; Gandolfi, M. T; Goodnow, T. T; Kaifer, A. E.; Philp, D.; Pietraszkiewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. R; Vicent, C ; Williams, D. J. J. Am. Chem. Soc 1992,114,193. 75. Stumpf, H. O.; Ouahab, L.; Pei, Y; Grandjean, D.; Kahn, O. Scknce 1993, 261, 447. 76. Dietrich-Buchecker, C. O.; Khemiss, A.; Sauvage, J.-P. J. Chem. Soc, Chem. Commun. 1986,1376.

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77. Dietrich-Buchecker, C. O.; Guilhem, J.; Pascard, C; Sauvage, J.-P. Angew. Chem,, Int. Ed. Engl. 1990,29,1154, 78. Bitsch, F.; Dietrich-Buchecker, CO.; Khemiss, A.-K.; Sauvage, J.-P.; Van Dorsselaer, A. J. Am. Chem. Soc. 1991, 775,4023. 79. Dietrich-Buchecker, C; Sauvage, J.-R Bull. Soc. Chim. Fr. 1992, 729,113.

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SILICON-BASED STARS, DENDRIMERS,AND HYPERBRANCHED POLYMERS

Lon J. Mathias and Terrell W. Carothers

I. II. III. IV. V.

INTRODUCTION STARS DENDRIMERS HYPERBRANCHED POLYMERS CONCLUSIONS REFERENCES

101 103 105 115 118 119

1. INTRODUCTION Recent intense research efforts have focused on the synthesis of multibranched polymers (i.e., cascade molecules) that can be characterized by their uniform branching, radial symmetry, dense packing, entanglementfree globular shapes, and large number of chain ends at their peripheries.

Advances in Dendritic Macromolecules Volume 2, pages 101-121. Copyright © 1995 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-939-7

101

102

LON J. MATHIAS and TERRELL W. CAROTHERS

Two distinct approaches to the synthesis of these multibranched polymers have evolved from the seminal works of Vogtle^ and Denkewalter.^ Tomalia's "dendrimers"^'* and Newkome's "arborols"^ were independently developed through a process termed "divergent" synthesis. This approach is characterized by polymer growth emanating from a central core via an iterative protection/deprotection reaction scheme. Polymer growth typically begins from a "core" molecule which undergoes exhaustive reaction with complementary monomers having two or more protected branch sites. Removal of the protecting groups and subsequent reaction of the liberated reactive sites leads to first-generation polymers. Repetition of this reaction process leads to polymers of desired molecular weight, molecular size and topology. The disadvantages of this synthetic approach include high synthetic cost (large excesses of reagents are typically employed), labor intensiveness, geometrically increasing number of "successful" reactions necessary for uniform polymer growth, and purification difficulties. The convergent synthetic approach, independently developed by Neenan and Miller^ and by Hawker and Frechet,^ begins at what will eventually become the outer surface of the dendrimer. Polymer "wedges" are synthesized via sequential reactions and contain single reactive functionalities at their loci. Wedges are then attached to a polyfunctional central core to complete dendrimer formation. The one major advantage of this methodology is its limited number of reactions compared to the increasingly large number of reactions necessary for divergent growth. A rapidly increasing number of cascade molecules has been synthesized and investigated. Some of the functional groups used in the formation of cascade structures include amines,^'^ amides,^'^ amidoamines,^ ethers,'^'^'^ hydrocarbons,^'^^ cations,^^ esters,^^ transition-metal complexes,^^ and silicons.^'^'^^ Silicon-based dendrimers distinguish themselves from other dendritic species in that they are usually fluids at room temperature, they possess very low Tg's, and they exclusively adopt globular geometries even at lower polymer generations. The multibranched silicon-based polymers offer novel alternatives to CN and CO-containing materials. Those reported to date range from stars containing multiple polymeric arms to highly symmetrical, three-dimensional dendrimers. This report organizes these silicon-containing polymers based on branching geometry and uniformity.

103

Stars, Dendrimers, and Polymers

II. STARS End-reactive polymers have been synthesized by "living" anionic polymerization using either multifunctional anionic initiators followed by functional group termination^^'^^ or utilization of blocked, functional anionic initiators followed by reaction with a multifunctional linker compound.^^ The latter method has the distinct advantage over the former in that gelation of multiple chain ends, so frequently encountered in the use of multifunctional anionic initiators, is alleviated through the use of monocarbanionic "arms" that are subsequently linked. The problem of gelation is particularly troublesome when performing polymerizations in nonpolar solvents, which in many instances are the solvents of choice for obtaining polymers with well-defined microstructures.^^ The use of blocked anionic initiators was prohibited in the synthesis of well-defined telechelic poly(dimethylsiloxanes) (PDMS) or polydienes with high c/5-1,4 contents because of initiator insolubility in nonpolar solvents. Dickstein developed thefirstblocked, amine-fiinctional initiator used for the anionic polymerization of well-defined poly(dimethylsiloxane) arms

• Y

1 '

HMPA Benzene/2S°C

MegSr

SiMeg

= INITIATOR

y

INITIATOR

v

r^of^s

"^OLJ + CI

CI Si—CI CI

4-ARM STAR POLYMER

"LIVING" PDMS ARMS

Figure 1. Anionic synthesis of star poly(dimethylsiloxanes) via blocked amine-functional initiators

LON J. MATHIAS and TERRELL W. CAROTHERS

104

which were subsequently coupled to multihalogenated silane cores forming PDMS stars (Figure 1),^^ telechelic stars^"^ and rigid-rod star-block copolymers.^^ A blocked, functional initiator is made by reacting p-iNJ^bis(trimethylsilyl)amino)styrene with ^-^c-butyllithium in benzene, and is used for anionically ring-open polymerizing hexamethylcyclotrisiloxane (D3) in the presence of promoters such as hexamethylphosphoroamide (HMPA), tetrahydrofuran (THF), or dimethyl sulfoxide (DMSO). The resulting "living", monodisperse poly(dimethylsiloxane)

I X^^^^r

4

+

(CHi)2CISiH

Pt/Cart)on ^'^^""^

»

? ^^

CI


J-^

CH3

O

'

REACTIVE END-CAPPER

^f'^fC

n-BuLi ^ REACTIVE END<:APPER

[^

1^ ^ - . X

}^r^

sr "CAPPED" PDMS ARM

LKI^

Tl(OCH(CH3)2)4 OH BENZENE

"UN-CAPPED" PDMS ARM

T"--Bu-n Bu-n

4-ARM STAR POLYMER

Figure 2. Anionic synthesis of four-arm star poly(dimethylsiloxanes) via coupling to titanium based cores

Stars, Dendrlmers, and Polymers

105

oligomers were then coupled to chlorotrimethylsilane, dichlorodimethylsilane, trichloromethylsilane, tetrachlorosilane, and 1,2bis(trichlorosilyl)ethane to make one- to six-arm star polymers. Several star polymers of theoretical molecular weights up to about 24000 were prepared in essentially quantitative yields with polydispersities ranging from 1.07 to 1.32. No polymer gelation or molecular weight broadening was observed from the coupling of "living" oligomers using this method. Imai and co-workers synthesized narrow-polydispersity poly(dimethylsiloxane) oligomers by the anionic ring-opening polymerization of hexamethylcyclotrisiloxane using n-butyllithium as initiator in THF. These oligomers were terminated with a "reactive end capper", 4-(dimethylchlorosilyl)butanoic acid trimethylsilyl ester and subsequently deprotected (reprecipitation into methanol) to give carboxylic acid-terminated PDMS arms. Coupling of these monodisperse PDMS arms to aluminum(ni) and titanium(IV) isopropoxides in benzene resulted in the formation of three- and four-arm stars, respectively (Figure 2)}^ Gelation of the resulting polymers was observed, presumably due to ionic aggregation in solution as was observed with similarly cored polybutadiene stars.^^'^^ Size-exclusion chromatographic (SEC) analysis of star polymers was prevented due to peak anomalies presumably caused by the ionic nature of metal-carboxylate bonds in the product. III. DENDRIMERS All silicon-containing dendrimers have evolved from the pioneering synthetic efforts of Rebrov, who, in 1989, synthesized the first hyperbranched poly(siloxanes).^^ Divergent synthesis of these polymers began with the reaction of trichloromethylsilane (core) and sodium diethoxymethylsilanolate (branching unit). The resulting first-generation polymer had telechelic ethoxysilane groups that were quantitatively converted to chlorosilanes via reaction with thionyl chloride. Repeated sequential reaction with excess sodium diethoxymethylsilanolate and thionyl chloride gave telechelic polymers up to the fourth generation with greater than 75% yield (Figure 3). Elemental analyses confirmed all polymer compositions. A general strategy for the synthesis of dendritic poly(siloxanes) with discrete molecular weights greater than 15000 (third generation) was developed by Masamune and co-workers in 1991 (Figure 4).^"^ Synthesis

106

LON J. MATHIAS and TERRELL W. CAROTHERS OEt J

Me Me

3 Naoil(OEt)2

d.

Gen.=:1

OEt J

Me

CI

^^i^'-O^ir'^i^'^®

SOCI2

CI—SI—CI CI—Sh

I

^*9

net

0E<

1)

Me

^^e

M§ mc

>

Me

i

•^^O^V.

6 NaOSi(OEt)2^

/^Cr-^C

^, r ^

Me

Me mc

i

Gen = 2

sCX^Ig s ocio

^

J Me

^0^ I

>r

EtO Me

12 NaOSi(OEt)2 ""^ '^«»»-^ll'-'C:i;2

•

Gen.= 3 0^

Me

Me ^sr

OEt

OEI

o o'

BVCT^o p

Me^^Si^

Sr"^®

Etc. ^ ^ ^ 4 . . Me

CI

^^^'-CxJ^^O-^'-'^®

T

S ^ C ^ ' V ^ npT

T

^«

Me

^«

Me-

(!)Et

Me .O^pO^ Me ^Si Me ^SCT Me J^Si

O

O

EtO^I

I

I.

^SL

Me" I ^OEt OEt

'"^ n O E t

POEt

figiire 3. Rebrov's seminal synthesis of hyperbranched poly(siloxanes)

of these SiH-terminated oligosiloxane dendrimers employed coupling of hydroxylated "cores" with SiH-containing halogenated silane extender molecules. The resulting surfaces of the silicon dendrimers were "coated" with Si-H moieties that were amenable to functional group transformation to modify physical properties. ^^Si NMR (nuclear magnetic resonance spectroscopy), mass spectral, and SEC analyses showed that the polymers were unimodal with discrete molecular weights and molecular weight distributions.

107

Stars, Dendrimers, and Polymers

H-hSloJ 6

LOSH—H Si

CH3^

®

/

' \ ^ - H

CH3'

-SioJ H-4-SiO

Pyridine Gen.= 1

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HO-HSiO, H2O

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\ /

a +

I^OgVJ—OH

Si

CH3^

pogU-H

V

,CH3

v

losU-H

3

pSh s/<

O-4~Si0j 6

V

CHa-^

/

,OSi-

OSI-

rosi-4 6

\i'

Figure 4. Masamune's systematic synthesis of silicon dendrimers

Kakimoto et al. divergently synthesized poly(siloxane) starburst polymers via an iterative electrophilic coupling of silanol-containing building blocks with aminosilane cores (Figure 5).^^^ Third-generation hyperbranched polymers were obtained with discrete molecular weights greater than 4,500. Intrinsic viscosity measurements were performed to allow calculation of Mark-Houwink constants K (4.7 x 10"^) and a (0.21) for these starburst polymers. The a value of 0.21 indicates that the resulting polymers are approximately spherical in geometry. Kakimoto and colleagues also developed a convergent synthetic scheme that utilized hydrosilation in making starburst dendrons and dendrimers with discrete molecular weights greater than 12,500 (fourth generation) (Figure 6).^^** The Mark-Houwink constants K and a were calculated as 1.33 x 10"^ and 0.45, respectively. The a value of 0.45 indicated that these polymers also adopted almost spherical geometries in THF. Higher generation polymers exhibited higher Tg's suggesting a decrease in segmental mobility associated with increasing polymer molecular weight and chain packing as the branch-unit density increases in the outer shell.

/ '"'..s~

''o I

\

\ Si,

cti3-$i0' '0

\!

\ Si, S 0 '

i

CH 3

0-Si-0'

\: Si,

\! Si,

0'

\ Si,

0'

dS<' I 0--$i-CH3

Figure 5. Kakirnoto's divergent synthesis of starburst poly(siloxanes)

5 5 * 5

no

X

iP

C H ~ ' C H h ,0' CH3

Si,

CH$

0, ,CH3

c"silQ ,CH3

CHhSi

C H 3 - f i

JaSi'"" ,CH3 Si, C H ~0,s,,CH3

NC

\

CH3

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)

CN

Figure 6. Kakimoto's convergent syntheses of starburst dendrons and dendrimers via hydrosilation

\

Cl-S\ l C- i S , ,

P

8 CI2CH3SiH

16 & M g ~ r

--______)

Pt. T I ~ F50' . C

Gem= 2

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\/

Figure 7. Roover's synthesis of carbosilane dendritic macromolecuies

114

LON J. MATHIAS and TERRELL W. CAROTHERS

Roovers et al. developed a methodology for the synthesis of carbosilane dendritic macromolecules with discrete molecular weights greater than 6000 (fourth generation) (Figure 7).^^ The Mark-Houwink constant a for these polymers was calculated as 0.40 in cyclohexane, indicating that these dendrimers adopted spherical geometries. These low molecular weight dendrimers were below their maximum in [r|], thus having a fractal dimension of sHghtly over 2. Carbosilane dendrimers containing 64 and 128 SiCl bonds oil their surfaces were used as coupling agents for monodisperse poly(butadienyl)lithium to form star poly(butadienes) with 64 and 128 arms, respectively.^^ Multibranched oligocyclics were synthesized by Buese and colleagues^^ via the hydrosilation of vinyl- and SiH-containing cyclosiloxanes in the presence of Karstedt's catalyst.^^ Other branched polymers were synthesized from the hydrosilation of vinyl- and SiH-containing cyclosiloxanes with a,co-dihydrogen or divinyloligo(dimethylsiloxanes). The resulting hyperbranched structures were obtained in greater \/ Si-O^ / \ / SHO^ /

\

^sto H

?' -Si /

^^ + 0

'O-Si

/\

SHO^ / Sk

~^Si^ 0 / O-Si

^Si ^O / O-Si^

\ / ,St-0^ /

0

/

'O-Si'

/ ^O-Si'

^ \ O •^Si

/ 'o-Si

SJ^ I ,0

,Sr-0

/

/ ^O-Si'

/\

/\ \,SHO, / o

\ / Sh-0^ / Sk.

O'

/ \

^Si^ ,0 / O-Si / \

^

O

/^Si

/ 'O-Si

^Si O / 'o-Si

/

su.

SK

p

,SHO, /

/

\

/\

figure 8. Buese's synthesis of multibranched oligocyclics via hydrosilation

Stars, Dendrimers, and Polymers

115

than 80% yield with excellent agreement between theoretical and actual molecular weights determined by vapor-phase osmometry. For example, 1,3,5,7-tetra(2-heptamethylcyclotetrasiloxane-yl-ethyl)-1,3,5,7-tetramethylcyclotetrasiloxane was prepared in greater than 82% yield from the hydrosilation of heptamethylcyclotetrasiloxane and octamethylcyclotetrasiloxane (Figure 8). Proton and *^C NMR analyses indicated that hydrosilation occurred with less than absolute regioselectivity, giving as much as 23% Markovnikov-type Si-H addition to vinyl groups.

IV. HYPERBRANCHED POLYMERS Tomalia's dendrimers and Newkome's arborols have precisely determined branch contents and branch lengths, but their synthetic requirements are demanding and time consuming. An alternative is to use multifunctional step-growth monomers, A-B^, where n determines the number of branches per repeat unit. Starburst perfluorinated poly(phenylenes) were synthesized by Bochkarev et al.^^ via anionic polymerization of tris(perfluorophenyl)germane, tris(perfluorophenyl)silane and tris(perfluorophenyl)stannane in THF using triethylamine as catalyst. Complete fluorination of the aromatic rings attached to the metal species allowed for the surprising formation of active anions via metal deprotonation by triethylamine (Et3N). Nucleophilic displacement of the fluorine atoms in para positions on the perfluorophenyl rings yielded dendritic structures (Figure 9) that were soluble in polar and aromatic solvents. The germanium system reached a "self-Umiting" molecular weight range of about 100000-170000 due to "steric screening" suggested to preclude further propagation. Structural verification was based on viscosity data (indicating spheroidlike characteristics), elemental analyses, light scattering and direct observation of individual dendrimers by electron microscopy. We have recently synthesized hyperbranched poly(siloxysilanes) via the "one-pot" hydrosilation polymerization of the A-B3 monomer, allyltris(dimethylsiloxy)silane.^^ Size-exclusion chromatography indicated that the resulting polymers had very narrow molecular weight distributions and corresponded to polystyrene standards of about 19,000. The polymers were shown to undergo postpolymerization hydrosilation reactions involving chain-end Si-H moieties and a variety of allyl- or vinyl-containing end cappers.^^ It was discovered that, during the course

116

0

LON J. MATHIAS and TERRELL W. CAROTHERS

m

Bj IB)

m

^ W>

M= Si. Ge and Sn

m T m

0

Figure 9. Bochkarev's anionic synthesis of starburst perfluorinated poly(phenylenes)

of polymerization, allyltris(dimethylsiloxy)silane underwent competitive six-membered ring cyclization (giving the pseudo B2 segment 2,2dimethyl-6,6-bis(dimethylsiloxy)-1 -oxa-2,6-disilacyclohexane) and linear propagation to form a polymer (Figure 10).^^ Self-catenation of the analogous monomer vinyltris(dimethylsiloxy)silane gave a mixture of polymers having five-membered cyclics (from core 2,2-dimethyl-5,5bis(dimethylsiloxy)-l-oxa-2,5-disilacyclopentane) and vinyls at their loci. These polymers exhibited bimodal SEC traces with their higher molecular weightfractions(end-capped with allyl phenyl ether) corresponding to polystyrene standards of about 250,000. To disfavor unwanted cyclization entropically, this general reaction scheme was extended to include monomers 6-hex-l-enyltris(dimethylsiloxy)silane and 8-oct-l-enyltris(dimethylsiloxy)silane. The resulting polymers gave no indications of cyclization and resulted in molecular weights of about 12,(XX). However, SEC traces were multimodal in nature caused by monomer contamination with internal olefins (notoriously sluggish or completely unreactive towards hydrosilation reac-

Stars, Dendhmers, and Polymers

117

% xy^i^^^^

O^'^'V/^^Sl-t-od HJ

\(. .SH-0—^H

^

!i±_v3^o^y

.Ve^o^y

^^^'ijs;y:^^'t;s^ Pseudo B«

O-Si-0

SiH

1

K"

-SHO-SHO-Sf

i

;i-o-^i

cfo

\

v

-SHCX^

;iH

^^m

figure 10. Self-polymerization of the A-B3 monomer, allyltris(dimethylsiloxy)silane

tions). ^^Si NMR analysis typically detected four polymer T" regions (triple oxygen substitution on silicon, where n denotes the degree of branching) (Figure 11) which integrated to an average ratio of approximately 29% T^, 44% T^ 21% T^ and only about 6% T^ branching in

118

H

LON J. MATHIAS and TERRELL W. CAROTHERS

i

l

l

—Sh-

—SI—

—SI—

—Sh-

R—Sh-OSIH

R—SI-OSiH

R—SI-OSl^

R—il-OSi^

—SI— H

—SI— H

—ShH

—SI— I

T°

T'


i

I

i

I

T'

i I

T'

Figure 11. Schematic representation of the possible branching environments available from the self-polymerization of A-B3 monomers (Note: R represents an alkenylene group and the jagged line represents the hydrosilation addition of monomer)

these polymers. Although polymer size, branching content, and number of surface Si-H moieties vary among molecules of any given sample prepared via this "one-pot" polymerization scheme, polymer synthesis is rapid, surface modification is quite versatile, and polymer purification is easy. These hyperbranched poly(siloxysilanes) can be adequately described as being uniform in the nature of their surface functionality, mostly spherical in shape, and structurally intermediate between linear and perfectly hyperbranched A-B3 polymers.

V. CONCLUSIONS Star and dendritic polymers based on silicon have been synthesized possessing well-defined molecular weights, molecular weight distributions and uniform branching contents. The former were synthesized by relatively conventional star-polymerization chemistry while the latter were obtained with silicon-specific reactions that allowed controllable chain extension. The dendrimers exhibited properties consistent with reduced hydrodynamic volume and highly condensed structures, but with low glass transition temperatures (Tg). Less well-defined hyperbranched polymers containing silane and/or siloxane moieties have also been synthesized through "one-pot" polymerizations. While this allows rapid formation of relatively high molecular materials, the degrees of branching and structural regularities of these systems are much less than those of the dendrimers. These materials do display the micellelike

Stars, Dendrimers, and Polymers

119

Structures desired and possess very low glass transition temperatures that lead to liquid like physical properties. Possible uses for these unusual molecular constructs rangefromdrug microcarriers to artificial erythrocytes and single-cell microreactors. Drug delivery would be facilitated by the liquid-like interiors of these systems, allowing the rate of release to be controlled by relative solubilities and diffusion. For artificial blood appUcations, incorporation of hydrophilic surface groups, especially oligooxyethylene-based materials, will allow good blood compatibility while the molecular interior can be modified by monomer functionalization before or after polymerization (e.g., fluorocarbon incorporation) to give an interior capable of dissolving and transporting blood gases. Use as microreactors could involve surface modification with hydrophilic and transport-active groups such as oligooxyethylenes or quaternary ammonium salts while maintaining a hydrophobic and oleophilic interior for dissolution of organic soluble starting materials and products. In all of these appUcations, modification of the interior and exterior portions of the molecules combines with enormously increased surface areas to make these attractive for investigation and commercial use. REFERENCES 1. a) Buhleier, E.; Wehner, W.; Vogtle, F. Synthesis 1978, 155; b) Vogtle, R; Weber, E. Angew. Chem. 1979, 97, 813; c) Vogtle, R; Weber, E. Angew. Chem. Int. Ed. Engl. 1979,18. 753. 2. Denkewalter, R. G.; Kolc, J.; Luskasavage, W J. U.S. Patent 4 289 872,1981. 3. Tomalia, D. A.; Naylor, A. M.; Goodard, W A. Angew. Chem., Int. Ed. Engl. 1990, 29, 138. 4. a) Tomalia, D. A.; Baker, H.; Dewald, H.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, R Polym. J. 1985,7 7,117; b) Tomalia, D. A.; Baker, H.; Dewald, H.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, R Macromolecules, 1986, 79, 2466; c) Padias, A B.; Hall, H. K., Jr.; Tomalia, D. A.; McConnell, J. R. Org. Chem. 1987, 52, 5305; d) Tomalia, D. A.; Hedstrand, D. M.; Wilson, L. R. Encyclopedia of Polymer Science and Engineering, 2nd ed.; John Wiley & Sons: New York, 1990; Index Volume, pp 46-92. 5. a) Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985, 50, 2004; b) Newkome, G. R.; Baker, G. R.; Saunders, M. J.; Russo, R S.; Gupta, V. K.; Yao, Z.; Miller, J. E.; Bouillion, K. J. Chem. Soc, Chem. Commun. 1986,752; c) Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K.; Russo, R S.; Saunders, M. J. J. Am. Chem. Soc. 1986,108, 849.

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LON J. MATHIAS and TERRELL W. CAROTHERS

6. a) Miller, T. M.; Neenan, T. X. Chem. Mater. 1990,2,349; b) Miller, T. M.; Neenan, T. X.; Zayas, R.; Blair, H. E. 7. Am. Chem. Soc. 1992,114,1018. 7. a) Hawker, C. J.; Fr^chet, J. M. J. J. Chem. Soc., Chem. Commun. 1990,1010; b) Hawker, C. J.; Fr^chet, J. M. J. J. Am. Chem. Soc. 1990, 772,7638; c) Hawker, C. J.; Fr^chet, J. M. J. Macromolecules 1990,25,4726. 8. Hall, H. K.; Polls, D. W. Polymer Bull. 1987, 77,409. 9. Kim, Y. H.; Webster, O. W. J. Am. Chem. Soc. 1990, 772,4592. 10. a) Wantanabe, H.; Yoshida, H.; Tokata, T. Macromolecules 1988, 27, 2175; b) Yoshida, H.; Wantanabe, H.; Tokata, T. Macromolecules 1991,24, 572. 11. a) Rengan, K.; Engel, R. J. Chem. Soc, Chem. Commun. 1990, 1084; b) Rengan, K.; Engel, R. J. Chem. Soc, Perkin Trans. 11991,987. 12. Hawker, C. J.; Lee, R. J.; Fr^chet, J. M. J. J. Am. Chem. Soc 1991, 775,4583. 13. a) Serroni, S.; Denti, G.; Campagna, S.; Juris, A.; Ciano, M.; Balzani, V. Angew. Chem. 1992,104,1540; b) Serroni, S.; Denti, G.; Campagna, S.; Juris, A.; Ciano, M.; Balzani, V. Angew. Chem. Int. Ed. Engl. 1992,57, 1493. 14. Uchida, H.; Kabe, Y; Yoshino, K.; Kawama, A.; Tsumuraya, T.; Masamune, S. J. Am. Chem. Soc 1990, 772, 7077. 15. a) Morikawa, A.; Kakimoto, M.; Imai, Y Macromolecules 1991, 24(12), 3469; b) Morikawa, A.; Kakimoto, M.; Imai, Y Macromolecules 1992,25, 3247. 16. a) Mathias, L. J.; Carothers, T. W J. Am. Chem. Soc 1991, 775,4043; b) Mathias, L. J.; Carothers, T. W; Bozen, R. M. Polym. Prepn, Am. Chem. Soc. Div. Polym. Chem. 1991,52(7;, 82. 17. a) Roovers, J.; Toporowski, P. M.; Zhou, L. L. Polym. Prepn, Am. Chem. Soc., Div. Polym. Chem. 1992,33(1), 182; b) Zhou, L. L.; Roovers, J. Macromolecules 1993, 26, 963. 18. Chang, R S.; Hughes,T. S.; Zhang, Y; Webster, G. R.; Poczynok, D.; Buese, M. A. J. Polym. ScL, Part A: Polym. Chem. 1993,57, 891. 19. Bochkarev, M. N.; Semchikov, Yu. D.; Silkin, V. B.; Sherstyanykh, V. I.; Maiorova, L. R; Razuvaev, G. A. Vysokomol. Soedin., Sen B 1989,57(9), 643. 20. Reed, S. F, Jr. J. Polym. Set. 1972,10,1087. 21. Schulz, D. N.; Sanada, J. C ; Willoughby, B. G. ACS Symp. Sen 1981,166,427. 22. a) Schulz, D. N.; Halasa, A. F J. Polym. Sci., Polym. Chem. Ed 1974, 72,153; b) Schulz, D. N.; Halasa, A. F J. Polym. Sci., Polym. Chem. Ed 1977, 75, 240. 23. Dickstein, W. H.; Lillya, C. R Macromolecules 1989,22,3882. 24. Dickstein, W. H.; Lillya, C. R Macromolecules 1989,22, 3886. 25. Bhattacharya, S. K.; Smith, C. A.; Dickstein, W. H. Macromolecules 1992,25,1373. 26. Kazama, H.; Tezula, Y; Imai, K. Macromolecules 1991,24,122. 27. Otocka, E. R; Hellman, M. Y; Blyler, L. L. J. Appl. Phys. 1969,40,4221. 28. a) Broze, G.; J6r6me, R.; Teyssi6, R Macromolecules 1981,14,224; b) Broze, G.; J6r6me, R.; Teyssi^, R Macromolecules 1982, 75,920. 29. Rebrov,E.A.;Muzafarov,A.M.;Papkov,VS.;Zhdanov,A.A.Dokl.Akad.Nauk. SSSR1989,309(2), 367.

Stars, Dendrimers, and Polymers

121

30. Roovers, J.; Zhou, L.; Toporowski, P. M.; van der Zwan, M.; latrou, H.; Hadjichristidis, N. Macromolecules 1993,26,4324. 31. Karstedt, B. D. U.S. Patent 3 775 452,1973. 32. Mathias, L. J.; Carothers, T. W. Polym. Prepn, Am. Chem. Soc. Div, Polym. Chem. 1991,32(3h 633. 33. Carothers, T. W.; Mathias, L. J. Submitted for publication.

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HIGHLY BRANCHED AROMATIC POLYMERS: THEIR PREPARATION AND APPLICATIONS

Young H. Kim

ABSTRACT I. INTRODUCTION II. POLYPHENYLENES A. Polymer Synthesis B. Characterization C. Chemical Modification of Polymer 3 D. Symmetrically Branched Polyphenylene E. Hydrophobic Binding Study of Polymer 3B F. Langmuir-Blodgett Films of Hyperbranched Polyphenylenes G. Blending with Other Polymers H. Star-Branched Polymerization III. POLYESTERS A. Single-Step Polymerization

Advances in Dendritic Macromolecules Volume 2, pages 123-156. Copyright © 1995 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-939-7

123

124 124 128 128 129 130 132 134 135 137 139 141 141

124

YOUNG H.KIM

B. Symmetrical Polyesters C. Applications IV. POLYPHENYLETHERS A. Synthesis B. Effect on Rheology V. POLYAMIDES A. Preparation B. Characterization C. Lyotropic Properties REFERENCES

143 144 145 145 150 151 151 154 155 155

ABSTRACT Preparation and characterization of highly branched aromatic polymers, polyphenylenes, polyesters, polyethers, and polyamides, were reviewed. These polymers were prepared from condensation of AB^-type monomers, which gave noncrosslinked, highly branched polymers. The polymer properties are vastly different compared to their linear analogs due to their resistance to chain entanglement and crystallization.

I. INTRODUCTION Branches in polymers play important roles in determining their properties, such as viscosity, density, and toughness. However, excessive branching is also known to cause deterioration of physical properties due to low probability of chain entanglement. Only recently, highly branched polymers have attracted increasing attention with the expectation that their unique structures will impart unusual properties creating novel applications. The highly branched polymer field has grownfromtwo fundamentally different disciplines. On one hand, well characterized small molecules, e.g., cascade compounds,* arborols,^ etc., were grown into higher molecular weight molecules by stepwise syntheses. As shown in Scheme 1 and 2, both divergent and convergent synthetic approaches were employed. These methods produce well-defined, large dendritic molecules. The convergent method also allows structural variation, as well as functional group variation. Possible uses for these materials are suggested in areas such as standards for particle size or molecular weight determination, lubricants, polymer-rheology modifiers, and molecular inclusion hosts, to mention but a few.

DIVERGENT SYNTHETIC SCHEME OF DENDRIMERS Protected

' b '

Core

G-1-P

G-1

G-2-P

w

-

I

& G-3-P

G-2

Scheme I .

CONVERGENT SYNTHETIC SCHEME OF DENDRIMERS Protected Monomer

v

Monomer

W-1 -P

4 ''

W-1

Scheme 2,

W-2-P

Highly Branched Aromatic Polymers

127

B B

Scheme 3.

Direct polymerization of the AB^-type monomers, where jc is 2 or greater, has also been attempted. This type of polymerization produces highly branched polymers having one A functional group and {x-l)n+l number of B functional, unreacted groups at the surface of the polymer, where n is the degree of the polymerization (Scheme 3).^ Through this methodology, highly branched copolymers can also be prepared with AB-type comonomers, resulting in the dilution of branching density and allowing further structural manipulation. Following Flory's seminal theoretical treatment of branched polymers, there have been numerous publications dealing with the theoretical as well as physical aspects of these highly branched molecules."^^^ Our research interest in thisfieldis based on the perception that these dendritic polymers could be useful as polymer-rheology control agents as well as spherical, multifunctional macromonomers. Hyperbranched polymers, which were not only thermally and chemically robust under the conditions used, but also could be economically obtained, were created to evaluate these concepts. The latter requirement led us to pursue the one-step polymerization of AB^-type monomers. We will review mostly the synthesis of aromatic polymers with "stable" chemical Unkages prepared by the single-step direct method, and we will briefly compare them with polymers made by more controlled multistep syntheses.

128

YOUNG H.KIM

11.

POLYPHENYLENES''^' A. Polymer Synthesis

Several chemo-selective aryl-aryl coupling reactions of aromatic halides and organometallics with transition-metal catalysts are known. ^^ For example, coupling reactions of arylboronic acids with aryl halides with Pd(0) catalyst,^^ arylmagnesium halides with aryl halides with Ni(II) catalysts,^^ and aryl trialkyl tin compounds with aryl halides with Pd(0) catalyst^^ are well known. The polyhalo-aromatic substances were converted into AB^-type monomers by selective metallation of one of the halo-fimctional groups in each monomer. Polymer 3 was best obtained in good yield under Suzuki's coupling conditions of refluxing a mixture of arylboronic acid and aryl halide in an organic solvent with aqueous carbonate and tetrakis(triphenylphosphine)palladium(O). The molecular weight of the resultant polymer depends on the organic solvent employed. Nitrobenzene, as the solvent, gave the highest molecular weights as summarized in Table 1. The polydispersities of the polymers prepared by this method are usually narrower than typical polymers prepared by condensation methods. Polymer 4 can also be prepared from the monoGrignard of 1,3,5-trichlorobenzene. The Grignard route is advantageous for large scale runs, but, in general, it gave polymers of greater polydispersity and a lower degree of branching. One possible cause of molecular weight limitations is the reactivity loss of the organometallic center due to increased steric hindrance from B(0H)2 Pd(0)

3 4

Scheme 4.

X»Bi X = CI

Highly Branched Aromatic Polymers

129

Table 1. The Effect of Coupling Reaction Conditions on the Molecular Weights of Polymers 3 and 4 Monomer

Metho(f

Polymerization

conditions

lA lA

A A

xylene with 1 N K2CO3 1 -methylnaphthalene

lA IB 2

A B B

nitrobenzene with 1 N Na2C03

M;

D'

3,820

1.50

6,560

2.02

32,000

1.13 1.81 18.2

with 1 N Na2C03

Notes:

anhydrous THF anhydrous THF, Mg turnings

3,910 6,470

Method A: Pd(0)-catalyzed boronic acid coupling reaction; Method B: Ni(II)-catalyzed coupling of phenyl Grignard compounds. Mj^ is the number average molecular weight. ^D is the polydispersity, M^/M^ where M^ is the weight average molecular weight.

increasing molecular weight. Another reasonable possibility is that the A functional group is consumed by intramolecular cyclization. Since there is only one A group per polymer molecule, such cyclization would rapidly abort polymer growth by a step-polymerization mechanism. B. Characterization

The molecular weights of these macromolecules are presented as gel permeation chromatographic (GPC) molecular weights against polystyrene standards, and are used only for qualitative purposes. It has usually been found that such GPC measurements of branched polymers underestimate the true molecular weights. In general, these polymers show enhanced solubility in various solvents. For example polymer 3 is readily soluble in o-dichlorobenzene (ODCB), tetrachloroethane, and tetrahydrofuran (THF), but not in CH2CI2. The high molecular weight polymer has diminished solubility when compared to its low molecular weight counterpart. Polymer 4 is the most soluble. These high solubilities can be explained by two synergistic properties of these polymers, namely, lack of crystalline packing and molecular entrapment of solvent within the cavities. The ^H NMR spectra of polymers 3 and 4 show broad peaks from 7.0-8.5 ppm. Infrared (IR) spectra of these polymers show two characteristic peaks at 847 and 740 cm~^ for 1,3,5-trisubstituted benzenes.

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YOUNG H.KIM

Elemental analysis of polymer 3 showed that most of the bromine predicted from theory was present. By contrast, polymer 4 showed a chlorine content lower than expected, indicating possible reductive elimination of chlorine. Hyperbranched polymer 3 is stable in air up to 550 °C, but bums at 650 °C. Under nitrogen, the polymer loses about 50% of its weight at 550 °C with the evolution of HBr, leaving an amorphous form of carbon. The polymer has a glass transition temperature (Tg) at 238 °C, but no melting point. The molecular weight of the polymer, in the range of Af„ from 2000-35,000, did not influence the Tg (M^ is the number average molecular weight.) C. Chemical Modification of Polymer 3

The halogen groups in polymers can be readily converted to other functional moieties by various exchange reactions affording options of converting polymer 3 or 4 into "multifunctional initiators" or macromonomers. Metal-halogen exchange of the readily THF-soluble polymer 3 with alkyllithiums gave lithiate 3A, which is insoluble in THF, but stable for hours at -78 °C. In a small scale reaction, the lithiation yield was shown to be over 90%, based on successful trapping experiments with chlorotrimethylsilane. When the anion is quenched with methanol (MeOH) or acetonitrile, IR peaks appear at 700 and 779 cm~^ due to monosubstituted benzene, as well as peaks corresponding to trisubstituted benzene. The lithiate can also be treated with various electrophiles, such as CO2, yielding the water-soluble carboxylate (3B). Hydrolysis of this polymer provides a water-insoluble, but THF-soluble, polyacid (3J). The list of electrophiles used and the resulting functional groups are shown in Scheme 5. The degree of functionalization can be estimated from nuclear magnetic resonance (NMR) integration and elemental analysis. Usually 70-80% of the bromine is converted to the desired functionalities. The polymer also can be modified by coupling reactions. Capping the reaction of 3A with p-methoxyphenylmagnesium bromide with a Ni(II) catalyst provided 30. Pd(0)-catalyzed coupling with 2methyl-3-butyn-2-ol gave the acetylene derivative, 3Q. Borane reduction of carboxy-functional groups in 3J gave the corresponding hydroxylmethyl derivative 3K, which in turn was easily converted to the chloromethyl derivative (3L). A potential macroinitiator, 3R, is prepared by dehydration of polyol, 3F. Product 3R is a multifunctional analog of

3G {CH3)2SO,

I

CH3

3H CO,

H+ -^

|—COOLi

•

|—COOH

3B

BH3 •

3J

wy

3K Ncs/ppr^

Imidazolium salt -^

3S

3L

-^

BBr, •

|—CH2OCH3

I—CHzBr

3C

3M

HCON(CH3)2 -^

|—CHO 3T

{CH3)2CO

CH3

CH3COC,H3

p

H2SO4

3R (C5H5) 3D R = (CH3) 3FRMC6H5) CHgOCgH^MgBr

BBr.

30

3P

HCsC(CH3)20H

CH3

I

=

NaOH

4-OI I OH CH3

3Q (CH3)3SiCI |—Si(CH3)3 3i

Scheme 5. 131

|—CH2OH

3N

132

Table 2.

YOUNG H. KIM

The Effect of Polymer Functional Croup on the Thernnal and Solution Properties of Polymers 3 and 4 Solubility

Polymer

Functional group

T^CQ

THF

CH2CI2

221

+ -

-

121

+ +

+

+ +

+ -

3 3B

Br

3G 3H

H CH3

31

(CH3)3Si

3J 3K

C02H CH20H

3L

CH2C1

182

+ +

+ -

30

p-anisol

223

+

+

3P

/?-hydroxylphenyl

+

3R

a-vinyl phenyl

+

4

CI

C02Li 177 141

96

+ +

in ether

water

+

Notes: ^ h e glass transition temperature (T ) is the midpoint of the glass transition at a heating rate of 15 °C/min. ++ means very soluble, + means slightly soluble, and - means not soluble.

l,3-bis(l-phenylvinylbenzene), which is a difunctional initiator for anionic polymerizations in hydrocarbon solvent.^^ Cleavage of the methyl ether groups of 3 0 gave 3P, and deprotection via loss of acetone from 3Q gave the arylacetylene (3N). The properties of these polymers, such as solubility and Tg, are greatly affected by the terminal functional groups (Table 2). Several derivatives, such as those containing p-anisol, a-vinylbenzene, and hydroxylmethyl groups, are CH2Cl2-soluble. The hydroxymethyl derivative 3K requires a small amount of an H-donor solvent for dissolution. Polymers containing nonpolar terminal groups, such as H, CH3 and Si(CH3)3, show much lower Tg's than polymer 3, while polymers possessing polar group substituents, such as CH2OH or COOH, did not show any thermal events up to 400 °C. D. Symmetrically Branched Polyphenylene Miller et al. reported^^'^^'^^ that highly symmetrical, mostly single-element, highly branched polyphenylenes were prepared by the stepwise

Highly Branched Aromatic Polymers

3(4): 3(4F):

133

R = C6H5 R = CeF5 R^

R

3(10): R = CeH5 3(10F): R = CgF5

Scheme 6.

convergent synthesis approach shown in Scheme 6. The building block was prepared using 1,3,5-tribromobenzene, through 3,5-dibromophenylboronic acid (lA), by coupling with 3,5-dibromo-l-trimethyl-silylbenzene, in which the silane moiety serves as a halide-protecting group. Once the desired size of the. wedge building block was obtained, it was coupled to the trifunctional core material, 1,3,5-tribromobenzene. Polyphenylenes consisting of 4 phenyls [3(4)], 10 phenyls [3(10)], or 22 phenyls [3(22)] were prepared. A dendrimer with up to 46 rings [3(46)], which should have a 31A diameter size, was also prepared. The ^H NMR spectra of these substances show well-separated, assignable peaks, and the GPC peaks were very narrow. Branched phenylenes with perfluorinated terminal phenyls were also prepared. In contrast with polymer 3, a unique feature of these highly symmetrical phenylenes is their crystallinity. As summarized in Table 3,3(46) can be partially crystallized, and all lower homologues can be fully crystallized. When these dendrimers, with more than 10 phenylenes, were quenched rapidly, they show a Tg, which increases with molecular weight. The fluorinated homologues [3(4F) and [3(10F)] have more crystallinity and higher melting temperatures (T^), but possess a lower Tg's than the hydrocarbon analogs. One interesting aspect is the comparison of these highly symmetric dendrimers with 3G, which has a compositional similarity to the symmetrical phenylenes. Since the Tg of 3 is invariant with molecular weight, we believe that its molecular weight is in a plateau region where the Tg does not increase with the molecular weight. In spite of this, it seems

134

YOUNG H.KIM

Table 3. The Glass Transition and Melting Temperatures of Branched Polyphenylenes Compounds 3G 3(4) 3(10) 3(22) 3(46)

T^TQ 127 none 126 190 220

T^CQ none 174 271 339 512

Notes: ^ h e glass transition temperature (T ) is the midpoint of the glass transition at a heating rateofl5°C/min. ^The melting temperature (T ) is the onset of melt at a heating rate of 15 °C/min.

surprising that the Tg of 3G is lower than that of 3(46). This might be related to the symmetry and regularity of the aromatic arrays of the symmetrical phenylenes, which impose a more highly ordered packing structure. The nature of motions at and below Tg in this class of molecules, which affect ranges and the heat capacity changes at Tg, is not fully understood. Polymers based on 1,3,5-trisubstituted phenylacetylenic wedges and 1,4-disubstituted phenylene acetylenic linear segments with terminal solubilizing groups have also been reported.^'* E. Hydrophobic Binding Study of Polymer 3B

The structure and molecular modeling of poly mer 3B, which resembles a unimolecular micelle, reveal that the average opening of the cavities in the polymer is in theSA range. The complexation of polymer 3B with p-toluidine, a guest molecule, was studied by NMR in D20.^^ All ^H NMR peaks for the methyl singlet and AB quartets of the /7-toluidine protons shifted upfield and broadened as the polymer was added. Sodium acetate was used as an intemal standard with a chemical shift of 5 2.100. At the 3B to /7-toluidine ratio of 0.53, the chemical shift of the methyl group is 5 1.76 at 1.28 M Na2S04, and 5 2.03 at 0.13 M Na2S04. When the 3B to p-toluidine ratios were greater than 2.5 in a 1.9 M Na2S04 solution, the chemical shift reached a limiting value of 6 1.59. The equilibrium constant of the complex was determined in a 1 M NaCl solution by varying the ratio between the host and guest molecules. Since

Highly Branched Aromatic Polymers

135

the polymer can form multiple complexes with p-toluidine when the host-to-guest ratio is low, an accurate equilibrium constant is difficult to obtain. Assuming that only a 1:1 complex is formed, an equilibrium constant of about 510 M"^ is estimated. This polymer solution also demonstrated the ability to dissolve hydrophobic molecules, such as naphthalene and methyl red. The experiment indicated that an array of aromatic polymeric chains is capable of generating an environment resembling a micellar structure, a finding that led us to further studies of the polymer's surface properties. F. Langmuir-Blodgett Films of Hyperbranched Polyphenylenes

In spite of an irregular polymer architecture, some amphiphilic, hyperbranched polyphenylene derivatives were found to assemble, forming quite uniform Langmuir monolayers at the water/air interface. For example, 3J assembled into a monolayer at the water/air interface and provided a surface similar to the Langmuir film of fatty acids in the nucleating of mineral crystallization on the water/air interface. The number average molecular weight and dispersity of the hyperbranched polyphenylene were 32,000 and 1.03, respectively. The quaternary salt 3S was prepared by reaction of the chloromethyl derivative 3L with a slight excess of A^-methylimidazole. Elemental analysis of the product, which precipitated from ether, indicated that about 35% of the theoretical amount of benzylic chloride was converted to this imidazolium salt 3S, which is water-insoluble and only slightly soluble in MeOH. In contrast to ionic derivatives, the bromo derivative (3) did not form a Langmuir monolayer. The related hydroxymethyl derivative 3K formed an unstable Langmuir film, which collapsed below 20 mN/m, while, 3S, which possesses a classical amphiphilic structure in a two-dimensional presentation, formed stable monolayer films with collapse pressures as high as 60 mN/m without much hysteresis (Figure 1). The tangent of the Il-A curve has an intercept at approximately 9.6 A^ per repeating unit. If one considers that the degree of polymerization is 400 from the GPC data, the radius of the area for an average polymer on the air/water interface is about 70 A, fairly approximating the mean radius of gyration ^^^ of polystyrene of same molecular weight, which is about 50 A.^^ Since the polymers have an ellipsoid rather than spherical shape, we speculate that the flat side of the ellipsoids are at the water/air interface, thus, occupying a larger area than expected. The additional

YOUNG H. KIM

136

35 - ;

\

\

1

1

1 "

30 ^ 25 -

E ^

20-

E ^ 1 5 C 10 5 -

0 4

[1

8

12

16

20

Area/Repeating Unit (A^) Figure 1. Hysteresis isotherm of polymer 3S on a water/air interface. The compression and decompression rate is 50 Mm/min.

volume of about 35% due to the imidazole unit could also contribute to the discrepancy. On the other hand, the possibility of various conformations due to atropisomerism of phenyls and cavities around the phenyl rings could have an opposite effect. Deposition of a monolayer film of 3S at 20 mN/m surface pressure on a silicon wafer was achieved by z-type with transfer efficiency consistently in the range of about 0.5-0.6 (Figure 2). Such low transfer may imply that the hyperbranched polymer can be squeezed under compression, through either conformational change or intercalation. The overcompression could be reUeved by transfer onto a solid substrate where the molecule occupies an area larger than on the water/air interface. The thickness of the deposited monolayer measured by ellipsometry was about 32A for thefirstfew layers, but this number declined slowly as the number of depositions increased. The homogeneity of thefilm,judged from the standard deviation of thefilmthickness, also deteriorated. The

Highly Branched Aromatic Polymers

137

(0

c

CO

2

4

6

8

10

Number of Layers Figure 2. The transfer of a Langmuir-Blodgett film of polymer 3S to a silicon wafer.

large discrepancy between the radius of the molecule on the water/air interface and the monolayer film thickness might also be related to the unique structural feature discussed above. The structure of these amphiphiles is radically different from that of conventional Langmuir film-forming amphiphiles, where segregation of the hydrophobic and hydrophilic parts of molecules at the air/water interface is a prerequisite. This is the first example of a LangmuirBlodgettfilmthat is fabricated with a micellelike substance. It is intriguing that amphiphilicity is still required to form a stable monolayer film of hyperbranched polymers, in spite of their fundamental structural differences from conventional amphiphiles. G. Blending with Other Polymers

If polymeric molecules were to show an interaction with 3 in the way that small aromatic compounds form complexes with 3B, such interac-

138

YOUNG H.KIM

tions could provide the necessary free energy for polymer miscibility. In the glassy state, the complexation could function as a physically reversible cross-linking of the polymer chain. In the molten state, where such static interaction would not be sustained, a spherical hyperbranched polymer could affect the rheology of another polymer. Polystyrene and poly(vinylchloride) (PVC) were chosen to test this hypothesis. Polystyrene Blend

These polymers can be blended either in solutions or in the melt. A blend of up to 2% of polymer 3 with polystyrene appeared clear, but turbid blends resultedfromhigher percentages of polymer 3. The Tg's of blended polymers containing up to 30% of polymer 3 did not change from that of pure polystyrene. Transmission electron microscope (TEM) analysis of the 5% blend showed that there are bimodal distributions of polymer 3 domains, a small amount of approximately 10 nm domains, and a large portion of approximately 1 \i domains. In spite of this evidence of possibly poor mixing, some noticeable changes were found in the rheology and thermal stability of polystyrene. In comparing two polystyrene blends, one with 5% of polymer 3 and the other with 0.1% (control), the melt viscosity of the 5% blend was about 50% at 180 °C and 80% at 120 °C, respectively. The eifect was more drastic at higher temperatures and higher shear rates. The addition of polymer 3 also seemed to improve the thermal stability of polystyrene. When the molten blend polymer was kept at 180 °C for some time, the melt viscosity of the 0.1% blend increased, whereas that of the 5% blend remained constant. Polystyrene blended with 2% of polymer 3 was injection molded into 1/8-inch wide flex and tensile bars for mechanical measurement. It had no effect on the flexural modulus of polystyrene, but a significant improvement in the initial modulus with a concomitant sacrifice in the maximum strength was obtained. Weak cross-Unking of polystyrene by polymer 3 through aryl-aryl interaction might be responsible for the high initial modulus. PVC Blend

For the most part, this pair of polymers was mixed in solution. In contrast to polystyrene, polymer 3 had no noticeable influence on the

Highly Branched Aromatic Polymers

139

0^ K> "-^

o • (0 (0

, /^5

0-^ -H

t •

o

•

D O

•

i o

0'

Filled: with 5 % HBP Open: with 0 . 1 % H B P Circle: atlOO'^C Diamond: at 120°C Square: at140°C

H

9

in

8 1000 -^
8

00 1

10

100

1000

.o 10^

10^

Shear Rate (/sec) Figure 3. Melt viscosity of PVC containing polymer 3 at 100-140 °C in a capillary rheometer.

properties of PVC. Addition of 5 weight % of 3 also had no significant effect on the rheology of PVC. The capillary melt viscosities of PVC containing 0.1% (control) and 5% of 3 are identical, as shown in Figure 3. There were also no changes in the Tg's of PVC blends containing up to 30% of 3. The difference in the effect of 3 on the rheologies of polystyrene and PVC suggested that compatibility of a polymer with a hyperbranched polymer is an important prerequisite. Even though the evidence may be circumstantial that 3 is compatible with polystyrene, a certain degree of compatibility is important to provide a rheological effect. H, Star-Branched Polymerization

Several strategies have been developed in the last few decades to make star-shaped polymers. Star polymers containing a microgel core can be

140

YOUNG H.KIM

made either by a "core first"^^ or an "arm first"^^ method, that employs bifunctional monomers to tie up reactive chain ends as a cross-linked core. These procedures allow one to make star polymers with more than 100 arms.^^ Better defined star polymers with fewer arms can also be made by coupUng reactive polymer chain ends, such as those in a "living" polymer, with multifunctional linking agents,^^ or by initiating polymerization with multifunctional initiators.^^ In principle, any hyperbranched polymer with suitable end groups could serve as a multifunctional initiator or linking agent for various types of polymerizations. The hyperbranched polymer 3 (M^ « 3,500) would have about 50 terminal functional groups capable of forming the same number of star arms. Such a possibility was explored mostly with short-arm star polymers. Thus a large fraction of the polymer moieties are polyphenylene. Since they have very high core segmental densities, the short chains should be extended. Star polymers with short chains deviate greatly from the normal behavior predicted by theory. Therefore, characterization of these star polymers by conventional methods may not necessarily be meaningful. First, star-shaped polymers with arms analogous to oUgomeric polyethylene were prepared by reaction of polymer 3A with chlorosilanes having one long-chain alkyl group to illustrate that the hyperbranched polymer can act as a multifunctional linking agent. The coupling yield decreased as the length of alkyl group increased. By GPC, the peak molecular weights of the polymers showed linear increases with the sizes of the arms. Similar to polymers with small functional groups, the alkyl silyl end groups controlled the physical properties of the polymers. Derivatives 3B, 3D, 3L and 3R can be used as initiators in various types of "living" polymerization to generate star polymers. Since ringopening "living" polymerization of p-propiolactone by aromatic carboxylate anion initiators is well known, the possibility of using carboxy-containing polymers^ 3B and 3J, for the polymerization of 2-methyl-2-propyl-3-propiolaptpne was investigated. Polypropiolactone of relatively low dispersity (D < 1.3) was obtained by using an initiator from the equilibration pf 3B with tetraheptylammonium bromide in toluene. The molecular weights of the resultant star polymers were about three times larger than those o^peeted for linear polymers. However, these polymers exhibited much lower molecular weights than expected. It seems that the efficiency in initiating star polymerization by these

Highly Branched Aromatic Polymers

141

multifunctional initiators was rather low. This observation agrees with a report that even three-arm star polymers could not be prepared efficiently from multifunctional initiators.^^ Anionic polymerization of poly (methyl methacrylate) (PMMA) using the Grignard reagent prepared from polymer 3L was also attempted for low molecular weight star polymers. The PMMA segment was essentially syndiotactic. ill. POLYESTERS Because of their uncomplicated syntheses, aromatic polyesters are the most widely studied class of highly branched polymers. The polyesters were prepared in a single step by condensation polymerization from aliphatic dihydroxy monoacids or by stepwise syntheses. A. Single-Step Polymerization Thermally stable copolymers of 3-(trimethylsiloxyl)- and 3,5bis(trimethylsiloxyl)benzoyl chloride (4A) or 3-acetoxy- and 3,5-diacetoxy-benzoic acid (4B) were prepai-ed with mole ratios of AB:AB2 monomer ranging from 160-5.^^ Polymers containing 10-20 mole % of branching monomers were insoluble in CHCI3 but soluble in polar solvents, such as MA^-dimethylformamide (DMF) or a mixture of pyridine and benzene. Compared to the linear homopolymer of 3-hydroxybenzoic acid, the branched polymer showed lower crystallinity and slower crystallization. There was an inverse linear relationship between percent crystallinity and the number of branches in the chain. Similarly, in an attempt to improve moldability and decrease anisotropy of rigid aromatic polyesters, 0.3-10 mole % of 1,3,5-trihydroxybenzene, 3,5-dihydroxybenzoic acid, and 5-hydroxyisophthalic acid were copolymerized with p-hydroxybenzoic acid/terephthalic acid/4,4'-dihydroxydiphenyl.^^ The branched polymer showed a lower orientation and possessed improved flex properties. Homopolymers of branching multifunctional monomers have also been reported. Aliphatic polyesters were prepared by condensing a polyhydroxy monocarboxylic acid of formula (HO)„-R-COOH, for example, 2,2-di(hydroxymethyl)propionic acid, in either DMF or xylene in the presence of an acid catalyst with azeotropic distillation of water. Since these polymers have a large number of functional groups, they are

142

YOUNG H.KIM

HO^ T

CI (CH3)3SiO^'^^*-'^OSi(CH3)3 4A

OSi(CH3)2(/-Bu) AcO^^^-^^^OAc 5A

4B

^

OH

OAc 5B

a op ^oA o^o X" j-^

i

o

OXK°

B2IO-X4

r

r/

Scheme 7.

useful as components of coating compositions.^'* Condensation of 3,5diacetoxybenzoic acid (4B) or 5-acetoxyisophthalic acid (5B) gives polymers 6A and 6B which show Tg's at 161 and 269.2 °C, respectively. These polymers were prepared under standard conditions for polyarylate condensation polymerization, under high temperature and vacuum to remove acetic acid. They show good solubility in various organic solvents, whereas 6B is soluble in aqueous alkali owing to its terminal carboxylic acid groups.^^ Similarly, the homopolymer of 4A was prepared by thermal self-condensation.^^ Highly soluble hyperbranched polymer 6C was obtained in 80% yield with weight average molecular weight (M^) equalling 30,000-200,000. The polydispersity and molecular weight of the polyester varied greatly with the polymerization temperature. The degree of branching of the polyester, as determined from its NMR spectra detailed in Section II, was 55-60%. This polyester, which after hydrolysis contained hydroxy functional groups at all chain extremities, has a Tg of 190 °C and very high thermal stability comparable to the analogous linear polyesters.

Highly Branched Aromatic Polymers

143

B. Symmetrical Polyesters

The stepwise convergent syntheses of a series of monodisperse dendritic polyesters, end capped with phenyl rings, has been reported.^^'^^ These polyesters are based on 1,3,5-benzenetricarboxylic acid ester, as the core material, and a protected 5-hydroxyisophthalic acid derivative 5A, as the building block. The hydroxy 1 group of 5-hydroxyisophthalic acid was protected with a f^rr-butyldimethylsilyl group and the carboxylic acids were converted to the corresponding acid chlorides. Reaction of the diacid chloride with phenol, which serves as the end cap, followed by removal of the silyl protecting group, gave a new substituted phenol, which could be used either as a next generation wedge or could be coupled to the core to generate a dendrimer. These cascade polymers consist of 4 [6(4)], 10 [6(10)], 22, and 46 benzene rings, and the largest, 6(46), is estimated to have a molecular diameter of 45 A. A study of the reaction kinetics suggests that the rate of reaction of the dendrimer wedges with the core is independent of the wedge size. These materials are stable at 500 °C under an inert gas and are highly soluble in typical organic solvents. A stepwise synthesis using 3,5-dihydroxybenzoic acid, as the building block, was also attempted in our laboratory.^^ The hydroxy] groups were protected with benzylbromide using K2C63 in acetone. Methyl 3,5-hydroxybenzoate, the core material, was subsequently prepared by methylation of 3,5-di(benzyloxy)benzoic acid, followed by hydrogenolysis of the benzyl group with Pd/C catalyst in ethanol. Under 37.5 psi hydrogen pressure, about 20 hours were needed for complete debenzylation. The acid chloride building block was prepared from the same protected acid with thionyl chloride. The first tier, 6D, was obtained in 86% yield by coupling the acid chloride with the dihydroxy core in THF containing 1.25 equivalents of triethylamine. This compound did not crystalhze, but showed a Tg at 29.5 °C by differential scanning calorimetry (DSC). We found, however, that the benzyl protecting group was unusually resistant to hydrogenolysis under the conditions described above. Reductive deprotection of the benzyl group in higher homologues was reported^^ to be facile. As in the case of polyphenylenes, the Tg's of symmetrical polyester dendrimers up to 46 rings demonstrated a steady increase with increasing molecular weight, and there was a large difference in the range of T 's

144

YOUNG H.KIM Table 4. The Class Transition and Melting Temperatures of Branched Aromatic Polyesters

6(4) 6(10) 6(22) 6(46) 6A 6B 6C 6D

End Groups

TgTC)

T^YC)

phenyl phenyl phenyl phenyl 3,5-diacetoxyphenyl 5-isophthalic 3,5-dihydroxyphenyl benzyl

none

176-178 none none none none none none none

100 133 141 161 269 190 29.5

Notes: ^ h e glass transition temperature (T ) is the midpoint of the glass transition at a heating rate of ft °C/min. The melting temperature (Tj^^) is the onset of melt at a heating rate of 15 °C/min.

between symmetrical dendrimers and single-step polymers (Table 4). Due to the nature of polymer construction, the single-step polymerization always rendered polymers with polar end functional groups. It was claimed that the Tg of branched polymer 6C was in the same range as that of a linear analog, whereas, the branched structure had little effect on the Tg. However, considering the ambiguity in the nature of motions related to Tg's and the contribution of the polar functional groups to the Tg, such an observation could be coincidental. Unlike the case of polyphenylenes, where polymers with polar functional groups did not show a Tg, polyesters with hydroxy or carboxy groups showed distinct Tg's. The carboxy chain-ended polymer showed a higher Tg. The large difference in Tg between 6(4) and 6D is noteworthy. Even though 6D has a more flexible benzyl end group, which could lower the Tg, the more symmetrical nature of 6(4) might have contributed to raising the Tg. C. Applications Since polyesters undergo facile transesterification, their use as rheology controlling agents in polyesters has been limited. However, since they contain a large number of hydroxyl or carboxy functional groups, which can be cross-linked, their use in coatings is suggested. Different degrees of crosslinking density could be achieved by employing various

Highly Branched Aromatic Polymers

145

mole ratios of the hyperbranched polymer to the multifunctional linker. For example, use of these polymers as cores for star-shaped polymers, as "beads" in linearly linked polymers, and as modules for modular cross-linked networks have been proposed.^^ IV. POLYPHENYLETHERS Even though there are several claims to the preparation of highly branched polyphenylene ethers, the characterization of these polymers has not been substantiated.^^ A. Synthesis

Low molecular weight polymer 8A, prepared from 2,4,6-tribromophenol (7A), has been known since the 1920's.'*° This phenol is an example of the AB3-type of monomer. It can be readily polymerized via an oxidativefree-radicalintermediate and is readily polymerized in a mixture of degassed water and benzene or toluene with 1 equivalent of NaOH and a catalytic amount of KjFeCCN)^. With 1 equivalent of calculated base, the polymerization solution became viscous in about 15 min., but only about a 30% yield of a white polymer was obtained after 12 hours. The molecular weight of this product, as determined by GPC, was low (M„ = 4730, D = 1.63). Its elemental analysis showed that the bromine content (68.34 %) was equal to theory and it had a Tg equal to 148.8 °C by DSC. Higher molecular weight polymers can be obtained in high yields by adding KOH to neutralize the phenol, assuring that the phenol dissolves completely in water prior to the addition of the initiator. Thus, on a 1 mole scale polymerization, a total of 1.3 moles of KOH was needed to dissolve the phenol completely in 1.5 1 water. A small portion of 7A was then added to insure neutrality. The final mole ratio of KOH to phenol was 1.29:1. Polymerization was carried out by adding 1.0 1 of toluene and 4.5 mmole (0.45 mole % per phenol group) of K3Fe(CN)6 in water. The product started to precipitate from solution within 2 hours, and the solution viscosity increased rapidly. After 24 hours at 20 "^C, the solution was neutralized with 6N HCl. Afterfiltrationand reprecipitation from THF into MeOH, a high molecular weight polymer (GPC: M^ = 152,000, D = 3.3) was obtained. In another run at 0.5 mole scale, a polymer was obtained in 91 % yield. Thermal gravimetric analysis (TGA) revealed the presence of about 5% of volatiles below 240 °C, which could

146

YOUNG H.KIM

be due to low molecular weight material or monomer. When the polymer was triturated with MeOH, about 8 weight % of substances was removed, and no further weight loss was found by TGA. Using NaOH instead of KOH under otherwise identical conditions, generally a lower molecular weight polymer (M^ = 14,200, D = 1.7) was obtained. A high molecular weight polymer (M„ = 54,000) can also be obtained using KI3 instead of K3Fe(CN)5 as the radical initiator. This polymer has poor solubility in THF and other chlorinated or aromatic solvents. A series of experiments was conducted to determine the effect of a phase transfer catalyst (PTC) on the polymerization. Under standard phase transfer conditions with tetrabutylammonium fluoride as the PTC, only a low molecular weight polymer (M^ = 1,100) was obtained. With a large excess of KOH in the aqueous phase, a high molecular weight (Mp = 113,000) polymer was obtained, but in low yield (10%). Under PTC conditions, initiation with KI3 gave a low yield of a low molecular weight polymer (M^ = 11,500). The low solubility of 8A could be due to excessive branching and low interbranch void regions, which are necessary for intercalation of solvent to enhance solubility kinetics. To circumvent these problems, a less dense AB2-type of phenolic monomer was explored. Since a symmetrical monomer, 3,5-dibromophenol, is not readily available, 2,4-dibromophenol 7B was employed. Unfortunately, no polymer was obtained from 7B under the conditions utilized in the polymerization of 7A. Using KI3 as an oxidant, iodate color dissipated rapidly, when added to the solution, indicating that the iodine is consumed by possible ortho iodination. This observation leads to the speculation that the free-radical electron density at the ortho-carhon is so high that the free radical is consumed in making biphenyl or phenylene ethereal dimers. In order to confirm this hypothesis, one equivalent of K3Fe(CN)6 and 2,4-dibromophenol was reacted with one equivalent of NaOH with the hope of isolating the dimers. None were isolated, but a polymer of M^ = 9210, D = 2.8 was obtained in fair yield. The crude polymer also contained a fair amount of the starting material and insolubles. To understand the scope of the reaction, the polymerization was conducted with various mole ratios of NaOH and K3Fe(CN)6 to phenol, and then the crude phenolic products were methylated with methyl sulfate. From the crude reaction mixtures, THF-insoluble fractions (A), THF-soluble but MeOH-insoluble fractions (B), and MeOH-soluble

Highly Branched Aromatic Polymers

147

Table 5. Methylation of Polymer 7B Amount of Phenol 2.52 g

5.04 g

5.04 g

5.04 g

Mole ratio of Phenol/Fe^'^/NaOH 10/8.1/10

total weight 20/40/20

total weight 20/21/250

total weight 20/10/20

total weight

Fraction^ A B C A B C A B C A B C

Product Weight GPC^ (M,^,D) 0.34 g 0.45 0.64 1.43 g 0.02 1.36 0.80 2.18 0.02 0.95 2.97 3.94 0.31 0.73 1.99 3.03

2 380, 6.4

2 110,6.5

2 780, 2.4

1 830, 6.8

Notes: ^Fraction A is THF-insoluble; Fraction B is THF-soluble but MeOH-insoluble; Fraction C is MeOH-soluble. Gel permeation chromatographic analysis of M^j, number average molecular weight and D, polydispersity M^^,/M^ where M^^ is the weight average molecular weight.

fractions (C) were isolated. Fraction C was found to be 2,4-dibromoanisole and the methylated monomer 7B. Fraction B consisted of low molecular weight polymers. Polymerization yield and molecular weight depended on the reaction conditions and are tabulated in Table 5. Slightly less than an equivalent of oxidant initiated the polymerization, but a large quantity of insoluble polymer resulted. Excess base either delayed or prevented polymerization, leaving unreacted monomer. If the coupUng reaction preceded in the manner expected for condensation of an AB2 monomer, there could be only one OH group per polymer and a molecular weight of 2500 corresponding to a degree of polymerization of about 15. Once methylation of the free phenolic moieties was complete and since each repeating unit contains three aromatic protons, there should be 45 aromatic protons and 3 methoxy

OH Bfv. .is^s^ ,Br

Br

i>V ^

7A

3-° OH Br

Br 7B

NaOH 1 eq. K3Fe(CN)6

Br

Bn

Br

Br

Scheme 8. 148

Highly Branched Aromatic Polymers

149

protons. In the ^H NMR spectrum, the intensity ratio of the aromatic and methoxy protons was four, indicating that, even though no dimer was found in the mixture, there must be some carbon-carbon radical coupling, in the manner shown in Scheme 8, giving more than one OH group per polymer molecule. Attempted copolymerization of 7A and 7B with a catalytic amount of K3Fe(CN)6 gave no polymer, confirming that 7B inhibits the free-radical coupling process. Thus it was instructive to compare these results with reactions of 4-bromo-2,6-dimethylphenol under siniilar conditions. It polymerized at the interface between the benzene and aqueous alkaline phases with a catalytic amount of oxidative initiator such as Pd02 or K3Fe(CN)6. The polymerization was assumed to proceed via an anion radical mechanism."*^ It was also polymerized in an organic solvent with a catalytic copper-amine reagent."*^"^^ Recently, Percec et al. reported"*^ a well-controlled polymerization under PTC conditions, using tetrabutylammonium hydrogen sulfate as the phase transfer reagent and oxygen as the oxidant. Their mechanistic study of the free-radical reaction of 4-bromo-2,6-dimethylphenol revealed that /?-bromo derivatives are unique in reactivity compared to other halide or alkyl derivatives. The bromide group has a negative inductive effect, so that the oxidation of p-bromophenolate is slower than other phenolates. Once the radical is formed, it is less stable and can undergo either carbon-carbon coupling to give a diphenoquinone or bromide displacement, resulting in consumption of the radical. Even though those phenols, possessing a free ortho-position, can possibly form dimers by C-O or C-C coupling, no dimers were found when a phenol and 2,4,6-tri-r-butylphenoxyl were reacted."^^ This indicates that steric effects play an important role in the coupling reaction. Since o-bromine even further reduces the electron density on oxygen in phenols, this unusual effect of the bromine substitutuent may be more drastic in 7B. The fact that more than one equivalent of oxidant was needed for successful reaction supports the idea that either free-radical formation is very slow (thermodynamic control) or that polymerization is taking place by radical-radical rather than radical-anion (S^lO coupling, thus consuming the free radicals."^^ There has not yet been any effort to construct symmetrical polyethers.

YOUNG H. KIM

150

B. Effect on Rheology

The Theological effect of 8A on polystyrene was investigated. This polymer generally showed much lower solubility in organic solvents compared to the corresponding hyperbranched polyphenylene. Since the miscibility of the hyperbranched polymer with the matrix polymer seemed to be important for its role in rheology control, the effect of 8A was not expected to be outstanding. Indeed, the melt viscosity of polystyrene containing 5 weight % of 8A (M^ = 50,000) was more or less the same as that of pure polystyrene as shown in Figure 4. Polystyrene containing higher molecular weight 8A showed higher melt viscosity. The rationale for these effects is not yet understood.

PS with 5% 500K PPE

1000 + in

o o

(0 • MM

>

00

PSwith 5 % 50K PPE

10 10

100

1000

10'

Shear Rate (sec '^) Figure 4. Melt viscosity of polystyrene containing polymer 8A in a capillary rheometer.

Highly Branched Aromatic Polymers

151

V. POLYAMIDES Even though the prospective importance of hyperbranched poly amides is as great as polyesters, much less attention has been given to hyperbranched aromatic polyamides. Due to the strong hydrogen bond, oligomeric aromatic polyamides are more crystalline and less soluble than polyesters. In spite of this, high molecular weight polymers can be prepared from AB2-type monomers."^^ For symmetrical dendrimers, only low molecular weight oligomers have been reported.^^ A. Preparation The building blocks were prepared from the corresponding aromatic amino acids."^^ Thus, 3-aminoisophthalic acid and 3,5-diaminobenzoic acid were reacted with thionyl chloride to form the corresponding sulfmylamino acid chloride derivatives (9A and lOA). These were then dissolved in ether and treated with dry, gaseous hydrochloric acid to give amino acid chloride hydrogen chlorides (9B and lOB). In an amide solvent, hydrogen chloride dissociates to give free amines and condensation occurs (Method A of Scheme 9). Alternately, the sulfinylamino acid chloride derivatives can be directly polymerized in an amide solvent with one equivalent of water based on the sulfinylamino group (Method B of Scheme 9). When the amino acid chlorides were used, the powdery monomers were added to an amide solvent chilled with an ice bath. The monomer dissolved within minutes, and the solution remained clear throughout the reaction. With the corresponding sulfmylamino acid chlorides, when one equivalent of water was added rapidly to the monomer solution at low temperature, the solution turned dark and this color persisted until the reaction was quenched into water. The polymers are usually obtained by precipitating into water, followed by filtration. Polymer 11A precipitated from water, but polymer IIB did not precipitate immediately from water. The precipitation of IIB was achieved only when a salt, such as ammonium sulfate, or a base was added to a mixture of A^-methylpyrrolidinone (NMP) and water. The hydrochloric acid generated during the polymerization converted the amine group of polymer IIB to the hydrochloride salt, ensuring the polymer's water solubility. The salt form of IIB is better obtained by quenching into an organic solvent, such as toluene or

Method B

HfltNMP

Method A ___)

NMP

Scheme 9.

154

YOUNG H.KIM

CH2CI2. The methyl ester of polymer 11A was prepared by the addition of MeOH at the end of the reaction. The amide solvent seems to bind tightly to the polymer. Even following vigorous drying after precipitation in water, a large amount of NMP, the polymerization solvent, was found, by NMR and TGA analysis, to be trapped within the polymer. B. Characterization Polymers l l A and IIB are soluble in amide solvents, such as NJ^-dimethylacetamide (DMAc), DMF, and NMP. In a comparative solubility experiment with mixtures of DMAc/NMP and DMAc/DMF, these polymers showed better solubility in the latter. Thus DMF exhibited a slightly higher dissolving power than NMP for these polymers. On the other hand, the hydrochloric acid salt of IIB showed much lower solubility characteristics. Only very dilute solutions can be prepared in NMP, and the solubility in DMAc and in DMF was low. When the polymer was prepared in CaCl2-saturated NMP at 1 weight % polymer concentration, the polymer remained in solution throughout the polymerization. However, in CaCl2-saturated DMAc, the polymer partially precipitated during polymerization. For polymerization of IIB, DMF seemed to be the poorest among these solvents. This solubility behavior was related to the basicity of the amide solvents. The polymer was soluble only after the hydrochloride was neutralized with the basic solvents. Therefore the more basic the solvent, the better for dissolving this polymeric salt. Unlike the hyperbranched polyphenylene, polymer l l A with COOH groups at the surface did not dissolve in aqueous alkaline solution. For a given polymer, the solubility characteristics can be correlated to the conditions of polymerization. Thus, when polymer 11A was prepared in NMP or NMP/CaCl2, ^^ dissolved rapidly in DMF at 20 °C. However, when the polymerization was conducted in the presence of a base such as Ca(0H)2, the polymer was insoluble in these amide solvents after isolation. Molecular weights of UA, determined by GPC using a DMAc/LiBr/H3P04/THF mixture as the carrier solvent, ranged from 24,00(M6,0(X) with polydispersity 2.0-3.2. In pure DMF as the carrier solvent, the exclusion volumes corresponded to molecular weights of 700,000-1,000,000, indicating that the polymer may form aggregates in the absence of complexing ions, even in a dilute solution. The aggrega-

Highly Branched Aromatic Polymers

155

tion is not due to the end group effect, because the methyl ester of this polymer also showed the same degree of association. C. Lyotropic Properties

Polymers llA and the hydrochloric acid salt of IIB showed lyotropic properties in concentrated amide solutions evidenced by shear birefringence under polarized light. A 60 weight % solution of UA was a hard gel under static conditions, but became more fluid as shear force was applied. The methyl ester of llA also showed birefringence at 20 °C, but it became isotropic at about 70 °C. This unusual behavior may be related to the propensity of the polymer to form aggregates in amide solvents as observed in the GPC experiment. Indeed, these polymers show no birefringence in amide solvents containing as little as 0.1 weight % CaCl2. The free base of polymer UB, which is highly sensitive to oxidation, did not exhibit birefringence in NMP solution. A preliminary X-ray diffraction study of polymer llA showed absolutely no crystallinity. A 70 weight % solution of this polymer in NMP showed an almost identical X-ray diffraction pattem with a slightly broader peak width, implying that the birefringence texture has more resemblance to that of the neumatic phase. REFERENCES 1. Buhleier, E.; Wehner, W.; Vogtle, F. Synthesis 1978, 155. 2. Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985,50,2003. 3. Flory, R J. Principles ofPolymer Chemistry, Cornell University Press: Ithaca, 1953, Chapter 9. 4. Aharoni, S. M.; Crosby, C. R., Ill; Walsh, E. K. Macromolecules 1982,75,1093-8. 5. Aharoni, S. M.; Murthy, N. S. Polym. Commun. 1983, 24, 132. 6. De Gennes, R G.; Hervet, H. J. Phys. Lett, 1983,44, 351. 7. Farin, D.; Avnir, D. Angew. Chem. 1991,103, 1409. 8. Klein, D. J. J. Chem. Phys. 1981, 75, 5186. 9. Lescanec, R. L.; Muthukumar, M. Macromolecules 1990,23, 2280. 10. Maciejewski, M. J. Macromol Scl, Chem. 1982, A17, 689. 11. Mansfield, M. L.; Klushin, L. 1.7. Phys. Chem. 1992,96, 3994. 12. Mourey, T. H.; Turner, S. R.; Rubinstein, M.; Fr^chet, J. M. J.; Hawker, C. J.; Wooley, K. L. Macromolecules 1992,25, 2401. 13. Naylor, A. M.; Goddard, W. A., III. Polym. Prepr., Am. Chem. Soc. Div. Polym. Chem. 19SS, 29, 2156. 14. Kim, Y. H.; Webster, O. W. Polym. Prepr, Am. Chem. Soc. Div. Polym. Chem. 1988, 29, 310.

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15. Kim, Y. H.; Webster, O. W. Macromolecules 1992,25.5561. 16. Lacrock, R. C. Comprehensive Organic Transformations: A Guide to Functional Group Preparations; VCH: New York, 1989. 17. Miyaura, N.; Yanagi, T.; Suzuki, A. Syn. Commun. 1981, 77, 513. 18. Yamamoto, T; Hayashi, Y; Yamamoto, A. Bull Chem. Soc. Jpn. 1978,57, 2091. 19. Beletskaya, I. P. J. Organometal. Chem. 1983,250,551. 20. Quirk, R. R; Chen, W. C. Makromol Chem. 1982,183,2071. 21. Miller, T. M.; Neenan, T. X. Chem. Mater. 1990,2, 346. 22. MiUer, T. M.; Kwock, E. W.; Neenan, T. X. Macromolecules 1992,25, 3143. 23. MiUer, T. M.; Neenan, T. X.; Zayas, R.; Bair, H. E. J. Am. Chem. Soc. 1992, 77^, 1018. 24. Moore, J. S.; Xu, Z. Macromolecules 1991,24, 5893. 25. Kim, Y H.; Webster, O. W. J. Am. Chem. Soc. 1990, 772,4592. 26. Rengan, K.; Engel, R. J. Chem. Soc, Perkin Trans. 11991,987. 27. Eschwey, H.; Hallensleben, M.; Burchard, W. Makromol. Chem. 1973,173, 235. 28. Worsfold, D. J.; Zilliox, J.; Rempp, R Can. J. Chem. 1969,47,3379. 29. Eschwey, H.; Hallensleben, M. L.; Burchard, W. Angew. Chem., Int. Ed. Engl. 1974, 75,412. 30. Hadjichristidis, M.; Guyot, A.; Fetters, L. J. Macromolecules 1978, 77, 668. 31. Fujimoto, T.; Tani, S.; Takano, K.; Ogata, M.; Nagasawa, M. Macromolecules 1978, 77,673. 32. Kircheldorf, H. R.; Zang, Q.; Schwarz, G. Polymer 1982,23, 1821. 33. Ueno, K. G.B. Patent, 2 132 626 1982. 34. Baker, A. S.; Walbridge, D. J. U.S. Patent 3 669 939,1972. 35. Figuly, G. D. U.S. Patent 5 136 014, 1992. 36. Hawker, C. J.; Lee, R.; Fr6chet, J. M. J. J. Am. Chem. Soc. 1991,113,4583. 37. Kwock, E. W; Neenan, T. X.; Miller, T. M. Chem. Mater 1991,3,775. 38. Kim, Y H.; Figuly, G. D. Unpublished results. 39. Serroni,S.; Denti, G.;Campagna, S.; Juris, A.; Ciano, M.; Balzani, V. Angew. Chem. 1992,104,1540. 40. Hunter, W. H.; Woollett, G. H. J. Am. Chem. Soc. 1921,43,135. 41. Staffine, G. D.; Price, C. C. J. Am. Chem. Soc. 1960,82,3632. 42. Blanchard, H. S.; Finkbeiner, H. L.; Russell, G. A. J. Polym. Sci. 1962,58,469. 43. Risse, W; Heitz, W; Freitag, D.; Bottenbruch, L. Makromol. Chem. 1985, 186, 1835. 44. Percec, V; Shaffer, T. D. J. Polym. Sci., Polym. Lett. Ed. 1986,24,439. 45. Bolon, D. A. J. Org. Chem. 1967,32,1584. 46. Percec, V.; Wang, J. H.; Clough, R. S. Makromol. Chem., Macromol. Symp. 1992, 54/55, 275. 47. Kim, Y H. J. Am. Chem. Soc. 1992,114,4947. 48. Kwolek, S. L.; Morgan, P. W; Schaefgen, J. R.; Gulrich, L. W Macromolecules 1977,10,1390.

DENDRITIC BOLAAMPHIPHILES AND RELATED MOLECULES

Gregory H. Escamilla

I. INTRODUCTION 11. NONIONIC BOLAAMPHIPHILES A. Molecular Assemblies B. Functional Vesicles C. Biological Activity D. Ion Transport III. IONIC BOLAAMPHIPHILES A. Molecular Assemblies B. Functional Vesicles C. Biologically Active D. Transports IV. CONCLUSION REFERENCES

Advances in Dendritic Macromolecules Volume 2, pages 157-190. Copyright © 1995 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-939-7

157

158 159 159 168 170 173 176 176 184 186 187 188 188

GREGORY H.ESCAMILLA

158

1. INTRODUCTION Amphiphiles, molecules possessing both hydrophilic (head group) and lipophilic (tail group) moieties,^ have formed the cornerstone of work on structure and functional application of micelles and membranes. One logical modification of the amphiphilic structure would simply be the addition of a second hydrophilic group to the other end of the lipophilic moiety to form the novel class of surfactants called bolaamphiphiles.^ A bolaamphiphile can be defined as two or more hydrophilic groups connected by lipophiUc functionalities (Figure 1). Other terms, such as bolaform amphiphile^ or two- (or more) directional arborol,^ have been used to describe molecules possessing this general architecture. BolaHO

9"

II / H(OCH2CH-,)6CC(C H )x

\ c H ^CC(CH2CH20)gH

o "0 7 ^ 0 ^ CH3(CH2)n<,
\

/ ^ O " \0H

i

(CH2)nCH3

Figure 1. Early examples of bolaamphiphiles (refs. 2, 9, 3, and 5 respectively).

Dendritic Bolaampliiphiles and Related Molecules

159

form electrolytes or bolytes, a term introduced initially by Fuoss and Edelson in 1951,^ are structurally similar, except that the hydrophiUc groups are ionic."* Since Fuhrhop and Mathieu^ reported the synthesis and self-assembly of several bolaamphiphiles, numerous researchers have explored and exploited their applicability to a variety of situations. Some have changed the basic bolaamphiphile form by appending long hydrocarbon chains to the head groups yielding a structural variation termed a "gemini surfactant".^ Menger and Littau initiated this term in 1991 to describe amphiphiles having, in sequence, a long hydrocarbon chain, an ionic group, a rigid spacer, a second ionic group, and another hydrocarbon chain.^ Rosen recently reviewed gemini surfactants and extended the definition of "gemini" to also include flexible spacers.^ Jayasuriya et al.^ introduced another variation with their polymeric bolaamphiphiles, where the surfactants are linked via the hydrophilic head groups. A search of current literature reveals the considerable utilitarian potential for bolaphiles, short for bolaamphiphiles, including: formation of ultrathin monolayer membranes, inclusion of functionalities into membranes, and disruption of biological membranes. This potential could be exploited as therapeutic agents,^'^^ "antisense" agents,^^'^^ catalysts in reactions,^^"^^ as well as models for the membranes found in thermophilic archaebacteria.^^ Synthetic bolaphilic membranes can be tailored to provide binding sites for guests,^^'^^ or other functionality can be incorporated, such as redox- and/or photoactive moieties."* The repertoire of bolaamphiphilic assemblies include: gels formed by specific two-directional arborols,^'*^^^ and rods and tubules formed by a-(L-lysine)-CD-aminobolaphiles.^^ Inclusion of polymerizable functionalities, in either the head groups or within the lipophilic spacer, can provide convenient routes to extended covalently linked domains.^'^^'^^ Bolaphiles also provide synthetic chemists with tools to explore novel molecular architectures, as well as interactions between juxtaposed structural elements. Examples cited herein illustrate recently reported work in this field.

li. NONIONIC BOLAAMPHIPHILES A. Molecular Assemblies Early in the study of cascade or dendritic systems, nontraditional assemblies (e.g., aqueous gels) were observed when noncovalent forces

GREGORY H. ESCAMILLA

160 O 6

DMF. K2CO3

•^^-Vi^^r^' _1 V /n \ r

RO-H ( ^0

'" >-0R

x-H"x

^^OR

R O ^ X.0 DMSO, K2CO3

r

8^ ^ W RO-^f ^ RO^\

O^OR

1

^ TI

HT^^M O^OR

9

10 ^.OH H2N—/

"OH

^OH DMSO.K2C()3 11

HO

n—'

^.I H

9

X.

OH f^A-OH

^ ^ \ = 2 or 3

Scheme 1. A general synthesis of two-directional arborols.

were coupled with the proper complementary molecular architecture. The series of two-directional "arborols", synthesized by Newkome et al.,^^'*^ demonstrated but one variation on the melody of self-assembly. Spherical dendritic hexa- or nona-alcohols end (or head) groups were separated by either a saturated or unsaturated hydrocarbon lipophiUc spacers. The syntheses of these arborols^^ were straightforward in that reaction of either an a,co-dihalo- or dimesyl-alkane with dimethyl malonate or triethyl methanetricarboxylate^"^ in DMF or DMSO with anhydrous K2CO3 gave a tetra- or hexaester, respectively. Completion of the spherical hydrophilic end groups was accomplished by reaction of tetra- or hexaesters with tris(hydroxymethyl)aminomethane (Scheme 1). These

Dendritic Bolaamphiphiles and Related Molecules

Figure 2. CPK representation for the proposed stacking of two-directional arborols. Side and top view.

alkane-linked, bimodal, spherical structures were termed [X]-n-[y]-arborols, where X and Y denote the number of polar groups and n denotes the number of connecting methylene units. Interestingly, upon dissolution of these arborols in water, at concentrations ranging from 2 to 10% (w/w), the aqueous solution gelled. Electron micrographs of the resultant gels showed uniform diameter needle-like fibers of undetermined length throughout thefieldof view. For example, an arborol comprised of a 10 methylene spacer and head groups with 9-hydroxyls (denoted as [9]-10-[9]) readily formed an aqueous gel at ca. 2% wt %. Gelation was explained via an aggregation model whereby one two-directional arborol is stacked upon the next in an orthogonal fashion, thus maximizing the lipophilic interactions and orienting the hydrophilic hydroxyls toward the aqueous solution (Figure 2). This arrangement favorably aligns both the lipophilic and the polar regions and minimizes hydrophobic-hydrophilic interactions: H-bonding between the juxtaposed head groups helps tie the members of the stack together; the intemal lipophilic interactions between neighboring spacers further contributes to the stability of the assembly. A visual analogy for this is likened to the orthogonal stacking of a circus clown's dumbbells (the terminal weights represent the hydrophilic end groups

161

162

GREGORY H. ESCAMILLA

and the dumbbell shaft represent the lipophilic spacer); the resultant stack of these "molecular dumbbells" forms an overall column possessing a ca. 30-A diameter with infinite length.^^ H-bonding networks formed between the hydroxyl covered columns and the surrounding water forms a semisoUd matrix. Computational models of these aggregates show that a minimum spacer length and terminal group size range are needed for optimal, complementary stacking and gelation to occur. For a saturated spacer, this minimal length is 8 methylenes for the end groups possessing 6 hydroxy Is and 10 methylenes for end groups with 9 hydroxyls.^^ In order to exploit the lipophilic core of the cylindrical aggregate, N,N\N'\N''''iQtrakis [2-hydroxy-1,1 -bis(hydroxymethyl)ethyl]hexadec8-yne-l,l,16,16-tetracarboxamide was prepared; this unsaturated arborol, possesses a centrally located alkyne moiety, and upon dissolution in water forms a gel comprised of a similar stacking motif to the saturated counterpart. The electron micrograph of this gel showed a unique aggregation pattern, in which bundles of intertwined aggregate columns were formed. The resultant, inherently helical pattern is in stark contrast to the needle-like structures formed by the related [9]-10-[9]-arborol. From computational models, the alkyne-based bolaphiles likely aggregate in a helical manner based on two factors: (1) as the spacer length increases, the angle formed by adjacent spacers (as viewed from along the major axis of the stack) decreases from 90° for a constant head group size, and (2) the electronic and steric effects caused by the increased rigidity and composition of the alkyne moiety. This was one of the first examples of automorphogensis, which was previously proposed by Lehn.25 The family of crown ether-based bolaamphiphiles described by Gokel et al.^^ form at least in appearance another molecular copy of a bola (Scheme 2). A series of 12 a,co-bis(A^-azacrown ether)s was prepared and shown to possess notable variations to the aggregation patterns relative to spacer length: spacers with 10-12 methylenes resulted in vesicles, whereas, spacers with greater than 16 methylenes formed micelles. The rationale proposed for this variation was that the longer spacers tended to fold at approximately midpoint forming u-shaped structures, thus favoring micelle formation. Vesicles and micelles, formed by these crown-ether-based bolaphiles, appear to be stabilized by intermonomeric endo- and ^jc?-vesicular H-bonding domains in acidic aqueous media.

Dendritic Bolaamphiphiles and Related Molecules

163

NEt3, benzene, 0-5** C, 48 hrs., rm. temp.

12

^ O

O—^

VJ LiAlH4, THF, 24hrs.,A

Scheme 2.

Preparation of bis-crown bolaphiles.

Similar importance of H-bonding for stable aggregate formation was noted for the two-directional arborols.^^ The importance of H-bonding for aggregate formation of the two-directional arborols and Gokel's crown ethers lead to speculation about a supramolecular assembly made up of alternating crown ether bolaphiles and arborols (Figure 3). Two arrangements of the bolaphiles into a stack were envisioned: an altemating stack with parallel spacers and arborol head groups resting in between neighboring crown ethers; altematively, computational studies favored a "mixed" arrangement similar to the proposed stacking pattem observed for the arborols. In the latter case,

164

GREGORY H.ESCAMILLA

Figure 3. CPK representation of proposed "mixed" stack. Side and top view.

the crown ethers were oriented with the plane containing the ether oxygens being roughly parallel to the major axis of the stack (Figure 3). Model stacks had the same positioning of the spacers relative to neighboring spacers in the stack as proposed for arborol stacks. The crown ether bolaphile spacer was one methylene moiety longer than the arborol spacer. This extra length optimized the H-bonding between the crown ethers and the neighboring arborols. The rods and tubules, described by Fuhrhop et al.,^^ possess orientations analogous to that of the two-directional arborols. Lysine-based bolaphile 16 (Figure 4) generates a monolayer rod; the addition of 11 methylene units and a second primary amide link to 16 gave the bolaamphiphile 17 and resulted in a different supramolecular assembly. In general, 17 formed tubules rather than rods; these tubules possess an internal dimension of ca. 50 nm and wall thickness of 4.4 nm.^^ The presence of chirality also has an affect on these molecular assembUes, since racemic lysine bolaphile 16 did not result in rod or tubule formation. No effects due to the chiral purity were observed with 17. The effect

Dendritic Bolaamphiphiles and Related Molecules

165

16

HjN _H HOOC

17 Figure 4. Unsymmetrical bolaphiles synthesized for the generation of monolayer rods and tubules.

of chirality in molecular monolayers was shown to depend on membrane curvature in a manner similar to that of bilayers.^^ Lehn et al, has reported^^ the directed self-assembly of complementary chiral components. The spacer was based on tartaric acid and the complementary head groups were derived from either uracil (U) or 2,6 diacylaminopyridine (P) (Figure 5). L(+)-, /)(-)- and me^c^-spacers were used to investigate the effects of chiraUty on the properties of the species formed. Mixtures of LU2 and LP2 (1-1) have optical textures resembling DNA fibers, with sinusoidal or helical arrangements. As solvent (e.g., CHCI3, dioxane, tetrahydrofiiran) evaporated, patterns appeared that were similar to banded structures described for Kevlar or hydroxypropylcellulose. The LL mixture forms a triple helix; whereas, the MM mixture gives a double helix. Individual units such as LU2 and LP2 form H-bonds in manner similar to nucleic base pairings, which stabilize the supramolecular helix structure.^^ In this case, the molecular recognition process at the molecular level is expressed via formation of a macroscopic mesophase. This molecular recognition induced self-assembly, which involves a molecular information process that leads to the generation of "intelligent" supramolecular materials. Self-aggregation of bolaphiles into 3-D crystallites at the air-water interface has also been studied.^^ When a,co-alkanediols^^ and diacids^^ were spread at the water surface, it was proposed that polar head groups

166

G REGORY H. ESC AMI LLA

HN" "^O

18 OR

NH ^ ^

(r

O

^O. . ^ ^

.^.

.o.

TU2

o

-

V

u-

o ^

-^

NH

19

HN^^NH

OR

6

O

AR TP2

Hill

NH O

R = Ci2H25

Figure 5. General form of the complementary chiral components. T designates the form of the tartaric spacer, either L(+), D(-), or M(meso).

serve as anchors and the spacers bend in a bridge-like conformation.^^ This conformation does not agree with the observed efficiency of induced ice nucleation by a,CD-alkanediols compared with the corresponding alkanols.^^ This inconsistency prompted the reinvestigation of these results using modem techniques, which indicate that a,(D-docosanediol aggregates with the aliphatic chain in an orientation approximately perpendicular to the surface (Figure 6).^^ It was noted^^ that this arrangement of spacers would lead to a high degree of exposed hydroxyl groups; one way of compensating for this orientation would be the intercalation of H2O molecules between the diol layers. A similar perpendicular orientation for a,(0-alkane diacids has been proposed.^^ An earUer paper by Tschierske and co-workers^^ dealt with bolaphilic polyols 21 as a novel class of amphotropic liquid crystals. They also noted that n-alkane-l,2-diols 20, with n > 5, exhibit liquid crystalline phases and can be greatly stabilized in their bolaamphiphilic form (Figure 7). A key element for increased stability of these assemblies was

Dendritic Bolaamphiphiles and Related Molecules

167

HO HO HO HO HO HO HO HO HO HO HO HO

OH OU OH OH OH OH OH OH OH OH OH OH ^'•* Water

Figure 6. Morphology of a,(0-decosanediol at the air-water interface.

that the head groups should function as both a proton donor and acceptor. This functional duality permitted the incorporation of the head groups into the H-bridged network, resulting in an increasing degree of stability. Rico et al. reported^^ the synthesis of the bis-gluconamides and bislactobionamides (Figure 8) in higher yields than for the comparable

CnH2n+l

/ OH 20

HO-^ HO

^OH \ / n

OH

21

Figure 7. General structures of amphiphilic and bolaamphiphilicpolyols.

168

G REGORY H. ESCAMILLA

R = H, Galactose n = 6-12

Figure 8. General structure of 6/s-gluconamides and 6/s-lactobionamides.

sugar bolaphiles (Scheme 3). Thompson and co-workers^"* also reported a series of chiral diether and tetraether phospholipids, which were explored as chemoselective thin films. B. Functional Vesicles

Fuhrhop et al.^^ demonstrated that incorporation of quinone moieties into either the head groups or within the hydrophobic spacer of a bolaphile gave redox-active membranes (Figure 9). Unsymmetrical bolaamphiphiles were used as models for photosynthetic electron acceptors (e.g. 29) and vesicle formation was verified by electron micrograph. The anticipated membrane organization would position the quinone moieties on the vesicle exterior. The location of the quinone moieties in this series was verified by their quantitative reduction by borohydride. Since borohydride does not diffuse through lipid membranes these "membrane quinones" must be part of the vesicle exterior. Anthraquinone-based bolaphile 30 (included in this nonionic section for convenience) was created in order to locate the quinone moiety within the center of a membrane; however, stable membrane formation was prevented due to steric considerations. It was possible to integrate this quinoid bolaphile into other host membranes, such as dihexyldecylphosphate. The absence of borohydride reduction supports the premise that the quinone functionality is located at the midpoint of the host membrane wall.^^ Structures 29, 30, and 31 were synthesized as

Dendritic Bolaamphiphiles and Related Molecules

169

OH OHI

H2N,^NH2 22 21

H2N,>-yNH2 25

OH

HO

H ^N-Q^N OH H H

HO

26

Scheme 3. General synthetic route used for the construction of 6/s-gluconamides and 6/s-lactobionamides.

possible "pool quinones" with appropriate redox characteristics.^^ Electron transfer was also demonstrated by light-induced charge transfer between cationic porphyrins dissolved in water with dihexyldecylphosphate and dimethyldioctadecylammonium bromide vesicles doped with

GREGORY H. ESC AMI LL A

170

COOH

OOH

31

Figure 9. Tailored bolaphiles used to incorporate quinone moieties within micellar structures.

C. Biological Activity

Jayasuriya et al.^ proposed bolaforai amphiphiles synthetically tailored to provide an effective geometry for improved membrane disruption. Variation of either head group(s) or spacer(s) could provide a specific "tunability," allowing microorganisms specific disruption. Bolaphiles were envisioned^^ to disrupt the membrane via simple insertion of the hydrophobic spacer into the lipid membrane creating a mismatch between the preferred geometries of the bolaphile and lipid. When sufficient molecular invasion occurs, destabilization of the membrane increases (Figure 10). Alkane spacers ranged from decane to eicosane; however, the maximum activity was observed with pentadecane. Spacers with central double or triple bonds were made with the expectation that these functionalities would enhance the disruptive properties of these bolaamphiphiles. In the olefinic series, the geometry and

Dendritic Bolaampliiphiles and Related Molecules

171

Hydrophilic

Hydrophobic

Figure 10. Mechanism proposed for membrane destabilization via insertion of varying length hydrophobic spacers into a phospholipid layer and the resulting local defect.

position of the double bond were less important factors for membrane disruption efficiency than simply overall length. Bolaphiles possessing an internal ethyne group exhibited behavior similar to the olefins in that placement of unsaturation did not appear to be of significant importance. A general trend, however, was that maximum disruptive activity required an increased spacer length relative to the saturated series. Jayasuriya et al. described^ the use of a polymeric string (Figure 11) of bolaamphiphiles in membrane disruption studies. A comparison between the polymeric ("supramolecular surfactants") verses the monomeric bolaamphiphiles demonstrated an increase of 3 orders of magnitude for the former in membrane disruptive activity. The precise origin of this amplification is not yet understood; however, several theories have been proposed: (1) by their very nature, the polymeric bolaamphiphiles possess covalent linkages, which localize the "bolaamphiphile defects" by achieving a high local concentration; (2) domains of the supramolecular surfactant within the bilayer will be in equilibrium with nonaggregated membrane-bound polymers; and (3) repeat unit defects in the polymer are intrinsically more disruptive than the free monomer. A polyester structurally related to these "supramolecular surfactants", exhibited substantial protection for human CD4+ lympho-

172

GREGORY H. ESCAMILLA 32 O

O

HCKCH^CH^O)^—e.(CHJn-C-0(CIi,CH20)gH O

O

[—(":.(CR,)n-l':-0(CH^CH20)^ ]z 33

o

^4

o

UOiCUfHp)^—C_(CHpx--C^C—(CH2)y--C--0(CH^CH^0)^H O

O

[—C--KCHpx—C=C—(CH2)y--C--0(CH,CH20)^]z 35 O

36

o

HCXCHXH^O)^—C—(CH,)x—C==C—(CHpy---C:—C)(CH2CH20)gH O

O

1—I!:—(CHjx—C=C—(CHJy—I!:—0(CH,CH,0),Jz 37 Figure 11. Membrane-disruptive bolaphiles and their polymeric analogues,

cytes against HIV-1 during in vitro studies,^ thus offering a new route intp nonionic membrane-disrupting agents, in which activity and specificity could be tailored through molecular design. Selectivity of the bolaphiles to discriminate among lipid bilayers of varying cholesterol content has been considered by Nagawa and Regen.^^ Their results demonstrate that modest differences in membrane composition and packing can lead to large differences in structural lability, and that synthetic agents can be created to exploit these differences.^^ The concept of "tunability" has been supported by the fact that 33 (n = 14) readily lyses R mirabilis but not erythrocytes.

173

Dendritic Bolaamphiphiles and Related Molecules D.

Ion Transport

In an extension of bolaphilic architecture, Fyles et al.^^ have assembled an ion channel mimic (Figure 12), from what they have termed a "modular construction set" (Figure 13). Twenty one ion channels were Head

o=/^^\=o

Y

Z Wall

<

0=^

0~>

Core

o

O

Y

z

o < > 38 Figure 12. Schematic representation of the ion channel mimic.

Core Units coo'

c^o^ coo" .^-"^ OOC^

O

r^^^

r^^^

o

oocs

o

o

coo-

ooc^^

O^

OOC^

O

O^

'COO'

OOC^

^v^

O

COO'

^O '^Y^

^\

ooc^o

O

O^

"OOC

OOCK,

OOC^

o

O

O^

"COO"

Head Groups '^'^^^°^r^^

„/~-COOH

_s.

.OH

Wall Units o

O

0

Figwre 13. Components of the "modular construction set." 174

0

Dendritic Boiaamphiphiles and Related Molecules

175

HO--' -^OH H0^7^0H

Core-4c(;2'

Scheme 4. Generalized synthesis of an ion channel mimic.

prepared and characterized through this modular approach. The authors envisaged a central "core" unit from which "wall" units radiate. A series of di-, tetra-, and hexacarboxylic acid derivatives of 18-crown-6 ether, serving as the cores, provided rigidity to direct the wall groups toward the two bilayer faces. The wall units, possessing the desirable oblong structural conformation, were composed of macrocyclic tetraesters derived from maleic anhydride; these macrocycles were selected via insight derived from literature data, model building, and molecular modeling studies (Scheme 4). Attachment of the walls to an appropriate core unit was followed by capping with one of three available head groups. The critical synthetic details conceming these ion channel mimics has been delineated.^^

176

GREGORY H. ESCAMILLA

Fyles et al.^^ described their results concerning the transport of alkali metal cations across vesicle bilayers mediated by these ion channels mimics. The relative activities of their most active transports were comparable to valinomycin but were 2- to 20-fold less active than gramicidin. Six examples in their modular series effectively acted as channels; four in this series acted as cation carriers. The range of observed transport activities, selectivities, and mechanism indicates that structural regulation of synthetic ion channel mimics is possible with this family of bolaphiles.^^ iii. IONIC BOLAAMPHIPHILES A. Molecular Assemblies

Roberts et al. "^ used bolaform phosphatidylcholine as a probe of water soluble phospholipase catalysis. These bolaphiles (Figure 14) contain two phosphatidylcholines, as the ionic head groups permitting the evaluation of the proposal that two phosphatidylcholines are required for phospholipase activity. Phospholipase activity was measured using micelles formed from these bolaphiles and phosphatidylcholine containing amphiphiles. Increased membrane stability of these bolaform

o

o o

o

43

Figure 14. Generalized structure of bolaform phosphatidylcholines.

Dendritic Bolaamphipliiles and Related Molecules

Ml

[2CH2N(CH,)2Ci CT(CH-)-^CfU:H.S-

^ v ^OCH^Ph

44

G=

-CH;

45

G=H

figure 15. Bolaphiles used for the generation of thermally stable membranes.

micelles lowered the rate of enzyme activity in comparison to micelles formed from the amphiphiles. The rationale for this observation was that reduction of the vertical diffusion of the individual bolaform phosphatidylcholine from the membrane was required for enzyme activity. A prime motivation for interest in synthetic bolaamphiphilic membranes was the enhanced membrane stability as found with archaebacterial membranes. Li and co-workers utilized the pioneering studies of Fuhrhop"^^ as well as the synthetic modifications described by Lo Nostro et al."^^ to generate bolaphiles 44 and 45 (Figure 15)."^^ As noted with archaebacterial membranes, these synthetic membranes tend to be rather stable and, in this particular case, stabilized toward temperature increases. This behavior was attributed to the location of these bolaphiles within the membrane, thus instilling a substantial resistance to their motion either along or out of the membrane."*^ Although the above examples dealt with molecular assembly of solvated bolaphiles, Ringsdorf and co-workers'^ have prepared self-assembled monolayers on negatively charged substrates. They noted literature precedence for the use of cationic bolaamphiphiles to reverse the surface charge of a mica substrate, thereby allowing subsequent adsorption of anionic polymers and construction of multilayers."^^ Organic

178

GREGORY H. ESCAMILLA

^' (C£)^'^^'^-'^^^^''-^ V_-/"

COO(CH:)6-NQ)

cr

46

Br"

©-'

(CH:)800C 47

l^r'

:00(CH2)II-NQ)

Br

^(£)N-(CH:

OOC €00(CH:)6HO' OH v r i ^ 49

Figure 16. Series of bolaphiles that adsorb onto mica surfaces.

monolayers, which are only a few nanometers in thickness, have possible applications in advanced optical and electronic sensors, biosensors, separation membranes, microlithography and pattern formation, and modification of surface properties."^ Thus, the influences of alkyl chain length upon self-assembled monolayers on mica were evaluated. Using phenylene based bolaphiles (Figure 16), the orientation of the bolaphile on the mica was shown to be dependent on spacer length: below a critical length, the bolaphile lays flat on the surface, while greater lengths adopt an end-on orientation. This behavior was explained by competition between hydrophobic and electrostatic effects. At short chain lengths, electrostatic effects dominate and the bolaphile lies flat on the surface. The ability to control self-assembly can be realized with the proper selection of the counterion. Reduction of the repulsion between the like charged head groups favors close packing, which is critical for the formation of layered structures.

Dendritic Bolaamphiphiles and Related Molecules

179

Head Group

Figure 17. Generalized structure of a "gemini surfactant."

An ammonium ion head group, a rigid spacer, and attachment of long alkyl chains to the head groups led to the family of bolaphiles that Menger has labeled as "gemini surfactants" (Figure 17)7 The rigid spacer inhibits m/ramolecular chain-chain associations, whereas a flexible spacer would allow an u-shaped conformation in which the surfactant could behave as conventional twin-tailed amphiphile.^ Menger and co-workers synthesized these surfactants in order to gain additional structural information concerning membranes as well as their self-assembly. Computer modeling of assemblies made up of gemini surfactants show structures, such as thread-like micelles. Many dynamic properties of gemini surfactants, such as rapidly increasing viscosity with small increases in concentration, are very different from amphiphiles."*^ A theoretical explanation of experimental results, obtained for modified (non rigid spacer) gemini surfactants, was presented by Andelman and Diamant."*^ They noted that the aggregate morphology for dimeric surfactants is related mainly to the influence of the spacer on the specific area Z. The geometrical parameter, that determines aggregate shape, is the "packing parameter" denoted by the formula,"*^"*^ p = \)/Zl

(1)

where X) is the volume occupied by the hydrophobic moiety of the surfactant molecule, 1 is its length, and Z is the specific area per molecule."^^ It was found that the specific area of the surfactant at the air-water interface was dependent on interplay of three distinct factors: the geometrical effect caused by lengthening the spacer moiety, which increases Z; interaction among the surfactant monomers, which tends to decrease Z after the spacer reaches a critical length; and the conformational

180

GREGORY H. ESCAMILLA Hl+2mCm

CniH2m+l

Br 50

10<m< 18 4 < y < 16

Figure 18. Generalized structure of alkanediyl-a,a)-b/s(dimethylalkylammonium bromide)bolaphiles.

entropy of the spacer chain, which increases rapidly as spacer length increases and enhances the effect of the second factor.'*^ Neglected in the theoretical discussions were factors, such as van der Waals attraction and the excluded volume of the surfactant's hydrophobic tails. The model was developed for a specific case but should be valid for any bolaphile, even those without hydrophobic tails.'*^ This is still a very narrow model that needs further work to establish its generality. Skoulios et al.^^ described the structure of lyotropic mesophases formed from alkanediyl-a,co-bis(dimethylalkylammonium bromide) bolaphiles (Figure 18). As spacer lengths increase from 4 to 8 methylenes units, the concentration range of the lyotropic mesophases decreases, whereas for spacers of 10 and 12 methylenes, water-surfactant mixtures remain micellar throughout the whole range of composition. At lengths longer than 13 methylenes, lyotropic mesophases reappear. Bolaphiles of this type did not exhibit thermotropic liquid crystals when heated to high temperatures. A columnar mesophase with a cylindrical morphology was observed in specific concentration ranges. Dimensions of the column were in agreement with a structural model having the alkyl tails of the head groups oriented toward the center of the column. Exchange of these bolaphiles between bulk aqueous phase and micelles was found to be a single step process,^^ in which both head group alkyl chains exit simultaneously from, or incorporate into, the micelles. Alkanediyl-a,cobis(dimethyl-alkylammonium bromide) was also studied with respect to its behavior at the water-air interface.^^ Based on surface tension measurements, the location of the spacer varies with respect to spacer length: spacers of less than 10 methylenes lies along the air-solution interface; spacers of 10 to 12 methylenes conformationally bridge into the air side of the interface.

Dendritic Bolaamphiphiles and Related Molecules

181

Br

Br"

51

CH^-^n ^

/

-

7^A, ° Br

52

Br53

Figure 19. Phenylene-based bolaphiles.

Ringsdorf et al.^^ described a series of three isomeric bolaphiles based on para-, meta-, and orr/io-phenylene derivatives with pyridinium head groups (Figure 19). Lyotropic mesophases were formed only by 51; however, 52 can form mesophases with the addition of 1-hexanol (1:1), as a co-surfactant. It was rationalized that the co-surfactant fits (Figure 20) between the hydrophobic alkyl chains of 52, thereby separating the charged head groups and thus stabilizing the macroassembly. A similar stabilization was seen in a,co-alkanediols and H2O as reported by Lahav

182

GREGORY H.ESCAMILLA

o#o*o#o4o Bolaphile

O

1-Hexanol

Figure 20. A representation of the "mixed" lyotropic nnesophase.

et al.^^ The introduction of rigid spacer units also stabilized the mesophase range of the bolamphiphile.^^ Bosch et al. reported the synthesis^"^ and later assembly properties'^ of bolaphiles (54, 55) prepared from dimeric acids. The objective was to demonstrate extension of the concept of supramolecular self-assembly to organic compounds having a substituted cyclohexane structure (Figure 21). Assemblies were observed with both bolaamphiphiles; however, 55 generates multilamellar arrangements whose structures depend on the counterion. Morphology of the aggregates was linked to the nature of the head groups and the nature of counterions. Nakatsuji et al.'^ have synthesized a dendritic series of bolaamphiphiles possessing three anionic head groups separated by spacers (Figure 22). Here, as with other examples, aggregates form at concen-

OSO^'Na

{, ^0S03 Na

X = I, CI, HCO3

Figure 21. General form of the cyclohexane based bolaphiles.

OR SO^'Na

"0 O O

Na "O^S"

-O

OR 56

Figure 22.

Generalized structure of a "three headed" bolaphile. 183

184

GREGORY H.ESCAMILLA

trations below critical micellar concentration (CMC).^'^^ Behavior of these bolaphiles in solution, in terms of CMC versus the number carbons in the lipophilic chains, runs counter to that observed for a homologous series of single-tailed surfactants; this behavior offers many new avenues of exploration to the synthetic chemist. B. Functional Vesicles

Bunton et al.^^ demonstrated catalytic behavior in the spontaneous hydrolysis of 2,4-dinitrophenyl phosphate promoted by alkane a,cobis(trimethylammonium) bolaphiles. The enhanced rate of hydrolysis followed the greater degree of organization within vesicles from surfactants possessing longer (Q-Cy) spacers. Notably, bolaphiles with 12 and 16 methylene spacers did not form micelles, but instead formed small clusters, and showed a lower rate enhancement versus micellizing surfactants. Fomasier et al.^^ utilized metallomicelles formed with either bolaphiles 58 or simple surfactants 57 as catalysts in the hydrolysis of

OH

57

Br

OH

58 Figure 23. Proximity of the charged head group to the binding site in 57 slows chelation of the metal relative to the bolaphile 58. M = Cu", Zn"; R = para-nitrophenyl picolinate.

Dendritic Bolaamphiphiies and Related Molecules

185

p-nitrophenyl picolinate. Micelles generatedfrompyridine bolaphile 57 (Figure 23) possessing Cu® or Zn^°^, enhanced the rate of hydrolysis compared with micelles generated from 6-{[(2-(n-hexadecyl)dimethylamino)ethyl]thio}methyl-2-(hydroxymethyl)pyridine bromide, which was not as effective a catalyst. Increased electrostatic repulsion between the terminal ammonium group and the terminal metal ion site possibly explain the difference in effectiveness of bolaform 58 versus classical micelle 57. Formation of a ternary complex consisting of substrate, metal, and bolaform amphiphile was suggested as the crux of the catalytic process.^^ These micelles exhibited substrate discrimination as indicated by the lack of catalytic enhancements when isomeric nicotinate or isonicotinate esters were utilized. Increased catalytic effectiveness of the micellar bolaamphiphiies was rationalized by: (1) hydrophobic factors that bring the substrate together with ligands and metal ions in a small volume, (2) the enhanced electrophilicity of divalent metal ions toward micellar-bound substrates, and (3) higher "local" pH at the micellar surface, relative to the bulk phase, which favors the acid dissociation of the hydroxy groups in the ternary complex.^^ Nolte and co-workers^^ recently reported a functional vesicle formed by assembly of hosts capable of binding guests, such as resorcinol and 4-(4'-nitrophenylazo)resorcinol (Figure 24). Two quaternary ammonium

Figure 24. Representation of bolaphile 59 used to prepare a functionalized vesicle

186

GREGORY H. ESCAMILLA

centers coupled with two long alkyl chains were incorporated in order to maintain the hydrophobic binding site at the exterior of the vesicle; the rigidity of the binding sites fixes the charged nitrogens in a specific orientation near the vesicle surface. In typical lipid fashion, the hydrophobic alkyl chains served to form the interior of the membrane. The combined interactions of solvent, binding sites, charged nitrogens, and hydrophobic alkyl chains govem the vesicular morphology, which was likened to a "golfball" due to its spherical shape and dimpled surface. Examination of a cast film of 59 by X-ray diffraction showed a clear periodicity of 53 A, which is approximately the length of two fully extended hexyldecylamine chains. Binding studies suggest that only half the total number of binding sites are available to react with guest. These data would indicate a bilayer membrane with a thickness of approximately 53 A. Nolte's "golfball" bears structural similarity to Menger's gemini surfactants,^ described earlier. Previous examples in this section have dealt with incorporation of moieties into the bolaphile for the expression of some desired chemical activity or property. Tirrell and co-workers^^ recently exploited the self-assembly properties of bolaphiles in another fashion. They used a bolaphile possessing a photopolymerizable spacer 47, and the preorganization of an assembled monolayer to generate polymerized layer, where the bolaphiles are covalently linked. Multiple layers of 47 were generated on a mica surface by alternating deposition of 47, followed by an anionic polyelectrolyte poly(2-acrylamido-2-methyl- 1-propanesulfonic acid) (PAMPSA), until the desired coating depth was reached. Photopolymerization was conducted at room temperature by irradiation for up to 30 minutes. Polymerization changes the apparent electrostatic properties of the layer interface and increases the lateral strength of the film. The nature of the first layer assembled on the substrate is the major factor controlling the stability of successive layers.^^ Applications of thin layers were noted previously in this review."^ C. Biologically Active Damha et al.^- have succeeded in making dendritically branched RNA-based bolaphiles in a convergent-growth approach (Figure 25). The resulting structure fits well within the description of a bolaamphiphile in that it is comprised of thymine and a modified adenosine spacer and terminal nucleotides as head groups. These branched RNAs

Dendritic Bolaamphiphiles and Related Molecules

TTTTT^ ^ATTTTT TTTTT^ \ / \ / TTTTT ATTTTrrmT 111 1 ITl'lTl A ;:ATTrTr^ \ TTTTT^ 60

187

Tim TTTTTA ^rmr /^-^ ^"^^^ TTTTT

Figure 25. An RNA-based bolaphile.

could be useful in capturing and binding matching nucleotide sequences, thus, opening doors to potential antisense agents or ligands for affinity purification of the branch recognition factors, which can catalyze the maturation or splicing of precursor messenger R N A . D.

Transports

Diederich et al.^^ reported an example of a bolaphile designed as a transport agent specifically to carry nucleotide 5'-triphosphates across liquid organic membranes. Certain highly charged nucleotides designed to act as inhibitors of H I V reverse transcriptase cannot penetrate cell membranes, hence the motivation for the design and creation of these synthetic carriers.^^ The bolaphile 6 1 (Figure 26) forms 1:1 complexes with a variety of nucleotide 5'-triphosphates and does not leak from a CH2CI2 liquid membrane. Efficient transport was shown via u - t y p e cell experiments; however, with liposomes these synthetic carriers do not mediate specific transport of nucleotide 5'-triphosphates. At certain concentrations the transport acts as a detergent breaking the liposomal structure and leading to nonspecific leakage. From their experiments, the

r 0

4 Br

0

Hi-c/ 61 Figure 26.

A bolaamphiphilic transport for nucleotide 5'-triphosphates.

188

GREGORY H. ESCAMILLA

authors caution extrapolating from the carrier efficiencies in liquid organic membrane experiment to liposomes or cellular membrane transport.

IV. CONCLUSION Beyond these examples, basic questions remain concerning bolaamphiphile conformations within micelles.^^ Evidence indicates that a bent conformation is adopted,^ but micelles have been observed with very small hydrophobic cores and sometimes are seen on electron micrographs with diameters that correspond to the length of the bolaphile.^^'^^ Natural bolaamphiphiles found in thermophilic bacteria with their stereochemistry and stability in harsh environments illustrate further areas to explore concerning molecular self-assembly. More robust membranes or chiral membranes derived from chiral bolaphiles could provide avenues to molecular recognition based on stereochemistry not only at one site, but over an entire membrane.*^ Synthetic chemists can tailor membranes to provide a desired morphology or potential catalytic function. Bolaamphiphiles, like cascade macromolecules,^- have gained increasing attention recently, since they offer insight to micellar systems that can mimic enzymes, act as therapeutic agents, or as tools to investigate molecular recognition and assemblages. The works cited herein illustrate the goal Lehn set forth for supramolecular chemistry—do not focus just on structures but rather the expression of a desired chemical, biological, or physical property.--^-^" REFERENCES 1. Nagarajan, R. Chem. Eng. Commun. 1987.55, 251. 2. Fuoss. R. M.; Edelson, D. J. 7. Am. Chem. Soc. 1951, 73, 269. 3. Newkome, G. R.: Baker, G. R.; Aral, S.: Saunders, M. J.: Russo, R S.: Gupta, V. K.; Yao. Z.-Q.; Miller, J. E.: BouiUon, K. / Chem. Soc, Chem. Commun. 1986, 752. 4. Fuhrhop. J.-H.: Fritsch, D. Ace. Chem. Res. 1986, 79, 130. 5. Fuhrhop, J.-H.: Mathieu, J. Angew. Chem. 1984, 96, 124: Ange\v. Chem., Int. Ed. Engl. 1984, 23, 100. 6. Menger, F M : Littau, C. A. / Am. Chem. Soc. 1993, 775, 10083. 7. Menger, F M.: Littau, C. A. J. Am. Chem. Soc. 1991, 772. 1451. 8. Rosen, M. J. Chemtech 1993, 30.

Dendritic Bolaamphiphiles and Related Molecules 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

23 24. 25 26 27, 28 29 30, 31 32 33 34 35 36. 37

189

Jayasuriya, N.; Bosak, S.; Regen. S. L. / Am. Chem. Soc. 1990,112, 5851. Jayasuriya, N.: Bosak, S.: Regen, S. L J. Am. Chem. Soc. 1990,112, 5844. Amato, I. Science 1993. 260, 491. Hudson, R. H. E.; Damha, M. J. J. Am. Chem. Soc. 1993, 775, 2119. Fomasier, R.: Scrimin, R; Tecilla, R: Tonellato, U. J. Am. Chem. Soc. 1989, 777, 224. Cipiciani, A.: Fracassini, M C ; Germani, R.: Savelli. G.: Bunton, C. A. J. Chem. Soc, Perkin Trans. 1987, 547. Bunton. C. A.; Dorwin. E. L.: Savelli. G.: Si, V. C. Red Tra\: Chim. Pays-Bas. 1990, 709, 64. Kim. J.-M: Thompson, D. H. Langmuir 1992, 5, 637. Schenning, A. R H. J.: de Bruin. B.: Feiters. M. C : Nolte. R. J. M. AngeM\ Chem. 1994, 106, \lA\\AngeM: Chem., Int. Ed. Engl 1994. 33, 1662. Newkome, G. R.; Baker. G. R.: Arai, S.: Saunders, M. J.; Russo. R S.; Theriot, K. J.: Moorefield, C. N.: Miller, J. E.: Bouillon, K. J. Am. Chem. Soc. 1990, 772. 8458. Newkome, G. R.; Lin, X.: Yaxiong. C : Escamilla, G. H. J. Org. Chem. 1993. 58, 3123. Newkome, G. R.: Moorefield, C. N.: Baker, G. R.: Behera, R. K.: Escamilla, G. H.; Saunders, M. J. Ange^v. Chem. 1992.104, 901: Ange^v. Chem., Int. Ed Engl. 1992, i7.917. Fuhrhop. J.-H.; Spiroski, D.: Boettcher. C. J. Am. Chem. Soc. 1993. 775. 1600. Gros. L.; Ringsdorf. H.: Schupp. H. AngeM: Chem. 1981. 93. 311: A/i^ew. Chem., Int. Ed. Engl. 19HI. 20. 305. Fendler. J.-H.: Tundo. R Ace. Chem. Res. 1984,17. 3. Lund, H.: Voigt, A. Organic Synthesis Collect.: Wiley: New York, 1943. Vol. IL p. 596. Lehn, J.-M. AngeM\ Chem. 1990, 702. 1347: Ange^v. Chem., Int. Ed Engl. 1990, 29. 1304. Munoz. S.: Mallen. J.: Nakano. A.: Chen, Z.: Gay, L: Echegoyen. L.: Gokel, G. W. J. Am. Chem. Soc 1993. 775. 1705. Fouquey. C : Lehn. J.-M.: Levelul. A.-M Adv. Mater 1990. 5. 254. Popovitz-Biro, R.: Majewski, J.: Margulis. L.: Cohen, S.: Leiserowitz. L.: Lahav. M. J. Phys. Chem. 1994. 98, 4970. Ueno. M.: Kawanabe. M.: Meguro. K. J. Colloid Interface Sci. 1975. 57. 32. Jeffers. R M.: Dean. J. J. Phys. Chem. 1965. 69. 2368. Popovitz-Biro. R.: Wang. J. L.: Majewski. J.: Shavit. E.: Leiserowtiz. L.: Lahav. NL J. Am. Chem. Soc. 1994,116, 1179. Henirich, F : Tschierske, C : Zaschke. H. Ange^v. Chem. Int. Ed. Engl. 1991. 30, 440. Garalli-Calvel. R.: Brisset, F: Rico. I.: Lattes. A. Syn. Comm. 1993, 23. 35. Thompson, D. H.: Svendsen. C. B.: Di Meglio. C : Anderson, V. C. J. Org. Chem. 1994,59,2945. Fuhrhop, J.-H.: Hungerbuhler. H.: Siggel, U. Langmuir 1990. 6, 1295. Siggel, U.: Hungerbuhler. H.: Fuhrhop J.-H. J. Chim. Phys. 1987. 84. 1055. Nagawa, Y: Regen. S. L. J. Am. Chem. Soc. 1991.113.1231.

190 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63.

GREGORY H. ESCAMILLA Fyles, T M ; James, T. D.: Pryhilka. A.; Zojaji, M. / Org. Chem. 1993, 58. 7456. Fyles, T. M.: James, T. D.; Kaye, K. C. J. Am. Chem. Soc. 1993, 775, 12315. Lewis, K. A.; Soltys, C. E.; Yu, K.; Robens, M. F Biochemistry 1994, i i , 5000. Fuhrhop, J.-H.; David, H.-H.; Mathieu, J.; Liman, U.: Winter, H.-J.; Boekman, E. J. Am .Chem. Soc. 1986, 108. 1785. Lo Nostro, P.; Briganti, G.; Chen, S.-H. J. Colloid Interface Sci. 1991,142. 214. Moss, R. A.;li, G.; Li, J.-M. J. Am. Chem. Soc. 1994, 776, 805. Mao, G.: Tsao, Y.-H.; Tirrell, M.; Davis, H. T.; Hessel, V.; van Esch, J.; Ringsdorf, H. Langmuir 1994.10. 4\14. Mao, G.; Tsao, Y.-H.; Tirrell, M.: Davis, H. T; Hessel, V.; Ringsdorf, H. Langmuir 1993,9,3461. Karabomi, S.: Esselink, K.; Hilbers, P A. J.; Smit. B.; Kanhauser, J.; van Os, N. M.; Zana, R. Science 1994, 266. 254. Diamant, H.; Andelman, D. Langmuir 1994,10. 2910. Israelachvilli, J.; Mitchell, D. J.; Ninham, B. W. J. Chem. Soc, Faraday Trans. 2 1976, 72. 1525. Israelachvilli, J. Intermolecidar & Surface Forces, 2nd ed. Academic Press: London, 1991, Chapter 17. Alami, E.; Levy, H.; Zana, R.; Skoulios, A. Langmuir 1993, 9, 940. Frindi, M.; Michels, B.; Levy, H.; Zana, R. Langmuir 1994,10. 1140. Alami, E.; Beinert, G.: Marie, P; Zana, R. Langmuir 1993, 9, 1465. Festag, R.; Hessel, V.; Lehmann, P; Ringsdorf,H.; Wendorff, J. H.Reel. Trav. Chim. Pays-Bas. 1994, 77i, 222. Bosch, M. P; Parra, J. L.; Sanchez-Baeza, F Can. J. Chem. 1993, 71. 2097. Bosch,P;Parra,J.L.;delaMaza,A.AAigor. Chem. 1994,106.2151.Angew. Chem., Int. Ed. Engl. 1994, J i , 2078. Masuyama, A.; Yokota, M.; Zhu, Y-P; Kida, T.; Nakatsuji, Y J. Chem. Soc, Chem. Commun. 1994, 1435. Mao, G.; Tsao, Y; TirreU, M.; Davis, H. T Langmuir 1993, 9, 3461. Li, T.; Krasne, S. J.; Persson, B.; Kaback, H. R.; Diederich, F J. Org. Chem. 1993, 58. 380. Fuhrhop, J.-H.; Bach, R. In Advances in Supramolecular Chemistry; G. W. Gokel, Ed.; JAI Press: Greenwich, CT, 1992, Vol. 2, p. 25. Zana, R.; Yiv, S.; Kale, K. M. J. Colloid Interface Sci. 1980, 77.456. Yiv, S.; Zana, R. J. Colloid Interface Sci. 1980, 77. 449. Mekelburger, H.-B.; Jaworek, W.; Vbgtle, F Angew. Chem. 1992, 104. 1609; Angew. Chem., Int. Ed. Engl. 1992, 31. 1571. Newkome, G. R.; Moorefield, C. N. Advances in Dendritic Macromolecules: G. R. Newkome, Ed.; JAI Press: Greenwich, CT, 1994, Vol. 1, pp. 1-68.

INDEX 5-Acetoxylsophthalic acid, 142 Aliphatic polyesters, 141 n-alkane-l,2-diols, 166 a,a>-Alkanediols, 165-166 Alkyne-based bolaphiles, 162 Allyltris(dimethylsiloxy)silane, 116,117 3-Aminosophthalic acid, 151 Ammonium-centered dendrimers cationic, 75 ionic, 87-93 Amphiphiles, 158 bolaform, 159, 170 twin-tailed, 179 Amphiphilicity, 137 Amphotropic liquid crystals, 166 Anionic initiators, 103-105 Anionic polymerization, 103105,115,141 Anionic surface dentrimers, 94 Anion radical mechanism, 149 Annulene derivatives, repetitive synthesis of, 45

Anthraquinone-based bolaphile, 168-169 [91-10-[91-Arboral, 162 Arborols, 2, 42, 84, 102, 124 {see also Dendritic macromolecules) molecular assemblies, 160,161 repetitive synthesis of, 42-43,44 two-directional, 160, 161, 163 Archaebacterial membranes, 177 Aromatic amino acids, 151 Aromatic polyesters, 21 Aromatic polymers, highly branched (see Highly branched aromatic polymers) Aryl-aryl interaction, 138 Arylboronic acids, coupling reactions, 128 Atropisomerism, 136 Automorphogensis, 162 Axial chirality, 68 Azacrown ethers, 162 Azacrowns, 54-55, 60, 84, 95 Azobenzene, 42, 64

191

192

INDEX

"Balloon" dendrimers, 88, 90, crown ether-based, 162 92 defects, 171 Benzene derivatives, 53 defined, 158 1,3,5-Benzenetricarboxylic acid, ionic, 176-188 143 biogically active, 186-187 Bidentate ligands, 79 functional vesicles, 184-186 Bilayer membranes, ionic molecular assemblies, 176bolaamphiphiles, 186 184 Binding, hydrophobic, 134-135 transports, 187-188 Biological activity molecular self-assembly, 164, ionic bolaamphiphiles, 186165, 179, 182, 186,188 monomeric, 171 187 nonionic, 159-176 nonionic bolaamphiphiles, biological activity, 170-172 170-172 functional vesicles, 168-169 2,2'-Bipyridine, 76 ion transport, 173-176 2,2'-Bipyridyl, 78 molecular assemblies, 159Bipyridylpyrazine bridging 168 ligands, 76-84 polymeric, 171 2,2'-Bipyrimidyl, 80 Bolaamphiphilic membranes, 2,2'-Biquinolyl, 82 171-172, 177 Birefringence, 155 Bolaform amphiphiles, 158, 170 3,5-Bis(bromomethyl)nitro(see also benzene, 53 Bolaamphiphiles) Bis-gluconamides, 167-168 "tunability" of, 170,172 Bis-lactobionamides, 167-168 Bolaform electrolyes, 158-159 Bis-o-phenanthroline com(see also plexes, 79 Bolaamphiphiles) 1,3-Bis( 1 -phenylvinylbenzene), Bolaform phosphatidylcholine, 132 2,3-Bis(2-pyridyl)pyrazine, 77, 176 Bolaphiles 80 alkyne-based, 162 2,5-Bis(2-pyridyl)pyrazine, 79, anthraquinone-based, 16880 169 /7-(iV,A^-Bis(trimethylsily)amino)chiral, 188 styrene, 104 cychohexane-based, 183 Block polymers, dendritic, 21-27 lysine-based, 164 Bolaamphiphiles phenylene-based, 181 cationic, 177 racemic lysine, 164 conformations within RNA-based, 186-187 micelles, 188

Index

193

synthesis of, 101-102 systematic divergent construction of, 74-75 tosylamide cascades, 46-55 Cascade polymers, symmetrical, 143 Catalysis, dendritic layer-block copolymers for, 23, 27 Catenanes, 76 Cation-exchange materials, 94 Cationic bolaamphiphiles, 177 Cationic porphyrins, 169 CD4+ lymphocytes, 171-172 Charged dendrimers, structural types, 75-76 Charge-transfer transitions, 82 Capillary melt viscosities, of Chemoselective thin films, 168 PVC blends, 139 Chiral bolaphiles, 188 Carbon-carbon radical couChiral cascade molecules, 66-69 pling, polyphenylers, Chiral dendrimers, 67-69 149 Chiral dendritic imines, 67 Carbosilane dendritic macroChirality, in molecular monomolecules, 113, 114 layers, 165 Carboxylate anions, 93 Chlorotrimethylsilane, 130 Cascade compounds, 124 Cholesterol content, 172 Cascade macromolecules, 188 Cascade molecules, 2, 41-70 {see ^^C nuclear magnetic resonance (NMR) spectroscopy, also Dendrimers; den10,12,115 dritic macromolecules) Cobalt Salen, 63-64 chiral, 66-69 Colunmar mesophase, 180 crystallization properties, 69 molecular assemblies, 159-160 Complexed transition-metal ions, 76-86 multiple cobalt complexes, Convergent-growth synthesis, 163-64 37 photoswitching dendrimers, benzene derivatives as core 64-66 units for, 53 polyamine dendrimers, 56-60 cascade molecules, 69 research recommendations, characterization of, 10-14 69-70 dendrimers, 124-126 Salen units, 61-63

"three-headed," 183 unsymmetrical, 165 Bolaphilic polyols, 166 Bolytes, 159 {see also Bolaamphiphiles) Borane reduction, 130 Branching in highly branched aromatic polymers, 124, 132-134, 139-141 star, 139-141 symmetrical, 132-134 4-Bromo-2,6-dimethylphenol, 149 4-Bromomethylbenzonitrile, 14

194

dendritic block copolymers, 21-27 dendritic macromolecules, 19, 33-36 development of, 4-9 growth process, 5-6 hexacyclene as core units for, 54-55 hybrid linear-dendritic block copolymers, 29-33 limitations of, 7-9 stepwise, of monodisperse dendritic polyesters, 143 suface functionality, 14-21 symmetrically branched polyphenylenes, 132-133 tosylamide cascades, 53-55 value of, 102 Copolymers, 149 highly branched, 127 Co-surfactants, 181 Cotton effects, 67 Coupling reactions arylboronic acids, 128 carbon-carbon radical, 149 Pd(0)-catalyzed, 128, 130 polyphenylethers, 145-150 radical, 149 Suzuki's, 128 Williamson, 6, 7 Critical miscellar concentration (CMC), 184 Crosslinking, 144-145 Crown dendrimers, 60 Crowned arborols, 84 Crown ether-based bolaamphilphiles, 162 H-bonding, 163-164 Crown imines, 62 Crown units, dendrimers, 54, 59

INDEX

Cyano bridging, 86 Cychohexane-based bolaphiles, 183 Cyclam, 42, 59-60 Cyclamdendrimer, firstgeneration amine, 63 Cyclovoltanmiograms, 64 Cylindrical morphology, 180 Debenzylation, 143 Dendrimers, 102 (see also Cascade molecules; ionic dendrimers) charged, structural types, 7576 crown units, 54 divergent synthesis, 49-52 first-generation, 75 generation zero, 75 initiator core, 75 ionic, 73-95 notation system, 75 repetitive synthesis, 42-45 silicon-based, 102-103, 105115,118 structural concept of, 74-75 third-generation, 49 Dendrimer wedges, 143 Dendritic aromatic polyesters, 21 Dendritic block copolymers, 2127 hybrid linear-, 29-33 layer-, 21, 22-27 segment-21, 22 surface-, 21, 36 Dendritic bolaamphiphiles {see Bolaamphiphiles) Dendritic imines, of tris(2aminoethyl)amine (TREN), 62

Index

Dendritic macromolecules {see also Cascade molecules) characterization of products, 10-14 convergent-growth synthesis, 1-37, 124 defined, 2 dipolar, 18 divergent-growth approach, 2,3 functional groups at chain ends, 14 glass-transition temperature, 35 interiors as microenvironments, 27 intrinsic viscosity, 33-34 monolayer formation, 36 physical properties, 33-36 relevance of, 2-3 research recommendations, 36-37 solubility, 35 surface functionality, 14-21 systematic nomenclature, 6 Dendritic macromonomers, copolymerization of, 2933 Dendritic micelles, 19-21 synthesis of, 25, 27 Dendritic oligoamines, cascade synthesis of, 56 Dendritic polyether macromolecules, synthesis of, 6-9 Dendritic polymers, as polymerrheology control agents, 127 Dendritic poly(siloxanes), synthesis of, 105-107

195

Dendritic toolbox, 68, 69 3,5-Diacetoxybenzoic acid, 142 2,6-Diacylaminopyridine, 165 3,5-Diaminobenzoic acid, 151 1,4-Diazabicyclo[2.2.2]octane, 92 3,5-Di(benxyloxy)benzoic acid, 143 3,5-Dibromo-1 -trimethylsilylbenzene, 133 2,3-Dibromoanisole, 147 2,4-Dibromophenol, 146 3,5-Dibromophenyl-boronic acid, 133 Diels-Alder oligomerization, 43 Differential scanning calorimetry (DSC), 143 3,5-Dihydroxybenzaldehyde, 14 3,5-Dihydroxybenzil alcohol, 6 3.5-Dihydroxybenzoate, 25 3,5-Dihydroxybenzoic acid, 21, 141, 143 3,5-Dihydroxybenzyl, 19, 35 2,2-Di(hydroxymethyl)propionic acid, 141 Diisobutylaluminumhydride (DIBAH), 56, 58, 61 Dimeric surfactants, 179 4-{N, A^-Dimethylamino-1 nitrobenzene, 27 Dimethyl malonate, 160 2,4-Dinitrophenyl phosphate, 184 Dinuclear complexes, 79, 80 l,2-DiphenyH,2diaminoethane, 66 Dipolar dendritic macromolecules, 18 Dipole moments, 18-19

196

Directed self-assembly, of chiral components, 165 Dirutheium complexes, 79, 80 Diruthenium(II) complexes, 77 Disconnection method, 4-5 Dispersity of hyperbranched polyphenylenes, 135 of polypropiolactone, 140 Divergent-growth synthesis, 2 development of, 74-75 growth process, 3, 5 silicon-based dendrimers, 105 tosylamide cascades, 46-52 value of, 102 Divinyloligo(dimethylsiloxanes), 114 a,co-Docosanediol, 166, 167 Dodecanitrile, 60 "DumbbeUs," 161-162 Electron micrographs, 161 Elemental analysis, 10 Ellipsometry, 136 Energy transfer paths, in transition-metal ions, 82 Ester chemistry, 22, 25 Ether chemistry, 25 Extended hexyldecylamine, 186 Fast atomic bombardment mass spectrometry (FABMS), 63 First-generation dendrimers, 75 Flexible spacers, 159 vs. rigid spacers, 179 Focal point convergent-growth approach and, 29

INDEX

hybrid linear-dendritic block copolymers, 29, 31 nuclear magnetic resonance (NMR) spectroscopy of, 10, 11 Fractals, 2, 42 (see also Dendritic macromolecules) Fullerenes, 7 Functional groups, at chain ends, 14 Functional vesicles ionic bolaamphiphiles, 185 nonionic bolaamphiphiles, 168-169 Gelation, 161 Gel permeation chromatography (GPC), 12, 129 "Gemini surfactants,'' 159, 179, 186 Generation zero dendrimers, 75 Glass transition temperature, 118 branched aromatic polyesters, 144 dendritic macromolecules, 35 H-bonding, in nonionic bolaamphiphiles, 161164 H-bridged networks, 167 Hermophilic bacteria, bolaamphiphiles in, 188 Hexacyclen, 42 Hexacyclene as core unit for polyamine dendrimers, 59-60 as core units for convergent synthetic strategy, 54-55 dedrimers, generations of, 60

Index

Hexakis-provitamin Be, 70 Hexyldecylamine, extended, 186 Highly branched aromatic polymers, 123-155 branching in, 124, 132-134, 139-141 polyamides, 151-155 polyesters, 141-145 polyp henylenes, 128-141 polyp henylethers, 145-150 High-pressure liquid chromatography (HPLC), 12 HIV reverse transriptase, 187 ^H nuclear magnetic resonance (NMR) spectroscopy, 10,11,17 Homopolymers, 141 Hybrid linear-dendritic block copolymers, 29-33 Hydrolosis, ionic bolaamphiphiles, 184-185 Hydrophobic aromatic polyether core, 20 Hydrophobic binding, 134-135 Hydrophobic-hydrophilic interactions, 161 Hydrophobic spacers, 168, 170171 Hydrosilation, 106, 115, 116-117 "one-pot," 115, 118 5-Hydroxyisophthalic acid, 141, 143 Hydroxyl-terminated dendrimers, 91 Hyperbranched macromolecules, 2 Hyperbranched polyamides, 151-155

197

Hyperbranched polymers, 115118 A-B3 polymers, 118 rheology and, 150 silicon-based, 115-118 spherical, 138 stability of, 130 star-shaped, 140 synthesis of, 114-115, 127 Hyperbranched polyphenylene Langmuir-Blodgett films of, 135-137 rheology and, 150 Hyperbranched poly(siloxysilanes), 115-118 Infrared spectrum, 10, 17 Initator core, dendrimers, 75 Intercalation, 146 Intramolecular chain-chain associations, 179 Intramolecular cyclization, 129 Intrinsic viscosity, 33-34 Ion channel mimic, 173, 175 Ionic dendrimers, 73-95 ammonium-centered, 87-93 molecular trains and catenanes, 94-95 multinuclear, 76-84 multinuclear linear metal arrays, 84-86 phosphonium-centered, 87-93 structural types, 75-76 surface-charged, 93-94 Ionic dendritic bolaamphiphiles, 176-188 biological activity, 186-187 functional vesicles, 184-186 molecular assemblies, 176-184 transports, 187-188

198

Ionic molecular catenanes, 94-95 Ionic molecular trains, 94-95 Ion transport, nonionic bolaamphiphiles, 173-176 (£)/(Z)-Isomerization, 42, 64 Karstedt's catalyst, 114 Langmuir-Blodgett films, of hyperbranched polyphenylenes, 135-137 Langmuir monolayers, 135 Layer-block copolymers, 21, 2227 LEGO strategy, 43 Linear imines, 62 Lipid membranes, 168 "Living" polymerization, 140 anionic, 103-105 Low-angle light scattering, 12 Lyotropic properties mesophases, 180 polyamides, 155 polyamids, 155 Lysine-based bolaphiles, 164 Macromonomers, 130 Mark-Houwink constants, 107, 114 Masking, in convergent-growth approach, 7-9 Mass spectrometry for chiral cascade molecules, 67 for dendritic macromolecules, 10 Melt viscosity, of PVC blends, 139 Membrane-disruptive bolaamphiphiles, 171-172

INDEX

Membranes archaebacterial, 177 bilayer, ionic bolaamphiphiles, 186 bolaamphiphilic, 171-172, 177 Upid, 168 redox-active, 168 stability of, 177 Merrifield resin, 94 Metal-halogen exchange, 130 Metallation, selective, 128 Metallomicelles, 184 Methyl 4-bromomethylbenzoate, 19 Methyl 3,5-hydroxybenzoate, 143 A^-Methylimidazole, 135 Micellar bolaamphiphiles, 184-185 Micelles, 162 bolaamphiphile conformations within, 188 dendritic, 19-21, 25, 27 metallomicelles, 184 unimolecular, 93, 134 Michael addition, 42, 58, 60, 75, 93 Microorganisms, disruption of, 170 Modeling hydrophobic binding, 134-135 ionic dendrimers, 80 multinuclear dendrimers, 80 triethanolamine ammonium dendrimers, 92 "Modular construction set," 173-175 Molecular assemblies ionic bolaamphiphiles, 176184 nonionic bolaamphiphiles, 159-168

Index

Molecular-based magnets, 95 Molecular dumbbells, 161-162 Molecular recognition, 23, 165, 188 Molecular self-assembly ionic bolaamphiphiles, 179, 182, 186,188 nonionic bolaamphiphiles, 164, 165 Molecular weight hyperbranched polyphenylenes, 135 measurements, gel permeation chromatographic (GPC), 129 polyamides, 151, 154 polyphenylenes, limitations, 128-129 polyphenylethers, 145 star polymers, 140 Monomeric bolaamphiphiles, 171 Multifunctional initiators, 130 Multilamellar arrangement, bolaamphiphiles, 182 Multinuclear dendrimers based on bipyridylpyrazine bridging ligands, 76-84 linear metal arrays, 84-86 Multiple cobalt complexes, cascade molecules, 63-64 Multiple-metal complexes, 63 Multiple Salen systems, 63 Neumatic phase, 155 Ni(II) catalysts, 128 4-(4'-Nitrophenylazo)resorcinol, 185 /7-Nitrophenyl picolinate, 185

199

Nomenclature, dendritic macromolecules, 6 Nonionic cascade molecules, 84 Nonionic dendritic bolaamphiphiles, 158-176 biological activity, 170-172 functional vesicles, 168-169 ion transport, 173-176 molecular assemblies, 159-168 Notation system, for dendrimers, 75 Nuclear magnetic resonance (NMR) spectroscopy, 10-12,17,89,106,115, 117-118 Nucleotide 5'-triphosphates, 187 Octahedral coordination, 78 Oligoamines, cascade synthesis of, 56 Oligooxyethylene, 118 "One-pot" hydrosilation, 115, 118 Osmium(II), 82 Oxidative intiators, 149 Packing parameter, 179 Pd(0)-catalyzed coupling reactions, 128, 130 Pentaarylphosphorane, 89 Pentaethylenehexamine, 58-59 Peptides, repetitive synthesis, 43 Perfluorinated poly(phenylenes), 115 Phase transfer catalyst (PTC), for polyphenylether polymerization, 146 o-Phenanthroline, 78 2,2:6',2''-Phenanthroline, 78 Phenylacetylenic wedges, 134

200

Phenylene-based bolaphiles, 181 Phosphatidylocholines, 176 Phosphine, 89 Phospholipase catalysis, 176 Phosphonium, 75, 87-93 Phosphorane/ phosphonium ion dendrimers, 90 Photopolymerization, 186 Photostationary equilibrium (PSE), 64 Photoswitching dendrimers azobenzene, 42, 64 cascade molecules, 64-66 first-generation, 65 UV-VIS spectrum, 65 Photosynthetic electron acceptors, 168 ^^P NMR spectrum, 89 Poly(2-acrylamido-2-methyl-1 propanesulfonic acid) (PAMPSA), 186 Polyamides, 151-155 characterization, 154-155 lyotropic properties, 155 molecular weights, 154 preparation, 151-154 Polyamine dendrimers, 56-60 cyclam as core unit, 59-60 hexacyclene as core unit, 5960 pentaethylenehexamine as core unit, 58-59 tris(2-aminoethyl)aniine (TREN) as core unit, 56-57 Polyaza compounds, 42 Polybutadiene stars, 105, 114 Polydienes, 103 Poly(dimethylsiloxane) oligomers, 105

INDEX

Poly(dimethylsiloxanes) (PDMS), 103 Polydispersity, 13, 128 Polyesters, 141-145 applications, 144-145 single-step polymerization, 141-142 symmetrical, 142-144 Polyether macromolecules, synthesis of, 6-9 Polyhydroxy monocarboxylic acid, 141 Polymeric bolaamphiphiles, 171 Polymerization degree of, 135 direct, 127 ionic bolaamphiphiles, 186 "Uving," 140 one-step, 127, 141-142 polyamids, 154 polyesters, 141-142 polyphenylethers, 145 step-, 129 Polymers {see also Highly branched aromatic polymers) blending polyphenylenes with, 137-139 chemical modification of, 130-132 growth, 102 star-branched, 139-141 synthesis, polyphenylenes, 128-129 "wedges," 102 Polymetallic complexes, 84-86 Poly(methyl)methacrylate (PMMA), 141 Polyphenolic dendrimers, 7

Index

Polyphenylenes, 128-141, 144 blending with other polymers, 137-139 characterization, 129-130 chemical modification of, 130-131 hydrophobic binding, 134-135 hyperbranched, LangmuirBlodgett films of, 135137 molecular weight limitations, 128-129 polyme synthesis, 128-129 solubility, 129 star-branched polymerization, 139-141 symmetrically branched, 132134 Polyphenylethers, 145-150 Theological effects, 150 synthesis, 145-149 Polyphosphonium ion materials, 92 Polypropiolactone, 140 Poly(siloxanes), 105 starburst polymers, 107, 109, 111 synthesis of, 105-107 Poly(siloxysilanes), 115-118 Polystyrene blends, 138 Theological effects on, 150 PolystyTene-equivalent moleculaT weights, 12 Pool quinones, 169 PoTOUs VycoT glass, 76 PToton analysis, 115 PVC blends, 138-139 Pyridine bolaphile, 184-185 Pyridoxal derivative, 70

201

QuatemaTy phosphonium ions, 88 Quinone moieties, 168-169 Racemic lysine bolaphile, 164 Radical coupling Tadical-anion (SRNIO, 149 Tadical-Tadical, 149 Reactive end cappeTS, 105 Redox-active membTanes, 168 Repetitive synthesis of annulene derivatives, 45 defined, 42-43 of dendrimcTS, 42-45 of Newkome's aTvoTols, 4243,44 ResoTcinol, 185 Rheology, 150 Rigid spaccTS, 159 vs. flexible spaceTS, 179 RNA-based bolaphiles, 186-187 Ruthenium(II), 76, 82, 84, 85-86 Ruthenium/Thenium complexes, 86 Salen units, cascade molecules, 61-63 SEC analysis, 12, 105, 106, 115116 Segment-block copolymcTs, 21, 22 Selective metallation, 128 Self-aggregation, 165 Self-assembly, 165, 179, 188 directed, 165 ionic bolaamphiphiles, 186 monolayers, 177-178 supramolecular, 164, 182 Semiconductor metals, 86 Shear birefringence, 155

202

Short-arm star polymers, 140 Si-H addition, 115 Silicon-based polymers dendrimers, 102-103, 105-115, 118 hyperbranched, 115-118 stars, 103-105, 118 Single-step polymerization, polyesters, 141-142 ^^Si nuclear magnetic resonance (NMR) spectroscopy, 106,117-118 Size-exclusion chromatography (SEC), 12, 105, 106, 115-116 Sodium diethoxymethylsilanolate, 105 Sodium dodecyl sulfate (SDS), 21 Solubility dendritic macromolecules, 35 polyphenylenes, 129 Solvatochromic probe, 27 Solvatocrhomic dendrimers, 34 Spacers hydrophobic, 168, 170-171 length of, 180 rigid vs. flexible, 179 Spherical hyperbranched polymers, 138 Star-branched polymers, 139-141 Starburst molecules, 2 {see also Dendrimers) Starburst perfluorinated poly(phenylenes), 115 Starburst poly(siloxane) polymers, 107, 109, 111 Starburst synthesis, 3 {see also Divergent-growth synthesis)

INDEX

"Star" ionic dendrimers, 90 Star poly(butadienes), 114 Star polymers, 139-141 short-arm, 140 silicon-based, 103-105, 118 "Star" tetraarylphosphonium ion, 89 Step-polymerization, 115, 129 Stereogenic centers, in transition-metalcentered dendrimers, 79 Steric screening, 115 "String" dendrimers, 92 Supramolecular chemistry, 188 Supramolecular effects, 94-95 Supramolecular helix structure, 165 Supramolecular self-assembly, 164, 182 Supramolecular surfactants, 171 Surface-block copolymers, 21 Surface-charged dendrimers, 9394 Surface functionalization characterization of, 17 control of, 14-21 convergent-growth approach, 19 dipole moments, 18-19 Surface tension measurements, 180 Surfactants CO-, 181

dimeric, 179 "gemini," 159, 179, 186 supramolecular, 171 Suzuki's coupling, 128 Symmetrical polyesters, 143-144 Tartaric acid, 165 Telechelic starts, 104

Index

2,2':6',2"-Terpyridine, 85 Tetrabutylammonium fluoride, 146 Tetracationic cyclophane, 94 Thermal gravimetric analysis (TGA), 145-146 Thermal self-condensation, 142 3-D crystallites, 165 "Three-headed" bolaphiles, 183 Tosylamide cascades, 46-55 convergent synthesis strategy, 53-55 divergent synthesis strategy, 46-52 generations of, 49 starting materials for, 47 X-ray structure, 47-49 3-(Tosylamino)azobenzene, 64 Transesterification, 144 Transition-metal ions, 75 complexed, dendrimers containing, 76-86 multinuclear dendrimers, 7684 multinuclear linear metal arrays, 84-86 preparation, 76 Transport agents ionic bolaamphiphiles, 187188 nonionic bolaamphiphiles, 173-176 1,3,5-Tribromobenzene, 133 2,4,6-Tribromophenol, 145 Trichloroethy 3,5-dihydroxybenzoate, 22 Triethanolamine, 90 Triethyl methanetricarboxylate, 160

203

Tri(p-methoxymethyl)phenylphospine, 88 Tris(2-aminoethyl)amine (TREN) as core unit for polyamine dendrimers, 56-57 dendritic imine of, 62 first-generation dendrimers, 63 Tris(2,2'-bipyridyl) bridging ligand, 80 Tris(hydroxymethyl)aminomethane, 160 1,1,1 -Tris(4'-hydroxyphenyl)ethane, 6, 7 Tris(perfluorophenyl)germane, 115 Tris(perfluorophenyl)silane, 115 Tris(perfluorophenyl)stannane, 115 l,3,5-Tris(2,2':6,2"-terpyriden-4'yl)benzene, 85-86 "Tunability," of bolaform amphiphiles, 170, 172 Twin-tailed amphiphiles, 179 Two-directional arborols, 163 Unimolecular micelles, 93, 134 UV-Vis specroscopy, 27 Vesicles, 162 functional, 168-169, 185 Vesicular morphology, 186 Vinyltris(dimethylsiloxy)silane, 116 Viscosity intrinsic, dendritic macromolecules, 33-34 melt, of PVC blends, 139 Vycor glass, porous, 76

204

"Wedges," 102 Williamson coupling, 6, 7 Williamson synthesis, 69 Wittig reaction, 43

INDEX

X-ray diffraction ionic bolaamphiphiles, 186 polyamids, 155 X-ray structure, tosylamide cascades, 47-49

Advances in Dendritic Macromolecules Edited by George R. Newkome, Department of Chemistry, University of South Florida Volume 1,1994,198 pp.

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ISBN 1-55938-696-7 CONTENTS: Introductionto the Series: An Editor's Foreword, Albert Padwa, Emory University. Preface, George R. Newkome, University of South Florida. A Review of Dendritic Macromolecules, George R. Newkome and Charles N. Moorefield, University of South Florida. Stiff Dendritic Macromolecules Based on Phenylacetylenes, Zhifu Xu, Benjamin Kyan, and Jeffery S. Moore, The University of Michigan. Preparation and Properties of Monodisperse Aromatic Dendritic Macromolecules, Thomas X. Neenan, Timothy M. Miller, Elizabeth W. Kwock, and Harvey E. Bair, AT&T Bell Laboratories. HighSpin PolyarylmethylPolyradicals,Andrzej Rajca, University of Nebraska. A Systematic Nomenclaturefor Cascade (Dendritic) Polymers, Gregory R. Baker and James K. Young, University of South Florida. Index.

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Advances in Theoretically Interesting Molecules Edited by Randolph P. Thummel, Department of Chemistry, University of Houston Volume 1 , 1989,467 pp. ISBN 0-89232-869-X

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CONTENTS: lntroductionto the Series: An Editor's Foreword, Albert Padwa. Preface, Randolph P. Thummel. Isobenzofurans, Bruce Rickbom. Dihydropyrenes: Bridged [14] Annulenes Par Excellence. A Comparison with Other Bridged Annulenes, Richard H. Mitchell. [I.m.n.] Hericenes and Related Exocyclic Polyenes Pierre Vogel. The Chemistry of Pentacyclo [ 5 . 4 . 0 . 0 ~ ~ ~ . 0 ~ Undecane , ~ ~ . 0 ~ ~ (PCUD) ~] and Related Systems, Alan P. Marchand. Cyclic Cumulenes, Richard P. Johnson. Author Index. Subject Index. Volume 2, 1992, 223 pp. ISBN 0-89232-953-X

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CONTENTS: List of Contributors. lntroduction to the Series: An Editor's Forward, Albert Padwa. Preface, Randolph P. Thummel. Cyclooctatetraenes: Conformational and x-Electronic Dynamics Within Polyolefinic [8] Annulene Frameworks, Leo A. Paquette. A Compilation and Analysis of Structural Data of Distorted Bridgehead Olefins and Amides, Timothy G. Lease and Kenneth J. Shea. Nonplanarity and Aromaticity in Polycyclic Benzenoid Hydrocarbons, William C. Hemdon and Paul C. Nowak. The Dewar Furan Story, Ronald N. Warrener. Author Index. Subject Index. Volume 3, 1995, 316 pp. ISBN 1-55938-698-3

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CONTENTS: List of Contributors. Preface, Randolph P. Thummel. Polynuclear Aromatic Hydrocarbons with Curved Surfaces: Hydrocarbons Possessing Carbon Frameworks Related to Buckminsterfullerene, Peter W. Rabideau and Andrzej Sygula. Chemistry of Cycloproparenes, Paul Muller. A Tale of Three Cities: Planar Dehydro [8] Annulenes and Their Reverberations, Henw N.C. Wong. lnfrared Spectroscopy of Highly Reactive Organic Species: The Identificationof Unstable Molecules and Reactive Intermediates Using AB lnitio Calculated lnfrared Spectra, 6 . Andes Hess, Jr. and Lidia Smentek-Mielczarek. The Mills-Nixon Effect?, Natia L. Frank and Jay S. Siegel. Radical Cations of Cyclopropane Systems -Conjungation and Homoconjugation with Alkene Functions, Heinz D. Roth. Subject Index. Author Index.