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ADVANCES IN DENDRlTlC MACROMOLECULES

Volume 2

1995

This Page Intentionally Left Blank

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


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.

C—Core—C I C

CL ) C-~C6re~C—\^L :cf—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

c

c

Xc

c

e—C—^C—^C C—Core C C^

c

C

°Xc c

.c

c.

c

X ^ R_f^, CL

x= c ^c

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 (

C = coupling site R = reactive group CL, = latent coupling site

R R-Core-R

X

X

3 C-

.

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.


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


il

10

fen" cc^

0-., €^V

/ - ^

OCH,

K2CO3 I8-C-6

b o

4L.

^

"^ OCHjCO,

0^°prô 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

/ ^

9 ^ ^^

DCC DPTS

Q

:

2£

^

°

^

^

o ^ ^ ^

6i ^ Scheme 8. 24

^

The Con vergent-Growth Approach

0^

fen 6

Or-.

0^

f

. ^ . Br

25

"W"" f

OCHjCCI,

K2CO3

J [G-2>Br

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^ô

^^Â 'teC

^

(0 X Z H

^â)66®'

"

I

ffi

in

6

28

I


29

ayu"

• E E

380-

E

•

5

• •

•

•

c o o

\ /

\/

'••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

> -

-

,

u M

/^

M

Na2S04

s H2N

^NH2

NN

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.


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^ 'NN

OCH3 ethe'Tcleavage

1)DIBAH

'2)C^H^ CN

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 TsHN

87

N\

R

NHTs

8 7 : .=

R

H o ^

OH

N"^CH3

Scheme 24.

Functionalized dendrimers.

70


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. Aâ/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.


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 wîiie 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.^^

Ionic Dendrimers

87 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 (CH3)3SiI

4X"

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

>-CH20CH3

3X-

;s^^^-CH2P-K^CH20CH3

3X-

0=P- i.

j)-CH2P-K.

27

Cl3SiH

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 36a

l.TsCl 2. N(CH2CH20H)

+ + + + 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

)3]3}4

17X-

92

ROBERT ENGEL /—\ 39 •'^

l.HOCHzCHjCl

rT\+y\

2.TsCl 3.Dabco(39)

^

^

+/

\+/\

"^ ^ / ^^^. 4TsO

I.HOCH2CH2CI

+/~Z\ ^

^

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

:NH3

l.H,C=CHC02CH3 ^ => 2. H2NCH2CH2NH2

:N(CH2CHoCONHCHoCH'>NH2)3 l.H2C=CHC02CH3^,.,^— :N(

repea.reagen. sequence n times • 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.

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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.

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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.


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

rôf^s

"ÔLJ + 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


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

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

% xyî^^^^

\(. .SH-0—^H

!i±_v3ô^y

.Veô^y

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

^^^'ijs;y:^^'t;s^ ^

Pseudo B«

O-Si-0

SiH

i

1

-SHO-SHO-Sf

^^m

K"

v ;i-o-î

cfo

\

-SHCX^

;iH

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

—Sh-


i

l

—SI—

l

—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


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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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.


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.


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-2

G-3-P

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.

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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


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 HCsC(CH3)20H

I

3P CH3

=

4-OI I OH CH3

3Q (CH3)3SiCI |—Si(CH3)3 3i

Scheme 5. 131

|—CH2OH

NaOH 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


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


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 - ;

\

30 ^ 25 -

E

^

E

20-

^ 1 5 C 10 5 -

0 4

\

1

1

1 "

[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


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


139

0^ "-^

o • (0 (0

, /^5

K>

0-^ -H

t •

o

•

D O

•

i o

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

H

0'

9

in

8 1000 -^ 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

ÔH \ / 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


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

O

32

O

HCKCH^CHÔ)^—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

HCXCHXHÔ)^—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

Core

o

O

Y

z

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

Core Units

coo'

cô^ coo"

.^-"^ OOC^

O

r^^^

r^^^

o

oocs

o

o

coo-

ooc^^

O^

OOC^

O

O^

'COO'

OOC^

^v^

O

COO'

Ô '^Y^

^\

oocô

O

O^

"OOC

OOCK,

OOC^

o

O

O^

"COO"

Head Groups „/~-COOH

'^'^^^°^r^^

_s.

.OH

Wall Units o

O

0

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

0

Dendritic Boiaamphiphiles and Related Molecules

175

HO--' -ÔH 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


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 ÔCH^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


^' (C£)^'^^'^-'^^^^''-^ V_-/"

COO(CH:)6-NQ)

cr

46

Br"

©-'

(CH:)800C 47

l^r'

:00(CH2)II-NQ)

^(£)N-(CH:

Br

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.


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.


181

Br

Br" 51

CH^-^n ^

/

-

7Â, ° 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


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


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

187

TTTTTA

Tim ^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

0

0

r

4 Br

Hi-c/ 61 Figure 26.

A bolaamphiphilic transport for nucleotide 5'-triphosphates.

188


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.

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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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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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