Supramolecular Polymer Chemistry

Edited by Akira Harada

57268File AttachmentCover.jpg

Edited by Akira Harada

Supramolecular Polymer

Chemistry

Related Titles

Schalley, C. A. (ed.)

Analytical Methods inSupramolecular ChemistrySecond Edition

2012

ISBN: 978-3-527-31505-5

Urban, M. W. (Ed.)

Handbook of Stimuli-Responsive Materials2011

ISBN: 978-3-527-32700-3

Samori, P., Cacialli, F. (Eds.)

Functional SupramolecularArchitecturesfor Organic Electronics and

Nanotechnology

2011

ISBN: 978-3-527-32611-2

Sauvage, J.-P., Gaspard, P. (Eds.)

From Non-Covalent Assembliesto Molecular Machines2011

ISBN: 978-3-527-32277-0

Atwood, J. L., Steed, J. W. (Eds.)

Organic Nanostructures2008

ISBN: 978-3-527-31836-0

van Leeuwen, P. W. N. M. (Ed.)

Supramolecular Catalysis2008

ISBN: 978-3-527-32191-9

Diederich, F., Stang, P. J.,Tykwinski, R. R. (Eds.)

Modern SupramolecularChemistryStrategies for Macrocycle Synthesis

2008

ISBN: 978-3-527-31826-1

Edited by Akira Harada

Supramolecular PolymerChemistry

The Editor

Prof. Akira HaradaOsaka UniversityDepartment of Macromolecular ScienceGraduate School of Science1-1 Machikaneyama-cho,ToyonakaOsaka 560-0043Japan

CoverThe graphic material used in the cover illustrationwas kindly provided by the editor Prof. Akira Harada.

All books published by Wiley-VCH are carefullyproduced. Nevertheless, authors, editors, andpublisher do not warrant the information containedin these books, including this book, to be free oferrors. Readers are advised to keep in mind thatstatements, data, illustrations, procedural details orother items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication DataA catalogue record for this book is available from theBritish Library.

Bibliographic information published bythe Deutsche NationalbibliothekThe Deutsche Nationalbibliothek lists this publica-tion in the Deutsche Nationalbibliografie; detailedbibliographic data are available on the Internet athttp://dnb.d-nb.de.

# 2012 Wiley-VCH Verlag & Co. KGaA,Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translationinto other languages). No part of this book may bereproduced in any form – by photoprinting,microfilm, or any other means – nor transmitted ortranslated into a machine language without writtenpermission from the publishers. Registered names,trademarks, etc. used in this book, even when notspecifically marked as such, are not to be consideredunprotected by law.

Cover Design Adam Design, WeinheimTypesetting Thomson Digital, Noida, IndiaPrinting and Binding Fabulous Printers Pte Ltd,Singapore

Printed in SingaporePrinted on acid-free paper

Print ISBN: 978-3-527-32321-0ePDF ISBN: 978-3-527-63980-9ePub ISBN: 978-3-527-63979-3Mobi ISBN: 978-3-527-63981-6oBook ISBN: 978-3-527-63978-6

Contents

Preface XIIIList of Contributors XV

Part One Formation of Supramolecular Polymers 1

1 Multiple Hydrogen-Bonded Supramolecular Polymers 3Wilco P.J. Appel, Marko M.L. Nieuwenhuizen, and E.W. Meijer

1.1 Introduction 31.1.1 Historical Background 31.1.2 Supramolecular Chemistry 41.1.3 Supramolecular Polymerization Mechanisms 41.2 General Concepts of Hydrogen-Bonding Motifs 61.2.1 Arrays of Multiple Hydrogen Bonds 61.2.2 Preorganization through Intramolecular Hydrogen Bonding 81.2.3 Tautomeric Equilibria 91.3 Hydrogen-Bonded Main-Chain Supramolecular Polymers 101.3.1 The Establishment of Supramolecular Polymers 101.3.2 Supramolecular Polymerizations 131.3.3 Hydrophobic Compartmentalization 141.4 From Supramolecular Polymers to Supramolecular Materials 161.4.1 Thermoplastic Elastomers 161.4.2 Phase Separation and Additional Lateral Interactions in

Supramolecular Polymers in the Solid State 181.4.3 Supramolecular Thermoplastic Elastomers Based on Additional

Lateral Interactions and Phase Separation 191.5 Future Perspectives 23

References 25

2 Cyclodextrin-Based Supramolecular Polymers 29Akira Harada and Yoshinori Takashima

2.1 Introduction 292.2 Supramolecular Polymers in the Solid State 292.2.1 Crystal Structures of CD Aliphatic Tethers 302.2.2 Crystal Structures of b-CDs Aromatic Tethers 31

V

2.3 Formation of Homo-Intramolecular and Intermolecular Complexes byCDs–Guest Conjugates 33

2.3.1 Supramolecular Structures Formed by 6-Modified a-CDs 332.3.2 Supramolecular Structures Formed by 6-Modified b-CDs 392.3.3 Supramolecular Structures Formed by 3-Modified a-CDs 402.3.4 Hetero-Supramolecular Structures Formed by Modified CDs 422.4 Formation of Intermolecular Complexes by CD and Guest Dimers 442.5 Artificial Molecular Muscle Based on c2-Daisy Chain 452.6 Conclusion and Outlook 48

References 48

3 Supra-Macromolecular Chemistry: Toward Design of New OrganicMaterials from Supramolecular Standpoints 51Kazunori Sugiyasu and Seiji Shinkai

3.1 Introduction 513.2 Small Molecules, Macromolecules, and Supramolecules:

Design of their Composite Materials 533.2.1 Interactions between Small Molecules and Macromolecules 533.2.2 Interactions between Small Molecules and Molecular Assemblies 563.2.3 Interactions between Molecular Assemblies 583.2.4 Interactions between Macromolecules 603.2.5 Interactions between Macromolecular Assemblies 633.2.6 Interactions between Macromolecules and Molecular Assemblies 653.3 Conclusion and Outlook 67

References 68

4 Polymerization with Ditopic Cavitand Monomers 71Francesca Tancini and Enrico Dalcanale

4.1 Introduction 714.2 Cavitands 724.3 Self-Assembly of Ditopic Cavitand Monomers 754.3.1 Structural Monomer Classification of Supramolecular

Polymerization 754.3.2 Homoditopic Cavitands Self-Assembled via Solvophobic p-p Stacking

Interactions 774.3.3 Heteroditopic Cavitands Combining Solvophobic Interactions

and Metal–Ligand Coordination 784.3.4 Heteroditopic Cavitands Combining Solvophobic Interactions

and Hydrogen Bonding 824.3.5 Heteroditopic Cavitands Self-assembled via Host–Guest

Interactions 844.3.6 Homoditopic Cavitands Self-assembled via Host–Guest

Interactions 884.4 Conclusions and Outlook 91

References 92

VI Contents

Part Two Supramolecular Polymers with Unique Structures 95

5 Polymers Containing Covalently Bonded and SupramolecularlyAttached Cyclodextrins as Side Groups 97Helmut Ritter, Monir Tabatabai, and Bernd-Kristof Müller

5.1 Polymers with Covalently Bonded Cyclodextrins as Side Groups 975.1.1 Synthesis and Polymerization of Monofunctional Cyclodextrin

Monomers 985.1.2 Polymer-Analogous Reaction with Monofunctional

Cyclodextrin 1005.1.3 Structure–Property Relationship of Polymers Containing

Cyclodextrins as Side Group 1025.2 Side Chain Polyrotaxanes and Polypseudorotaxanes 1055.2.1 Side Chain Polyrotaxanes 1065.2.2 Side Chain Polypseudorotaxane (Polymer (Polyaxis)/

Cyclodextrin (Rotor)) 111References 120

6 Antibody Dendrimers and DNA Catenanes 127Hiroyasu Yamaguchi and Akira Harada

6.1 Molecular Recognition in Biological Systems 1276.1.1 Supramolecular Complex Formation of Antibodies 1276.1.2 Supramolecular Complexes Prepared by DNAs 1296.1.3 Observation of Topological Structures of Supramolecular Complexes

by Atomic Force Microscopy (AFM) 1296.2 Antibody Supramolecules 1306.2.1 Structural Properties of Individual Antibody Molecules 1306.2.2 Supramolecular Formation of Antibodies with Multivalent

Antigens 1306.2.2.1 Supramolecular Formation of Antibodies with Divalent Antigens 1316.2.2.2 Direct Observation of Supramolecular Complexes of

Antibodies with Porphyrin Dimers 1336.2.2.3 Applications for the Highly Sensitive Detection Method of Small

Molecules by the Supramolecular Complexes between Antibodies andMultivalent Antigens 134

6.2.3 Supramolecular Dendrimers Constructed by IgM and ChemicallyModified IgG 136

6.2.3.1 Preparation of Antibody Dendrimers and their TopologicalStructures 136

6.2.3.2 Binding Properties of Antibody Dendrimers for Antigens 1366.3 DNA Supramolecules 1396.3.1 Imaging of Individual Plasmid DNA Molecules 1396.3.2 Preparation of Nicked DNA by the Addition of DNase I to

Plasmid DNA 1406.3.3 Catenation Reaction with Topoisomerase I 141

Contents VII

6.3.4 AFM Images of DNA Catenanes 1436.3.5 DNA [n]Catenanes Prepared by Irreversible Reaction with

DNA Ligase 1446.4 Conclusions 145

References 146

7 Crown Ether-Based Polymeric Rotaxanes 151Terry L. Price Jr. and Harry W. Gibson

7.1 Introduction 1517.2 Daisy Chains 1537.3 Supramolecular Polymers 1567.4 Dendritic Rotaxanes 1577.5 Dendronized Polymers 1587.6 Main chain Rotaxanes Based on Polymeric Crowns

(Including Crosslinked Systems) 1617.7 Side Chain Rotaxanes Based on Pendent Crowns 1667.8 Poly[2]rotaxanes 1707.9 Poly[3]rotaxanes 1737.10 Polymeric End Group Pseudorotaxanes 1767.11 Chain Extension and Block Copolymers from

End Groups 1767.12 Star Polymers from Crown Functionalized Polymers 179

References 181

Part Three Properties and Functions 183

8 Processive Rotaxane Catalysts 185Johannes A.A.W. Elemans, Alan E. Rowan, and Roeland J.M. Nolte

8.1 Introduction 1858.2 Results and Discussion 1858.2.1 Catalysis 1858.2.2 Threading 1878.3 Conclusion 192

References 192

9 Emerging Biomedical Functions through ‘Mobile’ Polyrotaxanes 195Nobuhiko Yui

9.1 Introduction 1959.2 Multivalent Interaction using Ligand-Conjugated

Polyrotaxanes 1969.3 The Formation of Polyrotaxane Loops as a Dynamic Interface 1979.4 Cytocleavable Polyrotaxanes for Gene Delivery 1999.5 Conclusion 2019.6 Appendix 203

References 204

VIII Contents

10 Slide-Ring Materials Using Polyrotaxane 205Kazuaki Kato and Kohzo Ito

10.1 Introduction 20510.2 Pulley Effect of Slide-Ring Materials 20810.3 Synthesis of Slide-Ring Materials 20910.4 Scattering Studies of Slide-Ring Gels 21110.5 Mechanical Properties of Slide-Ring Gels 21310.6 Sliding Graft Copolymers 21510.7 Recent Trends of Slide-Ring Materials 21610.7.1 Introduction: Diversification of the Main Chain Polymer 21610.7.2 Organic–Inorganic Hybrid Slide-Ring Materials 21910.7.3 Design of Materials from Intramolecular Dynamics of

Polyrotaxanes 22410.8 Concluding Remarks 226

References 227

11 Stimuli-Responsive Systems 231Akihito Hashidzume and Akira Harada

11.1 Introduction 23111.2 Stimuli and Responses 23111.2.1 Stimuli 23111.2.1.1 Temperature 23111.2.1.2 Pressure, Force, Stress, and Ultrasound 23211.2.1.3 pH 23311.2.1.4 Chemicals 23311.2.1.5 Electromagnetic Waves or Light 23311.2.1.6 Redox 23411.2.2 Responses 23411.2.2.1 Movement 23511.2.2.2 Capture and Release of Chemicals 23511.2.2.3 Chemical Reactions 23511.2.2.4 Change in Viscoelastic Properties, or Gel-to-Sol and Sol-to-Gel

Transitions 23611.2.2.5 Change in Color 23611.3 Examples of Stimuli-Responsive Supramolecular Polymer

Systems 23611.3.1 Temperature-Responsive Systems 23611.3.2 Pressure-, Force-, and Sonication-Responsive Systems 23911.3.3 pH-Responsive Systems 24111.3.4 Chemical-Responsive Systems 24611.3.5 Photo-Responsive Systems 24911.3.6 Redox-Responsive Systems 25511.3.7 Multi-Stimuli-Responsive Systems 25911.4 Concluding Remarks 261

References 261

Contents IX

12 Physical Organic Chemistry of Supramolecular Polymers 269Stephen L. Craig and Donghua Xu

12.1 Introduction and Background 26912.2 Linear Supramolecular Polymers 27012.2.1 N,C,N-Pincer Metal Complexes 27012.2.2 Linear SPs 27212.2.3 Theory Related to the Properties of Linear SPs 27412.2.4 Linear SPs in the Solid State 27512.3 Cross-Linked SPs Networks 27612.3.1 Reversibility in Semidilute Unentangled SPs

Networks 27612.3.2 Properties of Semidilute Entangled SPs Networks 28312.3.3 The Sticky Reptation Model 28512.4 Hybrid Polymer Gels 28612.5 Conclusion 288

References 288

13 Topological Polymer Chemistry: A Quest for StrangePolymer Rings 293Yasuyuki Tezuka

13.1 Introduction 29313.2 Systematic Classification of Nonlinear Polymer

Topologies 29313.3 Topological Isomerism 29613.4 Designing Unusual Polymer Rings by Electrostatic

Self-Assembly and Covalent Fixation 29813.5 Conclusion and Future Perspectives 302

References 303

14 Structure and Dynamic Behavior of OrganometallicRotaxanes 305Yuji Suzaki, Tomoko Abe, Eriko Chihara, Shintaro Murata, Masaki Horie,and Kohtaro Osakada

14.1 Introduction 30514.1.1 Crystals of Pseudorotaxanes 30714.1.2 Synthesis of Ferrocene-Containing [2]Rotaxanes by the

Threading-Followed-by-End-Capping Strategy 31214.1.3 Dethreacting Reaction of Rotaxane-Like Complex 31614.1.4 Photochemical Properties of Ferrocene-Containing

Rotaxanes 31814.1.5 Ferrocene-Containing [3]Rotaxane and Side-Chain

Polyrotaxane 32014.1.5.1 Strategies and Synthesis of [3]Rotaxanes 32014.1.5.2 Strategies and Synthesis of Side-Chain

Type Polyrotaxane 321

X Contents

14.2 Conclusion 32414.3 Appendix: Experimental Section 324

References 326

15 Polyrotaxane Network as a Topologically Cross-Linked Polymer:Synthesis and Properties 331Toshikazu Takata, Takayuki Arai, Yasuhiro Kohsaka, Masahiro Shioya,and Yasuhito Koyama

15.1 Introduction 33115.2 Linking of Wheels of Main-Chain-Type Polyrotaxane – Structurally

Defined Polyrotaxane Network 33115.3 Linking of Macrocyclic Units of Polymacrocycle with Axle Unit

to Directly Yield a Polyrotaxane Network 33615.3.1 Polyrotaxane Networks Having Crown Ethers as the Wheel at the

Cross-link Points (I) 33615.3.2 Polyrotaxane Network Having Crown Ethers as the Wheel at the

Cross-link Points (II) 33715.3.3 Polyrotaxane Network Having Cyclodextrins as Cross-link Points:

Effective Use of Oligocyclodextrin 33915.4 Linking of Wheels of Polyrotaxane Cross-linker to Afford Polyrotaxane

Network: Design of the Cross-linker 34215.5 Conclusion 344

References 345

16 From Chemical Topology to Molecular Machines 347Jean-Pierre Sauvage

16.1 Introduction 34716.2 Copper(I)-Templated Synthesis of Catenanes: the ‘Entwining’ Approach

and the ‘Gathering and Threading’ Strategy 34716.3 Molecular Knots 34916.4 Molecular Machines Based on Catenanes and Rotaxanes 35316.5 Two-Dimensional Interlocking Arrays 35416.6 A [3]rotaxane Acting as an Adjustable Receptor: Toward a

Molecular ‘Press’ 35516.7 Conclusion 356

References 356

Index 361

Contents XI

Preface

The chemistry of molecular recognition began more than 50 years ago with thediscovery of crown ethers as selective host molecules for alkali metal ions byDr. Pedersen. In the last 30 years, the chemistry of molecular recognition has greatlyexpanded. For example, Cram et al. incorporated host–guest chemistry and Lehncreated supramolecular chemistry. To date, numerous studies have been publishedon supramolecular complexes.

Moreover, in biological systems, macromolecular recognition by other macromo-lecules plays an important role in maintaining life (e.g., DNA duplication as well asenzyme–substrate and antigen–antibody interactions). Supramolecular polymercomplexes are crucial for the construction of biological structures such as micro-tubules, microfilaments, and cell–cell interactions.

Synthetic supramolecular polymers have great potential in the construction ofnew materials with unique structures and functions, because polymers contain vastamounts of information on theirmain-chains and side-chains. For example, in 1990,supramolecular polymers consisting of cyclodextrins and synthetic polymers werereported. Prof. Lehns textbook, Supramolecular Chemistry, which was published in1995, mentions supramolecular polymers. Prof. Meijer and Prof. Zimmermanreported supramolecular polymers linked by multiple hydrogen bonds. Since thennumerous other reports on supramolecular polymers have been published.

This book is geared toward current supramolecular polymer researchers as well asother interested individuals, including young researchers and students. Each chap-ter is written by experts who are actively engaged in supramolecular polymerresearch and have published important papers in the field.

I am honored to be a part of this project, and have eagerly anticipated receivingeach chapter. They have all exceeded my expectations, and together they form a bookthat will become a cornerstone in the field of supramolecular polymer research and,I believe, will help to shape research in the future.

Finally, I would like to express my sincere appreciation to the authors and to allwho have assisted in the preparation of this book.

Osaka Akira HaradaMay 2011

XIII

List of Contributors

XV

Tomoko AbeTokyo Institute of TechnologyChemical Resources LaboratoryR1-3, 4259 Nagatsuta, Midori-kuYokohama 226-8503Japan

Wilco P.J. AppelEindhoven University of TechnologyInstitute for Complex MolecularSystems, Laboratory of Macromolecularand Organic ChemistryDen Dolech 25612 AZ EindhovenThe Netherlands

Takayuki AraiTokyo Institute of TechnologyDepartment of Organic and PolymericMaterials2-12-1 (H-126), Ookayama, Meguro-kuTokyo 152-8552Japan

Eriko ChiharaTokyo Institute of TechnologyChemical Resources LaboratoryR1-3, 4259 Nagatsuta, Midori-kuYokohama 226-8503Japan

Stephen L. CraigDuke UniversityCenter for Biologically InspiredMaterials and Material SystemsDepartment of Chemistry3221 FFSC124 Science DriveDurham, NC 27708-0346USA

Enrico DalcanaleUniversity of ParmaDepartment of Organic and IndustrialChemistryViale G. P. Usberti 17/A43124 ParmaItaly

Johannes A.A.W. ElemansRadboud University NijmegenCluster for Molecular ChemistryHeyendaalseweg 1356525 AJ NijmegenThe Netherlands

Harry W. GibsonVirginia Polytechnic Institute & StateUniversityDepartment of Chemistry2105 Hahn HallBlacksburg, VA 24061-0001USA

Akira HaradaOsaka UniversityGraduate School of ScienceDepartment of Macromolecular Science1-1 Machikaneyama-cho, ToyonakaOsaka 560-0043Japan

Akihito HashidzumeOsaka UniversityGraduate School of ScienceDepartment of Macromolecular Science1-1 Machikaneyama-cho, ToyonakaOsaka 560-0043Japan

Masaki HorieNational Tsing Hua UniversityDepartment of Chemical EngineeringHsinchu, 30013Taiwan

Kohzo ItoThe University of TokyoGraduate School of Frontier SciencesDepartment of Advanced MaterialsScience, Group of New Materials andInterfaces5-1-5 Kashiwanoha, KashiwaChiba 277-8561Japan

Kazuaki KatoThe University of TokyoGraduate School of Frontier SciencesDepartment of Advanced MaterialsScience, Group of New Materials andInterfaces5-1-5 Kashiwanoha, KashiwaChiba 277-8561Japan

Yasuhiro KohsakaTokyo Institute of TechnologyDepartment of Organic and PolymericMaterials2-12-1 (H-126), Ookayama, Meguro-kuTokyo 152-8552Japan

Yasuhito KoyamaTokyo Institute of TechnologyDepartment of Organic and PolymericMaterials2-12-1 (H-126), Ookayama, Meguro-kuTokyo 152-8552Japan

E.W. Bert MeijerEindhoven University of TechnologyInstitute for Complex MolecularSystems, Laboratory of Macromolecularand Organic ChemistryDen Dolech 25612 AZ EindhovenThe Netherlands

Bernd-Kristof MüllerPharmpur GmbHMesserschmittring 3386343 KönigsbrunnGermany

Shintaro MurataTokyo Institute of TechnologyChemical Resources LaboratoryR1-3, 4259 Nagatsuta, Midori-kuYokohama 226-8503Japan

XVI List of Contributors

Marko M.L. NieuwenhuizenEindhoven University of TechnologyInstitute for Complex MolecularSystems, Laboratory of Macromolecularand Organic ChemistryDen Dolech 25612 AZ EindhovenThe Netherlands

Roeland J.M. NolteRadboud University NijmegenCluster for Molecular ChemistryHeyendaalseweg 1356525 AJ NijmegenThe Netherlands

Kohtaro OsakadaTokyo Institute of TechnologyChemical Resources LaboratoryR1-3, 4259 Nagatsuta, Midori-kuYokohama 226-8503Japan

Terry L. Price Jr.Virginia Polytechnic Institute & StateUniversityDepartment of Chemistry2105 Hahn HallBlacksburg, VA 24061-0001USA

Helmut RitterHeinrich Heine UniversityInstitute of Organic andMacromolecular ChemistryUniversitätsstr. 140225 DüsseldorfGermany

Alan E. RowanRadboud University NijmegenInstitute for Molecules and MaterialsHeyendaalseweg 1356525 AJ NijmegenThe Netherlands

Jean-Pierre SauvageUniversity Louis Pasteur/CNRSInstitute of Chemistry, Laboratory ofOrganic – Inorganic ChemistryInstitut Le Bel, U.M.R. 717767070 Strasbourg-CedexFrance

Seiji ShinkaiFukuoka, Japan and Sojo UniversityInstitute of Systems, InformationTechnologies and Nanotechnologies(ISIT)KumamotoJapan

Masahiro ShioyaTokyo Institute of TechnologyDepartment of Organic and PolymericMaterials2-12-1 (H-126), Ookayama, Meguro-kuTokyo 152-8552Japan

Kazunori SugiyasuNational Institute for Materials Science(NIMS)Organic Nanomaterials CenterMacromolecules Group1-2-1 SengenTsukuba 305-0047Japan

Yuji SuzakiTokyo Institute of TechnologyChemical Resources LaboratoryR1-3, 4259 Nagatsuta, Midori-kuYokohama 226-8503Japan

List of Contributors XVII

Monir TabatabaiHeinrich Heine UniversityInstitute of Organic andMacromolecular ChemistryUniversitätsstr. 140225 DüsseldorfGermany

Yoshinori TakashimaOsaka UniversityGraduate School of ScienceDepartment of Macromolecular Science1-1 Machikaneyama-cho, ToyonakaOsaka 560-0043Japan

Toshikazu TakataTokyo Institute of TechnologyDepartment of Organic andPolymeric Materials2-12-1 (H-126), Ookayama, Meguro-kuTokyo 152-8552Japan

Francesca TanciniUniversity of ParmaDepartment of Organic and IndustrialChemistryViale G. P. Usberti 17/A43124 ParmaItaly

Yasuyuki TezukaTokyo Institute of TechnologyDepartment of Organic andPolymeric Materials2-12-1-S8-41 Ookayama, Meguro-kuTokyo 152-8552Japan

Donghua XuDuke UniversityCenter for Biologically InspiredMaterials and Material SystemsDepartment of Chemistry3221 FFSC124 Science DriveDurham, NC 27708-0346USA

Hiroyasu YamaguchiOsaka UniversityGraduate School of ScienceDepartment of Macromolecular Science1-1 Machikaneyama-cho, ToyonakaOsaka 560-0043Japan

Nobuhiko YuiTokyo Medical and Dental UniversityInstitute of Biomaterials andBioengineering2-3-10, Kanda-Surugadai, ChiyodaTokyo 101-0062Japan

and

JST CRESTTokyo 102-0075Japan

XVIII List of Contributors

Part OneFormation of Supramolecular Polymers

Supramolecular Polymer Chemistry, First Edition. Edited by Akira Harada.� 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2012 by Wiley-VCH Verlag GmbH & Co. KGaA.

j1

1Multiple Hydrogen-Bonded Supramolecular PolymersWilco P.J. Appel, Marko M.L. Nieuwenhuizen, and E.W. Meijer

1.1Introduction

1.1.1Historical Background

Since the introduction of the first synthetic polymer more than a hundred years agoby Leo Hendrik Baekeland, covalent polymers have become indispensable ineveryday life. The term polymeric was first introduced in 1832 by J€ons JacobBerzelius to describe a compound with a higher molecular weight than that of thenormal compoundbutwith an identical empirical formula as a result of the repetitionof equal units [1]. In 1920, Hermann Staudinger defined polymers, which he calledmacromolecules, to be multiple covalently bound monomers. For this work he wasawarded with the Nobel Prize in 1953 [2]. Today, our knowledge of organic synthesisand polymer chemistry allows the preparation of virtually any monomer and itsassociated polymer. In addition, an in-depth understanding of living types ofpolymerization facilitates tuning of the molecular weight and molecular weightdistribution, at the same time creating the possibility to synthesize a wide variety ofcopolymers [3].

The macroscopic properties of polymers are directly linked to their molecularstructure. As a result, polymer chemists devised synthetic approaches to control thesequence architecture.More recently, the importance of introducing supramolecularinteractions between macromolecular chains has become evident, and many newoptions have been introduced. Thefinal step in this development would be to developpolymers entirely based on reversible, noncovalent interactions. Rather than linkingthe monomers in the desired arrangement via a series of polymerization reactions,themonomers are designed in such a way that they autonomously self-assemble intothe desired structure. As with covalent polymers, a variety of structures of theseso-called supramolecular polymers are possible. Block or graft copolymers, as well aspolymer networks, can be created in this way.

The first reports on supramolecular polymers date back to the time when manyscientists studied themechanismbywhich aggregates of smallmolecules gave rise to

j3

Supramolecular Polymer Chemistry, First Edition. Edited by Akira Harada.� 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2012 by Wiley-VCH Verlag GmbH & Co. KGaA.

increased viscosities. To the best of our knowledge it was LouiseHenrywho proposedthe idea of molecular polymerization by associative interactions in 1878, approxi-mately at the same time that van der Waals proposed his famous equation of state,which took intermolecular interactions in liquids into account, and was only 50 yearsafter Berzelius coined the term polymers. Stadler and coworkers were the first torecognize that hydrogen bonds can be used to bring polymers together [4]. Lehn andcoworkers synthesized the first main-chain supramolecular polymer based onhydrogen bonding [5]. In our group, we introduced the self-complementaryureido-pyrimidinone (UPy) quadruple hydrogen-bonding motif that shows a highdimerization constant and a long lifetime. In this chapter, we review the field ofsupramolecular polymers based on multiple hydrogen bonds and discuss somegeneral approaches to the creation of supramolecular materials based on multiplehydrogen-bonded supramolecular polymers.

1.1.2Supramolecular Chemistry

Jean-Marie Lehn defined supramolecular chemistry as . . . a highly interdisciplinaryfield of science covering the chemical, physical, and biological features of chemical speciesof higher complexity, which are held together and organized by means of intermolecular(noncovalent) binding interactions [5]. This exciting new field introduced thepossibility of self-sorting of subunits during the self-assembly process. At thesame time large, complex structures can be created by the assembly of smallsupramolecular building blocks, thereby allowing the elimination of elaboratesynthetic procedures. Complex self-assembly processes are widely recognized tohave played an important part in different elements of the origin of life. As aresult, many researchers explored different aspects of the field of supramolecularchemistry, using noncovalent interactions to self-assemble molecules into well-defined structures. Noncovalent interactions can vary in type and strength,ranging from very weak dipole-dipole interactions to very strong metal-ligand orion-ion interactions with binding energies that can approach that of covalentbonds [6]. The most obvious benefits of noncovalent interactions are theirreversible nature and their response to external factors such as temperature,concentration, and the polarity of the medium. A subtle interplay between theseexternal factors allows precise control of the self-assembly process. Due to theirdirectionality and the possibility to tune the dynamics and lifetime, hydrogenbonds are among the most interesting assembly units for supramolecular poly-mers. Before focusing on hydrogen bonding, we shall first address the differentmechanisms for the formation of supramolecular polymers.

1.1.3Supramolecular Polymerization Mechanisms

The mechanism of noncovalent polymerization in supramolecular chemistry ishighly dependent on the interactions that play their part in the self-assembly process.

4j 1 Multiple Hydrogen-Bonded Supramolecular Polymers

In contrast to covalent bonds, noncovalent interactions depend on temperature andconcentration, thereby affecting the degree of polymerization. The mechanisms ofsupramolecular polymerizations can be divided in three major classes, these beingisodesmic, cooperative, or ring-chain equilibria (Figure 1.1) [7].

Isodesmic polymerizations occur when the strength of noncovalent interactionsbetweenmonomers is unaffected by the length of the chain. Because each addition isequivalent, no critical temperature or concentration of monomers is required for thepolymerization to occur. Instead, the length of the polymer chains rises as theconcentration of monomers in the solution is increased, or as the temperaturedecreases.

The ring-chain mechanism is characterized by an equilibrium between closedrings and linear polymer chains. In this mechanism, below a certain monomerconcentration the ends of any small polymer chain react with each other to generateclosed rings. Above this critical concentration, linear chain formation becomesmore

Figure 1.1 Schematic representation of the major supramolecular polymerization mechanisms.Reprinted with permission from Nature Publishing Group [7].

1.1 Introduction j5

favored, and polymer growth is initiated. The degree of polymerization changesabruptly once the critical conditions are reached. The critical polymerization con-centration is largely dependent on the length and rigidity of the monomers.Especially at low concentrations, the presence of cyclic oligomers can drasticallyinfluence the macroscopic properties.

Cooperative polymerizations occur in the growth of ordered supramolecularpolymers in which there are additional interactions present besides the formationof linear polymers, such as those that form helices. This involves two distinctphases of self-assembly: a less favored nucleation phase followed by a favoredpolymerization phase. In this mechanism, the noncovalent bonds between mono-mers are weak, hindering the initial polymerization. After the formation of anucleus of a certain size, the association constant is increased, and furthermonomer addition becomes more favored, at which point the polymer growth isinitiated. Long polymer chains will form only above a minimum concentration ofmonomer and below a certain temperature, resulting in a sharp transition from aregime dominated by free monomers and small aggregates to a regime wherealmost all of the material is present as large polymers. For further details aboutsupramolecular polymerization mechanisms we would refer the reader to a recentreview by our group [7].

1.2General Concepts of Hydrogen-Bonding Motifs

The existence of the hydrogen bond was first suggested by Moore and Winmill in1912 [8], and it was defined in 1920 by Latimer and Rodebush as a hydrogen nucleusheld between 2 octets, constituting a weak bond [9]. In that time the concept of hydrogenbonding was used to explain physical properties and chemical reactivities due tointramolecular and intermolecular hydrogen bonding. Nowadays, we interprethydrogen bonds as highly directional electrostatic attractions between positivedipoles or charges on hydrogen and other electronegative atoms. In the field ofsupramolecular chemistry, hydrogen bonding is currently one of the most widelyapplied noncovalent interactions.

1.2.1Arrays of Multiple Hydrogen Bonds

Hydrogen bonding is especially suitable as a noncovalent interaction because of thehigh directionality of the hydrogen bonds. In general, the strength of a singlehydrogen bond depends on the strength of the hydrogen bond donor (D) andacceptor (A) involved, and can range from weak CH – p interactions to very strongFH – F� interactions. When multiple hydrogen bonds are arrayed to create linearhydrogen-bonding motifs, both their strength and directionality are increased.However, the binding strength of the motif is dependent not only on the type andnumber of hydrogen bonds, but also on the order of the hydrogen bonds in themotif.

6j 1 Multiple Hydrogen-Bonded Supramolecular Polymers

This important aspect of linear hydrogen-bonding motifs was pointed out byJorgensen et al.,who found a large variation in the association constants of threefoldhydrogen-bonding motifs. Although the ADA –DAD and DAA – ADD arrays exhibitan equal amount of hydrogen bonds, the association constants of these motifs weresignificantly different. This was attributed to the different order of the hydrogenbonds [10]. Since thehydrogenbonds in themotifs are in close proximity, the distanceof a hydrogen-bonding donor or acceptor to the neighbor of its counterpart is alsorelatively small, creating attractive or repulsive electrostatic secondary cross-inter-actions (Figure 1.2). This theory was later confirmed by Zimmerman et al., whocompleted the series with the AAA – DDD array and indeed found a significantlyhigher dimerization constant due to the presence of solely attractive secondaryinteractions [11].

These so-called secondary interactions have a significant influence on the asso-ciation constant of the correspondingmotif, changing the association constant of thetriple hydrogen-bonding motif by at least three orders of magnitude. Based on theseresults, Schneider et al. developed a method to calculate the free association energyfor linear hydrogen-bonding motifs taking into account the secondary interactions,each contributing 2.9 kJmol�1 to the binding energy, and expanded it to quadruplehydrogen-bonding motifs [12].

NN

N

O

HH

Sug

NN

N

NO

H

NH

H

NN

N

NN

NH

H

HH

NN

O

OR

N

N

N

Ph

Ph

N

N

NHH

HH

H

H

OC3H7O

OC3H7O

HAr

Ka = 102 M-1

Ka = 104-105 M-1

Ka = >105 M-1

A

A

A

D

D

D

A

A

A

D

D

D

A

A

A D

D

D

Figure 1.2 Influence of attractive and repulsive secondary interactions on the associationconstant of threefold hydrogen-bonding motifs [10, 11]. Reprinted with permission from The RoyalSociety of Chemistry [13].

1.2 General Concepts of Hydrogen-Bonding Motifs j7

1.2.2Preorganization through Intramolecular Hydrogen Bonding

Throughout the development of supramolecular chemistry, our knowledge ofhydrogen-bonding motifs expanded rapidly. To attain high association constants,multiple hydrogen-bondingmotifs were developed. Our group developed quadruplehydrogen-bonding motifs based on diaminotriazines and diaminopyrimidines inwhich a remarkably high dimerization constant was achieved when an amidemoietywas replaced by a ureidomoiety (Figure 1.3) [14]. A large deviation in the values of theexperimentally determined dimerization constants of the ureido molecules wasobserved when compared to the calculations as proposed by Scheider et al.However,the experimental values for the amide molecules were in agreement with thecalculated values. The large difference between the experimental and the predicteddimerization constants was attributed to the presence of an intramolecular hydrogenbond between the ureido NH and the nitrogen in the ring. This intramolecularhydrogen bond stabilizes the cis conformation of the ureido moiety and forces thecarbonyl in plane with the aromatic ring. This causes prearrangement of the DADAhydrogen-bondingmotif and results in an increase in the association constant by twoor three orders of magnitude.

To reduce the number of repulsive secondary interactions, thereby increasingthe association constant, our group introduced the self-complementary 2-ureido-4[1H]-pyrimidinone (UPy) quadruple hydrogen-bonding DDAA motif [15]. Theintramolecular hydrogen bond prearranges the motif, resulting in a nearlyplanar DDAA motif (Figure 1.4) [16]. Due to the reduced number of repulsivesecondary interactions and the intramolecular hydrogen bond, the dimerizationconstant was found to be 6� 107M�1 in chloroform, with a long lifetime of0.1 s [17].

N

N NNH

O

n-C5H11

HC5H11

O

N

N NNH

O

N

HCH3

On-C4H9 H

N

N

N

NNH

O

CH3H

H

N

N

N

NNH

O

NH

H

n-C4H9 H

Ar

Ar

Ka = 170 M-1 Ka = 530 M-1

Ka = 2 x 105 M-1 Ka = 2 x 104 M-1

Figure 1.3 Quadruple hydrogen-bondingmotifs with their corresponding dimerization constants,revealing the effect of the intramolecular hydrogen bond on the dimerization constant [14].

8j 1 Multiple Hydrogen-Bonded Supramolecular Polymers

1.2.3Tautomeric Equilibria

Although the UPy motif exhibits a high dimerization constant, the type of aggregatethat is obtained during self-assembly is highly dependent on the substituent onthe 6-position of the pyrimidinone ring, since different tautomeric forms can bepresent [16]. With electron-withdrawing or -donating substituents, the tautomericequilibrium is shifted to the pyrimidin-4-ol tautomer,which is self-complementary asa DADA hydrogen-bonding motif (Figure 1.5). Due to more repulsive secondary

Figure 1.4 2-Ureido-4[1H]-pyrimidinone dimer and its corresponding single-crystal structure.Reprinted with permission from the American Chemical Society [16].

Kdim = 6 x 107 M-1

Kdim = 9 x 105 M-1

N

N

R

O

H

N

H

N

O

H

N

N NO

H

N

O

H

R

H

N

N

O

R

H

N

H

N

O

H

N

N

O

R

H

N

H

N

O

H

N

N

O

R

H

N

H

N

O

H

N

N NO

H

N

O

H

R

H

N

ONN

H

N

O

H

R

H

6[1H]-pyrimidinonemonomer

4[1H]-pyrimidinonemonomer

4[1H]-pyrimidinonedimer

monomerPyrimidin-4-ol dimerPyrimidin-4-ol

A A

A A

D D

D D

A

A A

AD

D D

D

Figure 1.5 Tautomeric equilibria in the 2-ureido-pyrimidinone motif. Reprinted with permissionfrom The Royal Society of Chemistry [13].

1.2 General Concepts of Hydrogen-Bonding Motifs j9

interactions, the dimerization constant of this DADAmotif is lowered to 9� 105M�1in chloroform [18]. The tautomeric equilibrium showed a high dependence on thesolvent, and also showed concentration dependence. This illustrates that under-standing the tautomeric equilibria is crucial for predicting the properties of hydro-gen-bonding motifs.

Nowadays, the synthesis of new hydrogen-bonding motifs is almost unrestrict-ed. Current hydrogen-bonding motifs used in supramolecular chemistry are notonly purely derived from organic chemistry, but are also derived from hydrogenbonding as found in nature, for example by using the hydrogen-bonding motifsfound in DNA base pairs [19] or using peptide mimics (Figure 1.6) [20, 21]. Sincethe start of supramolecular chemistry, many different hydrogen-bonding motifshave been reported, ranging from monovalent up to dodecavalent hydrogenbonds [21], with dimerization constants up to 7� 109M�1 [22]. However, it hasto be noted that some of the reported hydrogen-bonding motifs require amultistep synthetic pathway, which lowers the overall yield tremendously, therebymaking them less attractive to use.

1.3Hydrogen-Bonded Main-Chain Supramolecular Polymers

1.3.1The Establishment of Supramolecular Polymers

In macromolecular chemistry, the monomeric units are held together by covalentbonds. In 1990, Jean-Marie Lehn introduced a new area within the field of polymerchemistry by creating a polymer inwhich themonomeric units were held together byhydrogen bonds, resulting in a liquid crystalline supramolecular polymer(Figure 1.7) [23]. This initiated the field of supramolecular polymer chemistry,generating materials with reversible interactions, and thereby introducing theopportunity to produce materials with properties that otherwise would have beenimpossible or difficult to obtain.

Inspired by this work, Griffin et al. developed main-chain supramolecular poly-mers based on pyridine/benzoic acid hydrogen bonding, also obtaining liquidcrystalline supramolecular polymers [24]. Our group introduced supramolecularpolymers based on the ureido-pyrimidinone motif. Due to the high dimerizationconstant present in the UPy motif, supramolecular polymers were formed with ahigh degree of polymerization even in semi-dilute solution [15].

We have defined supramolecular polymers as . . .polymeric arrays of monomericunits that are brought together by reversible and highly directional secondary interactions,resulting in polymeric properties in dilute and concentrated solutions, as well as in the bulk.The monomeric units of the supramolecular polymers themselves do not possess a repetitionof chemical fragments. The directionality and strength of the supramolecular bonding areimportant features of these systems, that can be regarded as polymers and behave accordingto well-established theories of polymer physics. In the past the term living polymers hasbeen used for this type of polymer. However, to exclude confusion with the important field of

10j 1 Multiple Hydrogen-Bonded Supramolecular Polymers