Following a brief introduction, the book goes on to discuss various synthetic approaches to sequence-controlled polymers, including template polymerization, genetic engineering and solid-phase chemistry. Moreover, monomer sequence regulation in classical polymerization techniques such as step-growth polymerization, living ionic polymerizations and controlled radical polymerizations are explained, before concluding with a look at the future for sequence-controlled polymers.
With its unique coverage of this interdisciplinary field, the text will prove invaluable to polymer and environmental chemists, as well as biochemists and bioengineers.
Table of Contents
1 Defining the Field of Sequence-Controlled Polymers 1
Jean-François Lutz
1.1 Introduction 1
1.2 Glossary 4
1.3 Sequence Regulation in Biopolymers 7
1.3.1 Nucleic Acids 7
1.3.2 Proteins 7
1.4 Bio-Inspired Sequence-Regulated Approaches 8
1.5 Sequence Regulation in Synthetic Macromolecules 9
1.5.1 Step-Growth Polymerizations 11
1.5.2 Chain-Growth Polymerizations 11
1.5.3 Multistep Growth Polymerizations 13
1.6 Characterization of SCPs 15
1.7 Impact in Materials Science 17
1.8 SomeWords About the Future 19
References 20
2 Kinetics and Thermodynamics of Sequence Regulation 27
Pierre Gaspard
2.1 Introduction 27
2.2 Generalities 28
2.2.1 Characterization of Sequences and Information 28
2.2.1.1 Single-Molecule Level of Description 28
2.2.1.2 Many-Molecule Level of Description 29
2.2.2 Precise or Loose Sequence Control during Copolymerization 30
2.2.3 Conditions for Growth or Dissolution 31
2.2.4 Kinetic Equations 32
2.3 Thermodynamics 33
2.3.1 Free Copolymerization 34
2.3.2 Template-Directed Copolymerization 35
2.3.3 Depolymerization 35
2.4 Kinetics Yielding Bernoulli Chains 36
2.5 Kinetics Yielding Markov Chains 36
2.6 Kinetics Yielding Non-Markovian Chains 40
2.7 Effect of Sequence Disorder on Ceiling and Floor Temperatures 40
2.8 Mechanical Power of Sequence Disorder 43
2.9 Template-Directed Copolymerization 44
2.10 Conclusion 45
Acknowledgments 45
References 46
3 Nucleic Acid-Templated Synthesis of Sequence-Defined Synthetic Polymers 49
Zhen Chen and David R. Liu
3.1 Introduction 49
3.2 Enzymatic Templated Syntheses of Non-Natural Nucleic Acids 50
3.2.1 Polymerase-Catalyzed Syntheses of Backbone-Modified Nucleic Acids 50
3.2.2 Polymerase-Catalyzed Syntheses of Nucleobase-Modified Nucleic Acids 52
3.2.3 Polymerase-Catalyzed Syntheses of Sugar-Modified Nucleic Acids 54
3.2.4 Ligase-Catalyzed Syntheses of Non-Natural Nucleic Acids 58
3.3 Ribosomal Synthesis of Non-Natural Peptides 59
3.4 Nonenzymatic Polymerization of Nucleic Acids 61
3.5 Nonenzymatic Polymerization of Non-Nucleic Acid Polymers 67
3.6 Conclusion and Outlook 71
Acknowledgments 73
References 73
4 Design of Sequence-Specific Polymers by Genetic Engineering 91
Davoud Mozhdehi, Kelli M. Luginbuhl, Stefan Roberts, and Ashutosh Chilkoti
4.1 Introduction 91
4.2 Design of Repetitive Protein Polymers 93
4.3 Methods for the Genetic Synthesis of Repetitive Protein Polymers 96
4.4 Expression of Repetitive Protein Polymers 100
4.5 Expanding the Chemical Repertoire of Protein Polymers 100
4.5.1 Chemo-Enzymatic Modification 101
4.5.2 Incorporation of Noncanonical Amino Acids 104
4.5.3 Post-TranslationalModifications 105
4.6 Summary and Outlook 107
References 108
5 Peptide Synthesis and Beyond the Use of Sequence-Defined Segments for Materials Science 117
Niels ten Brummelhuis, PatrickWilke, and Hans G. Börner
5.1 Introduction 117
5.2 The History of Solid-Phase-Supported Peptide Synthesis 118
5.3 Supports for the Chemical Synthesis of Peptides 120
5.4 Synthesis of Peptide–Polymer Conjugates 122
5.5 Identification of Functional Sequences 125
5.5.1 Phage Display 125
5.5.2 Split-and-Mix Libraries and SPOT Synthesis 130
5.5.3 Applications of Libraries 134
5.5.4 Dynamic Covalent (Pseudo)Peptide Libraries 136
5.6 Sequence–Property Relationships 136
5.7 Translation of Sequence to Synthetic Precision Polymer Platforms 137
5.8 Conclusion 141
References 141
6 Iterative SyntheticMethods for the Assembly of Sequence-Controlled Non-Natural Polymers 159
Christopher Alabi
6.1 Introduction 159
6.2 The Solid-Phase Approach 161
6.2.1 Type of Solid Supports 161
6.2.2 Iterative Assembly using Single Heterobifunctional Monomers 162
6.2.3 Iterative Assembly usingMultiple HeterobifunctionalMonomers 163
6.3 The Liquid-Phase Approach 164
6.3.1 Requirements for Liquid-Phase Supports 165
6.3.2 Examples of Iterative Liquid-Phase Methodologies 165
6.3.3 The Fluorous Liquid-Phase Approach 167
6.4 The Template Approach 168
6.5 A Support-Free Approach 170
6.6 Outlook 175
References 176
7 Sequence-Controlled Peptoid Polymers: Bridging the Gap between Biology and Synthetic Polymers 183
Mark A. Kline, Li Guo, and Ronald N. Zuckermann
7.1 Introduction 183
7.1.1 Closing the Gap between Biological Polymers and Synthetic Polymers 184
7.1.2 Enhancing Synthetic Polymers with Sequence Control 184
7.2 Peptoids – Bridging the Gap 187
7.3 Polypeptoid Synthesis 189
7.3.1 Solution Polymerization Method 189
7.3.2 Solid-Phase Synthesis Method 190
7.3.2.1 Solid-Phase Peptide Synthesis 190
7.3.2.2 Solid-Phase Peptoid Synthesis 192
7.3.2.3 Solid-Phase Submonomer Synthesis Method 192
7.3.3 Combinatorial Synthesis 197
7.3.4 Polypeptoid Analysis 197
7.4 Discovering Peptoid Properties Derived from Sequence Control 198
7.4.1 Peptoids as Potential Therapeutics 199
7.4.2 Peptoids with Controlled Conformation 199
7.4.2.1 Peptoid Properties Dominated by Side Chains 201
7.4.2.2 The Effect of Bulky Side Chains 201
7.4.2.3 The Peptoid Backbone Differs from a Peptide Backbone 202
7.4.2.4 Cyclic Peptoids 205
7.4.3 PeptoidsThat Function as Biomaterials 205
7.4.3.1 Antimicrobial and Antifouling Peptoids 206
7.4.3.2 Lipidated Peptoids for Drug Delivery 206
7.4.4 Ordered Supramolecular Assemblies: Toward Hierarchal Structures with Function 206
7.4.4.1 Supramolecular Self-Assembly from Uncharged Amphiphilic Diblock Copolypeptoids 207
7.4.4.2 Structures from Amphiphilic, Ionic-Aromatic Diblock Copolypeptoids 207
7.4.4.3 Free-Floating Two-Dimensional Peptoid Nanosheets with Crystalline Order 211
7.5 Conclusion 214
Acknowledgments 215
References 215
8 Sequence and Architectural Control in Glycopolymer Synthesis 229
Yamin Abdouni, Gokhan Yilmaz, and C. Remzi Becer
8.1 Introduction: Glycopolymer–Lectin Binding 229
8.2 Sequence-Controlled Glycopolymers 230
8.2.1 Sequence-Defined Glycooligomers 231
8.2.2 Sequence Control via Time-Regulated Additions 234
8.2.3 Sequence Control via Time-Regulated Chain Extensions 235
8.2.4 Sequence Control via Orthogonal Reactions 237
8.3 Self-Assembly of Glycopolymers 238
8.3.1 Self-Assembly Based on Amphiphilicity 238
8.3.2 Temperature-Triggered Self-Assemblies 242
8.3.3 pH-Responsive Self-Assemblies 243
8.3.4 Self-Assembly Based on Electrostatic Interactions 245
8.4 Single-Chain Folding of Glycopolymers:The Future? 248
8.4.1 Selective Point Folding 249
8.4.2 Repeat Unit Folding 249
8.5 General Conclusion and Future Outlook 251
Acknowledgments 251
References 251
9 Sequence Regulation in Chain-Growth Polymerizations 257
Makoto Ouchi
9.1 Introduction 257
9.2 Alternating Copolymerization 259
9.2.1 Addition Polymerization 259
9.2.2 Alternating ROMP 261
9.3 Iterative Single-Unit Addition with Living Polymerization 262
9.3.1 Iterative Process along with Purification via Peak Separation 263
9.3.2 Iterative Process along with Transformation of Pendant Group 266
9.4 Template-Assisted Polymerization 267
9.4.1 Template Initiator 268
9.4.2 Template Inimer 269
9.5 Cyclopolymerization 270
9.6 Ring-Opening Polymerization of Sequence-Programmed Monomer 272
9.7 Conclusion 274
References 274
10 Sequence-Controlled Polymers by Chain Polymerization 281
Junpo He, Jie Ren, and ErlitaMastan
10.1 Introduction 281
10.2 Sequence-Controlled Polymers by Various Polymerization Mechanisms 282
10.2.1 Anionic Polymerization 282
10.2.2 Cationic Polymerization 289
10.2.3 Ring-Opening Polymerization (ROP) 290
10.2.4 Ring-Opening Metathesis Polymerization (ROMP) 292
10.2.4.1 Regioselective ROMP of Substituted Cyclooctene 292
10.2.4.2 Regioselective ROMP of Macrocyclic Compounds 294
10.2.4.3 Alternating Copolymerization 296
10.2.4.4 Kinetic Control for Polymers with Sequence-Defined Functionalities 299
10.2.5 Radical Polymerization 300
10.2.5.1 Polymers with Alternating AB Sequence 301
10.2.5.2 Polymer with ABB (1 : 2) Sequence 305
10.2.5.3 Polymers with Site-Specific Functionalization 307
10.2.5.4 Polymers with Precisely Controlled Sequence at Monomer Level 309
10.2.5.5 Other Sequence-Controlled Polymers 312
10.2.6 Coordination Polymerization 315
10.3 Concluding Remarks 316
References 317
11 Sequence-Controlled Polymers via Cationic Polymerization 327
Sadahito Aoshima and Arihiro Kanazawa
11.1 Introduction 327
11.2 Recent Developments in Living Cationic Polymerization 328
11.2.1 Design of Initiating Systems for Living Polymerization 328
11.2.2 Base-Assisting Living Systems with Various Metal Halides 329
11.2.3 New Monomers for Cationic Polymerization 330
11.3 Sequence-Regulated Functional Polymers 331
11.3.1 Synthesis of New Block, Gradient, and End-Functionalized Polymers 331
11.3.2 Synthesis of Various Alternating Polymers by Controlled Cationic Polymerization 334
11.3.3 Synthesis of New Ring Polymers 336
11.4 Sequence Control Based on the Cationic Copolymerization of Vinyl and Cyclic Monomers 337
11.4.1 Strategy for Sequence Control by Copolymerizing Different Types of Monomers 337
11.4.2 Concurrent Cationic Vinyl-Addition and Ring-Opening Copolymerization of VEs and Oxiranes 338
11.4.3 Terpolymerization via the Exclusive One-way Cycle of Crossover Propagation Reactions 341
11.4.4 Concurrent Cationic Vinyl-Addition and Ring-Opening CopolymerizationMediated by Long-Lived Species 344
References 345
12 Periodic Copolymers by Step-Growth Polymerization 349
Zi-Long Li and Zi-Chen Li
12.1 Introduction 349
12.2 Carbon-Chain Periodic Polymers 352
12.2.1 Acyclic Diene Metathesis Polymerization 352
12.2.2 Atom Transfer Radical Coupling 355
12.2.3 C(sp3)–C(sp3) Coupling 355
12.2.4 Atom Transfer Radical Polyaddition 356
12.3 Hetero-Chain Periodic Polymers 357
12.3.1 Polycondensation or Polyaddition of Oligomonomers 357
12.3.1.1 Polycondensation 357
12.3.1.2 Polyaddition via Click Reactions 359
12.3.1.3 Radical Addition–Coupling Polymerization 362
12.3.2 One-Pot SequentialMonomer Addition and Polymerization 364
12.3.3 Multicomponent Polymerizations 364
12.4 Conclusions and Outlook 369
References 372
13 Click and Click-Inspired Chemistry for the Design of Sequence-Controlled Polymers 379
Steven Martens, Joshua O. Holloway, and Filip E. Du Prez
13.1 Introduction to “Click” and Click-Inspired ReactionsWithin the Area of Sequence-Controlled Polymers 379
13.2 Click and Click-Inspired Reactions for Sequence Building 380
13.2.1 Copper(I)-Catalyzed Azide/Alkyne Cycloaddition 380
13.2.2 Thiol–X and Thiolactone Chemistries 386
13.2.3 Diels–Alder: Photo-Triggered and Thermally Induced Reactions 395
13.3 Conclusions and Outlook 400
References 400
14 One-Pot Sequence-Controlled (SC) Multiblock Copolymers via Copper-Mediated Polymerization 417
Athina Anastasaki, RichardWhitfield, Vasiliki Nikolaou, Nghia P. Truong, Glen R. Jones, Nikolaos G. Engelis, Evelina Liarou,Michael R.Whittaker, and David M. Haddleton
14.1 Introduction 417
14.2 Criteria for the Successful Synthesis of SC Multiblock Copolymers 419
14.3 Historical Background toward the Development of One-Pot SC Multiblocks 419
14.4 Access to SC Acrylic Multiblock Copolymers 420
14.4.1 The Cu(0)-Wire-Mediated RDRP Approach 420
14.4.1.1 When to Use Cu(0)-Wire-Mediated RDRP 422
14.4.1.2 When Not to UseThis Technique 422
14.4.1.3 Protocol for the Synthesis of Acrylic Multiblock Copolymers via Cu(0)-Wire-Mediated RDRP 423
14.4.2 Light-Mediated Copper Polymerization for the Synthesis of Acrylic Multiblock Copolymers 424
14.4.2.1 Attributes of the Light-Mediated Copper Polymerization Technique 426
14.4.2.2 Reasons Not to SelectThis Technique 426
14.4.2.3 Protocol for the Synthesis of Acrylic Multiblock Copolymers via Light-Mediated Copper Polymerization 426
14.5 Access to SC AcrylamideMultiblock Copolymers (The CuBr/Me6Tren Disproportionation Technique) 427
14.5.1 Why Use the CuBr/Me6Tren Disproportionation Technique 428
14.5.2 Reasons Not to SelectThis Technique 428
14.5.3 Protocol for the Synthesis of Acrylic Multiblock Copolymers via CuBr/Me6Tren Disproportionation Technique 429
14.6 Perspective and Outlook 429
References 430
15 Properties and Applications of Sequence-Controlled Polymers 435
Jordan H. Swisher, Jamie A. Nowalk,Michael A.Washington, and Tara Y.Meyer
15.1 Introduction 435
15.1.1 Definitions 436
15.1.2 Types of Sequence-Dependent Properties 437
15.1.3 Categories of Sequence Comparison Studies 438
15.2 Molecular Properties 439
15.2.1 Monomer Order 439
15.2.2 Electronic/Vibrational Properties and Reactivity 439
15.3 Solution-Phase Properties 439
15.3.1 Folding 441
15.3.2 Recognition 443
15.3.3 Aggregation 444
15.4 Sequence Dependence of Bulk-Phase Properties 445
15.4.1 Category I – Block Composition 446
15.4.1.1 Block Dispersity 446
15.4.1.2 Block Frequency 446
15.4.2 Category II –Monomer Distribution 449
15.4.2.1 Tacticity 449
15.4.2.2 Alternating versus Random (and Block) 453
15.4.2.3 Gradient Copolymers 454
15.4.3 Category III – Precision Placement 454
15.4.4 Category IV– Side-Chain Sequence 458
15.4.5 Category V–Complex Sequences 458
15.5 Conclusions and Outlook 461
15.5.1 Solution-Phase Properties 462
15.5.2 Bulk-Phase Properties 464
15.5.3 The Future 466
References 466
16 Tandem Mass Spectrometry Sequencing of Sequence-Controlled and Sequence-Defined Synthetic Polymers 479
Laurence Charles
16.1 Introduction 479
16.2 MS/MS Principle 480
16.3 MS/MS of Sequence-Controlled Copolymers 482
16.4 MS/MS of Sequence-Defined Polymers 485
16.4.1 Biomimetics 485
16.4.2 Sequence-Defined Copolymers for Information Storage 490
16.5 Conclusions and Perspectives 498
References 500
Index 505
