Molecularly Imprinted Materials: Science and Technology

Front cover......Page 1
Foreword......Page 8
Preface......Page 10
Contents......Page 12
Contributors......Page 16
I. INTRODUCTION......Page 20
II. WHAT IS MOLECULAR IMPRINTING?......Page 21
III. IMPRINTING TERMINOLOGY......Page 22
IV. APPROACHES TO MOLECULAR IMPRINTING......Page 23
V. HOW TO PREPARE A MOLECULARLY IMPRINTED POLYMER......Page 24
A. The Imprinting Effect......Page 25
B. Strategy for Demonstrating a Real Imprinting Effect......Page 26
VII. CONFIGURATIONS OF MOLECULARLY IMPRINTED POLYMERS......Page 28
IX. MIPs—FOR WHAT PURPOSE?......Page 29
REFERENCES......Page 30
II. HOW DID THEY GET INVOLVED?......Page 32
III. WHAT ARE THE MAIN PROBLEMS AND LIMITATIONS OF IMPRINTING AT THE PRESENT TIME?......Page 38
IV. WHAT IMPRINTING PROJECTS ARE THEY WORKING ON AT PRESENT?......Page 39
V. WHERE WILL MIPS BE APPLIED AND WHERE WILL RESEARCH GO IN THE FUTURE?......Page 40
REFERENCES......Page 41
I. INTRODUCTION......Page 44
B. Noncovalent Types of Interactions......Page 48
C. Monomers and Cross-Linkers......Page 54
D. Solvents......Page 55
III. AREAS FOR IMPROVEMENT IN NONCOVALENTLY IMPRINTED POLYMERS......Page 57
IV. EXAMPLES OF MOLECULARLY IMPRINTED POLYMERS: TYPICAL TECHNIQUES AND RECIPES......Page 58
A. Preparation of a Theophylline MIP and the Corresponding Nonimprinted Polymer......Page 60
B. Evaluating Theophylline MIP and NP with Batch-Mode Binding Assays......Page 62
A. Preparation of a (R)-Isoproterenol Imprinted Polymer......Page 64
B. Evaluating the (R)-Isoproterenol MIP Using HPLC......Page 67
VII. IMPRINTING WITH IMMOBILIZED TEMPLATES......Page 68
VIII. ‘‘ANTI-IDIOTYPIC IMPRINTING’’ AND ‘‘DIRECT MOLDING’’: THE NEXT GENERATION OF MIPs......Page 70
ACKNOWLEDGMENTS......Page 71
REFERENCES......Page 72
I. INTRODUCTION......Page 78
II. AN EXAMPLE FOR IMPRINTING WITH COVALENT INTERACTIONS......Page 80
III. OPTIMIZATION OF THE POLYMER STRUCTURE......Page 81
IV. GENERAL ASPECTS OF THE BINDING SITE INTERACTION......Page 83
V. DIFFERENT POSSIBILITIES OF COVALENT BINDING A. Boronic Acid-Containing Binding Site Functional Monomers......Page 87
B. Using Azomethines, Ketals, and Sulfides for Covalent Binding......Page 92
B. Benzamidines and Guanidines as Binding Sites......Page 96
C. Imprinted Polymers with Multiple Hydrogen Bonded Templates......Page 101
D. Imprinting with Polymerizable Cyclodextrins Employing Host–Guest Inclusion......Page 103
E. Stoichiometric Noncovalent Interactions for the Imprinting of Ampicillin......Page 104
VIII. PROTOCOLS OF THE PREPARATION OF TWO TYPICAL EXAMPLES OF IMPRINTED POLYMERS A. Polymer from Scheme 2......Page 106
B. Polymer from Template 14 and Binding Site 3......Page 107
REFERENCES......Page 108
I. WHY USE A SEMI-COVALENT APPROACH?......Page 112
II. SEMI-COVALENT APPROACH USING CARBOXYLIC ESTER TEMPLATES......Page 113
III. SEMI-COVALENT APPROACH USING SPACERS......Page 117
A. Carbonate Esters......Page 118
B. Carbamates......Page 124
D. Salicylamide Spacer......Page 126
E. Silicon-Based Spacers......Page 128
C. Comments......Page 130
C. Comments......Page 131
B. Method......Page 132
VII. PROTOCOL 4: TEMPLATE REMOVAL [10] A. Reagents and Equipment......Page 133
B. Method......Page 134
B. Method......Page 135
B. Dendrimer-Based Monomolecular Imprints......Page 136
C. Ring-Opening Metathesis Polymerization with a Semi-Covalent Imprinting Strategy......Page 138
REFERENCES......Page 139
I. INTRODUCTION......Page 142
II. SELECTIVE ORGANIC TRANSFORMATIONS......Page 143
A. Hydride Transfer Reductions......Page 144
B. Hydrolysis Reactions......Page 155
C. Carbon–Carbon Bond Forming Reactions......Page 163
III. MOLECULARLY IMPRINTED POLYMERS DESIGNED FOR RECOGNITION AND SEPARATION......Page 166
A. Imprinted Microenvironments for Controlling Metal Coordination......Page 167
B. Selective Recognition of Imprinted Templates......Page 173
C. MIPs as HPLC Stationary Phases......Page 185
REFERENCES......Page 197
II. BUILDING BLOCKS IN MOLECULAR IMPRINTING......Page 200
III. THE FUNCTIONAL ELEMENT (FE)......Page 201
IV. FUNCTIONAL AND STRUCTURAL MONOMERS......Page 202
V. OVERVIEW OF ORGANIC BUILDING BLOCKS USED IN MOLECULAR IMPRINTING......Page 204
A. Structural Building Blocks......Page 220
B. Functional Building Blocks......Page 221
A. General Considerations......Page 222
EXPERIMENTAL PROTOCOL M1 (ADAPTED FROM REFS. 2,3) Synthesis of 4-Vinylbenzyliminodiacetic Acid (M1)......Page 223
EXPERIMENTAL PROTOCOL X1 (ADAPTED FROM REFS. 9,10) Synthesis of Divinylbenzene (X1)......Page 226
EXPERIMENTAL PROTOCOL X1 (ADAPTED FROM REFS. 11,12) Synthesis of Divinylbenzene (X1) Alternative Route......Page 227
EXPERIMENTAL PROTOCOL X11 (ADAPTED FROM REF. 16) Synthesis of N,O-Bisacryloyl-L-Phenylalaninol......Page 228
Bisacryloyl-1,3-Diaminobenzene (X16)......Page 229
D. Side Reactions......Page 231
B. Monomer Compatibility......Page 232
C. Side Reactions......Page 233
REFERENCES......Page 234
I. WHY DO WE NEED TO ADOPT A COMBINATORIAL APPROACH TO THE SYNTHESIS OF MIPs?......Page 244
II. THE DISCOVERY OF NEW IMPRINTING PROTOCOLS: FROM WHERE DO WE START?......Page 245
A. Some Hints on the Choice of System Components......Page 246
III. TOOLS FOR COMBINATORIAL APPROACHES: MINIMIPS, ऀ㘠ጀ圀䔀䰀䰀 䴀䤀倀......Page 248
V. PROTOCOL 1: GENERAL MONOMER OPTIMIZATION A. Reagents and Equipment......Page 250
B. Method......Page 251
VI. EXAMPLE 1: TERBUTYLAZINE A. Screening the Functional Monomers for the Imprinting of Terbutylazine......Page 253
VII. EXAMPLE 2: SCREENING THE FUNCTIONAL MONOMERS FOR THE IMPRINTING OF PHENYTOIN......Page 256
VIII. EXAMPLE 3: SCREENING THE FUNCTIONAL MONOMERS FOR THE IMPRINTING OF NIFEDIPINE......Page 258
IX. EXAMPLE 4: SCREENING THE FUNCTIONAL MONOMERS FOR THE IMPRINTING OF METHOTREXATE......Page 259
A. Feasibility Test for the Imprinting of a Lead Drug......Page 261
X. OPTIMIZATION OF IMPRINTING PROTOCOLS A. Statistics and Chemometrics......Page 262
B. Checklist......Page 265
XI. CONCLUSIONS......Page 266
REFERENCES......Page 267
I. INTRODUCTION......Page 268
II. IMPRINTING OF POLYMER PARTICLES......Page 269
III. IMPRINTED POLYMER COMPOSITE PARTICLES......Page 272
IV. SURFACE IMPRINTING FOR SENSOR APPLICATIONS......Page 276
V. IMPRINTED SURFACES FOR RECOGNITION OF BIOPOLYMERS......Page 287
VI. CATALYTIC-IMPRINTED SURFACES......Page 289
VII. IMMOBILIZED TEMPLATES: IMPRINTING OF BIOMOLECULES, INORGANIC CRYSTALS AND CELLS......Page 292
VIII. CONCLUDING REMARKS......Page 296
REFERENCES......Page 297
I. INTRODUCTION......Page 304
II. MOLECULAR DESIGN AND CREATION OF SCAFFOLD IMPRINTING SITES......Page 305
III. TEMPLATE CLASSIFICATION OF SCAFFOLDING MONOMERS HAVING MULTI-COMPLEXABLE TEMPLATE......Page 306
A. Uses of Scaffold Monomers......Page 307
B. Large Molecule Elements as Imprinting Scaffold......Page 310
IV. CLASSIFICATION OF POLYMER MATRIX AS SCAFFOLDING IMPRINTING MEDIA......Page 313
B. Polymer Aggregates as a Scaffold Imprinting Media......Page 316
C. Prepolymer-Crosslinker Systems as Scaffolding Imprint Matrix......Page 319
VI. CONCLUSION......Page 321
REFERENCES......Page 322
I. INTRODUCTION......Page 326
II. NONCOVALENT IMPRINTING......Page 328
III. POTENTIAL FOR SELECTIVE CATALYSIS VIA COVALENT IMPRINTING......Page 329
IV. EXAMPLE 1—COVALENT IMPRINTING OF PRIMARY AMINE SITES INTO BULK SILICA......Page 332
A. Example 1—Protocol......Page 337
V. EXAMPLE 2—COMPARISON OF NONCOVALENT AND COVALENT IMPRINTING STRATEGIES FOR THE DEVELOPMENT OF CHEMICAL SENSORS......Page 338
A. Example 2—Protocol (Excerpted Verbatim from Ref. 47)......Page 342
REFERENCES......Page 344
I. INTRODUCTION......Page 348
II. THERMAL POSTMODIFICATION......Page 349
A. Modifications of the Functional Monomer......Page 351
IV. GUEST DIRECTED ESTERIFICATION OF AN EA9A MIP WITH PHENYLDIAZOMETHANE......Page 357
A. Chemical Modification of the Crosslinker......Page 360
REFERENCES......Page 362
I. INTRODUCTION......Page 366
II. SOL–GEL PROCESSING......Page 367
III. SOL–GEL PROCESSING AND MOLECULAR IMPRINTING......Page 369
V. TEMPLATES FOR IMPRINTING SYNTHESIS......Page 371
VI. BATCH EQUILIBRIUM TESTS......Page 372
AND Si(OR)......Page 373
VIII. HIERARCHICAL IMPRINTING WITH BRIDGED-POLYSILSESQUIOXANE HYBRID HOSTS [7]......Page 374
IX. TYPICAL EXPERIMENTAL PROCEDURE [6,7]......Page 376
REFERENCES......Page 378
I. INTRODUCTION......Page 382
II. THERMODYNAMIC CONSIDERATIONS A. A General Model for Describing Molecular Recognition Phenomena......Page 383
B. Determination of DGbind......Page 384
C. The Physical Factors Influencing DGbind......Page 385
III. APPLICATION OF THERMODYNAMIC PRINCIPLES TO LIGAND–POLYMER BINDING......Page 388
A. Theory—Molecular Mechanics......Page 391
B. Computer Simulation Using Molecular Mechanics......Page 392
D. Simulated Annealing......Page 394
V. COMPUTATIONAL DESIGN OF IMPRINTED POLYMERS......Page 395
VI. CASE STUDY 1: MICROCYSTIN-LR, COMPUTATIONAL DESIGN OF AN IMPRINTED POLYMER FOR MICROCYSTIN-LR A. Virtual Library Design and Monomer Screening......Page 396
B. Computationally Designed Imprinted Polymer for Microcystin-LR: Synthesis and Testing......Page 399
VII. CASE STUDY 2: THE DESIGN, SYNTHESIS, AND EVALUATION OF EPHEDRINE SELECTIVE MIPs......Page 401
REFERENCES......Page 408
I. INTRODUCTION......Page 414
II. ANALYSIS OF SELECTIVITY IN IMPRINTED POLYMERS A. Batch Rebinding......Page 415
B. Chromatography......Page 416
III. EVALUATION OF TEMPLATES......Page 417
A. Types of Interactions......Page 418
B. Number of Possible Interactions......Page 420
C. Spatial Disposition......Page 421
D. Sterics......Page 424
E. Conformational Effects......Page 425
IV. POLYMER FORMULATION A. Choice of Functional Monomer–Complementary Interactions......Page 426
B. Choice of Cross-Linking Monomer......Page 428
C. Ratio of Monomers and Templates......Page 429
D. Choice of Solvent (Porogen)......Page 430
E. Initiator......Page 433
REFERENCES......Page 434
II. BINDING ISOTHERMS......Page 438
III. BINDING MODELS......Page 440
A. Homogeneous Binding Models......Page 441
B. Heterogeneous Binding Models......Page 442
IV. CONCLUSION......Page 451
REFERENCES......Page 452
II. EMULSION POLYMERIZATION......Page 454
III. DISPERSION POLYMERIZATION......Page 458
IV. EXPERIMENTAL PROTOCOL 1 A. Molecular Imprinting of 17b-Estradiol Using Precipitation Polymerization......Page 461
V. SUSPENSION POLYMERIZATION......Page 462
VI. IMPRINTING ON PREFORMED BEADS......Page 463
VII. EXPERIMENTAL PROTOCOL 2 A. Molecular Imprinting Using Silica Beads as Shape Template......Page 468
IX. CONCLUDING REMARKS......Page 469
REFERENCES......Page 470
II. DEFINITIONS AND CONCEPTS......Page 474
III. PREPARATION METHODS A. General Considerations......Page 477
B. Main Synthesis Strategies for MIP Films and Membranes......Page 479
C. Syntheses of Supported MIP Films......Page 481
D. Preparation of Self-Supported MIP Films and Membranes......Page 487
IV. MIP FILMS AS RECEPTOR LAYERS......Page 490
A. Direct Response to Template Binding......Page 491
B. Triggered Response to Template Binding......Page 492
A. ‘‘Gate Effect’’ of Microporous MIP Membranes......Page 493
B. Facilitated or Retarded Template Transport Through Microporous MIP Membranes......Page 494
C. Microporous MIP Membrane’s Structure and Transport Mechanism......Page 497
D. Macroporous Membrane Adsorbers......Page 498
C. Membrane Separation......Page 501
VII. CONCLUSIONS......Page 502
NOMENCLATURE......Page 503
REFERENCES......Page 504
I. WHY MOLECULARLY IMPRINTED POLYMER MICROMONOLITHS?......Page 510
II. THE IN SITU PREPARATION OF NONIMPRINTED MONOLITHS......Page 511
III. IN SITU PREPARATION OF MIP MONOLITHS FOR CAPILLARY ELECTROCHROMATOGRAPHY......Page 514
B. Method......Page 518
V. PREPARATION OF MIP MONOLITHIC RODS FOR HPLC......Page 520
B. Method......Page 521
VIII. MIP MICROMONOLITHS FABRICATED THROUGH MICROMOLDING IN CAPILLARIES......Page 524
IX. MICROMOLDING IN CAPILLARIES FOR THE GENERATION OF MOLECULARLY IMPRINTED POLYMER MICROMONOLITHS A. Reagents and Equipment......Page 525
B. Method......Page 526
X. MIP MICROMONOLITHS GENERATED BY MICROSTEREOLITHOGRAPHY......Page 528
B. Method......Page 531
REFERENCES......Page 532
II. BASICS: THE CHROMATOGRAPHIC PROCESS......Page 536
III. THE MOLECULARLY IMPRINTED STATIONARY PHASE......Page 541
IV. RETENTION MECHANISMS ON MOLECULARLY IMPRINTED STATIONARY PHASES......Page 545
A. Hydrogen Bonding Interactions......Page 547
C. Hydrophobic Interactions......Page 548
VI. APPLICATIONS OF MOLECULARLY IMPRINTED STATIONARY PHASES A. Enantioseparation......Page 549
B. On-Line Solid Phase Extraction......Page 551
C. Affinity Screening of Combinatorial Libraries......Page 555
D. Sensor Based on Liquid Chromatography......Page 557
VII. FRONTAL CHROMATOGRAPHY WITH MOLECULARLY IMPRINTED STATIONARY PHASES......Page 559
B. Method......Page 561
C. Comments......Page 563
B. Method......Page 564
C. Comments......Page 565
B. Method......Page 566
REFERENCES......Page 567
I. INTRODUCTION......Page 572
II. CAPILLARY ELECTROCHROMATOGRAPHY......Page 574
A. In Situ Generation of MIP......Page 577
B. External Preparation of MIP......Page 583
IV. USING MIP IN CAPILLARIES—POTENTIAL PROBLEMS A. Detection of Analytes......Page 590
D. Frits in Capillaries......Page 592
V. DISCUSSION......Page 594
REFERENCES......Page 595
A. Prelude to Metal Ion Imprinting......Page 598
B. Overview of the Synthesis of Metal Ion Selective Molecularly Imprinted Polymers......Page 600
III. METAL COMPLEX FORMATION FOLLOWED BY POLYMERIZATION AND CROSS-LINKING A. Reagents and Equipment......Page 603
B. Method......Page 604
A. The Beginnings......Page 606
B. Expanding the Scope......Page 608
C. Metal Ion Imprinted Sol Gels......Page 613
V. METAL ION IMPRINTED POLYMERS WITH SPECIFIC MORPHOLOGIES A. Surface Imprinting......Page 614
B. Metal Ion Permeable Membranes......Page 615
VI. CONCLUSIONS......Page 617
REFERENCES......Page 618
I. INTRODUCTION......Page 622
II. CHARACTERIZATION OF MIP ADSORBENTS FOR SPE APPLICATION......Page 623
IV. SORBENT CONFIGURATIONS AND ELUTION CONDITION......Page 629
V. EXPERIMENTAL PROTOCOL 1 A. Solid Phase Extraction of 7-Diethylamino-4-Methylcoumarin: Characterization of SPE Adsorbents......Page 630
VII. EXPERIMENTAL PROTOCOL 2 A. Solid Phase Extraction for Product Purification......Page 632
VIII. CONCLUSION AND OUTLOOK......Page 635
REFERENCES......Page 636
I. INTRODUCTION......Page 638
II. STEREO- AND REGIO-SELECTIVE REACTIONS WITH MIPs......Page 639
III. IMPRINTING WITH A TRANSITION STATE ANALOGUE......Page 642
IV. IMPRINTING WITH A METAL CATALYST......Page 647
V. INORGANIC POLYMERS AS CATALYTIC MIPs......Page 653
VI. SUMMARY AND OUTLOOK......Page 656
REFERENCES......Page 657
II. IMMUNOASSAYS BASED ON BIOLOGICAL ANTIBODIES A. Biological Antibodies......Page 660
B. Immunoassay Formats......Page 663
C. The First RIA......Page 665
D. The First MIA......Page 666
E. Potential Advantages of MIPs......Page 668
III. SETTING UP AN MIA......Page 669
A. Preparation of the MIP......Page 672
C. Calculating the Amount of Probe per Experiment......Page 673
D. Establishing the Binding of the Probe......Page 674
E. Optimizing the Assay Solvent......Page 675
F. The Competition Assay with Analyte and Possible Interferents......Page 676
G. Assessing the Heterogeneity of Binding Sites......Page 678
H. Validating the Method with Real Samples......Page 680
A. In Organic Solvents......Page 681
B. In Aqueous Solvents......Page 683
C. Binding Site Heterogeneity......Page 685
V. VARIATIONS A. Novel Polymer Formats......Page 687
B. Novel Probes......Page 690
C. Novel Assay Formats......Page 697
REFERENCES......Page 699
I. INTRODUCTION......Page 704
II. GENERAL CONSIDERATIONS......Page 705
A. General Detection Principles......Page 706
C. The Polymer Generates the Signal......Page 707
IV. MASS-SENSITIVE TRANSDUCERS......Page 708
V. ELECTROCHEMICAL TRANSDUCERS......Page 710
VI. INTERFACING THE MIP WITH THE TRANSDUCER......Page 711
VII. OUTLOOK......Page 713
IX. EXPERIMENTAL PROTOCOL 1 A. Construction of an Acoustic Sensor Combining an Imprinted Polymer with a Quartz Crystal Microbalance Transducer [25]......Page 714
X. EXPERIMENTAL PROTOCOL 2 A. Example for the Preparation of an MIP-Based Voltammetric Sensor using a Competitive Format with an Electroactive Probe [33]......Page 715
REFERENCES......Page 716
I. INTRODUCTION......Page 720
II. IMPRINTED POLYMERS FOR THE DETECTION OF FLUORESCENT ANALYTES......Page 721
III. IMPRINTED POLYMERS AS THE RECOGNITIONMOIETY FOR THE FLUORESCENT DETECTION OF NONFLUORESCENT ANALYTES USING A FLUORESCENTLY LABELED ANALOG IN COMPETITIVE ASSAYS......Page 725
IV. MIP FLUORESCENT SENSORS THAT HAVE A FLUOROPHORE INCORPORATED......Page 728
A. The Detection of Analytes that are Capable of Modifying the Fluorescent Properties of the Fluorescent Reporter in Imprinted Polymers......Page 729
B. Protocol of the Preparation of the Fluorescent Sensor for D-Fructose [35,36]......Page 731
C. The Use of an External Fluorescence Quencher or Modifier......Page 737
D. Protocols for Preparation of the Fluorescent Sensor for......Page 738
V. OTHER SENSORS......Page 740
VI. CONCLUSIONS AND PERSPECTIVES......Page 741
REFERENCES......Page 742
SUPPLIERS......Page 746
EQUIPMENT......Page 747
Index......Page 748
Back cover......Page 754