The coupling of mass spectrometry or nuclear magnetic resonance to chromatography has broadened the possibilities for determining organic reaction mechanisms. And while many results have been published reporting these, even more can be achieved through modern computational methods. Combining computational and theoretical techniques with advanced chromatographic methods offers a powerful tool for quantitatively determining molecular interactions . This book presents the possibilities for characterising biological applications by combining analytical and computational chemistries. Written by the author of "HPLC: A Practical Guide" (RSC, 1999), the book examines not only the behaviour of biological reactions per se, but also describes the behaviour of biological molecules in chromatography systems. Various software packages are reviewed, and most computations can be performed on a standard PC using accessible software. Consideration is given to a variety of chromatographic techniques and strategies for high-sensitivity detection are presented.The first book of its kind, it will inspire readers to explore the possibilities of combining these techniques in their own work, whether at an industrial or academic level.
Chapter 1 Introduction 1 (10)
1.1 Fundamental Phenomena in 1 (4)
Chromatography
1.2 Human Serum Albumin-Drug Binding 5 (1)
Affinity Based on Liquid Chromatography
1.3 Proteins as Affinity Phases 6 (1)
1.4 Mechanisms of Highly Sensitive 7 (4)
Detection
References 8 (3)
Chapter 2 Basic Concepts of Molecular 11 (7)
Interaction Energy Values
2.1 Introduction 11 (1)
2.2 Hydrophobic Interactions (van der 12 (1)
Waals Forces)
2.3 Hydrogen Bonding 13 (2)
2.4 Coulombic Forces (Ion-Ion 15 (1)
Interactions)
2.5 Steric Hindrance (Enantiomer 16 (2)
Recognition)
References 17 (1)
Chapter 3 The Design of Model Phases for 18 (21)
Chromatography
3.1 Graphitized (Graphite) Carbon Phases 18 (3)
3.2 Methyl and Hydroxyl Groups of Organic 21 (5)
Phases
3.3 The Structure of Silica Gels 26 (3)
3.3.1 Construction of Model Silica Gels 26 (1)
3.3.2 Chemical Modification of Surface 27 (2)
Silanol Groups
3.4 Three-Dimensional Model Phases 29 (10)
References 37 (2)
Chapter 4 Retention in Gas Chromatography 39 (24)
4.1 Introduction 39 (1)
4.2 Retention of Volatile Compounds on 40 (2)
Graphitized Carbon
4.3 Retention on Methylsilicone 42 (9)
4.4 Retention on Carbowax™ 51 (2)
(Polyethyleneglycol)
4.5 Retention on a 50% 53 (5)
Methylphenylsilicone Phase
4.6 Classification of Gas Chromatography 58 (5)
References 59 (4)
Chapter 5 Retention in Normal-Phase Liquid 63 (28)
Chromatography
5.1 Retention of Saccharides on 63 (3)
Graphitized Carbon
5.2 Retention of Aromatic Compounds on 66 (7)
Graphitized Carbon
5.3 Retention of Polycyclic Aromatic 73 (2)
Hydrocarbons on Silica Gels
5.4 The Effect of Acidic and Basic 75 (5)
Components in the Eluent
5.5 The Effect of Organic Solvents in the 80 (11)
Eluent
References 88 (3)
Chapter 6 Retention in Reversed-Phase 91 (62)
Liquid Chromatography
6.1 Basic Concepts of Reversed-Phase 91 (3)
Liquid Chromatography
6.1.1 Adsorption of Pyridine 92 (1)
6.1.2 Alkyl Chain Length Effect of 93 (1)
Bonded Phases
6.2 Prediction of Dissociation Constants 94 (7)
6.3 Chromatographic Behavior on 101(6)
Graphitized Carbon
6.4 Model Phase Selectivity for Phenolic 107(5)
Compounds
6.5 Model Phase Selectivity for Benzoic 112(6)
Acid Derivatives
6.6 Chromatography of Aromatic Acids 118(5)
6.7 Chromatography of Acidic Drugs 123(5)
6.8 Chromatography of Basic Drugs 128(7)
6.9 The Organic Modifier Effect 135(13)
6.9.1 Solvents in Liquid Chromatography 135(1)
6.9.2 Basic Study of the Organic 136(8)
Modifier Effect
6.9.3 Alkyl Benzenes as Standard 144(4)
Compounds for Phenols
6.10 Summary 148(5)
References 149(4)
Chapter 7 Retention in Ion-Exchange Liquid 153(20)
Chromatography
7.1 Basic Concepts of Ion-Exchange 153(5)
Mechanisms
7.1.1 Cation Exchange 154(2)
7.1.2 Anion Exchange 156(2)
7.2 Retention of Ions on Graphitized 158(2)
Carbon
7.3 Cation Exchange for Basic Drugs 160(7)
7.3.1 Quantitative Analysis of log k In 160(1)
Silico
7.3.2 Inductive Effect on the pKa of 161(3)
Basic Drugs
7.3.3 Three-Dimensional Model Ion 164(3)
Exchanger
7.4 Anion Exchange for Acidic Compounds 167(6)
7.4.1 Quantitative Analysis of 167(2)
Retention In Silico
7.4.2 Inductive Effect on pKa 169(1)
7.4.3 Quantitative Analysis of log k In 170(2)
Silico
References 172(1)
Chapter 8 Enantioseparation 173(31)
8.1 Enantiomer Recognition in 173(14)
Normal-Phase Liquid Chromatography
8.1.1 Enantiomer Recognition of Phases 173(4)
1 and 2
8.1.2 Enantiomer Recognition of Phases 177(10)
3--6
8.2 Enantiomer Recognition in 187(1)
Ligand-Exchange Liquid Chromatography
8.3 Diastereomer Recognition in 188(8)
Reversed-Phase Liquid Chromatography
8.4 Enantiomer Recognition of Derivatized 196(8)
β-Cyclodextrin
References 201(3)
Chapter 9 Human Serum Albumin--Drug Binding 204(31)
Affinity Based on Liquid Chromatography
9.1 Introduction 204(3)
9.2 Measurement of HSA-Drug Binding 207(4)
Affinity using HSA
9.3 Measurement of HSA-Drug Binding 211(1)
Affinity using Liquid Chromatography
9.4 Measurement of HSA--Drug Binding 212(4)
Affinity without HSA: Part 1
9.5 Measurement of HSA--Drug Binding 216(4)
Affinity without HSA: Part 2
9.6 Prediction of HSA--Drug Binding 220(6)
Affinity In Silico
9.7 Glycosylation effect on HSA--Warfarin 226(2)
Interactions
9.7.1 Purification of HSA Samples 226(1)
9.7.2 Glycosylation Effect 227(1)
9.8 Modified Hummel-Dreyer Method 228(7)
References 229(6)
Chapter 10 Quantitative Analyses of Protein 235(15)
Affinity Chromatography
10.1 Introduction 235(1)
10.2 Model Study of Protein--Drug Docking 236(4)
10.3 Selectivity of Monoamine Oxidase 240(2)
10.3.1 Introduction 240(1)
10.3.2 Conformational Analysis 240(2)
10.4 Selectivity of D-amino acid oxidase 242(8)
10.4.1 Introduction 242(2)
10.4.2 Preparation and Evaluation of 244(3)
Mutants
References 247(3)
Chapter 11 Mechanisms of Highly Sensitive 250(22)
Detection
11.1 Detection of Bromate in Ion Liquid 250(7)
Chromatography
11.1.1 Introduction 250(1)
11.1.2 Theory 251(1)
11.1.3 In Silico Analysis of the 252(5)
Reaction Mechanisms
11.2 Chemiluminescence Detection 257(10)
11.2.1 Introduction 257(1)
11.2.2 Theory 258(1)
11.2.3 Computational Chemical Analysis 259(5)
of Reaction Processes
11.2.4 Chemiluminescence Intensity 264(3)
Related to Toxicity
11.3 Derivatization Reagents for the 267(5)
Highly Sensitive Analysis of Amino Acids
11.3.1 Introduction 267(1)
11.3.2 In Silico Prediction of 268(4)
Derivatized Amino Acid Spectra
Abbreviations 272(1)
References 273(5)
Appendix 278(49)
Subject Index 327
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