Chemistry for the 21st Century

Here, numerous winners of the Wolf prize from all chemical disciplines provide an overview of the new ideas and approaches that will shape this dynamic science over the forthcoming decades and so will have a decisive influence on our living conditions. This glimpse of the future is naturally based on the findings granted us by the rapid increase in chemical research during the 20th century. It may be said that a silent "revolution" took place, the positive results of which are still not fully predicted.

For example, chemists in research laboratories nowadays are able to develop drugs in increasingly short times to treat diseases once thought incurable. They can design new materials that withstand extreme conditions, and predict the properties of compounds that no one has even seen yet. In this exceptional book those breakthroughs of modern chemistry are illustrated and explained by leading scientists.

It stems from the high-quality papers given at the prestigious ceremony to accompany the presentation of the 20th Wolf Prize. It is an extraordinary source for every chemist in industry and academia to get an overview of the highlights of modern chemistry.

Main topics:

• Some Reflections on Chemistry: Molecular, Supramolecular and Beyond.
• Chemical Synthesis and Biological Studies of the Epothilones: Microtubule Stabilizing Agents with Enhanced Activity Against Multidrug-Resistant Cell Lines and Tumors.
• The Spirotetrahydrofuran Motif: Its Role in Enhancing Ligation in Belted Ionophores, Biasing Cyclohexane Conformation, and Restricting Nucleoside/Nucleotide Conformation.
• Heterogeneous catalysis: From 'black art' to atomic understanding.
• Drugs for a New Millennium.
• Protein folding and beyond.
• The Enzymology of Biological Nitrogen Fixation.
• The Chemistry of Nitrogen in Soils.
• Spherical Molecular Assemblies: A class of Hosts for the Next Millennium.
• The Combinatorial Approach to Materials Discovery.
• On One Hand but Not the Other: The Challenge of the Origin and Survival of Homochirality in Prebiotic Chemistry.
• Chemical Reaction Dynamics Looks to the understanding of Complex Systems.
• The Past, Present, and Future of Quantum Chemistry.
• Quantum Alchemy.
• Quantum Chemistry in the Next Millennium: The Next step.

Table of Contents:

1

Some Reflections on Chemistry - Molecular, Supramolecular and Beyond 1

1.1

From Structure to Information. The Challenge of Instructed Chemistry 1

1.2

Steps Towards Complexity 3

1.3

Chemistry and Biology, Creativity and Art 5

2

Chemical Synthesis and Biological Studies of the Epothilones - Microtubule Stabilizing Agents with Enhanced Activity Against Multidrug-Resistant Cell Lines and Tumors 8

2.1

Introduction 8

2.2

Total Synthesis of Epothilones 9

2.3

First Generation Syntheses of Epothilones A and B 9

2.4

First Generation Synthesis of the Acyl Domain 10

2.5

Investigation of C9-C10 Bond Construction Through Ring Closing Metathesis 12

2.6

B-Alkyl Suzuki Strategy 12

2.7

Macrolactonization and Macroaldolization Approaches 16

2.8

A New and More Efficient Synthesis of Epothilone B 18

2.9

Dianion Equivalents Corresponding to the Polypropionate Domain of Epothilone B 19

2.10

B-Alkyl Suzuki Merger 20

2.11

Stereoselective Noyori Reduction 21

2.12

Discovery of a Remarkable Long-Range Effect on the Double Diastereoface Selectivity in an Aldol Condensation 22

2.13

Preparation of Other Epothilone Analogs 25

2.14

Biological Evaluation of Epothilones 26

2.15

SAR Analysis of Epothilones: The Zone Approach 26

2.16

In Vitro Analysis Comparison to Paclitaxel and Related Agents 28

2.17

In Vivo Analysis: Comparisons to Paclitaxe l30

2.18

Conclusions 33

2.19

Acknowledgements 33

3

The Spirotetrahydrofuran Motif: its Role in Enhancing Ligation in Belted Ionophores, Biasing Cy clohexane Conformation, and Restricting Nucleoside/Nucleotide Conformation 37

3.1

Introduction 37

3.2

syn-1,3,5-Orientation on a Cyclohexane Core 40

3.3

Maximally Substituted Hexa(spirotetrahydrofuranyl)-cyclohexanes 43

3.4

Spirocyclic Restriction of Nucleosides/Nucleotides 49

3.5

Acknowledgement 51

4

Heterogeneous Catalysis: from "Black Art" to Atomic Understanding 54

4.1

Introduction 54

4.2

A Case Study: Ammonia Synthesis 55

4.3

The Surface Science Approach 57

4.4

The Atomic Mechanism of a Catalytic Reaction: Oxidation of Carbon Monoxide 62

4.5

Further Aspects 66

5

Drugs for a New Millennium 70

5.1

Introduction 70

5.2

Cell Death 70

5.3

Stroke and Myocardial Infarct 71

5.4

Schizophrenia 75

5.4.1

Neuroleptic Drug Development 76

5.4.2

Drug Psychoses 79

5.5

Drugs of Abuse 81

5.5.1

Definitions and Varieties 81

5.5.2

Approaches to Treatment: Focus on Cocaine 83

5.6

Conclusions and New Directions 85

5.7

Acknowledgements 87

6

Protein Folding and Beyond 89

6.1

Introduction 89

6.1.1

Computational Protein Folding 91

6.1.2

All-atom Simulations of Protein Unfolding and Short Peptide Folding 92

6.2

All-Atom Simulations of Folding of Small Proteins 93

6.2.1

Concomitant Hydrophobic Collapse and Partial Helix Formation 93

6.2.2

A Marginally Stable Intermediate State 94

6.3

A Perspective View 96

7

The Enzymology of Biological Nitrogen Fixation 102

7.1

Early History 102

7.2

Practical Applications 103

7.3

Biochemistry of N₂ Fixation 104

7.4

First Product of N₂ Fixation 105

7.5

Studies with ¹⁵N as a Tracer 105

7.6

N₂ Fixation with Cell-Free Preparations 106

7.7

Nitrogenase Consists of Two Proteins 107

7.8

ATP Furnishes Energy for Fixation 108

7.9

H₂ an Obligatory Product of the Nitrogenase Reaction 108

7.10

N₂ and HD Formation 109

7.11

Electron Transfer Sequence 109

7.12

Alternative Substrates 110

7.13

N₂ Fixation in Non-Leguminous Plants 110

7.14

Control of Nitrogenase 111

7.15

Magnitude of Chemical and Biological N₂ Fixation 111

7.16

Associative Biological N₂ Fixation 112

7.17

Genetics of Biological N₂ Fixation 112

7.18

Composition and Structure of Nitrogenases 113

7.19

Selection of N₂ Fixers 113

8

The Chemistry of Nitrogen in Soils 117

8.1

Introduction 117

8.2

Nitrogen Fixation and Ensuing Reactions 117

8.3

Amino Acids, Amino Sugars, and Ammonia in Soils 118

8.4

Nucleic Acid Bases in Soils 121

8.5

Bioavailability of the NH-N Fraction 121

8.6

Chemistry of the UH-N Fraction 122

8.7

Chemistry of the NH-N Fraction 122

8.8

Pyrolysis-field ionization mass spectrometry (Py-FIMS) and Curie-point pyrolysis-gas chroma tography/mass spectrometry (CpPy-GC/MS) of soils 124

8.9

Origins of Major N Compounds Identified 125

8.10

¹⁵N MR analysis of soils 126

8.11

Distribution of N in Soils 127

8.12

Concluding Comments 127

9

Spherical Molecular Assemblies: A Class of Hosts for the Next Millennium 130

9.1

Introduction 130

9.1.1

Supramolecular Chemistry 130

9.1.2

Towards Supramolecular Synthesis 131

9.1.3

Self-Assembly 131

9.2

Overview 132

9.3

A Spherical Molecular Assembly Held Together by 60 Hydrogen Bonds 132

9.3.1

Polyhedron Model - Snub Cube 133

9.4

General Principles for Spherical Host Design 134

9.4.1

Spheroid Design 134

9.4.2

Self-Assembly 134

9.4.3

Subunits for Spheroid Design and Self-Assembly 135

9.4.4

Platonic Solids 137

9.4.5

Archimedean Solids 138

9.4.6

Models for Spheroid Design 139

9.5

Examples from the Laboratory and from Nature 140

9.5.1

Platonic Solids 140

9.5.1.1

Tetrahedral Systems (T_d, T_h, T) 140

9.5.1.2

Octahedral Systems (O_h, O) 141

9.5.1.3

Icosahedral Systems (I_h, I) 142

9.5.2

Archimedean Solids 143

9.5.2.1

Trunctated Tetrahedron (1) 143

9.5.2.2

Cuboctahedron (2) 144

9.5.2.3

Trunctated Octahedron (4) 144

9.5.2.4

Rhombicuboctahedron (5) 145

9.5.2.5

Snub Cube (6) 145

9.5.2.6

Trunctated Icosahedron (10) 145

9.5.3

Archimedean Duals and Irregular Polygons 146

9.5.3.1

Rhombic Dodecahedron (2) 146

9.5.4

Irregular Polygons 147

9.6

Why the Platonic and Archimedean Solids? 147

9.7

Conclusion 148

10

The Combinatorial Approach to Materials Discovery 151

10.1

Introduction 151

10.2

History of Rapid Synthesis Approaches in Materials Research 152

10.2.1

Early Work 152

10.2.3

Recent Innovations 154

10.2.4

The Continuous Compositional Spread (CCS) Approach 156

10.3

Systematized Search for a New High- Thin-film Material 158

10.3.1

General Considerations for Investigating New Materials Systems 158

10.3.2

The Problem: Finding New High Dielectric-Constant Materials 159

10.3.3

Measurement Strategy and Figure of Merit 161

10.3.4

Electrical and Compositional Evaluation 162

10.4

Identification of a Promising Candidate and Discussion of Trends 164

10.4.1

Initial Survey 164

10.4.2

The Zr-Sn-Ti-O System 164

10.4.3

Single-Target Synthesis and Detailed Electrical Characterization 167

10.4.4

HfTT Analog 168

10.4.5

Other Systems 168

10.4.6

Other Problems for Which a Combinatorial Approach is Well Suited 171

10.4.7

New Magnetic Materials 171

10.4.8

Superconductors 172

10.4.9

Thermoelectric materials 172

10.4.10

Piezoelectric materials 172

10.4.11

Ferroelectric Materials 173

10.4.12

Optical Materials 173

10.4.13

Catalysts 173

10.5

Concluding Comments 173

11

On One Hand But Not The Other: The Challenge of the Origin and Survival of Homochirality in Prebiotic Chemistry 175

11.1

Symmetry Breaking and Chiral Induction 177

11.1.1

Is it Intrinsic? 177

11.1.2

Is it Fluctuational? 179

11.1.3

Is it Extrinsic? 181

11.2

Experimental Studies of Chiral Induction 181

11.2.1

Intrinsic Mechanisms 182

11.2.2

Fluctuational Mechanisms 183

11.2.3

Extrinsic Mechanisms 185

11.3

Chiral Amplification and Takeover 186

11.3.1

Autoamplification by Polymerization/Depolymerization 187

11.3.2

Enantiomeric Amplification by Change of Phase 189

11.3.3

Metal-Assisted Enantiomeric Amplification 189

11.3.4

Amplification by Molecular Propagation from a Chiral Center 191

11.3.5

Amplification by CPL Photoinduction 192

11.4

The Sequestration of Chirality 193

11.4.1

Porous Minerals 194

11.4.2

Amphiphilic Vesicles 195

11.5

Setting the Scene for Life 196

11.6

The Rocky Road to Life? 198

11.7

Concluding Remarks 202

11.8

Acknowledgments 202

12

Chemical Reaction Dynamics Looks to the Understanding of Complex Systems 209 Acknowledgement 217

13

The Past, Present, and Future of Quantum Chemistry 219 Introduction 219

13.2

The History and Present Status of Quantum Chemistry 221

13.2.1

The Gaussian Programs 221

13.2.2

Coupled Cluster Theory 222

13.2.3

Multireference Approaches 224

13.2.4

Analytic Gradient Techniques 226

13.2.5

Density-Functional Theory 228

13.2.6

Integral-Direct Methods 230

13.3

The Future of Quantum Chemistry 231

13.3.1

Extensions to Large Systems 232

13.3.2

Pursuit of Spectroscopic Accuracy 235

13.3.3

Potential Energy Surfaces for Reaction Dynamics 238

13.4

Conclusions 241

13.5

Acknowledgements 242

13.6

Appendix: Nomenclature 242

14

Quantum Alchemy 247

14.1

From Alchemy to Quantum Theory 247

14.2

Applying Quantum Theory 248

14.3

Total Energy Calculations 256

14.4

Novel Materials 262

14.5

The Future 266 Acknowledgements 268

15

Quantum Theory Project 271

15.1

Introduction 271

15.2

Background 271

15.3

Wave Function Theory 274

15.4

Density Functional Theory 278

15.5

Ab Initio Density Functional Theory 281

15.5.1

Exact Exchange 281

15.5.2

Exact Correlation 283 Acknowledgements 284 Index 287

*Editor's Note: The brief summary and the contents of the books are reported as provided by the author or the publishers. Authors and publishers are encouraged to send review copies of their recent books of potential interest to readers of Molecules to the Editor-in-Chief (Dr. Shu-Kun Lin, MDPI, Saengergasse 25, CH-4054 Basel, Switzerland. Tel. +41 79 322 3379, Fax +41 61 302 8918, E-mail: [email protected]). Some books will be offered to the scholarly community for the purpose of preparing full-length reviews.