Foreword xiii
About the Author xv
Preface xvii
Part I Frameworks 1
1 Introduction 3
1.1 Theoretical and Computational Chemistry 3
1.2 Multiscale Modeling 5
1.3 Orbital-based Theories 7
1.4 Density Functional Theory 13
1.5 Scope of This Book 18
2 Conceptual Density Functional Theory 23
2.1 Hypotheses and Brief History 23
2.2 Basic Formulation 25
2.3 Basic Concepts and Principles 33
2.4 Extensions 38
2.5 Concluding Remarks 46
3 Density-associated Quantities 53
3.1 Electron Density 54
3.2 Density Gradient and Laplacian 60
3.3 Topological Analysis 62
3.4 Quantum Theory of Atoms in Molecules 63
3.5 DAQ-based Indices 65
3.6 DAQs in Excited States 68
3.7 DAQ in Momentum Space 70
3.8 Concluding Remarks 71
4 Information-theoretic Approach 75
4.1 Overview 75
4.2 ITA Quantities 76
4.3 Four ITA Representations 80
4.4 Three ITA Principles 84
4.5 Two Identities Among ITA Quantities 87
4.6 Information Functional Theory 88
4.7 Applications for ITA Quantities 88
4.8 Conclusions and Outlook 89
5 Orbital-free Density Functional Theory 97
5.1 Overview 97
5.2 Theoretical Framework 100Contents vii
5.3 Descriptors from OF-DFT 110
5.4 Applications of OF-DFT 114
5.5 Concluding Remarks 114
6 Recent Advances in Density-based Frameworks 119
6.1 Relationship Among Four Frameworks 120
6.2 Topological Analysis of ITA Quantities 124
6.3 Energetic Information 126
6.4 ITA Extended to Pair Density 130
6.5 Extension to Excited States 132
6.6 Merging with Machine Learning 133
6.7 Concluding Remarks and Outlook 134
Part II Applications 139
7 Covalent and Noncovalent Interactions 141
7.1 Introduction 141
7.2 Orbital-based Approaches 143
7.3 Density-based Approaches 145
7.4 Energetics of Bonding 154
7.5 Recent Developments 156
7.6 Concluding Remarks 159
8 Cooperativity and Frustration 163
8.1 Introduction 163
8.2 Traditional Theory of Cooperativity 164
8.3 Quantification of Cooperativity in Density Functional Theory 166
8.4 Classical Theory of Frustration 172
8.5 Quantification of Frustration in DFT 174
8.6 Principle of Cooperativity and Frustrativity 178
8.7 Recent Advances 179
8.8 Outlook: From Cooperation and Frustration to Emergence 180
9 Homochirality and Principle of Chirality Hierarchy 183
9.1 What Is Chirality? 183
9.2 Homochirality and Theories of Homochirality 185
9.3 Types of Chirality and Chirality Hierarchy 186
9.4 Chirality Transmission 189
9.5 Chirality Hierarchy Case Study: Helices 189
9.6 Chirality Hierarchy Case Study: Propellers 192
9.7 Principle of Chirality Hierarchy 195
9.8 Concluding Remarks 196
10 Electrophilicity and Nucleophilicity 201
10.1 Introduction 201
10.2 Experimental Scales 203
10.3 Quantification in Conceptual Density Functional Theory 205
10.4 Quantification in ITA 211
10.5 Regioselectivity 214
10.6 Benchmark CDFT and ITA Quantifications 215
10.7 Ortho/Para and Meta Group Directing Effect 219
10.8 Concluding Remarks 221
11 Steric Effect and Stereoselectivity 225
11.1 Steric Effect 225
11.2 Stereoselectivity 228
11.3 Experimental Scales of Steric Effect 232
11.4 Steric Effect: A Density-based Quantification 234
11.5 Validation by Taft's Steric Parameters 238
11.6 Stereoselectivity: A Density-based Description 239
11.7 Quantification of Stereoselectivity 241
11.8 Summary and Conclusions 242
12 Acidity and Basicity 247
12.1 Introduction 247
12.2 Br¸nstedâ"Lowry Acidity and Basicity 249
12.3 CDFT and Br¸nstedâ"Lowry Acidity and Basicity 253
12.4 LA and LB 256
12.5 HSAB Principle 260
12.6 CDFT, ITA, and LA and LB 261
12.7 Outlook: A Unified View of Acidâ"Base Chemistry 265
13 Aromaticity and Antiaromaticity 271
13.1 Introduction 271
13.2 Aromaticity and Antiaromaticity in Ground State 272
13.3 Other Types of Aromaticity and Antiaromaticity 276
13.4 Descriptors of Aromaticity and Antiaromaticity 278
13.5 QTAIM, DFT, CDFT, and Aromaticity 283
13.6 ITA, Aromaticity, and Antiaromaticity 285
13.7 Concluding Remarks: Toward a Unified Understanding 288
14 Catalysis 295
14.1 Introduction 295
14.2 Theoretical Aspects of Catalysis 300
14.3 Understanding Catalysis with Physicochemical Effects 303
14.4 Catalytic Cycle and Mechanistic Aspects of Catalysis 305
14.5 Emerging Areas and Main Challenges of Catalysis 310
14.6 Toward the Ultimate Theory of Catalysis 314
14.7 Conclusions 318
15 Excited States 323
15.1 Fundamentals of Excited States 324
15.2 Theoretical Frameworks of Excited States 325
15.3 Case Studies of Excited States 328
15.4 Density-based Insights for Excited States 331
15.5 Frontiers of Excited State Research 336
15.6 Summary and Outlook 338
16 Miscellaneous Applications 343
16.1 Conformational Stability 344
16.2 Anomeric and Related Effects 345
16.3 SN2 Reactions 347
16.4 Proton-coupled Electron Transfer 348
16.5 Metal Specificity 349
16.6 Oxidation States 350
16.7 Impacts of EEFs 351
16.8 Polarizability for Macromolecules 353
16.9 Merging with ML 354
16.10 Summary and Outlook 356
Part III Perspectives 361
17 From Chemical Concepts to Chemical Understanding 363
17.1 Introduction 363
17.2 Ontology, Chemical Ontology, and Relations with Physics and Biology 364
17.3 Chemical Epistemology 368xii Contents
17.4 Representations of Hypotheses 370
17.5 Ontological Views of Hypotheses in MOT, VBT, and DFT 372
17.6 Chemical Understanding 374
17.7 Chemical Concepts as the Foundation 376
17.8 Ontological and Epistemological Requirements for Future Theories 379
18 Chemical Understanding with Machine Learning and Quantum Computers 383
18.1 Introduction 383
18.2 The Ultimate Challenge of In Silico Simulations in Chemistry 385
18.3 Prior Paradigms: Orbital- and Density-based Frameworks 387
18.4 Machine Learning as a New Paradigm 389
18.5 The Coming Era of Quantum Computers 392
18.6 How to Harvest Chemical Understanding from Theories 394
18.7 From Multiscale Modeling to Hierarchical Modeling 396
18.8 Concluding Synthesis: Toward a Unified View of Chemical Understanding 399
References 399
Index 403
