Modeling of Molecular Properties -- Contents -- Preface -- List of Contributors -- Part One: Theory and Concepts -- 1 Accurate Dispersion-Corrected Density Functionals for General Chemistry Applications -- 1.1 Introduction -- 1.2 Theoretical Background -- 1.2.1 Double-Hybrid Density Functionals -- 1.2.2 London-Dispersion-Corrected DFT -- 1.3 Examples -- 1.3.1 GMTKN30 -- 1.3.2 A Mechanistic Study with B2PLYP-D -- 1.3.3 Double-Hybrids for Excited States -- 1.4 Summary and Conclusions -- References -- 2 Free-Energy Surfaces and Chemical Reaction Mechanisms and Kinetics -- 2.1 Introduction -- 2.2 Elementary Reactions -- 2.3 Two Consecutive Steps -- 2.4 Multiple Consecutive Steps -- 2.5 Competing Reactions -- 2.6 Catalysis -- 2.7 Conclusions -- References -- 3 The Art of Choosing the Right Quantum Chemical Excited-State Method for Large Molecular Systems -- 3.1 Introduction -- 3.2 Existing Excited-State Methods for Medium-Sized and Large Molecules -- 3.2.1 Wavefunction-Based ab initio Methods -- 3.2.2 Density-Based Methods -- 3.3 Analysis of Electronic Transitions -- 3.4 Calculation of Static Absorption and Fluorescence Spectra -- 3.5 Dark States -- 3.5.1 Excited Electronic States with Large Double Excitation Character -- 3.5.2 Charge-Transfer Excited States -- 3.6 Summary and Conclusions -- References -- 4 Assigning and Understanding NMR Shifts of Paramagnetic Metal Complexes -- 4.1 The Aim and Scope of the Chapter -- 4.2 Basic Theory of Paramagnetic NMR -- 4.2.1 The Origin of the Hyper.ne Shift -- 4.2.1.1 The Contact Shift -- 4.2.1.2 The Pseudocontact Shift -- 4.2.2 Relaxation and Line Widths -- 4.2.2.1 Electronic Relaxation -- 4.2.2.2 Dipolar Relaxation -- 4.2.2.3 Contact Relaxation -- 4.2.2.4 Curie Relaxation -- 4.2.3 Advice for Recording Paramagnetic NMR Spectra -- 4.3 Signal Assignments -- 4.3.1 Comparison of Similar Compounds.

4.3.2 Separation of Contact and Pseudocontact Shift -- 4.3.3 Estimating the Dipolar Contributions -- 4.3.4 DFT-Calculation of Spin-Densities -- 4.4 Case Studies -- 4.4.1 Organochromium Complexes -- 4.4.2 Nickel Complexes -- References -- 5 Tracing Ultrafast Electron Dynamics by Modern Propagator Approaches -- 5.1 Charge Migration Processes -- 5.1.1 Theoretical Considerations of Charge Migration -- 5.2 Interatomic Coulombic Decay in Noble Gas Clusters -- 5.2.1 Theoretical Considerations of ICD -- References -- 6 Natural Bond Orbitals and Lewis-Like Structures of Copper Blue Proteins -- 6.1 Introduction: Localized Bonding Concepts in Copper Chemistry -- 6.2 Localized Bonds and Molecular Geometries in Polyatomic Cu Complexes -- 6.3 Copper Blue Proteins and Localized Bonds -- 6.4 Summary -- References -- 7 Predictive Modeling of Molecular Properties: Can We Go Beyond Interpretation? -- 7.1 Introduction -- 7.2 Models and Modeling -- 7.3 Parameterized Classical and Quantum Mechanical Theories -- 7.4 Predictive Energies and Structures -- 7.5 Other Gas-Phase Properties -- 7.6 Solvent Effects: The Major Problem -- 7.7 Reaction Selectivity -- 7.8 Biological and Pharmaceutical Modeling -- 7.8.1 SAR Modeling -- 7.8.2 Force Fields, Docking, and Scoring -- 7.9 Conclusions -- References -- 8 Interpretation and Prediction of Properties of Transition Metal Coordination Compounds -- 8.1 Introduction -- 8.2 Molecular Structure Optimization -- 8.3 Correlation of Molecular Structures and Properties -- 8.4 Computation of Molecular Properties -- 8.5 A Case Study: Electronic and Magnetic Properties of Cyano-Bridged Homodinuclear Copper(II) Complexes -- 8.6 Conclusions -- References -- 9 How to Realize the Full Potential of DFT: Build a Force Field Out of It -- 9.1 Introduction -- 9.2 Spin-Crossover in Fe(II) Complexes -- 9.3 Ligand Field Molecular Mechanics.

9.3.1 Training Data: Fe(II)-Amine Complexes -- 9.3.2 LFMM Parameter Fitting -- 9.4 Molecular Discovery for New SCO Complexes -- 9.5 Dynamic Behavior of SCO Complexes -- 9.6 Light-Induced Excited Spin-State Trapping -- 9.7 Summary and Future Prospects -- References -- Part Two: Applications in Homogeneous Catalysis -- 10 Density Functional Theory for Transition Metal Chemistry: The Case of a Water-Splitting Ruthenium Cluster -- 10.1 Introduction -- 10.2 Shortcomings of Present-Day Density Functionals -- 10.2.1 Delocalization Error/Self-Interaction Error -- 10.2.2 Spin-Polarization/Static-Correlation Error -- 10.3 Strategies for Constructing Density Functionals -- 10.4 A Practical Example: Catalytic Water Splitting -- 10.4.1 A Binuclear Ruthenium Water-Splitting Catalyst -- 10.4.2 Comparison of Different Density Functionals -- 10.4.3 Comparison with Experimental Data -- 10.4.4 The Oxo and the Superoxo Structure of the Reactive [Ru2O2]3+ Species -- 10.4.5 Interaction with the Environment: Explicit Solvation of [Ru2O2]3+ -- 10.4.6 Formation and Structure of the [Ru2(OH2)O2]3+ Intermediate -- 10.5 Conclusions -- References -- 11 Rational and Efficient Development of a New Class of Highly Active Ring-Opening Metathesis Polymerization Catalysts -- 11.1 Introduction -- 11.2 A New Lead Structure: Introduction of Chelating, Bulky, Electron-Rich Bisphosphines with Small Bite Angles -- 11.3 ROMP Activity of the Neutral Systems -- 11.4 Cationic Carbene Complexes: Synthesis and Structure -- 11.4.1 A Comparison of Carbene versus Carbyne Hydride Isomers: L2ClRu=CH+2 versus L2Cl(H)Ru≡CH+ -- 11.4.2 DFT Calculations -- 11.5 Olefin Metathesis with Cationic Carbene Complexes: Mechanistic Considerations -- 11.5.1 A Gas-Phase Study of Cationic Carbene Complexes -- 11.5.2 Screening Results -- 11.5.3 Mechanistic Results -- 11.5.3.1 Isotope Effects.

11.5.3.2 Olefin π-Complex Pre-Equilibrium -- 11.5.3.3 Backbiting -- 11.5.4 Direct Comparison of Active Species -- 11.6 ROMP Kinetics in Solution -- 11.6.1 Bite Angle Influence on ROMP Activity -- 11.6.2 ROMP Activity: A comparison with First- and Second-Generation Grubbs Systems in Solution -- 11.7 Summary and Outlook -- References -- 12 Effects of Substituents on the Regioselectivity of Palladium-Catalyzed Allylic Substitutions: A DFT Study -- 12.1 Introduction -- 12.2 Computational Details -- 12.3 Results and Discussion -- 12.3.1 Calculations of the π-Allyl Complexes -- 12.3.1.1 Geometries of the π-Allyl Complexes -- 12.3.1.2 Charge Analysis of the π-Allyl Complexes -- 12.3.1.3 Frontier Orbital Analysis -- 12.3.2 Calculations of Transition States and Product Olefin Complexes -- 12.3.3 Transition State Analysis -- 12.3.4 Olefin Complexes -- 12.4 Conclusions -- References -- 13 Dicopper Catalysts for the Azide Alkyne Cycloaddition: A Mechanistic DFT Study -- 13.1 Introduction -- 13.2 Theoretical Methods -- 13.3 Discussion of the CuAAC Mechanism -- 13.4 Conclusion and Summary -- References -- 14 From Dynamics to Kinetics: Investigation of Interconverting Stereoisomers and Catalyzed Reactions -- 14.1 Investigation of Interconversions by Gas Chromatography -- 14.2 Evaluation Tools -- 14.3 Investigation of Catalyzed Reactions -- 14.3.1 Catalytic Studies with On-Column Reaction Chromatography -- 14.4 Perspectives -- References -- 15 Mechanistic Dichotomies in Coupling-Isomerization-Claisen Pericyclic Domino Reactions in Experiment and Theory -- 15.1 Introduction -- 15.2 Computation of the Concluding Intramolecular Diels-Alder Reaction in the Domino Formation of (Tetrahydroisobenzofuran) spiro-Benzofuranones or spiro-Indolones -- 15.3 Computation of the Pericyclic Dichotomies of Propargyl Tritylethers -- 15.4 Conclusions -- References.

Part Three: Applications in Pharmaceutical and Biological Chemistry -- 16 Computational Design of New Protein Catalysts -- 16.1 Introduction -- 16.2 The Inside-Out Approach -- 16.3 Catalyst Selection and the Catalytic Unit -- 16.4 Theozymes -- 16.4.1 Background -- 16.4.2 Definition -- 16.4.3 Selection of Catalytic Groups -- 16.4.4 Theozyme Diversity -- 16.4.5 Applications of Theozymes -- 16.5 Scaffold Selection and Theozyme Incorporation -- 16.5.1 Overview and Background -- 16.5.2 RosettaMatch -- 16.5.3 Gess -- 16.6 Design -- 16.6.1 Overview -- 16.6.2 RosettaDesign -- 16.7 Evaluating Matches and Designs -- 16.7.1 Filtering and Ranking Matches -- 16.7.1.1 EDGE -- 16.7.1.2 SASA -- 16.7.2 Ranking and Evaluating Designs -- 16.7.2.1 Empirical Criteria -- 16.7.2.2 Reverting Unnecessary Mutations -- 16.7.2.3 Molecular Dynamics Evaluation -- 16.8 Experiments -- 16.9 Successful Enzyme Designs -- 16.9.1 Retro-Aldol Reaction -- 16.9.2 Kemp Elimination -- 16.9.3 Diels-Alder Cycloaddition -- 16.10 Rational Redesign and Directed Evolution of Designed Enzymes with Low Activities -- 16.10.1 Iterative Approach to de novo Enzyme Design: Rational Redesign -- 16.10.2 Directed Evolution of KE70 -- 16.11 Summary -- References -- 17 Computer- Assisted Drug Design -- 17.1 Neuraminidase Inhibitors -- 17.1.1 Physiological Function of Neuraminidase -- 17.1.2 The Substrate: Sialic Acid -- 17.1.3 The Development of Zanamivir -- 17.1.4 Development of the Orally Active Agent Oseltamivir -- 17.2 Cyclooxygenase Inhibitors -- 17.2.1 Cyclooxygenase (Cox) -- 17.2.1.1 Physiological Functions of Cox-1 and Cox-2 -- 17.2.1.2 Structural Comparison of Cox-1 and Cox-2 -- 17.2.2 Molecular Structures of Typical Cox-1 Selective Inhibitors -- 17.2.3 Molecular Structure of Typical Cox-2 Selective Inhibitors -- 17.3 Concluding Remarks -- References -- 18 Statics of Biomacromolecules.

18.1 Introduction.