Symmetry, Spectroscopy, and Crystallography

Robert Glaser is Emeritus Professor of Chemistry at Ben-Gurion University of the Negev, Beer-Sheva, Israel. He also holds an appointment as Visiting Professor in the Cross-Border Program in Biological Chemistry Budejoice (Budaweis), Czech Republic, administered by the University of South Bohemia/Universität Johannes Kepler in Linz, Austria. He also teaches at the Feinberg Graduate School of the Weizmann Institute of Science in Rehovot, Israel. Robert Glaser received his BA in chemistry at the University of Pennsylvania (USA) in 1963. Upon graduation he worked as a development chemist in the Structural Adhesives Division of the Pittsburg Plate Glass Company. Concurrently, he undertook part-time MSc studies in polymer chemistry at the Polytechnic Institute of Brooklyn, USA. After three years he began full-time studies, graduating Rutgers State University, USA, in 1969. From 1969 - 1971 he spent a two-year postdoctoral fellowship at Princeton University (USA) under guidance of Prof. P. von Rague Schleyer and Prof. R. Landgridge. After immigrating to Israel in 1971, he built up a new Department of Chemistry at the recently established University of the Negev in Beer-Sheva, where he became full professor in 1997. He has authored over 100 publications on the topic of organic and inorganic stereochemistry, molecular modeling, computer assisted drug design, and structure determination via NMR spectroscopic techniques.

• From the Author’s Desk XIII1 Symmetry/Pseudosymmetry: Chirality in Molecules, in Nature, and in the Cosmos 11.1 Introduction 11.2 Rudimentary GroupTheory, Isometry, and Symmetry 41.3 Asymmetric versus Chiral: The I-Symmetry of Viral Capsids 71.4 The Birth of Chirality as a Chemical Concept 91.5 Apparent Symmetry (High-Fidelity Pseudosymmetry) and the Quantification of Distortion from the Ideal 111.6 Chirality in Form and Architecture: Symmetry versus Broken Symmetry 161.7 Chirality in Nature: Tropical Storms, Gastropods (Shells), and Fish 171.8 Extraterrestrial Macroscale Chirality: Spiral Galaxies, Martian Sand Devils, Jovian Great Red Spot, Neptune’s Great Dark Spot, and Venusian South-Pole Cloud Vortex 201.9 Analyses of Amino Acid Chirality in Extraterrestrial Samples with Gas–Liquid Chromatography Chiral Columns 232 Enantiospecificity of Pheromones, Sweeteners, Fragrances, and Drugs 252.1 Enantiospecificity of Pheromones, Sweeteners, and Fragrances 252.2 The Importance of Chirality in Drug Therapy 273 Bonding Parameters and the Effect of Local Environment on Molecular Structure 333.1 Symmetry Arguments and the Effect of the Environment on Molecular Structure 333.2 The Effect of Local Environment on Molecular Models and Molecular Structure 343.3 Torsion Angles and Molecular Conformation 353.4 Symmetry Considerations of Atomic Orbital Hybridization and Bonding Parameters 394 Historical Development of Structural Chemistry: From Alchemy to Modern Structural Theory 414.1 Hemihedralism in Quartz Crystals: Setting the Stage for the Birth of Stereochemistry 414.2 Tartaric Acid and Alchemy 454.3 Hemihedralism in Crystalline Tartaric Acid Salts: The Birth of Molecular Chirality 464.4 Gift for Prelog’s Retirement: A Matched Pair of u′,x′-Hemihedral Faced Right- and Left-Handed Quartz Crystals 544.5 Early Structural Representations of Organic Substances and the Development of Modern Structural Concepts 554.6 Fischer Projections to Determine α- and β-Anomeric Configurations 645 Chiroptical Properties 675.1 The Language of Symmetry, Isomerism, and the Characterization of Symmetry Relationships within and between Molecules 675.2 Chiroptical Properties: Circular Birefringence, Optical Rotatory Dispersion, and Circular Dichroism 685.3 Miller Indices and Fractional Coordinates in Crystallography 745.4 Scanning Tunneling Microscopy 785.5 Direct Visualization of an Enantiomer’s Absolute Configuration in the Gas Phase 826 Symmetry Comparison of Molecular Subunits: Symmetry in Nuclear Magnetic Resonance Spectroscopy and in Dynamic NMR 856.1 Symmetry in NMR Spectroscopy 856.2 Symmetry Comparison of Molecular Subunits, Topicity Relationships 876.3 Dynamic Stereochemistry, Dynamic Nuclear Magnetic Resonance Spectroscopy (DNMR) 906.4 Use of Permutations in DNMR for Topomerization-, Enantiomerization-, and Diastereomerization-Exchange Processes 927 Prochirality, Asymmetric Hydrogenation Reactions, and the Curtin–Hammett Principle 997.1 Prochirality of Enantiotopic Subunits 997.2 Homogeneous Hydrogenation by RhodiumI/Achiral Diphosphine Catalysts Differentiates the Diastereotopic Prochiral Faces of Olefins 1017.3 Homogeneous Hydrogenation by RhodiumI/(Chiral Diphosphine) Catalysts Differentiates the Enantiotopic Prochiral Faces of Olefins: The Curtin–Hammett Principle 1048 Stereogenic Elements, Chirotopicity, Permutational Isomers, and Gear-Like CorrelatedMotion of Molecular Subunits 1138.1 Stereogenicity, Stereogenic Elements, Chirotopicity, and the Ambiguity of Some Stereochemical Terms 1138.2 Triarylamine Propellers 1158.3 Dynamic Stereochemistry of Permutational Isomers: Correlated Motion in Triarylamines 1168.4 Relative Stereochemical Descriptors: Retro-Inverso Isomers 1229 Symmetry in Extended Periodic Arrays of Molecular Crystals and the Relevance of Penrose Tiling Rules for Nonperiodic Quasicrystal Packing 1279.1 Symmetry in Extended Arrays/Molecular Crystals 1279.2 Achiral Periodic Arrays of Chiral Objects and Racemic Compound Crystal Lattices 1329.3 Chiral Periodic Arrays 1329.4 Occupancy of Special Positions in Periodic Arrays 1369.5 The Bragg Law and X-Ray Diffraction 1399.6 The Interferogram Phenomenon in Single-Crystal X-Ray Crystallography 1409.7 X-Ray Fiber Diffraction 1439.8 Penrose Tiling Matching Rules, Quasicrystal Packing, and Dodecahedrane 14510 MultipleMolecules in the Asymmetric Unit, “Faking It”; Pseudosymmetry Emulation of Achiral Higher Order Space Filling in Kryptoracemate Chiral Crystals 14910.1 Multiple Molecules within an Asymmetric Unit 14910.2 “Faking It”: Pseudosymmetry Emulation of Achiral Higher-Order Space Filling in Kryptoracemate Chiral Crystals 15110.3 Desymmetrization of Platonic-Solid Geometries Resulting from Crystallographic Symmetry Constraints 16110.4 Mobility of Cubane and Dodecahedrane (CH)n Spherical Molecules within a Crystal Lattice 16411 Platonic-Solid Geometry Molecules and Crystallographic Constraints upon Molecular Geometry, Symmetry Distortions from Ideality 16911.1 Geometrical Considerations in High-Symmetry Molecules 16911.2 Syntheses Strategies of High-Symmetry Chiral Molecules 17111.3 Ethano-Bridge Enantiomerization of T-Symmetry Molecules 17311.4 Self-Assembly of T-Symmetry Chiral Molecules 17611.5 Enantiomerization of T-Symmetry Clusters 18011.6 Tetradentate Edge-Linker Units Separated by a Spacer 18311.7 Self-Assembly of O-Symmetry Chiral Molecules 18411.8 O-Symmetry Ferritin Protein Octahedral Shell 18511.9 Desymmetrization Resulting from Symmetry and Chemical Constraints 18612 Solid-State NMR Spectroscopic/X-Ray Crystallographic Investigation of Conformational Polymorphism/Pseudopolymorphism in Crystalline Stable and Labile Hydrated Drugs 18912.1 Divalent Anions Linking Conformationally Different Ammonium Cations 18912.2 Cross Polarization/Magic Angle Spinning Solid-State NMR and X-Ray Crystallographic Studies on the Elusive “Trihydrate” Form of Scopolamine⋅Hydrobromide, an Anticholinergic Drug 19113 NMR Spectroscopic Differentiation of Diastereomeric Isomers Having Special Positions of Molecular Symmetry 20513.1 NMR Anisochronism of Nuclei at Special Positions of Molecular Symmetry 20513.2 Pattern Recognition: A Graphical Approach to Deciphering Multiplet Patterns 20714 Stereochemistry of Medium Ring Conformations 21314.1 A Short Primer on Medium Ring Stereochemistry 21314.2 Assignment of Equatorial-/Axial-Substituent Descriptors to Rings of Any Size 21414.3 NMR Structure Determination of Medium-Ring Solution-State Conformations 21614.4 Dynamic Disorder in Crystals 22115 The PharmacophoreMethod for Computer Assisted Drug Design 22915.1 The Pharmacophore, Neurotransmitters and Synapse 22915.2 The Pharmacophore Method for Computer Assisted Drug Design 23115.3 Determination of the Dopamine Reuptake Site Pharmacophore 23315.4 Methylphenidate (Ritalin⋅HCl) and (−)-Cocaine⋅HCl 23515.5 Ritalin Versus Cocaine: Binding Affinity and Inhibitory Concentration 23815.6 Second Generation Pharmacophore:The Orientation of the NH Proton 24215.7 Avoidance of Adjacent Gauche+Gauche− Interactions 24415.8 Static Disorder in N-Methyl Ritalin Crystals 24615.9 Development of Specific Dopamine Reuptake Inhibitors (SDRI) 25016 The X-Ray Structure–Based Method of Rational Design 25516.1 X-Ray Crystallographic Structure–Based Molecular Design 25516.2 The Different Primary Ammonium and Quaternary Aminium Binding Modes 25816.3 Search for Unused Binding Sites 26316.4 Primary Ammonium and Quaternary Aminium Binding Modes in CB[7 and 8] Complexes of Diamantane-4,9-Substituted Guests 26517 Helical Stereochemistry 26917.1 Helical Stereochemistry 26917.2 2nn-Symmetry Achiral Helical Pathways 27317.3 “La Coupe du Roi”: Chiral Apple Halves Produced by a 42-Bisection 27817.4 Intermeshing MolecularThreefold Helices: Symmetry, Chemical, and Phase Considerations 28117.5 X-Ray Fiber versus Single-Crystal Diffraction Models 289References 293Index 301