Molecular Modelling of Vitamin B12 and Its Analogues

Description

For many years, the chemistry of vitamin B12 and its derivatives has been investigated for their inherent eco-friendly and nontoxic nature. This vitamin, also known as cobalamin, is an organic complex that contains a cobalt ion in its structure. Its derivatives are vital bio-inorganic cofactors and possess complex and rich photolytic properties, facilitated by their excited states. This book compiles and details cutting-edge research in the application of vitamin B12 as an environmentally benign catalyst for several organic reactions. It discusses the recent advances and current understanding of the photolytic properties of vitamin B12 derivatives from the perspective of the density functional theory (DFT). The book is of interest for anyone involved in nanotechnology, macromolecular science, cancer, and drug-delivery research. Cover Half Title Title Page Copyright Page Table of Contents Preface 1. Introduction 1.1 Background 1.2 Causes of Vitamin B12 Deficiency 1.3 Uses and Effectiveness 1.4 Side Effects and Safety 1.5 Functions of Vitamin B12 1.6 Exercises 2. Structure, Constitution and Properties of Vitamin B12 2.1 Vitamin B12 Structure 2.2 Main Properties of Vitamin B12 2.3 Exercises 3. Nomenclature 4. B12 Organometallic Reactivity 4.1 Introduction 4.2 Cobaloxime Model Systems 4.2.1 Formation of CoX Bonds 4.2.2 Cleavage of Co–C Bonds 4.2.3 Electrochemistry 4.2.4 Alkene Coupling 4.2.5 Ring Expansion Reactions 4.3 Computational Studies on Organometallic Chemistry 5. Coenzyme B12–Dependent Enzymes 5.1 Introduction 5.2 Methylcobalamin 5.2.1 Methionine Synthase 5.2.2 Methylated-thiol-Coenzyme M Methyltransferase 5.3 Adenosylcobalamin 5.4 Hydroxocobalamin 5.5 Cobamamide 5.6 Cyanocobalamin 6. Recent Trends 6.1 Introduction 6.2 Vitamin B12 for Cyanide Detection and Detoxification 6.3 Vitamin B12 for Diagnosis and Therapy 6.3.1 Diabetes Mellitus 6.3.2 Cardiovascular Disease 6.3.3 Epilepsy 6.3.4 Cancer 6.3.5 Dementia 6.3.6 Renal Disease 6.4 Antivitamins B12 6.5 Vitamin B12 in Biological Systems 7. Catalysis 7.1 Introduction 7.2 Concept of Catalysis 7.3 Types of Catalysis 7.3.1 Homogenous Catalysis 7.3.2 Heterogeneous Catalysis 7.4 Vitamin B12: A Unique Natural Organometallic Catalyst 7.5 Catalytic Features of Cobalamins 7.5.1 Availability 7.5.2 Balance between Stability and Reactivity 7.5.3 Recoverability 7.5.4 High Activity-to-Dosage Ratio 7.6 Chemistry of the Organometallic Co–C Bond in Vitamin B12 Derivatives 7.7 Factors Controlling the Co–C Bond Cleavage 7.7.1 Positional Influence of Neighbouring Ligands 7.7.1.1 Trans influence of the alpha axial ligand 7.7.1.2 Cis influence of the equatorial ligand 7.7.2 Nature of the Alpha Axial Ligand 7.7.3 Presence of an Enzyme 7.7.3.1 Caging effect 7.7.3.2 Distortion effect 7.7.3.3 Mutual stabilisation between the Co2+ state and the enzyme 7.8 Exercises 8. Vitamin B12–Catalysed Reactions 8.1 Introduction 8.2 Vitamin B12 Enzymes and Their Functions 8.2.1 B12-Binding and B12-Transporting Proteins 8.2.2 Methyltransferases 8.2.3 Cobalamin-Dependent Enzymes 8.3 Cobalamin-Mediated Organic Reactions 8.3.1 Rearrangement (Isomerisation) 8.3.2 Methyl Transfer Reaction (Transmethylation) 8.3.3 Dehalogenation 8.3.4 C–C and C–X Multiple Bond Hydrogenation 8.3.5 1,4-Addition to Double Bonds 8.3.5.1 Scheffold principles of cobalamin-mediated 1,4-addition reactions 8.3.6 Ring-Opening Reactions 8.3.7 Coupling Reactions 8.3.7.1 Halide coupling reaction of alkyl halides (Scheme 8.7a) 8.3.7.2 Alkene coupling reaction of styrene derivatives (Scheme 8.7b) 8.3.8 Cyclopropanation 8.3.9 Oxidation 8.3.10 Ring Expansion Reactions 8.4 Exercises 9. Vitamin B12 Derivatives 9.1 Vitamin B12 as an Active Ingredient of Supplements 9.2 Efficacy Spectrum of Bioactive Vitamin B12 Forms 9.2.1 Cyanocobalamin vs. Hydroxocobalamin 9.2.2 Cyanocobalamin vs. Methylcobalamin 9.2.3 Exercises 9.3 Methylcobalamin 9.3.1 Mechanisms Underlying the Analgesic Action of MeCbl 9.3.1.1 Enhancing the nerve conduction velocity 9.3.1.2 Improving the rejuvenation of wounded nerves 9.3.1.3 Constraining ectopic spontaneous release 9.3.2 Exercises 9.4 Adenosylcobalamin 9.4.1 Exercises 9.5 Cyanocobalamin 9.5.1 Chemical Reactions 9.5.2 Exercises 9.6 Hydroxocobalamin 9.6.1 Special Effects of Hydroxocobalamin 9.6.1.1 Long-lasting effects and sustained release 9.6.1.2 Detoxing and quitting smoking 9.6.1.3 Blocking nitrosative stress 9.6.1.4 Hydroxocobalamin supplements: pills and capsules 9.6.2 Exercises 10. Theoretical Approach 10.1 Mechanism of the S1 Excited-State Internal Conversion in Vitamin B12 10.2 Influence of the α (Axial)−Ligand 10.3 Electronic and Steric Effects 10.4 Bond Dissociation Energies 10.4.1 Exercises 10.5 Structural and Electronic Properties of Vitamin B12 Index