Molecular Orbital Theory In Drug Research

Medicinal Chemistry, Volume 10: Molecular Orbital Theory in Drug Research is a 12-chapter text that emerged from a series of lectures presented to graduate students in medicinal chemistry at the University of Michigan. After dealing with the general considerations of drug phenomena and quantum theory, this book goes on exploring the various molecular orbital calculation methods and the significance of molecular orbital indices. The subsequent chapters on the applications of molecular orbital theory are organized on the basis of physical chemical phenomena concluded from the studies described to be involved in the biological activity. These chapters also look into the correlations between indices reflecting covalent bond formation and biological activity. This text further examines the charge transfer mechanisms of several drug classes. The remaining chapters are devoted to the use of molecular orbital theory in several aspects of drug research, including molecular conformation, acid-base phenomena, hydrogen bonding, and dispersion forces. This work is directed to the advanced undergraduate or graduate students in medicinal chemistry or pharmacology, as well as to the practicing scientists interested in acquiring some understanding of molecular orbital theory. Theoretical chemists seeking information on biological phenomena amenable to semiempirical molecular orbital study will find this book invaluable.

Preface

I. General Considerations of Drug Phenomena

I. Drug-Receptor Reactions

II. Drug-Receptor Interaction Forces

III. Consequences of Drug-Receptor Interaction

IV. The Study of Drug-Receptor Events

References

II. General Considerations of Quantum Theory

I. Classical Mechanics

II. Quantum Mechanics

III. Atomic and Molecular Structure

IV. Molecular Orbitals

References

Supplemental Reading

III. Molecular Orbital Calculations

I. Hückel π-Electron Approximation

II. Modified π-Electron Hückel Methods

III. Self-Consistent Field π-Electron Method

IV. Methods of Treating σ Bonds

V. All-Valence Methods

VI. Analysis of Methods

References

IV. Significance of Molecular Orbital Indices

I. Properties Related to Total Energy

II. Properties Related to Orbital Energies

III. Properties Related to Charge

References

V. Practical Considerations of Molecular Orbital Applications

I. Biological Events

II. Biological Data

III. MO Calculations

References

VI. Drug Mechanisms Treated as Covalent Bond Phenomena

I. Antimicrobial Agents

II. Ester Hydrolysis

III. Agricultural Agents

IV. Enzymic Acetyl Group Transfer

V. Skin Photosensitizing Agents

VI. Chemical Carcinogenesis of Hydrocarbons

VII. General Summary

References

VII. Charge Transfer Mechanisms

I. Antimalarial Drugs

II. Hallucinogenic Activity

III. Carcinogenic Hydrocarbons

IV. Solution Stabilization of Menadione

V. Local Anesthetics

VI. Phenothiazine Tranquilizers

VII. Nicotinic Agents

VIII. Imidazoline Analgesics

IX. Benzothiadiazine Antihypertensive Agents

X. General Comments

References

VIII. Molecular Conformation

I. Muscarinic Pharmacophore

II. Nicotinic Pharmacophore

III. Histamine Pharmacophores

IV. Serotonin Pharmacophore

V. Cortisol and Antiinflammation

VI. α-Adrenergic Agents

VII. Nucleoside Conformation

VIII. Sugar Conformation

IX. Amino Acid Conformation

X. Summary

References

IX. Acid-Base Phenomena

I. General Considerations

II. Dissociation of Amino Acids

III. Basicity and Folic Acid Inhibition

IV. Sulfonamide Activity

V. Summary

References

X. Hydrogen Bonding

I. Theory

II. Anticonvulsants

III. Purine and Pyrimidine Base Pairing

IV. Cholinesterase Inhibitor Binding

References

XI. Dispersion Forces

I. Dispersion Force Theory

II. Molecular Orbital Treatment of Dispersion

References

XII. Future Directions of Molecular Orbital Studies

I. Methods

II. Future Areas of Study

III. Final Summary

References

Author Index

Subject Index