On the Relationship between Electronic State of Molecules and their Biological Actions. I. The Nicotinic Action of Choline Phenyl Ether and the Enzymatic Decomposition of Phenyl Acetate

Abstract

Abstract 1. Applying the frontier electron method of Fukui et al., it was attempted to explain the effectiveness of nicotinic action of some choline phenyl ether derivatives and the substrate specificity of some phenyl acetates in the enzymatic hydrolysis. 2. A fairly good correlation could be proved between the frontier electron density (fr) or its superdelocalizability (Sr) of a certain position of these compounds and their potency or susceptibility to hydrolysis. 3. Assuming that the active site of receptor (or enzyme) has also π-electron systems and a drug-receptor (or -enzyme) complex is formed by hyperconjugation through π-electron systems, a general formulation of the effect of such a hyperconjugation on the perturbation energy of their system was attempted. It was demonstrated, qualitatively at least, by our calculations, that the larger the fr of drug molecules or their Sr the larger the perturbation energy and so a possibility of above-mentioned correlation was predicted to some extent from the quantum-chemical basis.