The relationship between anesthetic potency (minimum alveolar concentration) and molecular shape; structural studies...

We have explored the ability of molecular mechanics energy calculation as a probe to obtain quantitative information about the molecular shape and energies of inhalational anesthetics. (Molecular mechanics is a readily accessible, nonquantum mechanical method of computing detailed molecular structure from energetical viewpoint.) From this aspect, the structure-activity relationships of ten inhalational anesthetics were studied. Using this method, stable conformers of these anesthetics are deduced with various physicochemical parameters. The importance of dipole interaction as the major determinant of stable conformation was suggested, and reasonable correlations between anesthetic potency (minimum alveolar concentration: MAC) and components of dipole moments, with reference to the specific sites of molecules, were obtained. The results indicate that there are important polar components which play a major role in anesthesia.