Quantum chemical studies of the metabolism of the inhalation anesthetics methoxyflurane, enflurane, and isoflurane

Biodegradation of the inhalation anesthetics methoxyflurane, enflurane, and isoflurane is thought to occur by oxidative O dealkylation and dechlorination. In an attempt to understand their known metabolic behavior, the authors calculated the conformational and electronic properties of the three compounds and proposed intermediate metabolites using two semiempirical molecular orbital methods, iterative extended Huckel theory and perturbative configuration interaction using localized orbitals. The conformational similarities obtained for the three compounds pointed to electronic properties as the main factors involved, and using these they were able to establish criteria which could account for their known relative extent of metabolism and the formation of a number of identified intermediates.