The oxidation of cyclic sulfides by tetramethyldioxetane and the isobutanal/O2/peroxidase system: Oxygen transfer versus electron transfer

Abstract

The oxidation of chlorpromazine (CPZ) by tetramethyldioxetane (TMD) and isobutanal (IBAL)/O2/horseradish peroxidase (HRP) system was investigated. The reaction with TMD proved to be of the oxygen transfer type, generating chlorpromazine-5-oxide (CPZO) and tetramethylethylene-oxide, and not by single-electron transfer, as previously reported. In contrast, the reaction of CPZ with IBAL/O2/HRP leads to formation of chlorpromazine cation radical, through reaction with active intermediates Compound I and II, following its dismutation and hydrolysis to CPZO. For comparison, 10-methylphenothiazine was also tested. Despite the fact that both systems are known to generate oxidizing triplet acetone, this species does not participate in the oxidation path in either case.