Mechanisms of Sulfoxidation Catalyzed by High-Valent Intermediates of Heme Enzymes:  Electron-Transfer vs Oxygen-Transfer Mechanism

Abstract

Mechanisms of sulfoxidation catalyzed by high-valent intermediates of heme enzymes have been investigated by direct observation of sulfide-induced reduction of three different compound I species including HRP (horseradish peroxidase), the His64Ser myoglobin (Mb) mutant, and O Fe IV TMP + • ( 1 ) (TMP = 5,10,15,20-tetramesitylporphyrin dianion). The reaction of thioanisole and compound I of HRP (10 μM, pH 7.0, 298 K) gives the resting state of HRP with accumulation of compound II as an intermediate. The yield of sulfoxide by a stoichiometric reaction of HRP compound I with thioanisole was only 25% ± 5%. On the other hand, the same sulfoxidation by both 1 and His64Ser Mb compound I exclusively exhibited a two-electron process, resulting in quantitative formation of sulfoxide. When 1,5-dithiacyclooctane (DTCO) is employed as a substrate, the reaction of His64Ser Mb compound I with DTCO exhibits rapid formation of compound II, which decays to the ferric state due to the low oxidation potential of DTCO. The observed rate constants (log k obs ) of the reactions of 1 and compounds I of HRP and His64Ser Mb with a series of p -substituted thioanisoles correlate with the one-electron oxidation potentials ( E 0 ox ) of the sulfides. A comparison of these correlations with the established correlation between log k obs and E 0 ox for the corresponding electron-transfer reactions of substituted N, N -dimethylanilines has revealed that the sulfoxidation reactions of compound I of HRP with the sulfides proceed via electron transfer while the sulfoxidations catalyzed by 1 and compound I of His64Ser Mb occur via direct oxygen transfer.