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Porro CS, Sutcliffe MJ, de Visser SP: Quantum mechanics/molecular mechanics studies on the sulfoxidation of dimethyl sulfide by compound I and compound 0 of cytochrome P450: which is the better oxidant?. J Phys Chem A. 2009 Oct 29;113(43):11635-42.
The cytochromes P450 are ubiquitous enzymes that are involved in key metabolizing processes in the body through the monoxygenation of substrates; however, their active oxidant is elusive. There have been reports that implicate that two oxidants, namely, the iron (IV)-oxo porphyrin cation radical (compound I) and the iron (III)-hydroperoxo complex (compound 0), both act as oxidants of sulfoxidation reactions, which contrasts theoretical studies on alkene epoxidation by compounds I and 0 that implicated compound 0 as a sluggish oxidant. To resolve this controversy and to establish the potency of compound I and compound 0 in sulfoxidation reactions, we have studied dimethyl sulfide sulfoxidation by both oxidants using the quantum mechanics/molecular mechanics (QM/MM) technique on cytochrome P450 enzymes and have set up a model of two P450 isozymes: P450 (cam) and P450 (BM3). The calculations support earlier gas-phase density functional theory modeling and show that compound 0 is a sluggish oxidant that is unable to compete with compound I. Furthermore, compound I is shown to react with dimethyl sulfide via single-state reactivity on a dominant quartet spin state surface. |
2(0,0,0,2) |