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?

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• 作者：Cristina S. Porro ; Michael J. Sutcliffe ; Sam P. de Visser
• 刊名：Journal of Physical Chemistry A
• 出版年：2009
• 出版时间：October 29, 2009
• 年：2009
• 卷：113
• 期：43
• 页码：11635-11642
• 全文大小：312K
• 年卷期：v.113,no.43(October 29, 2009)
• ISSN：1520-5215

文摘

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.