10.1021/jp9023926.s001 Cristina S. Porro Cristina S. Porro Michael J. Sutcliffe Michael J. Sutcliffe Sam P. de Visser Sam P. de Visser 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? American Chemical Society 2009 compound 0 cytochrome P 450 enzymes sulfoxidation reactions oxidant P 450 isozymes dimethyl sulfide sulfoxidation 450BM QM 2009-10-29 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/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_/2817553 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<sub>cam</sub> and P450<sub>BM3</sub>. 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.