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.