DFT Study Of The S-oxidation Of P-methylthio-N, N-dimethylaniline By Cytochrome P450

Cytochrome P450 is one of the most versatile enzymes in nature.It uses dioxygen and two reducing equivalents to catalyze the monooxygenation reactions of wide variety of substrates so that can function as oxidant that safeguards organisms against exnobiotics,metabolizes drugs,and leads to biosynthesis of vital compounds. There still remain mechanistic uncertainties and long-standing unresolved issues which pose tantalizing challenges to mechanistic chemistry although a few decades of considerable effort has been dedicated to elucidate the mechanisms of P450 catalyzed reactions.A DFT calculations were carried out for the study of sulfoxidation by the enzyme cytochrome P450 by taking p-methylthio-N,N-dimethylaniline(p-MT-DMA) as substrate.Calculations compared the sulfoxidation of p-MT-DMA by the the high-valent oxo-ferryl species,known as Compoundâ… (Cpdâ… ),and the precursor species,so called Compound 0(Cpd 0).It has been revealed that when taking Cpdâ… as the oxidant,it will go through low spin(LS) states,and the barrier of the bond activation transition state in LS is 8.3 kcal/mol(E1)/3.8 kcal/mol(E2).Our results demonstrate that Compoundâ… leads to an extremely fast process,while Compound 0 will be at least six orders of magnitude slower.We suggest that most likely,thiafatty acids promote Compoundâ… formation.In this manner we provides a clear answer to a major mechanistic of sulfoxidation of p-MT-DMA.