title: Sulfoxide, Sulfur, and Nitrogen Oxidation and Dealkylation by Cytochrome P450.
abstract: The oxidation and dealkylation of dimethylsulfoxide (DMSO), dimethylsulfide (DMS), and trimethylamine (TMA) by cytochrome P450 has been studied with density functional theory calculations. The results show that the oxidation reactions always occur on the doublet spin surface, whereas dealkylations can take place for both the doublet and quartet spin states. Moreover, DMS is more reactive than DMSO, and S-oxidation is more favorable than S-dealkylation, whereas N-dealkylation is more favorable than N-oxidation. This is in perfect agreement with experimental results, showing that density functional activation energies are reliable and comparable for widely different reactions with cytochrome P450.
authors.affiliation: Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark, and the Department of Theoretical Chemistry, Lund University, P.O.B. 124, SE-22100 Lund, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Rydberg
authors.affiliation: Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark, and the Department of Theoretical Chemistry, Lund University, P.O.B. 124, SE-22100 Lund, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ryde
authors.affiliation: Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark, and the Department of Theoretical Chemistry, Lund University, P.O.B. 124, SE-22100 Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Olsen