A kinetic study of dimethyl sulfoxide reductase based on density functional theory

We present a density functional theory study on the oxygen atom transfer (OAT) reaction of dimethyl sulfoxide (DMSO) with model complexes resembling a functional synthetic analogue of the molybdoenzyme DMSO reductase. The good agreement between our calculated Gibbs free energy profile and data derived from experimental kinetic parameters supports the reaction mechanisms of the oxygen atom transfer proposed in this study. When the mechanism involves the formation of a DMSO-bound intermediate, the calculations on the free energy surface provide valuable information that explains the origin of the apparent contradiction between the experimental findings and previous theoretical calculations with respect to the rate-limiting step of the reaction mechanism. The enzymatic mechanism of the OAT reaction is more complex than the mechanism of any synthetic analogue, mainly due to the formation of an enzyme-substrate adduct prior to the appearance of the substrate-bound intermediate. This study also presents a possible mechanism for the formation of such an adduct and the subsequent oxygen atom transfer. The mechanism involves a proton transfer to and from the substrate.