A Computational Comparison of Oxygen Atom Transfer Catalyzed by Dimethyl Sulf­oxide Reductase with Mo and W

Abstract

AbstractA thorough computational study has been performed to investigate oxygen atom transfer (OAT) reactions catalyzed by dimethyl sulfoxide reductase (DMSOR) with a catalytic molybdenum or tungsten ion. Thirteen different density functional theory (DFT) methods have been employed to obtain structural parameters along the reaction pathway, and single‐point energies were computed with local correlation coupled‐cluster methods [LCCSD(T0)]. For both Mo and W, most DFT methods indicate that the enzyme follows a two‐step mechanism with a stable intermediate in which a DMSO molecule coordinates to the metal ion in the +IV oxidation state, and this is also confirmed by the LCCSD(T0) energies. The W‐substituted models have a 26–30 kJ/mol lower activation barrier for the OAT reaction, and the reaction is 63–70 kJ/mol more exothermic than that with Mo. Different DFT methods give widely different activation and reaction energies, which roughly depend on the amount of exact exchange in the method; these differences are also reflected in the structures, especially for the rate‐limiting transition state. Consequently, there is quite a large variation in energies and various energy corrections (thermal, solvation, dispersion, and relativistic; up to 39 kJ/mol) depending on which DFT method is used to obtain the geometries. Therefore, a mechanism predicted by a single method should be viewed with caution.