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

A 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 twostep 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 6370 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