Abstract
The catalytic mechanism of molybdenum containing CO dehydrogenase has been studied using hybrid DFT methods with quite large chemical models. The recent highโresolution Xโray structure, showing the surprising presence of copper linked to molybdenum, was used as a starting point. A pathway was initially found with a low barrier for C๏ฃฟO bond formation and CO~2~ release. However, this pathway did not include the formation of any S๏ฃฟCO~2~ species, which had been suggested by experiments with an nโbutylisocyanide inhibitor. When these SCO~2~ structures were studied they were found to lead to deep minima, making CO~2~ release much more difficult. A large effort was spent, including investigations of other spin states, varying the number of protons and electrons, adding water, etc., until a plausible pathway for S๏ฃฟC bond cleavage was found. In this pathway a water molecule is inserted in between molybdenum and the SCO~2~ group. Full catalytic cycles, including electron and proton transfers, are constructed both with and without S๏ฃฟC bond formation. When these pathways are extended to two full catalytic cycles it can be understood why the formation of the S๏ฃฟC bond actually makes catalysis faster, even though the individual step of CO~2~ release becomes much more difficult. These results agree well with experimental findings. ยฉ 2005 Wiley Periodicals, Inc. J Comput Chem 26: 888โ898, 2005