Carbon Monoxide Dehydrogenase Reaction Mechanism: A Likely Case of Abnormal CO2 Insertion to a Ni-H- Bond

Ni-containing carbon monoxide dehydrogenases (CODH), present in many anaerobic microorganisms, catalyze the reversible oxidation of CO to CO2 at the so-called C-cluster. This atypical active site is composed of a [NiFe3S4] cluster and a single unusual iron ion called ferrous component II or Feu that is bridged to the cluster via one sulfide ion. After additional refinement of recently published high-resolution structures of COOHx-, OHx-, and CN-bound CODH from Carboxydothermus hydrogenoformans (Jeoung and Dobbek Science 2007, 318, 1461-1464; J. Am. Chem. Soc. 2009, 131, 9922-9923), we have used computational methods on the predominant resulting structures to investigate the spectroscopically well-characterized catalytic intermediates, C-red1 and the two-electron more-reduced C-red2. Several models were geometry-optimized for both states using hybrid quantum mechanical/molecular mechanical potentials. The comparison of calculated Mossbauer parameters of these active site models with experimental data allows us to propose that the C-red1 state has a Fe-u-Ni2+ bridging hydroxide ligand and the Cred2 state has a hydride terminally bound to Ni2+. Using our combined structural and theoretical data, we put forward a revised version of an earlier proposal for the catalytic cycle of Ni-containing CODH (Volbeda and Fontecilla-Camps Dalton Trans. 2005, 21, 3443-3450) that agrees with available spectroscopic and structural data. This mechanism involves an abnormal CO2 insertion into the Ni2+-H- bond.