Enzymatic Mechanism of Fe-Only Hydrogenase: Density Functional Study on H−H Making/Breaking at the Diiron Cluster with Concerted Proton and Electron Transfers

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Abstract
The mechanism of the enzymatic hydrogen bond forming/breaking (2H+ + 2e ⇆ H2) and the plausible charge and spin states of the catalytic diiron subcluster [FeFe]H of the H cluster in Fe-only hydrogenases are probed computationally by the density functional theory. It is found that the active center [FeFe]H can be rationally simulated as {[H](CH3S)(CO)(CN-)Fep(COb)(μ-SRS)Fed(CO)(CN-)L}, where the monovalence [H] stands for the [4Fe4S]H2+ subcluster bridged to the [FeFe]H moiety, (CH3S) represents a Cys−S, and (COb) represents a bridging CO. L could be a CO, H2O, H-, H2, or a vacant coordination site on Fed. Model structures of possible redox states are optimized and compared with the X-ray crystallographic structures and FTIR experimental data. On the basis of the optimal structures, we study the most favorable path of concerted proton transfer and electron transfer in H2-forming/breaking reactions at [FeFe]H. Previous mechanisms derived from quantum chemical computations of Fe-only hydrogenases (Cao, Z.; Hall, M. B. J. Am. Chem. Soc. 2001, 123, 3734; Fan, H.; Hall, M. B. J. Am. Chem. Soc. 2001, 123, 3828) involved an unidentified bridging residue (μ-SRS), which is either a propanedithiolate or dithiomethylamine. Our proposed mechanism, however, does not require such a ligand but makes use of a shuttle of oxidation states of the iron atoms and a reaction site between the two iron atoms. Therefore, the hydride Hb- (bridged to Fep and Fed) and η2-H2 at Fep or Fed most possibly play key roles in the dihydrogen reversible oxidation at the [FeFe]H active center. This suggested way of H2 formation/splitting is reminiscent of the mechanism of [NiFe] hydrogenases and therefore would unify the mechanisms of the two related enzymes.