Mechanism of H-H activation by nickel-iron hydrogenase

DFT quantum chemical methods are used to probe the mechanism of the nickel-iron hydrogenases. Starting from the experimental X-ray structure, all plausible oxidation states and spin states were investigated, The structure and reactivity pattern of the NiFe cluster are best reproduced by assuming a NiFe(II,III) oxidation state assignment of the resting state of the cluster. In our proposed mechanism of H-2 oxidation by the enzyme, H-2 first binds to Fe in the form of a molecular hydrogen complex, which then undergoes heterolytic splitting. This process is spin-dependent and does not occur for the high-spin sextet state. In the key step, hydride transfer to iron and proton transfer to the adjacent cysteinethiolate ligand is accompanied by decoordination of the protonated cysteinethiol from Ni while remaining bound to iron. Simultaneously, the cyanide ligand on iron binds with the nickel atom in a rare bridging binding mode. After the H-2 dissociation, the hydride bound to Fe can then be transferred to Ni which should be a necessary preliminary for subsequent hydrogen atom or electron transport. The transition state for hydrogen splitting was located, and the resulting calculated energy barrier is in remarkably good agreement with the experimental value.