Ab Initio Electronic Structure Calculation of [4Fe-3S] Cluster of Hydrogenase as Dihydrogen Dissociation/Production Catalyst

Hydrogenases catalyze both the dissociation and production of dihydrogen (H2). Most hydrogenases are inactivated rapidly and reactivated slowly (in vitro), in the presence of dioxygen (O2) and H2, respectively. However, membranebound [NiFe] hydrogenases (MBHs) sustain their activity even together with O2, which is termed “O2 tolerance”. In previous experimental analyses, an MBH was shown to include a hydroxyl ion (OH−) bound to an Fe of the superoxidized [4Fe-3S]5+ cluster in the proximity of the [NiFe] catalytic cluster. In this study, the functional role of the OH− in the O2 tolerance was investigated by ab initio electronic structure calculation of the [4Fe-3S] proximal cluster. The analysis revealed that the OH− significantly altered the electronic structure, thereby inducing the delocalization of the lowest unoccupied molecular orbital (LUMO) toward the [NiFe] catalytic cluster, which may intermediate the electron transfer between the catalytic and proximal clusters. This can promote the O2-tolerant catalytic cycle in the hydrogenase reaction.