1 research outputs found
Regioselectivity of H Cluster Oxidation
The H<sub>2</sub>-evolving potential of [FeFe] hydrogenases is severely limited by the oxygen sensitivity of this class of enzymes. Recent experimental studies on hydrogenase from C. reinhardtii point to O<sub>2</sub>-induced structural changes in the [Fe<sub>4</sub>S<sub>4</sub>] subsite of the H cluster. Here, we investigate the mechanistic basis of this observation by means of density functional theory. Unexpectedly, we find that the isolated H cluster shows a pathological catalytic activity for the formation of reactive oxygen species such as O<sub>2</sub><sup>β</sup> and HO<sub>2</sub><sup>β</sup>. After protonation of O<sub>2</sub><sup>β</sup>, an OOH radical may coordinate to the Fe atoms of the cubane, whereas H<sub>2</sub>O<sub>2</sub> specifically reacts with the S atoms of the cubane-coordinating cysteine residues. Both pathways are accompanied by significant structural distortions that compromise cluster integrity and thus catalytic activity. These results explain the experimental observation that O<sub>2</sub>-induced inhibition is accompanied by distortions of the [Fe<sub>4</sub>S<sub>4</sub>] moiety and account for the irreversibility of this process