The roles of chalcogenides in O₂ protection of H₂ase active sites

At some point, all HER (Hydrogen Evolution Reaction) catalysts, important in sustainable H₂O splitting technology, will encounter O₂ and O₂-damage. The [NiFeSe]-H₂ases and some of the [NiFeS]-H₂ases, biocatalysts for reversible H₂ production from protons and electrons, are exemplars of oxygen tolerant HER catalysts in nature. In the hydrogenase active sites oxygen damage may be extensive (irreversible) as it is for the [FeFe]-H₂ase or moderate (reversible) for the [NiFe]-H₂ases. The affinity of oxygen for sulfur, in [NiFeS]-H₂ase, and selenium, in [NiFeSe]-H₂ase, yielding oxygenated chalcogens results in maintenance of the core NiFe unit, and myriad observable but inactive states, which can be reductively repaired. In contrast, the [FeFe]-H₂ase active site has less possibilities for chalcogen-oxygen uptake and a greater chance for O₂-attack on iron. Exposure to O₂ typically leads to irreversible damage. Despite the evidence of S/Se-oxygenation in the active sites of hydrogenases, there are limited reported synthetic models. This perspective will give an overview of the studies of O₂ reactions with the hydrogenases and biomimetics with focus on our recent studies that compare sulfur and selenium containing synthetic analogues of the [NiFe]-H₂ase active sites.