Why is a proton transformed into a hydride by [NiFe] hydrogenases? An intrinsic reactivity analysis based on conceptual DFT

Abstract

The hydrogen evolution reaction (HER) catalysed by [NiFe] hydrogenases entails a series of chemical events involving great mechanistic interest. In an attempt to understand and delve into the question about ‘Why does nature work in that way?’, an in-depth intrinsic reactivity analysis based on conceptual DFT has been carried out focusing on the so-called I1 to Ni-C step, i.e. our work tries to answer how and why the proton attached to the reactive sulphur atom from one of the exo-cyclic cysteine residues is transformed into a bridging hydride to be shared between the Ni/Fe metals in the active site of [NiFe] hydrogenases, which involves not only H migration, but also a change of the charge state on Ni from Ni(I) to Ni(III). Our DFT results suggest that the transformation is motivated by spontaneous rearrangements of the electron density, and stabilisation comes from the decrease of both electronic activity and electrophilicity index from Ni.