Correction: Hydrogen-activation mechanism of [Fe] hydrogenase revealed by multi-scale modeling

ISSN:2041-6520ISSN:2041-653

Electric-Field Effects on the [FeFe]-Hydrogenase Active Site

The effect of a homogeneous electric field—as exerted by the protein environment and by an electrode potential—on the reactivity of the active site of [FeFe] hydrogenases is unravelled by density functional theory calculations.ISSN:1359-7345ISSN:1364-548

Theoretical ⁵⁷Fe Mössbauer Spectroscopy for Structure Elucidation of [Fe] Hydrogenase Active Site Intermediates

[Fe] hydrogenase is a hydrogen activating enzyme that features a monoiron active site, which can be well characterized by Mössbauer spectroscopy. Mössbauer spectra have been measured of the CO and CN^– inhibited species as well as under turnover conditions [Shima, S. et al., J. Am. Chem. Soc., 2005, 127, 10430]. This study presents calculated Mössbauer parameters for various active-site models of [Fe] hydrogenase to provide structural information about the species observed in experiment. Because theoretical Mössbauer spectroscopy requires the parametrization of observables from <i>first-principles</i> calculations (i.e., electric-field gradients and contact densities) to the experimental observables (i.e., quadrupole splittings and isomer shifts), nonrelativistic and relativistic density functional theory methods are parametrized against a reference set of Fe complexes specifically selected for the application to the Fe center in [Fe] hydrogenase. With this methodology, the measured parameters for the CO and CN^– inhibited complexes can be reproduced. Evidence for the protonation states of the hydroxyl group in close proximity to the active site and for the thiolate ligand, which could participate in proton transfer, is obtained. The unknown resting state measured in the presence of the substrate and under pure H₂ atmosphere is identified to be a water-coordinated complex. Consistent with previous assignments based on infrared and X-ray absorption near-edge spectroscopy, all measured Mössbauer data can be reproduced with the active site’s iron atom being in oxidation state +2

Activation Barriers of Oxygen Transformation at the Active Site of [FeFe] Hydrogenases

Oxygen activation at the active sites of [FeFe] hydrogenases has been proposed to be the initial step of irreversible oxygen-induced inhibition of these enzymes. On the basis of a first theoretical study into the thermodynamics of O₂ activation [<i>Inorg. Chem.</i> <b>2009</b>, 48, 7127] we here investigate the kinetics of possible reaction paths at the distal iron atom of the active site by means of density functional theory. A sequence of steps is proposed to either form a reactive oxygen species (ROS) or fully reduce O₂ to water. In this reaction cascade, two branching points are identified where water formation directly competes with harmful oxygen activation reactions. The latter are water formation by O–O bond cleavage of a hydrogen peroxide-bound intermediate competing with H₂O₂ dissociation and CO₂ formation by a putative iron-oxo species competing with protonation of the iron-oxo species to form a hydroxyo ligand. Furthermore, we show that proton transfer to activated oxygen is fast and that proton supply to the active site is vital to prevent ROS dissociation. If sufficiently many reduction equivalents are available, oxygen activation reactions are accelerated, and oxygen reduction to water becomes possible