QM/MM studies of Ni–Fe hydrogenases: the effect of enzyme environment on the structure and energies of the inactive and active states

Abstract

The catalytically active (Ni-SI and Ni-R) and inactive states (Ni-A and Ni-B) of Ni-Fe hydrogenases have been studied using density functional theory (DFT) methods. Both isolated clusters and clusters embedded in the enzyme have been used to model the Ni-A, Ni-B, Ni-SI and Ni-R states. The BP86 and B3LYP functionals were employed, and hybrid quantum mechanical (QM)/molecular mechanical (MM) methods were used for the embedded calculations. The QM/MM studies, rather than the isolated cluster calculations, were generally found to give structures which correlated better with X-ray data. The structure of the unready state (Ni-A), was correctly predicted by the QM/MM, but not by the isolated cluster calculation. Comparison with the observed crystal structure favoured the catalytically active state, Ni-SI, to be the protonated (Ni-SI(II)), rather than the unprotonated state (Ni-SI(I)). In the QM/MM studies, the binding of H(2) to Ni-SI(II) is preferred at the Ni (Ni-R(Ni)), rather than at the Fe centre (Ni-R(Fe)), in agreement with xenon binding studies, and in contrast to isolated cluster studies. These calculations cannot say with certainty which functional should be favoured, nor the preferred spin state of the catalytically active species. However, the lack of any predicted structure in which H(2) binds to the Fe centre, does favour a low spin state for Ni-SI(II), and the use of the BP86 functional. This is in agreement with recent high level ab initio calculations of a model of the Ni-SI(I) state.

Intermediates in the Catalytic Cycle of [NiFe] Hydrogenase: Functional Spectroscopy of the Active Site

“…[95] However, there are studies that have reproduced the experimental FTIR frequencies considering a low-spin (S = 0) nickel centre; [96,97] high level ab initio calculations also predict a singlet state for the Ni-SI r/a states rather than a triplet. [98] Theoretical results are very dependent on the computed ground state and the functionals applied, thus no unique answer has been obtained so far regarding the actual spin state of these EPR-silent states. All models, however, are in agreement with an elongated Ni-Fe distance of 2.8 or greater for this state, which is significantly longer than the one found for the most reduced EPR-silent state, Ni-R, as discussed below.…”

A molecular cage of nickel(ii) and copper(i): a [{Ni(L)2}2(CuI)6] cluster resembling the active site of nickel-containing enzymes

“…[18][19][20][21] Development of model complexes with this kind of NiÁ Á ÁH interaction may help to better understand the mechanistic insights of the [NiFe] hydrogenase and to obtain improved structural and functional mimics. Furthermore, the Ni-m 3 -S-Cu motifs forming the cage in 2 resemble the A-cluster of the CODH/ACS with a low-spin square-planar nickel (Ni d ) and bridging m 3 -thiolates connecting the tetrahedral copper (M p ).…”

Computational Insights into the Reaction Mechanisms of Nickel‐Catalyzed Hydrofunctionalizations and Nickel‐Dependent Enzymes

“…suggested that H 2 binds at the Ni center by using a 290‐atom cluster model . Calculations of another QM‐cluster model (30 atoms) favor the Fe‐binding model, but the QM/MM calculations mainly prefer the Ni‐binding model (except by using B3LYP in the triplet state) . Recently, Ryde and Pierloot performed high‐level quantum‐chemical calculations on the H 2 binding in the active site by using the QM/MM‐optimized geometries .…”