# Reaction Mechanism of [NiFe] Hydrogenase Studied by Computational Methods.
> [NiFe]ヒドロゲナーゼの反応機構に関する計算化学的解析


## Abstract

The catalytic mechanism of [NiFe] hydrogenase, which reversibly converts molecular hydrogen into protons and electrons, was examined using multiple computational approaches. Structural geometries were derived from QM/MM calculations, while energetics were refined through large-scale QM computations encompassing 819 atoms. Free energies were estimated via QM/MM thermodynamic cycle perturbation, and electronic structures of intermediate states were characterized by DMRG-CASSCF methods. The results indicate that the Ni-L intermediate does not participate in the catalytic cycle. Rather, one-electron reduction of the Ni-C state triggers transfer of the bridging hydride to the sulfur of Cys546 as a proton, with simultaneous two-electron transfer to the Ni center. This step constitutes the rate-determining barrier at 58 kJ/mol, consistent with the experimentally measured rate of 750 ± 90 s⁻¹ (~52 kJ/mol). H–H bond cleavage proceeds with a comparatively low barrier of 33 kJ/mol. Reaction energies were found to depend on QM region size, basis set selection, and the choice of density functional.

### Mechanism

Following one-electron reduction of the Ni-C state, the bridging hydride transfers as a proton to Cys546 sulfur while two electrons migrate to the Ni ion; this constitutes the rate-limiting step at 58 kJ/mol. H–H bond cleavage occurs with a lower barrier of 33 kJ/mol.

## Bibliographic

- **Authors**: Dong G, Phung QM, Pierloot K, Ryde U
- **Journal**: Inorg Chem
- **Year**: 2018 (2018-12-17)
- **PMID**: [30500163](https://pubmed.ncbi.nlm.nih.gov/30500163/)
- **DOI**: [10.1021/acs.inorgchem.8b02590](https://doi.org/10.1021/acs.inorgchem.8b02590)
- **Study type**: other
- **Delivery route**: not specified
- **Effect reported**: not assessed

## Delivery context

The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)

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> **Cite as**: H2 Papers — PMID 30500163. https://h2-papers.org/en/papers/30500163
> **Source**: PubMed PMID [30500163](https://pubmed.ncbi.nlm.nih.gov/30500163/)