How Geometric Constraints Control the Hydride Position and Activity in [NiFe]-Hydrogenases and Their Biomimetic Complexes

The <b>Ni-R</b> active site in [NiFe]-hydrogenase features a bridging hydride between the Ni and Fe, displaced toward the Ni. However, all synthetic <b>Ni-R</b> models reported to date exhibit a hydride displaced toward Fe and display low turnover frequencies for H₂ evolution. Understanding the factors governing the hydride position and activity of <b>Ni-R</b> and biomimetic complexes is crucial for developing efficient hydrogen-evolving catalysts. By utilizing the CCSD theory, DFT, NBO, and QTAIM analysis, we investigated these factors in a <b>Ni-R</b> active-site model (<b>1</b>), and two representative biomimetic complexes, <b>2*</b> and <b>3</b>. Our results reveal that the Ni site of <b>1</b> inherently prefers a square-planar [S₂NiSH] configuration with an apically positioned thiolate and that hydride positioning is governed by the strength of [Ni-H-Fe] three-center two-electron bonding, which is modulated by the geometric torsion between the Ni terminal ligands and the bridging thiolates. By modifying the linkers between the Ni terminal ligands and bridging thiolate ligands of <b>2*</b> and <b>3</b>, we designed virtual biomimetic complexes (<b>4-10</b>). These complexes exhibit improved hydride nucleophilicity and increased potential for H₂ formation, providing valuable insights into how geometric and electronic factors influence hydride activity and informing the design of more effective biomimetic hydrogenase models.