Relation between coordination geometry and stereoelectronic properties in DFT models of the CO-inhibited [FeFe]-hydrogenase cofactor

In this work DFT has been used to characterize model complexes structurally related to the CO-inhibited form (Hox-CO) of [FeFe]-hydrogenases. The investigation of a recently synthesized diiron complex ([Fe2{MeSCH2C(Me)(CH2S)2}(CN)2(CO)4]−, [M. Razavet, S.J. Borg, S.J. George, S.P. Best, S.A. Fairhurst, C.J. Pickett, Chem. Commun. 2002, 700–701]) that closely reproduces most features of the inhibited enzyme cofactor, led to the conclusion that the computation of DFT energy differences, as well as the comparison between computed and experimental IR and EPR spectra, does not allow to confidently distinguish among isomers differing for the position of CO and CN ligands, an issue which is relevant not only to fully understand the mechanism of CO-mediated inhibition of the enzyme, but more generally to further understand the factors affecting substrates coordination to the enzyme active site. The latter observation prompted us to probe the effect of the electronic properties of ligands on the structural features of a series of [Fe2(SCH2XCH2S)(CN)2(CO)3(L)]n− complexes related to the Hox-CO form of the enzyme but differing for the nature of L (CO, (CH3)2S, CH3S−, CH3O− and F−) and X (CH2, NH and O). Results revealed that the electronic properties of ligands, as well as the nature of the chelating group bridging the two iron atoms, can affect the coordination geometry of the distal metal center. In particular, it turned out that the inclusion of hard ligands in the Fe coordination sphere could be a viable strategy to selectively favour isomers featuring two CO groups trans to each other. On the other hand, the substitution of propanedithiolate with a di(thiomethyl)amine residue led to the selective stabilization of structures featuring a CN ligand in trans to the μ-CO group, thanks to the formation of an intramolecular hydrogen bond. The relevance of these DFT results for the design of novel biomimetic models of the CO-inhibited [FeFe]-hydrogenases active site is discussed.