Tetrad or triad? insights from a versatile Fe(ii) structural and functional model of the 3-histidine 1-carboxylate tetrad in C–C bond cleaving dioxygenase enzymes

Abstract

A new N₃O coordinate ferrous complex modeling the 3-histidine-1-carboxylate tetrad – a dioxygenase active site – was synthesized and crystallographically characterized, ([Fe(II)(N-(ethyl-N′Me2)(Py)(2-t-ButPhOH))(OTf)]), 1. Complex 1 displays versatile C–C bond cleavage activity towards 2-hydroxyacetophenone, 3-hydroxyflavone, and 3,3-dihydroxypentan-2,4-dione in the presence of O₂. This reactivity was studied through UV-vis and NMR spectroscopy alongside DFT calculations. The latter suggests that 1 forms an Fe(III)O₂ adduct during the oxidation of 2-hydroxyacetophenone. Additionally, 1 displays direct activation of O₂ in the absence of substrate, allowing it to access reactivity akin to more traditional N₂O enzymatic coordination motifs. This versatility points to the need to reconsider mechanisms in N₃O coordinate enzymatic systems and biomimetic models thereof. Moreover, this research makes the case that carefully designed N₃O complexes merit further investigation as functional mimics of the canonical non-heme iron dioxygenase enzyme coordination environment.