Which is the real oxidant in competitive ligand self-hydroxylation and substrate oxidation-a biomimetic iron(II)-hydroperoxo species or an oxo-iron(IV)-hydroxy one?

Nonheme iron(II)-hydroperoxo species (Fe-(η-OOH)) 1 and the concomitant oxo-iron(IV)-hydroxyl one 2 are proposed as the key intermediates of a large class of 2-oxoglutarate dependent dioxygenases (, isopenicillin synthase). Extensive biomimetic experiments have been exerted to identify which one is the real oxidant and to reveal the structure-function relationship of them, whereas the mechanistic picture is still elusive. To this end, density functional theory (DFT) calculations were performed to systematically study the mechanistic details of ligand self-hydroxylation and competitive substrate oxidation by these two species supported by a tridentate ligand Fe(Tp)(benzilate) (Tp = hydrotris(3,5-diphenylpyrazole-1-yl)borate). The calculated results revealed that the structure and the conversion of the Fe-(η-OOH) complex 1 are obviously different from the ferric Fe-OOH one. The orientation of the Fe-OOH moiety of 1 is side-on, while that of the ferric Fe-OOH species is end-on. The conversion of 1 to the high-valent iron-oxo species is exothermic, while the conversion of the ferric Fe-OOH species to the high-valent species is endothermic. Thus, the sluggish 1 does not act as the oxidant and readily decays to the robust 2. The activation energy of intramolecular ligand self-hydroxylation in 2 is 14.8 kcal mol and intermolecular substrate oxidations (, thioanisole sulfoxidation) with a lower barrier show a strong inhibiting ability toward ligand self-hydroxylation, while those with a higher barrier (, cyclohexane hydroxylation) have no effect. Our theoretical results fit nicely with the experimental observations and will enrich the knowledge of the metal-oxygen intermediate and play a positive role in the rational design of new biomimetic catalysts.