Superoxide Oxidation by a Thiolate-Ligated Iron Complex and Anion Inhibition

Superoxide (O₂^•-) is a toxic radical, generated via the adventitious reduction of dioxygen (O₂), which has been implicated in a number of human disease states. Nonheme iron enzymes, superoxide reductase (SOR) and superoxide dismutase (SOD), detoxify O₂^•- via reduction to afford H₂O₂ and disproportionation to afford O₂ and H₂O₂, respectively. The former contains a thiolate in the coordination sphere, which has been proposed to prevent O₂^•- oxidation to O₂. The work described herein shows that, in contrast to this, oxidized thiolate-ligated [Fe^III(S^Me2N₄(tren)(THF)]²⁺ (1-THF) is capable of oxidizing O₂^•- to O₂. Coordinating anions, Cl^- and OAc^-, are shown to inhibit dioxygen evolution, implicating an inner-sphere mechanism. Previously we showed that the reduced thiolate-ligated [Fe^II(S^Me2N₄(tren))]⁺ (1) is capable of reducing O₂^•- via a proton-dependent inner-sphere mechanism involving a transient Fe(III)-OOH intermediate. A transient ferric-superoxo intermediate, [Fe^III(S^Me2N₄(tren))(O₂)]⁺ (3), is detected by electronic absorption spectroscopy at -130 °C in the reaction between 1-THF and KO₂ and shown to evolve O₂ upon slight warming to -115 °C. The DFT calculated O-O (1.306 Å) and Fe-O (1.943 Å) bond lengths of 3 are typical of ferric-superoxo complexes, and the time-dependent DFT calculated electronic absorption spectrum of 3 reproduces the experimental spectrum. The electronic structure of 3 is shown to consist of two antiferromagnetically coupled (J^calc = -180 cm^-1) unpaired electrons, one in a superoxo π*(O-O) orbital and the other in an antibonding π*(Fe(d)-S(p)) orbital.