Heme-Fe^III Superoxide, Peroxide and Hydroperoxide Thermodynamic Relationships: Fe^III-O₂^•- Complex H-Atom Abstraction...

Establishing redox and thermodynamic relationships between metal-ion-bound O₂ and its reduced (and protonated) derivatives is critically important for a full understanding of (bio)chemical processes involving dioxygen processing. Here, a ferric heme peroxide complex, [(F₈)Fe^III-(O₂^2-)]^- () (F₈ = tetrakis(2,6-difluorophenyl)porphyrinate), and a superoxide complex, [(F₈)Fe^III-(O₂^•-)] (), are shown to be redox interconvertible. Using Cr(η-C₆H₆)₂, an equilibrium state where and are present is established in tetrahydrofuran (THF) at -80 °C, allowing determination of the reduction potential of as -1.17 V vs Fc^+/0. could be protonated with 2,6-lutidinium triflate, yielding the low-spin ferric hydroperoxide species, [(F₈)Fe^III-(OOH)] (). Partial conversion of back to using a derivatized phosphazene base gave a / equilibrium mixture, leading to the determination of pK_a = 28.8 for (THF, -80 °C). With the measured reduction potential and pK_a, the O-H bond dissociation free energy (BDFE) of hydroperoxide species was calculated to be 73.5 kcal/mol, employing the thermodynamic square scheme and Bordwell relationship. This calculated O-H BDFE of , in fact, lines up with an experimental demonstration of the oxidizing ability of via hydrogen atom transfer (HAT) from TEMPO-H (2,2,6,6-tetramethylpiperdine-N-hydroxide, BDFE = 66.5 kcal/mol in THF), forming the hydroperoxide species and TEMPO radical. Kinetic studies carried out with TEMPO-H(D) reveal second-order behavior, k_H = 0.5, k_D = 0.08 M^-1 s^-1 (THF, -80 °C); thus, the hydrogen/deuterium kinetic isotope effect (KIE) = 6, consistent with H-atom abstraction by being the rate-determining step. This appears to be the first case where experimentally derived thermodynamics lead to a ferric heme hydroperoxide OO-H BDFE determination, that Fe^III-OOH species being formed via HAT reactivity of the partner ferric heme superoxide complex.