Heme-FeIII Superoxide, Peroxide and Hydroperoxide Thermodynamic Relationships: FeIII-O2 •– Complex H‑Atom Abstraction Reactivity

• Published in: Journal of the American Chemical Society 2020-02, Vol.142 (6), p.3104-3116
• Main Authors: Kim, Hyun, Rogler, Patrick J, Sharma, Savita K, Schaefer, Andrew W, Solomon, Edward I, Karlin, Kenneth D
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.9b12571

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)­FeIII-(O2 2–)]− ( P ) (F8 = tetrakis­(2,6-difluorophenyl)­porphyrinate), and a superoxide complex, [(F8)­FeIII-(O2 •–)] ( S ), are shown to be redox interconvertible. Using Cr­(η-C6H6)2, an equilibrium state where S and P are present is established in tetrahydrofuran (THF) at −80 °C, allowing determination of the reduction potential of S as −1.17 V vs Fc+/0. P could be protonated with 2,6-lutidinium triflate, yielding the low-spin ferric hydroperoxide species, [(F8)­FeIII-(OOH)] ( HP ). Partial conversion of HP back to P using a derivatized phosphazene base gave a P / HP equilibrium mixture, leading to the determination of pK a = 28.8 for HP (THF, −80 °C). With the measured reduction potential and pK a, the O–H bond dissociation free energy (BDFE) of hydroperoxide species HP was calculated to be 73.5 kcal/mol, employing the thermodynamic square scheme and Bordwell relationship. This calculated O–H BDFE of HP , in fact, lines up with an experimental demonstration of the oxidizing ability of S 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 HP 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 S 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 FeIII-OOH species being formed via HAT reactivity of the partner ferric heme superoxide complex.