Enhanced Rates of C-H Bond Cleavage by a Hydrogen-Bonded Synthetic Heme High-Valent Iron(IV) Oxo Complex

Abstract

Secondary coordination sphere interactions are critical in facilitating the formation, stabilization, and enhanced reactivity of high-valent oxidants required for essential biochemical processes. Herein, we compare the C-H bond oxidizing capabilities of spectroscopically characterized synthetic heme iron(IV) oxo complexes, F₈Cmpd-II (F₈ = tetrakis(2,6-difluorophenyl)porphyrinate), and a 2,6-lutidinium triflate (LutH⁺) Lewis acid adduct involving ferryl O-atom hydrogen-bonding, F₈Cmpd-II(LutH⁺). Second-order rate constants utilizing C-H and C-D substrates were obtained by UV-vis spectroscopic monitoring, while products were characterized and quantified by EPR spectroscopy and gas chromatography (GC). With xanthene, F₈Cmpd-II(LutH⁺) reacts 40 times faster (k₂ = 14.2 M^-1 s^-1; -90 °C) than does F₈Cmpd-II, giving bixanthene plus xanthone and the heme product [F₈Fe^IIIOH₂]⁺. For substrates with greater C-H bond dissociation energies (BDEs) F₈Cmpd-II(LutH⁺) reacts with the second order rate constants k₂(9,10-dihydroanthracene; DHA) = 0.485 M^-1 s^-1 and k₂(fluorene) = 0.102 M^-1 s^-1 (-90 °C); by contrast, F₈Cmpd-II is unreactive toward these substrates. For xanthene vs xanthene-(d₂), large, nonclassical deuterium kinetic isotope effects are roughly estimated for both F₈Cmpd-II and F₈Cmpd-II(LutH⁺). The deuterated H-bonded analog, F₈Cmpd-II(LutD⁺), was also prepared; for the reaction with DHA, an inverse KIE (compared to F₈Cmpd-II(LutH⁺)) was observed. This work originates/inaugurates experimental investigation of the reactivity of authentic H-bonded heme-based Fe^IV═O compounds, critically establishing the importance of oxo H-bonding (or protonation) in heme complexes and enzyme active sites.