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

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, F 8 Cmpd-II (F 8 = tetrakis(2,6-difluorophenyl)porphyrinate), and a 2,6-lutidinium triflate (LutH + ) Lewis acid adduct involving ferryl O-atom hydrogen-bonding, F 8 Cmpd-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, F 8 Cmpd-II(LutH + ) reacts 40 times faster ( k 2 = 14.2 M -1 s -1 ; -90 °C) than does F 8 Cmpd-II, giving bixanthene plus xanthone and the heme product [F 8 Fe III OH 2 ] + . For substrates with greater C-H bond dissociation energies (BDEs) F 8 Cmpd-II(LutH + ) reacts with the second order rate constants k 2 (9,10-dihydroanthracene; DHA) = 0.485 M -1 s -1 and k 2 (fluorene) = 0.102 M -1 s -1 (-90 °C); by contrast, F 8 Cmpd-II is unreactive toward these substrates. For xanthene vs xanthene-( d 2 ), large, nonclassical deuterium kinetic isotope effects are roughly estimated for both F 8 Cmpd-II and F 8 Cmpd-II(LutH + ). The deuterated H-bonded analog, F 8 Cmpd-II(LutD + ), was also prepared; for the reaction with DHA, an inverse KIE (compared to F 8 Cmpd-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.