Modeling Heme Peroxidase: Heme Saddling Facilitates Reactions with Hyperperoxides To Form High-Valent FeIV-Oxo Species

Saddle-shaped hemes have been discovered in the structures of most peroxidases. How such a macrocycle deformation affects the reaction of Fe^III hemes with hydrogen peroxide (H₂O₂) to form high-valent Fe-oxo species remains uncertain. Through examination of the ESI-MS spectra, absorption changes and ¹H NMR chemical shifts, we investigated the reactions of two Fe^III porphyrins with different degrees of saddling deformation, namely Fe^III(OETPP)ClO₄ ( 1^OE ) and Fe^III(OMTPP)ClO₄ ( 1^OM ), with tert-butyl hydroperoxide (tBuOOH) in CH₂Cl₂ at ?40 °C, which quickly resulted in O?O bond homolysis from a highly unstable Fe^III-alkylperoxo intermediate, Fe^III-O(H)OR ( 2 ) into Fe^IV-oxo porphyrins ( 3 ). Insight into the reaction mechanism was obtained from tBuOOH]-dependent kinetics. At ?40 °C, the reaction of 1^OE with tBuOOH exhibited an equilibrium constant (K_a=362.3 M^?1) and rate constant (k=1.87×10^?2 s^M?>1) for the homolytic cleavage of the 2 O?O bond that were 2.1 and 1.4 times higher, respectively, than those exhibited by 1^OM (K_a=171.8 M^?1 and k=1.36×10^?2 s^?1). DFT calculations indicated that an Fe^III porphyrin with greater saddling deformation can achieve a higher HOMO (Fe(d ,d )-porphyrin(a_2u)]) to strengthen the orbital interaction with the LUMO (O?O bond σ*) to facilitate O?O cleavage.