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

Abstract

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 (H₂ O₂ ) to form high-valent Fe-oxo species remains uncertain. Through examination of the ESI-MS spectra, absorption changes and ¹ H 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 CH₂ Cl₂ 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 ${}_{z{}^2}$ ,d ${}_{x{}^2-y{}^2}$ )-porphyrin(a_2u )]) to strengthen the orbital interaction with the LUMO (O-O bond σ*) to facilitate O-O cleavage.

Keywords: O−O bond homolysis; heme; high-valent iron-oxo; peroxidases; saddle-shaped porphyrins.