Modeling Heme Peroxidase: Heme Saddling Facilitates Reactions with Hyperperoxides To Form High-Valent Fe IV -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 (H 2 O 2 ) 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)ClO 4 (1 OE ) and Fe III (OMTPP)ClO 4 (1 OM ), with tert-butyl hydroperoxide (tBuOOH) in CH 2 Cl 2 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.