Affiliation:
1. Department of Applied Chemistry Kyung Hee University Yongin‐si Gyeonggi‐do Republic of Korea
Abstract
AbstractHydrogen abstraction is essential for CH bond activation by Compound I in cytochrome P450 and is influenced by various factors, including spin states, bond dissociation energies of the CH and FeOH bonds, axial ligands, and quantum mechanical tunneling. The role of axial ligands has been extensively studied, but it is still not fully understood. To explore their role, we used density functional theory calculations to determine whether a linear free energy relationship is established for the hydrogen transfer reaction, according to changes in axial ligands. The B3LYP* functional exhibits a strong linear correlation, but the slopes are inconsistent with the characteristics of the transition state. Natural bond orbital analysis reveals no direct orbital interaction between axial ligands and the reaction center of hydrogen transfer. The electron‐donating orbitals of the axial ligands weaken the FeO bond, lowering the energy barrier, but they do not directly participate in the intrinsic hydrogen transfer. During the reaction, the FeO bond length increases significantly before the hydrogen transfer itself, generating an asynchronous shift in the bond orders, and most of the activation energy is used for the increase in the FeO bond rather than the hydrogen transfer itself. This study may explain why there is no apparent correlation between the rate constants and the FeO bond strength.