Reaction Mechanism of Compound I Formation in Heme Peroxidases: A Density Functional Theory Study

The mechanisms for O−O bond breaking in heme peroxidases have been studied using hybrid density functional theory (DFT-B3LYP). The chemical model used to study the reaction includes both the distal and the proximal imidazole. The reaction starts with the transfer of a proton from the peroxide to the distal imidazole, which is found to occur without any barrier using the present model. In the next step, the proton is donated back from the histidine to the other oxygen of the peroxide, with a simultaneous breaking of the O−O bond of the peroxide. This part of the reaction is found to be quite complicated with involvement of three different potential surfaces. The transition state is found to be determined by a crossing between two of these surfaces. The calculated barrier, as determined by the crossing point using a frozen reaction coordinate, is 10.4 kcal/mol, which is in reasonable agreement with the experimental barrier height of 6.5 kcal/mol. After passage of the barrier, compound I is formed. This comp...