Theoretical Study On Catalytic Oxidation Of Aromatic C-H Bond By P450 Active Center

The oxidation reaction of arenes has attracted extensive attention because the products have important industrial value.Theα-C-H bond in the arene side chain can be selectively oxidized to generate aromatic alcohol,and aromatic C-H bond in the benzene ring can also be selectively oxidized to produce phenol.Cytochrome P450can realize the selective catalytic oxidation of C-H bond in arenes under mild conditions.At present,the oxidation of C-H bond in arenes catalyzed by P450 has been studied using experimental and theoretical methods.But the effects of arenes structure and P450 active center structure on the reactivity need to be further studied.In this dissertation,the oxidation reaction of theα-C-H bond in the arene side chain and the aromatic C-H bond in the benzene ring catalyzed by P450 active center were studied using density functional theory.The effects of arenes substituents and P450axial ligand on the reactivity were discussed and the essential factors affecting the reactivity were clarified.The research contents and conclusions are mainly divided into the following three parts:1.The oxidations of theα-C-H bond in o-and p-nitro-substituted arenes catalyzed by P450 active center were studied using density functional theory.By calculating the bond dissociation energy of theα-C-H bond and the activation energy of theα-C-H bond oxidation in arenes by high-valent iron-oxo porphyrin,the reactivity difference between o-nitro-substituted arenes and p-nitro-substituted arenes was investigated.The results show that the conjugation effect between nitro and benzene ring in p-nitro-substituted arenes reduces the bond dissociation energy of theα-C-H bond and the activation energy of theα-C-H bond oxidation by high-valent iron-oxo porphyrin is low.In o-nitro-substituted arenes,there are not only conjugation effect,but also steric hindrance effect.The steric hindrance effect is dominant in o-nitro-substituted arenes.The bond dissociation energy of theα-C-H bond and the activation energy of theα-C-H bond oxidation by high-valent iron-oxo porphyrin increase due to the steric hindrance effect.The distortion of the arene molecule is the main factor affecting the reactivity of theα-C-H bond oxidation of arenes.2.The o-hydroxylation of anisole and nitrobenzene catalyzed by P450 active center were studied using density functional theory.The effect of methoxy and nitro groups on the o-hydroxylation were investigated by calculating the potential energy profile of the whole reaction and analyzing the geometric and electronic properties of the intermediates and transition structures in the reaction.The results show that the activation of aromatic C-H bond in benzene ring is the rate determining step of the whole reaction.The energy barrier of aromatic C-H bond activation in nitrobenzene is higher than that of anisole,and the difference of activation energy mainly comes from the higher distortion energy of nitrobenzene molecule.There is free energy barrier or have lower energy barrier in the process of proton shuttle and proton rebound.The intermediates produced by anisole is more conducive to performing proton shuttle and proton rebound reaction and finally producing phenolic compounds because of the stronger electrostatic interaction.3.The oxidation of p-xylene by high-valent iron-oxo porphyrins with different axial ligands（SH^-,Cl^-,F^-,CH₃CN）were studied using density functional theory.The effects of axial ligands on the hydroxylation of p-xylene catalyzed by P450 active center were investigated by analyzing the structure properties of high-valent iron-oxo porphyrins with different axial ligands and the reaction activation energy of theα-C-H bond hydroxylation and aromatic C-H bond hydroxylation of p-xylene.Compared with anionic axial ligands（SH^-,Cl^-and F^-）,neutral axial ligand CH₃CN can better enhance the radical characteristics of active oxygen atom and electronic capability of high-valent iron-oxo porphyrin,and further improve the oxidation reactivity of theα-C-H bond hydroxylation and aromatic C-H bond hydroxylation of p-xylene by high-valent iron-oxo porphyrins.