Mechanistic insights into axial ligation effects on electron transfer and selective C−H activation catalyzed by iron-oxo analogues

IF 3 3区化学 Q3 CHEMISTRY, PHYSICAL

Computational and Theoretical Chemistry Pub Date : 2025-02-17 DOI:10.1016/j.comptc.2025.115146

Yang Zeng , Xue Jiang , Yujun Si , Lijun Yang

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Abstract

Iron(IV)-oxo porphyrin (Cpd I) is the main catalytically active intermediate in the cytochrome P450 enzymatic cycle. During the C(sp³)-H bond activation, the Cpd I abstracts hydrogen atom from substrate, forming a transient Fe(III)-hydroxo (Cpd II) species and substrate radical. In this study, DFT reported the regioselectivity of CH activation and the effect of axial ligand, using experimentally characterized hemes containing L = none, imidazole, SCH₃, OCH₃, Cl, and CN to simulate no axial ligand, His, Cys, Ser, and inorganic ligands for comparison. The results show that axial ligands can affect the spin density of complex and exhibit lower energy barrier for C2H activation compared to C4H in lidocaine. Ligands OCH₃ and SCH₃ demonstrate superior regioselectivity for C2H activation. For Cpd II, the ligands CN, SCH₃ and OCH₃ are advantageous for C1H abstraction. The findings enhance understanding of the ligand effect in Cpd I and provide novel insights into P450 enzyme catalytic mechanisms.

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来源期刊

Computational and Theoretical Chemistry CHEMISTRY, PHYSICAL-

CiteScore

4.20

自引率

10.70%

发文量

331

审稿时长

31 days

期刊介绍： Computational and Theoretical Chemistry publishes high quality, original reports of significance in computational and theoretical chemistry including those that deal with problems of structure, properties, energetics, weak interactions, reaction mechanisms, catalysis, and reaction rates involving atoms, molecules, clusters, surfaces, and bulk matter.