Interplay between two degenerate spin state determines the hydroxylation of 4-nitrophenol catalyzed via Cytochrome P450

• Published in: Inorganic chemistry communications Vol. 132; p. 108857
• Main Authors: Awasthi, Nidhi, Yadav, Rolly, Shukla, Anamika, Kumar, Devesh
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2021
• Subjects: Basis set; Cytochrome P450; Density Functional Theory; Metalloenzyme; Basis set; Metalloenzyme; Cytochrome P450; Density Functional Theory
• ISSN: 1387-7003; 1879-0259
• DOI: 10.1016/j.inoche.2021.108857

[Display omitted] •Aromatic hydroxylation of 4-nitrophenol with P450 at ortho position has been reported.•All energies of reactant complex, transition state, intermediate state, product complex are calculated by using DFT method with basis set 6-31G/b3lyp.•Rate determining steps with high and low spin surfaces are calculated.•At the low spin surface a suicidal complex is formed.•The reaction mechanism shows spin selective path with single state reactivity (SSR). 4-Nitrophenol is formed during the synthesis of paracetamol. It is used in various xenobiotic metabolism processes and other essential biochemical processes. It is metabolized via cytochrome P450 enzyme. The present work reported the hydroxylations of 4-nitrophenol at the ortho position by Cytochrome P450 metalloenzyme. Truncated model of putative active oxidant i.e. ferryl oxo porphyrin cation radical [FeIV(O)(heme+)], referred as Cpd I in cytochrome P450 enzymes has been used to mimic the behavior of enzyme. In the current investigations, 4-nitrophenol (Substrate) is modeled with Cpd I and reaction mechanism for two degenerate spin states named as doublet (LS) and quartet (HS) is performed to dwell the overall potential energy landscape, along with electronic structures and properties of reactant complex (RC), transition states (TS), intermediates (IM) and product complex (PC). The reaction is stepwise with electrophillic addition as the rate determining step, spin selectivity product formation is observed only at high spin (HS) surface. So, the present reaction pathway is single state reactivity (SSR) by forming the suicidal complex at low spin state (LS).