Li Ji

Cytochrome P450 enzymes are highly versatile biological catalysts in our body that react with a broad range of substrates. Key functions in the liver include the metabolism of drugs and xenobiotics. One particular metabolic pathway that is poorly understood relates to the P450 activation of aliphatic groups leading to either hydroxylation or desaturation pathways. A DFT and QM/MM study has been carried out on the factors that determine the regioselectivity of aliphatic hydroxylation over desatur

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimple syntheses and alkylation reactions of 3-iodo-o-carborane and 9,12-diiodo-o-carboraneJi Li, Cameron F. Logan, and Maitland Jones Jr.Cite this: Inorg. Chem. 1991, 30, 25, 4866–4868Publication Date (Print):December 1, 1991Publication History Published online1 May 2002Published inissue 1 December 1991https://pubs.acs.org/doi/10.1021/ic00025a037https://doi.org/10.1021/ic00025a037research-articleACS PublicationsRequest reuse permissionsArticle Views10

Only one path applies: to date, five different mechanisms have been suggested for the P450-catalyzed N-hydroxylation of primary aromatic amines. Computational analysis employing density functional theory demonstrates that only the H-atom-transfer pathway, that is H abstraction from an amine N followed by a radical rebound step, on a low-spin route can contribute to the aromatic hydroxylamine formation.

Understanding metabolic mechanisms is critical and remains a difficult task in the risk assessment of emerging pollutants. Triphenyl phosphate (TPHP), a widely used aryl phosphorus flame retardant (aryl-PFR), has been frequently detected in the environment, and its major metabolite was considered as diphenyl phosphate (DPHP). However, knowledge of the mechanism for TPHP leading to DPHP and other metabolites is lacking. Our in vitro study shows that TPHP is metabolized into its diester metabolite

Understanding the bioactivation mechanisms to predict toxic metabolites is critical for risk assessment of phenolic endocrine-disrupting chemicals (EDCs). One mechanism involves ipso-substitution, which may contribute to the total turnover of phenolic EDCs, yet the detailed mechanism and its relationship with other mechanisms are unknown. We used density functional theory to investigate the P450-catalyzed ipso-substitution mechanism of the prominent xenoestrogen bisphenol A. The ipso-substitutio

Phenols are ubiquitous environmental pollutants, whose biotransformation involving phenol coupling catalyzed by cytochromes P450 may produce more lipophilic and toxic metabolites. Density functional theory (DFT) computations were performed to explore the debated phenol-coupling mechanisms, taking triclosan as a model substrate. We find that a diradical pathway facilitated by compound I and protonated compound II of P450 is favored vs alternative radical addition or electron-transfer mechanisms.

Verbascoside is a natural antioxidant extracted from Pedicularis striata Pall (Jueyehesen). After being treated with 20 mumol/l verbascoside, the growth curve and mitotic index of human gastric adenocarcinoma MGc80-3 cells decreased remarkably, cell doubling time was delayed, the cellular growth inhibitory rate amounted to 53.2%, cell surface charge assayed by cell electrophoresis obviously changed, the electrophoresis rate dropped from 3.51 microns/s/v/cm to 2.74, i.e., the percent of retardati

The mutagenic and carcinogenic potency of α-CH(n)-nitrosamines such as N-nitrosodimethylamine (NDMA) is caused by their P450-catalyzed α-hydroxylation and subsequent dealkylation, yielding alkyl diazonium ions (R-N≡N(+)) as potent electrophiles. Alternatively, P450s may also catalyze their denitrosation as metabolic detoxification. DFT calculations at the UB3LYP/LANL2DZ(Fe)/6-31G+**(H,C,N,O,S)//LANL2DZ(Fe)/6-31G(H,C,N,O,S) level of theory show that H-abstraction from the α-C of NDMA as initial m

Reductive dehalogenation involving cobalamin has been proved to be a promising strategy for decontamination of the polluted environment. However, cob(I)alamin can act both as a strong reductant and a powerful nucleophile, and thus, several competing dehalogenation pathways may be involved. This work uses experimentally calibrated density functional theory on a realistic cobalamin model to resolve controversies of cobalamin-mediated reduction of chloroethylenes by exploring mechanisms of electron

Precision biotransformation is an envisioned strategy offering detailed insights into biotransformation pathways in real environmental settings using experimentally guided high-accuracy quantum chemistry. Emerging pollutants, whose metabolites are easily overlooked but may cause idiosyncratic toxicity, are important targets of such a strategy. We demonstrate here that complex metabolic reactions of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) catalyzed by human CYP450 enzymes can be mapped via

Metabolism, especially by CYP450 enzymes, is the main reason for mediating the toxification and detoxification of xenobiotics in humans, while some uncommon metabolic pathways, especially for emerging pollutants, probably causing idiosyncratic toxicity are easily overlooked. The pollution of sulfonamide antibiotics in aqueous system has attracted increasing public attention. Hydroxylation of the central amine group can trigger a series of metabolic processes of sulfonamide antibiotics in humans;

Abstract For the exploration of the intrinsic reactivity of two key active species in the catalytic cycle of horseradish peroxidase (HRP), Compound I (HRP‐I) and Compound II (HRP‐II), we generated in situ [Fe IV O(TMP +. )(2‐MeIm)] + and [Fe IV O(TMP)(2‐MeIm)] 0 (TMP=5,10,15,20‐tetramesitylporphyrin; 2‐MeIm=2‐methylimidazole) as biomimetics for HRP‐I and HRP‐II, respectively. Their catalytic activities in epoxidation, hydrogen abstraction, and heteroatom oxidation reactions were studied in ace