Journal
CHEMICAL RESEARCH IN TOXICOLOGY
Volume 32, Issue 4, Pages 603-612Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrestox.8b00297
Keywords
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Funding
- National Natural Science Foundation of China [21577082, 21507073, 91644214]
- National Major Science and Technology Program for Water Pollution Control and Treatment [2017ZX07202-002]
- Young Scholars Program of Shandong University [2018WLJH54]
- Taishan Scholars [ts201712003]
- Shenzhen science and technology research and development funds [JCYJ20160510165106371]
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The metabolic activation and transformation of naphthalene by the cytochrome P450 enzyme (CYP 1B1) plays an important role in its potential carcinogenicity. The process has been explored by a quantum mechanics/molecular mechanics (QM/MM) computational method. Molecular dynamic simulations were performed to explore the interaction between naphthalene and CYP 1B1. Naphthalene involves alpha- and beta-carbon, the electrophilic addition of which would result in different reaction pathways. Our computational results show that both additions on alpha- and beta-carbon can generate naphthalene 1,2-oxide. The activation barrier for the addition on beta-carbon is higher than that for the alpha-carbon by 2.6 kcal.mol(-1), which is possibly caused by the proximity between beta-carbon and the iron-oxo group of Cpd I in the system. We also found that naphthalene 1,2-oxide is unstable and the O-C bond cleavage easily occurs via cellular hydronium ion, hydroxyl radical/anion; then it will convert to the potential ultimate carcinogen 1,2-naphthoquinone. The results demonstrate and inform a detailed process of generating naphthalene 1,2-oxide and new predictions for its conversion.
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