Premium
Quantum chemical metabolism‐based simulation of carcinogenic potency of benzene derivatives
Author(s) -
D'Yachkov Pavel N.,
Kharchevnikova Nina V.,
Zholdakova Zoya I.,
Fjodorova Nathalia,
Novich Mariana,
Vrachko Marian
Publication year - 2010
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.22226
Subject(s) - chemistry , carcinogen , nitro , mndo , benzene , medicinal chemistry , molecule , stereochemistry , computational chemistry , organic chemistry , alkyl
Abstract Using an oxenoid model, we investigated dependences of carcinogenic potency of the benzenes C 6 H 5 ‐X on a nature of substituents X. According to the model, a P450 enzyme breaks a dioxygen molecule and generates the oxens, which readily react with substrates. We suggest that a stability of the intermediate OC 6 H 6 ‐X with tetrahedrally coordinated C atom relative to the molecule C 6 H 5 ‐X determines a rate of substrate biotransformation. Using MO LCAO MNDO approach, we calculated the total energies of molecules C 6 H 6 ‐X and arene oxides OC 6 H 6 ‐X. A difference Δ E min of these values determines activation energy of oxidation reaction. The compounds with the low Δ E min values are noncarcinogenic. Benzene derivatives with high Δ E min values belong to carcinogenic compounds series. The carcinogenicity of amino‐ and nitro‐substituted benzenes is also determined by N‐oxidation of amino and reduction of the nitro group. As the phenylhydroxylamines XC 6 H 4 NHOH and nitrenium ions XC 6 OH 4 NH + are the common metabolites of the nitro‐ and amino‐substituted benzenes and nitrenium ions XC 6 H 4 NH + are the ultimate carcinogens, we use the differences Δ E N = E (XC 6 H 4 NH + ) − E (XC 6 H 4 NHOH) as the second parameter characterizing the carcinogenic activity of amino‐ and nitro‐substituted benzenes. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010