In Silico study of carcinogenic o‐Quinone metabolites derived from polycyclic aromatic hydrocarbons (PAHs)

A computational density functional theory study on the structural and electronic properties of several polycyclic aromatic hydrocarbon (PAH) ortho‐quinones was performed and the possible mechanism of DNA‐adduct formation was analyzed to evaluate its thermodynamic viability. Molecular docking techniques were applied to examine the noncovalent interactions developed when a model PAH ortho‐quinone intercalates between the DNA double helix. Quantum‐chemical ONIOM (our Own N‐layer Integrated molecular Orbital molecular Mechanics) calculations within the structure of a DNA fragment were carried out to evaluate the significant steps of noncovalent complex and covalent adduct formation. The solvent effect was also considered by employing a continuum solvation model. The present calculations suggest that initial noncovalent interactions of the PAH o‐quinone within the DNA double helix could determine the feasibility of benzo[a]pyrene‐7,8‐dione‐DNA covalent adduct formation, and that dispersion‐corrected functionals are more suitable for locating the noncovalent complex. Copyright © 2012 John Wiley & Sons, Ltd.