Amino, nitro, chloro, hydroxyl and methyl substitutions may inhibit the binding of PAHs with DNA

Abstract

The binding of PAHs with DNA to form PAH-DNA adducts is a crucial step in PAH-induced carcinogenesis. How functional groups affect this binding is largely unknown. Here, we observed that functional group substitutions strongly inhibited PAH-DNA binding. Additionally, -OH substitution has the most potent inhibitory effect as it causes the smallest change in the electrostatic surface potential. Fourier transform infrared spectroscopy and molecular docking analyses demonstrated that PAH derivatives bind with guanine via intercalation and groove binding and then non-specifically insert into the major/minor grooves of DNA. Quantum chemical calculations suggested that hydrogen/halogen bonding may be essential in affecting the binding of functional group-substituted PAHs with DNA. It was further revealed that Log K_OA and the PAH derivatives' melting points correlated significantly with binding affinity, implying that changes in the physicochemical characteristics are important factors. This study opens a new window for understanding the relationship between highly toxic PAH derivatives and genetic materials.

Keywords: Binding; Computational chemistry; DNA; Functional groups; Polycyclic aromatic hydrocarbons.