Amino and hydroxy substitution influences pyrene–DNA binding

Abstract

Polycyclic aromatic hydrocarbon (PAH)–DNA binding is an essential step in PAH-induced carcinogenesis. A large number of PAHs contain substituents, it is unclear whether functional groups will influence the PAH–DNA binding. Here, we investigated amino (-NH2) and hydroxy (-OH) substitution on pyrene–DNA binding. Because of the considerable effects of electrostatic surface potential (ESP), -NH2 substitution significantly facilitated binding by increasing the binding constant (log KA) from 4.14 L mol−1 to 12.31 L mol−1, while -OH substitution inhibited binding by reducing log KA to 3.68 L mol−1. Spectroscopy results revealed that pyrene and its derivatives were able to bind with thymine to induce DNA damage or double helix distortion. Quantum chemical calculations showed that -NH2 substitution induces hydrogen bond formation, thereby enhancing the binding of pyrene with DNA; moreover, binding force changes due to -OH substitution may not be an essential factor. All structural descriptors were not correlated with the quenching constant (KSV) or binding constant, indicating that changes in physicochemical properties shows no influence on pyrene–DNA binding. The results of this study will improve our understanding of the contribution of functional groups to PAH–DNA binding.