Amino and hydroxy substitution in fluences pyrene-DNA binding

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 K-A) from 4.14 L mol(-1) to 12.31 L mol(-1), while -OH substitution inhibited binding by reducing log K-A 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 (K-SV) 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. (C) 2020 Elsevier B.V. All rights reserved.