Abstract：
Polycyclic aromatic hydrocarbons (PAHs) are potent inhibitors of DNA that can induce genetic damage, abnormal gene expression, and metabolic disorders upon interfacing with biological macromolecules. However, the mechanism of their interactions with DNA remains elusive. Therefore, this study selected three representative PAHs, including phenanthrene (Phen), pyrene (Pyre), and benzo[a]pyrene (B[a]P), and explored their binding mechanisms with the double-strand DNA (dsDNA) from different species, including 1J1V (Escherichia coli), 6J5B (Arabidopsis thaliana), and 6Q1V (Homo sapiens). The results revealed that binding between PAHs and dsDNA occurred in the groove via van der Waals forces and π-π stacking, with the carboxyl oxygen atom of the thymine (T)-base within dsDNA being the key binding site. This result was further confirmed by the spectroscopic experiments, where significant changes in the peak of the T-base were observed after PAHs-dsDNA binding. More interestingly, the total binding energies of Pyre with the three dsDNA were -138.800 kJ/mol (Pyre-1J1V), -105.523 kJ/mol (Pyre-6J5B), and -127.567 kJ/mol (Pyre-6Q1V), respectively, all of which were higher than those of Phen and B[a]P. This suggests that that Pyre has the strongest dsDNA binding ability. Additionally, analysis of the thermodynamic parameters indicated that the interactions between the three PAHs and dsDNA were exothermic reactions. In contrast, the Pyre-dsDNA interaction predominantly involved van der Waals forces and hydrogen bonding due to the enthalpy change (∆H) < 0 and entropy change (∆S) < 0, while the Phen-dsDNA and B[a]P-dsDNA interactions predominantly involved hydrophobic forces due to ∆H > 0 and ∆S > 0. Furthermore, Pyre caused local distortion of dsDNA, which was more pronounced under atomic force microscopy (AFM). In summary, this study has unveiled a new phenomenon of binding between PAHs and dsDNA. This sheds light on the carcinogenic potential and environmental impacts of PAHs pollution.
摘要：
多环芳烃（PAHs）是DNA的有效抑制剂，可以诱导遗传损伤，异常基因表达，与生物大分子相互作用时的代谢紊乱。然而,它们与DNA相互作用的机制仍然难以捉摸。因此,本研究选择了三种有代表性的多环芳烃，包括菲（Phen），芘(Pyre),和苯并[a]芘(B[a]P)，并探索了它们与来自不同物种的双链DNA（dsDNA）的结合机制，包括1J1V（大肠杆菌），6J5B（拟南芥），和6Q1V（智人）。结果表明，PAHs与dsDNA之间的结合通过范德华力和π-π堆叠发生在凹槽中，dsDNA中胸腺嘧啶(T)-碱基的羧基氧原子是关键结合位点。光谱实验进一步证实了这一结果，其中在PAHs-dsDNA结合后观察到T碱基峰的显著变化。更有趣的是，Pyre与三个dsDNA的总结合能为-138.800kJ/mol（Pyre-1J1V），-105.523kJ/mol(Pyre-6J5B),和-127.567kJ/mol（Pyre-6Q1V），分别,所有这些都高于Phen和B[a]P。这表明Pyre具有最强的dsDNA结合能力。此外,热力学参数分析表明，三种PAHs与dsDNA之间的相互作用是放热反应。相比之下,Pyre-dsDNA相互作用主要涉及范德华力和氢键，这是由于焓变（ΔH）<0和熵变（ΔS）<0，而Phen-dsDNA和B[a]P-dsDNA相互作用主要涉及疏水性力，这是由于ΔH>0和ΔS>0。此外，Pyre导致dsDNA局部失真,在原子力显微镜（AFM）下更为明显。总之,这项研究揭示了PAHs与dsDNA结合的新现象。这揭示了PAHs污染的致癌潜力和环境影响。
