Departamento de Química Física, Universidad de Murcia Murcia, Spain.
Chimie et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR Centre National de la Recherche Scientifique, Université de Nantes Nantes, France ; Institut Universitaire de France Paris, France.
Front Chem. 2015 Mar 6;3:13. doi: 10.3389/fchem.2015.00013. eCollection 2015.
We investigate the attack of the nitrogen dioxide radical (NO(•) 2) to the guanine-cytosine (GC) base pair and the subsequent tautomeric reactions able to induce mutations, by means of density functional theory (DFT) calculations. The conducted simulations allow us to identify the most reactive sites of the GC base pair. Indeed, the computed relative energies demonstrate that the addition of the NO(•) 2 radical to the C8 position of the guanine base forms to the most stable adduct. Although the initial adducts might evolve to non-canonical structures via inter-base hydrogen bonds rearrangements, the probability for the proton exchange to occur lies in the same range as that observed for undamaged DNA. As a result, tautomeric errors in NO2-attacked DNA arises at the same rate as in canonical DNA, with no macroscopic impact on the overall stability of DNA. The potential mutagenic effects of the GC-NO(•) 2 radical adducts likely involve side reactions, e.g., the GC deprotonation to the solvent, rather than proton exchange between guanine and cytosine basis.
我们通过密度泛函理论（DFT）计算研究了二氧化氮自由基（NO(•) 2）对鸟嘌呤-胞嘧啶（GC）碱基对的攻击以及随后可能导致突变的互变异构反应。进行的模拟允许我们识别 GC 碱基对的最易反应位点。实际上，计算出的相对能量表明，NO(•) 2自由基添加到鸟嘌呤碱基的 C8 位置形成最稳定的加合物。尽管初始加合物可能通过碱基间氢键重排演变为非规范结构，但质子交换发生的概率与未受损 DNA 中观察到的概率相同。因此，NO2 攻击 DNA 中的互变异构错误以与规范 DNA 相同的速率发生，对 DNA 的整体稳定性没有宏观影响。GC-NO(•) 2 自由基加合物的潜在诱变效应可能涉及侧反应，例如 GC 到溶剂的去质子化，而不是鸟嘌呤和胞嘧啶碱基之间的质子交换。
