Department of Medicinal and Applied Chemistry and Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Phys Chem Chem Phys. 2011 Feb 21;13(7):2674-81. doi: 10.1039/c0cp01419b. Epub 2010 Dec 9.
The formation of base pair radical anions is closely related to many fascinating research fields in biology and chemistry such as radiation damage to DNA and electron transport in DNA. However, the relevant knowledge so far mainly comes from studies on isolated base pair radical anions, and their behavior in the DNA environment is less understood. In this study, we focus on how the nucleobase sequence affects the properties of the guanine-cytosine (GC) base pair radical anion. The energetic barrier and reaction energy for the proton transfer along the N(1)(G)-H···N(3)(C) hydrogen bond and the stability of GC˙(-) (i.e., electron affinity of GC) embedded in different sequences of base-pair trimer were evaluated using density functional theory. The computational results demonstrated that the presence of neighboring base pairs has an important influence on the behavior of GC˙(-) in the gas phase. The excess electron was found to be localized on the embedded GC and the charge leakage to neighboring base pairs was very minor in all of the investigated sequences. Accordingly, the sequence behavior of the proton-transfer reaction and the stability of GC˙(-) is chiefly governed by electrostatic interactions with adjacent base pairs. However, the effect of base stacking, due to its electrostatic nature, is severely screened upon hydration, and thus, the sequence dependence of the properties of GC˙(-) in aqueous environment becomes relatively weak and less than that observed in the gas phase. The effect of geometry relaxation associated with neighboring base pairs as well as the possibility of proton transfer along the N(2)(G)-H···O(2)(C) channel have also been investigated. The implications of the present findings to the electron transport and radiation damage of DNA are discussed.
碱基对自由基阴离子的形成与生物学和化学领域的许多迷人的研究领域密切相关，例如 DNA 的辐射损伤和 DNA 中的电子传递。然而，迄今为止，相关知识主要来自于对孤立碱基对自由基阴离子的研究，对其在 DNA 环境中的行为了解较少。在这项研究中，我们关注核碱基序列如何影响鸟嘌呤-胞嘧啶（GC）碱基对自由基阴离子的性质。使用密度泛函理论评估了质子沿着 N(1)(G)-H···N(3)(C)氢键转移的能量势垒和反应能，以及嵌入不同碱基对三联体序列中的 GC˙(-)（即 GC 的电子亲合势）的稳定性。计算结果表明，相邻碱基对的存在对 GC˙(-)在气相中的行为有重要影响。在所有研究的序列中，都发现过剩电子定域在嵌入的 GC 上，并且电荷泄漏到相邻的碱基对上非常小。因此，质子转移反应的序列行为和 GC˙(-)的稳定性主要由与相邻碱基对的静电相互作用决定。然而，由于其静电性质，碱基堆积的影响在水合作用下被严重屏蔽，因此，GC˙(-)在水相中的性质的序列依赖性变得相对较弱，并且比在气相中观察到的要弱。还研究了与相邻碱基对相关的几何弛豫以及沿着 N(2)(G)-H···O(2)(C)通道进行质子转移的可能性。讨论了本研究结果对 DNA 中电子传递和辐射损伤的意义。
