Haranczyk Maciej, Holliday John, Willett Peter, Gutowski Maciej
Department of Chemistry, University of Gdańsk, 80-952 Gdańsk, Poland.
J Comput Chem. 2008 Jun;29(8):1277-91. doi: 10.1002/jcc.20886.
Recently, we reported the discovery of adiabatically bound anions of guanine that might be involved in the processes of DNA damage by low-energy electrons and in charge transfer through DNA. These anions correspond to some tautomers that have been ignored thus far. They were identified using a hybrid quantum mechanical-combinatorial approach in which an energy-based screening was performed on the library of 499 tautomers with their relative energies calculated with quantum chemistry methods. In the current study, we analyze the adiabatically bound anions of guanine in two aspects: (1) the geometries and excess electron distributions are analyzed and compared with anions of the most stable neutrals to identify the sources of stability; (2) the chemical space of guanine tautomers is explored to verify if these new tautomers are contained in a particular subspace of the tautomeric space. The first task involves the development of novel approaches-the quantum chemical data like electron density, orbital, and information on its bonding/antibonding character are coded into holograms and analyzed using chemoinformatics techniques. The second task is completed using substructure analysis and clustering techniques performed on molecules represented by 2D fingerprints. The major conclusion is that the high stability of adiabatically bound anions originates from the bonding character of the pi orbital occupied by the excess electron. This compensates for the antibonding character that usually causes significant buckling of the ring. Also, the excess electron is more homogenously distributed over both rings than in the case of anions of the most stable neutral species. In terms of 2D substructure, the most stable anionic tautomers generally have additional hydrogen atoms at C8 and/or C2 and they do not have hydrogen atoms attached to C4, C5, and C6. They also form an "island of stability" in the tautomeric space of guanine.
最近，我们报道了鸟嘌呤绝热束缚阴离子的发现，这些阴离子可能参与低能电子对DNA的损伤过程以及DNA中的电荷转移。这些阴离子对应于一些迄今为止被忽视的互变异构体。它们是通过一种量子力学 - 组合混合方法鉴定的，其中对499种互变异构体库进行了基于能量的筛选，并用量子化学方法计算了它们的相对能量。在当前的研究中，我们从两个方面分析鸟嘌呤的绝热束缚阴离子：（1）分析几何结构和多余电子分布，并与最稳定中性分子的阴离子进行比较，以确定稳定性的来源；（2）探索鸟嘌呤互变异构体的化学空间，以验证这些新的互变异构体是否包含在互变异构空间的特定子空间中。第一项任务涉及开发新方法——将电子密度、轨道等量子化学数据及其键合/反键特征信息编码成交叉体图，并使用化学信息学技术进行分析。第二项任务是通过对由二维指纹表示的分子进行子结构分析和聚类技术来完成的。主要结论是，绝热束缚阴离子的高稳定性源于多余电子占据的π轨道的键合特征。这补偿了通常会导致环显著弯曲的反键特征。此外，与最稳定中性物种的阴离子相比，多余电子在两个环上的分布更均匀。就二维子结构而言，最稳定的阴离子互变异构体通常在C8和/或C2处有额外的氢原子，并且它们在C4、C5和C6处没有连接氢原子。它们还在鸟嘌呤的互变异构空间中形成了一个“稳定性岛”。
