Vazquez Marco-Vinicio, Martínez Ana
Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Circuito Exterior Sin Número, Ciudad Universitaria, Apdo. Postal 70-360, México D. F., 04510, México.
J Phys Chem A. 2007 Oct 4;111(39):9931-9. doi: 10.1021/jp068577b. Epub 2007 Sep 12.
Metal atoms play a major role in the chemical behavior of biological systems. In this work, known issues of the metal-base interactions, such as the stabilization of different tautomers of cytosine that could be incompatible with the DNA double helix, are researched using DFT methods. Ca-, Zn-, and Cd-cytosine in neutral and ionic forms were studied at the B3LYP/LANL2DZ level. Several neutral and ionic isomers were found within an interval of 10 kcal/mol of relative stability, with the most stable isomer in each group being a compound derived from the canonical isomer of cytosine, except for the dications where two iso-energetic isomers were found. Interatomic lengths from each metal atom to the nearest atoms in cytosine's ring were larger than 2 A, discouraging the possibility of a covalent interaction, as supported by additional evidence from molecular orbitals. The interaction between metal and cytosine, electrostatic in nature, is reinforced with the increase of the metal's nuclear charge. Additionally, the ionization energies of the metal-cytosine compounds exhibit a significant reduction (below 6 eV) compared with that of plain cytosine (8.7 eV), posing an interesting possibility with respect to the experimental determination of the photoelectron spectra of these compounds. Analyses of the energetics of the global reactions to form cationic species show that metal cations bind more strongly to neutral cytosine than to neutral metals. Metal dications form the most stable compounds with neutral cytosine, and the stabilities of these systems decrease as (Zn-cyt)2+ > (Cd-cyt)2+ > (Ca-cyt)2+. Aromaticities computed via the HOMA indexes also support the observation regarding the greater affinity of cytosine for metal cations.
金属原子在生物系统的化学行为中起着重要作用。在这项工作中，使用密度泛函理论（DFT）方法研究了金属-碱基相互作用的已知问题，例如胞嘧啶不同互变异构体的稳定性，这些互变异构体可能与DNA双螺旋不兼容。在B3LYP/LANL2DZ水平上研究了中性和离子形式的钙-胞嘧啶、锌-胞嘧啶和镉-胞嘧啶。在相对稳定性相差10千卡/摩尔的范围内发现了几种中性和离子异构体，每组中最稳定的异构体是源自胞嘧啶标准异构体的化合物，但二价阳离子情况除外，在二价阳离子中发现了两种能量相同的异构体。每个金属原子到胞嘧啶环中最近原子的原子间长度大于2埃，这排除了共价相互作用的可能性，分子轨道的额外证据也支持了这一点。金属与胞嘧啶之间本质上是静电相互作用，随着金属核电荷的增加而增强。此外，与纯胞嘧啶（8.7电子伏特）相比，金属-胞嘧啶化合物的电离能显著降低（低于6电子伏特），这为这些化合物光电子能谱的实验测定带来了有趣的可能性。对形成阳离子物种的全局反应能量学的分析表明，金属阳离子与中性胞嘧啶的结合比与中性金属的结合更强。金属二价阳离子与中性胞嘧啶形成最稳定的化合物，这些体系的稳定性顺序为（锌-胞嘧啶）2+ >（镉-胞嘧啶）2+ >（钙-胞嘧啶）2+。通过HOMA指数计算的芳香性也支持了胞嘧啶对金属阳离子具有更大亲和力的观察结果。
