Dominguez-Martin Alicia, Galli Simona, Dobado José A, Santamaría-Díaz Noelia, Pérez-Romero Antonio, Galindo Miguel A
Departamento de Química Inorgánica, Universidad de Granada, Av. Fuentenueva s/n, 18071 Granada, Spain.
Dipartimento di Scienza e Alta Tecnologia, Università dell'Insubria, via Valleggio 11, 22100 Como, Italy.
Inorg Chem. 2020 Jul 6;59(13):9325-9338. doi: 10.1021/acs.inorgchem.0c01210. Epub 2020 Jun 18.
The formation of copper(II)-mediated base pairs involving pyridine-2,6-dicarboxylate derivatives and canonical nucleosides has proven to be a smart approach to introduce copper(II) ions at specific locations of DNA duplexes. However, the structural characteristics of these metalized base pairs have not yet been revealed, and their effect on DNA structures is difficult to assess. Herein, for the first time, we report on the different structural details of copper-mediated base pairs formed by themselves and in DNA duplexes. The individual base pairs [Cu(mcheld)(-Cyt)(HO)]·3HO (), [Cu(mcheld)(-Ade)(HO)]·2HO (), [Cu(mcheld)(-Gua)(HO)] (), and [Cu(mcheld)(-Ade)(HO)]·HO () were obtained from the reaction of the metal complex [Cu(mcheld)(HO)] () (mcheld = 4-methoxypyridine-2,6-dicarboxylic acid) with model nucleosides (Cyt = -methylcytosine, Ade = -ethyladenine, Gua = -propylguanine, Ade = -propyl-7-deazaadenine). The crystal structure of the five complexes was determined by means of single-crystal X-ray diffraction. Furthermore, the formation of the and base pairs in the middle of DNA duplexes, duplex (917 atoms) and (649 atoms), respectively, was studied using highly demanding computational calculations. These theoretical studies aimed to validate, from a structural point of view, whether base pairs of the kind can be included in a DNA double helix and how this situation affects the double-helical structure. The results indicate that the and base pairs can be formed in a DNA molecule without significant structural constraints. In addition, the double-helix DNA structure remains virtually unchanged when it contains these Cu(II)-mediated base pairs.
涉及吡啶 - 2,6 - 二羧酸衍生物和标准核苷的铜（II）介导碱基对的形成已被证明是在DNA双链体特定位置引入铜（II）离子的巧妙方法。然而，这些金属化碱基对的结构特征尚未揭示，并且它们对DNA结构的影响难以评估。在此，我们首次报道了由其自身形成以及在DNA双链体中形成的铜介导碱基对的不同结构细节。单个碱基对[Cu(mcheld)(-Cyt)(HO)]·3HO ()、[Cu(mcheld)(-Ade)(HO)]·2HO ()、[Cu(mcheld)(-Gua)(HO)] ()和[Cu(mcheld)(-Ade)(HO)]·HO ()是通过金属配合物[Cu(mcheld)(HO)] ()（mcheld = 4 - 甲氧基吡啶 - 2,6 - 二羧酸）与模型核苷（Cyt = - 甲基胞嘧啶，Ade = - 乙基腺嘌呤，Gua = - 丙基鸟嘌呤，Ade = - 丙基 - 7 - 脱氮腺嘌呤）反应得到的。通过单晶X射线衍射确定了这五种配合物的晶体结构。此外，分别使用要求很高的计算计算研究了在DNA双链体duplex (917个原子)和 (649个原子)中间 和 碱基对的形成。这些理论研究旨在从结构角度验证这种类型的碱基对是否可以包含在DNA双螺旋中以及这种情况如何影响双螺旋结构。结果表明， 和 碱基对可以在DNA分子中形成而没有明显的结构限制。此外，当双螺旋DNA结构包含这些铜（II）介导的碱基对时，其结构几乎保持不变。
