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钌(II) 多吡啶配合物与 DNA 错配和无碱基位点的相互作用。

Interactions of Ru(II) polypyridyl complexes with DNA mismatches and abasic sites.

机构信息

Biophysics Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai 600 020, India.

出版信息

Dalton Trans. 2015 May 21;44(19):9044-51. doi: 10.1039/c5dt00807g.

Abstract

Polypyridyl based ruthenium(II) complexes, Ru(bpy)2(furphen)2 (1) and Ru(bpy)2(imiphen)2 (2) {furphen: 2-(furan-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline and imiphen: 2-(1H-imidazol-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline} were synthesized and characterized by ESI-MS, NMR, UV-Visible and fluorescence spectroscopic techniques. The interaction of Ru(II) complexes with calf-thymus DNA (CT DNA) as well as oligonucleotides containing mismatches and abasic sites was studied along with unmodified control DNA. Based on absorption titration studies, binding constants (Kb) for the interaction of complexes 1 and 2 with DNA were found to be 6.7 ± 0.2 × 10(3) and 4.9 ± 0.2 × 10(4) M(-1), respectively. Hydrodynamic studies revealed weak interactions between the two complexes and CT-DNA. Luminescence studies revealed that both the complexes exhibit a five-fold increase in emission upon addition of CT-DNA. The integrated emission intensity of complexes 1 and 2 with CC mismatch oligonucleotides was 1.5 and 1.2 fold higher than that of control GC match oligonucleotides, respectively. Both the complexes did not show any specificity towards abasic or other mismatch sites except for CC mismatch. The results from this study provide an insight into the requirements of ligand shape in recognising DNA mutations such as mismatch and selectivity between DNA mismatches.

摘要

基于多吡啶的钌(II)配合物[Ru(bpy)2(furphen)] (PF6)2 (1) 和 [Ru(bpy)2(imiphen)] (PF6)2 (2) {furphen: 2-(呋喃-2-基)-1H-咪唑并[4,5-f][1,10]菲咯啉和 imiphen: 2-(1H-咪唑-2-基)-1H-咪唑并[4,5-f][1,10]菲咯啉} 通过 ESI-MS、NMR、UV-Visible 和荧光光谱技术进行了合成和表征。研究了 Ru(II)配合物与小牛胸腺 DNA(CT DNA)以及含有错配和碱基缺失的寡核苷酸的相互作用,同时还研究了未经修饰的对照 DNA。基于吸收滴定研究,发现配合物 1 和 2 与 DNA 的结合常数 (Kb) 分别为 6.7 ± 0.2 × 10(3) 和 4.9 ± 0.2 × 10(4) M(-1)。流体力学研究表明,两种配合物与 CT-DNA 之间存在弱相互作用。荧光研究表明,两种配合物在加入 CT-DNA 后发射强度均增加了五倍。与 CC 错配寡核苷酸相比,配合物 1 和 2 与 CC 错配寡核苷酸的集成发射强度分别提高了 1.5 和 1.2 倍。两种配合物除了 CC 错配之外,对碱基缺失或其他错配位点均没有特异性。这项研究的结果提供了对识别 DNA 突变(如错配)和 DNA 错配之间选择性所需的配体形状的深入了解。

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