基于配体分子3MLCT态发光性质研究[Ru(phen)2dppz]2+与人体端粒i-Motif DNA相互作用机理

研究DNA与配体分子相互作用为设计DNA结构探针，及以DNA为靶点的抗肿瘤药物等提供理论依据。因为[Ru(phen)2dppz]2+明显的分子光开关效应，一直是该领域研究的焦点。四链体DNA空间立体结构多样，还可通过抑制端粒酶活性阻碍肿瘤细胞增殖，是一个很好的研究配体与DNA相互作用的体系。然而，[Ru(phen)2dppz]2+与四链体DNA相互作用的研究十分匮乏。所以，本项目拟以[Ru(phen)2dppz]2+的3MLCT态发光指数作为探针，并结合稳态光谱，系统研究rac、Λ和Δ-[Ru(phen)2dppz]2+与不同构型人体端粒i-Motif DNA单体及二聚体的结合模式，全面揭示[Ru(phen)2dppz]2+与i-Motif DNA的相互作用机理。该项目可为研究DNA与配体相互作用提供有效的实验方法，还有助于深入认识四链体DNA抑制端粒酶活性、调节致癌基因表达等科学问题。

Since the binding of ligand molecules and DNA tetraplex (G-quadruplex and i-Motif DNA) could inhibit the reactivity of telomere enzyme and control the oncogene expression, the investigation on the interaction mechanism between them may provide valuable information for the rational design of DNA probes and anticancer drugs. Comparing with B-DNA duplex, the structure of DNA tetraplex are quite different such as hydrogen-bonding structure, base stacking as well as the ability of water accessible. On the basis of structure characters, the interaction mechanisms of ligand molecules and DNA tetraplex are anticipated to be entirely different with B-DNA. Obviously, research on the interaction mechanisms of ligand molecules and DNA tetraplex has more significant importance. Ruthenium complexes [Ru(phen)2dppz]2+, which reveals obviously light switch effect, have attracted significant attention in this field. Until now, although some studies about the interaction between [Ru(phen)2dppz]2+ and DNA tetraplex have been reported, it still remains elusive to a large extent for the interaction mechanism. This may originate from the absence of interpretation for enormous problems in disclosing the interaction mechanism, such as the binding ratio, the isomer selectivity or binding constants and so on. The techniques on the research of interaction mechanism between ligand molecules and DNA tetraplex are also thought to be limiting the development in this field. Thus, we are motivated to investigate the binding mechanisms of monomeric and dimeric i-Motif DNA and [Ru(phen)2dppz]2+ by detecting the luminescence dynamics of 3MLCT of [Ru(phen)2dppz]2+ using transient emission spectroscopy, and combining with other methods such as UV-vis absorption, fluorescence and CD spectroscopy. Our results are anticipated to not only illustrate the interaction mechanism of [Ru(phen)2dppz]2+ binding to both the monomer and dimer of i-Motif DNA, but also provide a novel dynamic experimental method for investigating the interactions mechanism of DNA and ruthenium complexes.