Based on the ability of terpyridines to react with G-quadruplex DNA (G4) structures along with the interest aroused by Zn as an essential metal centre in many biological processes, we have synthesized and characterized six Zn chloride or nitrate complexes containing terpyridine ligands with different 4′-substituents. In addition, we have studied their interaction with G4 and their cytotoxicity. Our experimental results revealed that the leaving group exerts a strong influence on the cytotoxicity, since the complexes bearing chloride were more cytotoxic than their nitrate analogues and an effect of the terpyridine ligand was also observed. The thermal stabilization profiles showed that the greatest stabilization of hybrid G4, Tel22, was observed for the Zn complexes bearing the terpyridine ligand that contained one or two methylated 4-(imidazol-1-yl)phenyl substituents, 3Cl and 3(L)₂, respectively, probably due to their extra positive charge. Stability and aquation studies for these complexes were carried out and no ligand release was detected. Complexes 3Cl and 3(L)₂ were successfully internalized by SW480 cells and they seemed to be localized mainly in the nucleolus. The highest cytotoxicity, G4 selectivity and G4 affinity determined by fluorescence and ITC experiments, and subcellular localization quantified by ICP-MS measurements, rendered 3Cl a very interesting complex from a biological standpoint.

中文翻译：

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使用Zn（II）吡啶吡啶衍生物靶向G-四链体结构：SAR研究。

基于三联吡啶与G-四链体DNA（G4）结构反应的能力以及锌在许多生物过程中引起的作为重要金属中心的兴趣，我们合成并表征了六种含三联吡啶配体的氯化锌或硝酸盐配合物， 4'-取代基。此外，我们研究了它们与G4的相互作用及其细胞毒性。我们的实验结果表明，离去基团对细胞毒性具有很强的影响，因为带有氯化物的配合物比其硝酸盐类似物具有更高的细胞毒性，并且还观察到了联吡啶配体的作用。热稳定曲线表明，混合动力G4 Tel22，3Cl和3（L）₂分别可能是由于其额外的正电荷。对这些配合物进行了稳定性和水合研究，未发现配体释放。配合物3Cl和3（L）₂已被SW480细胞成功内在化，它们似乎主要位于核仁中。通过荧光和ITC实验确定的最高细胞毒性，G4选择性和G4亲和力，以及通过ICP-MS测量定量的亚细胞定位，从生物学的角度使3Cl成为非常有趣的复合物。