A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4′-(4-substituent phenyl)-2′,2′:6′,2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI–MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC₅₀ values of 0.223 μM and 0.335 μM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.

Graphical abstract

中文翻译：

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具有取代的 4′-苯基-2′,2′:6′,2″-三联吡啶配体的氯化镍络合物：合成、表征、抗增殖活性和生物分子相互作用

二氯化镍与10个4′-(4-取代基苯基)-2′,2′:6′,2″-三联吡啶配体反应合成了一系列Ni(II)三明治状配位化合物及其结构经元素分析、FT-IR、ESI-MS、固态紫外光谱和X射线单晶衍射分析证实。使用三种人类癌细胞系和一种正常人类细胞系进行抗增殖潜力研究：人肺癌细胞系（A549）、人食管癌细胞系（Eca-109）、人肝癌细胞（Bel-7402）和正常人肝细胞（HL-7702）。结果表明，这些镍配合物对癌细胞具有良好的抑制作用，优于临床常用的化疗药物顺铂。其中，配合物3（-甲氧基）和7（-氟）对Eca-109细胞系具有较强的抑制能力，IC ₅₀值分别为0.223 μM和0.335 μM，配合物4和6表现出一定的细胞选择性，配合物6具有抑制癌症的作用。当控制浓度时，细胞会轻微毒害正常细胞。通过紫外滴定和CD光谱研究了这些复合物与CT-DNA结合的能力，并利用CD光谱研究了复合物作用下BSA二级结构的变化。通过分子对接软件模拟了这些复合物与DNA、DNA-Topo I和牛血清蛋白的结合，对接结果和最佳结合构象数据表明它们以嵌入结合的方式与DNA相互作用，这与实验结果。这些复合物在与DNA-Topo I对接时更倾向于向裂解位点移动，从而起到酶裂解的作用，而BSA则通过与有效结合位点结合来促进复合物的作用。

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