Selvakumaran Nagamani, Bhuvanesh Nattamai S P, Karvembu Ramasamy
Department of Chemistry, National Institute of Technology, Tiruchirappalli 620 015, India.
Dalton Trans. 2014 Nov 21;43(43):16395-410. doi: 10.1039/c4dt01859a.
Self-assembled metallamacrocyclic Cu(II) and Ni(II) complexes of the types [Cu(L1-O,S)]3 (1), [Ni(L1-O,S)]3 (2), [Cu(L2-O,S)]2 (3) and [Ni(L2-O,S)]2 (4) [H2L1 = 3,3,3',3'-tetrabenzyl-1,1'-terephthaloylbis(thiourea) and H2L2 = 3,3,3',3'-tetrabenzyl-1,1'-isophthaloylbis(thiourea)] were synthesized and characterized by analytical, spectroscopic (UV-Vis, FT-IR, mass, (1)H & (13)C NMR and EPR) and single crystal X-ray diffraction techniques. The crystal structures of [Ni(L1-O,S)]3 and [Cu(L2-O,S)(Py)]2 showed the formation of self-assembled 3:3 and 2:2 metallamacrocyclic Cu(II) and Ni(II) complexes respectively. The binding affinity and binding mode of the trinuclear complexes toward CT DNA were determined by UV-Vis spectrophotometric titrations and the fluorescent indicator displacement (FID) assay. The interaction of the ligand (H2L1) and the complexes (1 and 2) with BSA was investigated using UV-Vis and fluorescence spectroscopic methods. Absorption and emission spectral studies indicate that the complexes 1 and 2 interact with CT DNA and BSA protein more strongly than their parent ligand. Both the complexes (1 and 2) cleaved the pBR 322 plasmid DNA in the absence of an external agent. Complex 1 [IC50 = 22.36 (A549) and 10 μM (MCF7)] exhibited higher cytotoxicity than cyclophosphamide against A549 and MCF7 cancer cell lines. The IC50 value of 2 (29.24) is lower in the A549 cell line and slightly higher (18.04) in the MCF7 cell line than that of cyclophosphamide [IC50 = 41.84 (A549) and 11.89 μM (MCF7)].
合成了[Cu(L1-O,S)]3 (1)、[Ni(L1-O,S)]3 (2)、[Cu(L2-O,S)]2 (3)和[Ni(L2-O,S)]2 (4) 类型的自组装金属大环铜（II）和镍（II）配合物[H2L1 = 3,3,3',3'-四苄基-1,1'-对苯二甲酰双（硫脲），H2L2 = 3,3,3',3'-四苄基-1,1'-间苯二甲酰双（硫脲）]，并通过分析、光谱（紫外可见光谱、傅里叶变换红外光谱、质谱、（1）H和（13）C核磁共振以及电子顺磁共振）和单晶X射线衍射技术对其进行了表征。[Ni(L1-O,S)]3和[Cu(L2-O,S)(Py)]2的晶体结构分别显示形成了自组装的3:3和2:2金属大环铜（II）和镍（II）配合物。通过紫外可见分光光度滴定和荧光指示剂置换（FID）测定法确定了三核配合物对CT DNA的结合亲和力和结合模式。使用紫外可见光谱和荧光光谱方法研究了配体（H2L1）和配合物（1和2）与牛血清白蛋白（BSA）的相互作用。吸收和发射光谱研究表明，配合物1和2与CT DNA和BSA蛋白的相互作用比其母体配体更强。两种配合物（1和2）在没有外部试剂的情况下都能切割pBR 322质粒DNA。配合物1 [IC50 = 22.36（A549）和10 μM（MCF7）]对A549和MCF7癌细胞系表现出比环磷酰胺更高的细胞毒性。配合物2（29.24）在A549细胞系中的IC50值低于环磷酰胺[IC50 = 41.84（A549）和11.89 μM（MCF7）]，在MCF7细胞系中略高（18.04）。
