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配体取代和平面性对顺磁 Ni(II) 配合物与 DNA/BSA 相互作用、自由基清除和细胞毒性的影响:系统研究。

Effect of substitution and planarity of the ligand on DNA/BSA interaction, free radical scavenging and cytotoxicity of diamagnetic Ni(II) complexes: a systematic investigation.

机构信息

Department of Chemistry, Bharathiar University, Coimbatore, India.

出版信息

Dalton Trans. 2011 Oct 14;40(38):9690-702. doi: 10.1039/c1dt10767d. Epub 2011 Aug 22.

Abstract

Four new bivalent nickel hydrazone complexes have been synthesised from the reactions of [NiCl(2)(PPh(3))(2)] with H(2)L {L = dianion of the hydrazones derived from the condensation of salicylaldehyde or o-hydroxy acetophenone with p-toluic acid hydrazide (H(2)L(1)) (1), (H(2)L(2)) (2) and o-hydroxy acetophenone or o-hydroxy naphthaldehyde with benzhydrazide (H(2)L(3)) (3) and (H(2)L(4)) (4)} and formulated as [Ni(L(1))(PPh(3))] (5), [Ni(L(2))(PPh(3))] (6), [Ni(L(3))(PPh(3))] (7) and [Ni(L(4))(PPh(3))] (8). Structural characterization of complexes 5-8 were accomplished by using various physico-chemical techniques. In order to study the influence of substitution in the ligand and its planarity on the biological activity of complexes 5-8 containing them, suitable hydrazone ligands 1-4 have been selected in this study. Single crystal diffraction data of complexes 5, 7 and 8 proved the geometry of the complexes to be distorted square planar with a 1 : 1 ratio between the metal ion and the coordinated hydrazones. To provide more insight on the mode of action of complexes 5-8 under biological conditions, additional experiments involving their interaction with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) were monitored by UV-visible and fluorescence titrations respectively. Further, the ligands 1-4 and corresponding nickel(ii) chelates 5-8 have been tested for their scavenging effect towards OH and O(2)(-) radicals. The effect of complexes 5-8 to arrest the growth of HeLa and Hep-2 tumour cell lines has been studied along with the cell viability against the non-cancerous NIH 3T3 cells under in vitro conditions.

摘要

四种新的双价镍腙配合物已通过[NiCl(2)(PPh(3))(2)]与 H(2)L(L 是水杨醛或邻羟基苯乙酮与对甲苯酸肼缩合得到的腙的二阴离子(H(2)L(1))(1),(H(2)L(2))(2)和邻羟基苯乙酮或邻羟基萘醛与苯甲酰肼(H(2)L(3))(3)和(H(2)L(4))(4))的反应合成,并表示为Ni(L(1))(PPh(3))Ni(L(2))(PPh(3))Ni(L(3))(PPh(3))Ni(L(4))(PPh(3))。复合物 5-8 的结构特征是通过使用各种物理化学技术完成的。为了研究配体取代及其平面性对含它们的配合物 5-8 生物活性的影响,本研究中选择了合适的腙配体 1-4。复合物 5、7 和 8 的单晶衍射数据证明了这些复合物的几何形状为扭曲的正方形平面,金属离子与配位腙之间的比例为 1:1。为了更深入地了解复合物 5-8 在生物条件下的作用模式,通过紫外-可见和荧光滴定分别监测了它们与小牛胸腺 DNA(CT DNA)和牛血清白蛋白(BSA)相互作用的额外实验。此外,还测试了配体 1-4 和相应的镍(ii)螯合物 5-8 对 OH 和 O(2)(-)自由基的清除作用。研究了复合物 5-8 对 HeLa 和 Hep-2 肿瘤细胞系生长的抑制作用以及在体外条件下对非癌细胞 NIH 3T3 细胞的细胞活力。

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