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双核 Ni(II) 配合物,含 ONS 供体希夫碱配体:制备、光谱表征、X 射线晶体学和生物研究。

Binuclear Ni(II) complexes containing ONS donor Schiff base ligands: Preparation, spectral characterization, X-ray crystallography and biological exploration.

机构信息

Department of Chemistry, Bharathiar University, Coimbatore 641 046, India.

Department of Biotechnology, Vignan's Foundation for Science, Technology and Research (Deemed to be University), Guntur 522 213, India.

出版信息

J Inorg Biochem. 2020 Oct;211:111176. doi: 10.1016/j.jinorgbio.2020.111176. Epub 2020 Jul 18.

Abstract

Four binuclear Ni(II) complexes [[Ni(H-DEAsal-tsc)(μ-dppm)]·2Cl (1), [Ni(DEAsal-mtsc)(μ-dppm)] (2), [Ni(DEAsal-etsc)(μ-dppm)] (3) and [Ni(DEAsal-ptsc)(μ-dppm)] (4)] were synthesized from the ligands namely 4(N,N)-diethylaminosalicylaldehyde-4(N)-thiosemicarbazone [H-DEAsal-tsc] HL/4(N,N)-diethylaminosalicylaldehyde-4(N)-methyl thiosemicarbazone [H-DEAsal-mtsc] HL/4(N,N)-diethylaminosalicylaldehyde-4(N)-ethyl thiosemicarbazone [H-DEAsal-etsc] HL/4(N,N)diethylaminosalicylaldehyde-4(N)-phenyl thiosemicarbazone [H-DEAsal-ptsc] HL and 1,1'-bis(diphenylphosphino)methane (dppm) and characterized by a number of spectro analytical techniques. The molecular structure of complexes [Ni(H-DEAsal-tsc)(μ-dppm)]·2Cl (1) and [Ni(DEAsal-ptsc)(μ-dppm)] (4) have been confirmed by single crystal X-ray diffraction studies. The analysis indicated that in complex 1, the ligand [H-DEAsal-tsc] coordinated as monobasic tridentate donor through phenolic oxygen, azomethine nitrogen and thione sulfur atoms. However, in complex 4, the ligand [H-DEAsal-ptsc] behaved as dibasic tridentate donor with thiolate sulfur coordination. Their ability to bind with Calf Thymus Deoxyribonucleic acid (CT-DNA) and Bovine Serum Albumin (BSA) were analysed spectrometrically. Intercalative interaction of the complexes with DNA was confirmed by ethidium bromide (EB) displacement studies and DNA viscosity measurements. The interaction mechanism of the complexes with BSA was found as static. In vitro antiproliferative studies of the ligands and complexes in A549 (human lung carcinoma cancer), MCF-7 (human breast cancer) and HeLa (human cervical cancer) cell lines witnessed significant cytotoxic nature of the complexes with low IC values (in μM) than the standard metallo-drug cisplatin. Further, the results of Lactate Dehydrogenase (LDH) and Nitric oxide (NO) release assays supported the effectiveness of the complexes on the above said cancer cells.

摘要

四种双核 Ni(II)配合物 [[Ni(H-DEAsal-tsc)(μ-dppm)]·2Cl (1), [Ni(DEAsal-mtsc)(μ-dppm)] (2), [Ni(DEAsal-etsc)(μ-dppm)] (3) 和 [Ni(DEAsal-ptsc)(μ-dppm)] (4)] 是由配体 4(N,N)-二乙基氨基水杨醛-4(N)-硫代半卡巴腙 [H-DEAsal-tsc] HL/4(N,N)-二乙基氨基水杨醛-4(N)-甲基硫代半卡巴腙 [H-DEAsal-mtsc] HL/4(N,N)-二乙基氨基水杨醛-4(N)-乙基硫代半卡巴腙 [H-DEAsal-etsc] HL/4(N,N)二乙基氨基水杨醛-4(N)-苯基硫代半卡巴腙 [H-DEAsal-ptsc] HL 和 1,1'-双(二苯基膦)甲烷 (dppm) 合成的,并通过多种光谱分析技术进行了表征。配合物 [Ni(H-DEAsal-tsc)(μ-dppm)]·2Cl (1) 和 [Ni(DEAsal-ptsc)(μ-dppm)] (4) 的分子结构已通过单晶 X 射线衍射研究得到证实。分析表明,在配合物 1 中,配体 [H-DEAsal-tsc] 通过酚氧、亚胺氮和硫原子以单碱性三齿供体配位。然而,在配合物 4 中,配体 [H-DEAsal-ptsc] 表现为双碱性三齿供体,硫原子配位。通过光谱法分析了它们与小牛胸腺 DNA (CT-DNA) 和牛血清白蛋白 (BSA) 的结合能力。通过溴化乙锭 (EB) 置换研究和 DNA 粘度测量证实了配合物与 DNA 的插入相互作用。配合物与 BSA 的相互作用机制被发现为静态。在 A549(人肺癌癌细胞)、MCF-7(人乳腺癌)和 HeLa(人宫颈癌)细胞系中的配体和配合物的体外增殖研究表明,配合物具有显著的细胞毒性,其 IC 值(以 μM 计)低于标准金属药物顺铂。此外,乳酸脱氢酶 (LDH) 和一氧化氮 (NO) 释放测定的结果支持了配合物对上述癌细胞的有效性。

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