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基于菲咯啉的铜(II)/锌(II)配合物的合成、X射线晶体结构、DNA/牛血清白蛋白结合、DNA切割及细胞毒性研究

Synthesis, X-ray crystal structure, DNA/BSA binding, DNA cleavage and cytotoxicity studies of phenanthroline based copper(II)/zinc(II) complexes.

作者信息

Wang Qingming, Mao Han, Wang Wenling, Zhu Huimin, Dai Lihui, Chen Yanli, Tang Xinhui

机构信息

School of Pharmacy, Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, Yancheng Teachers' University, Yancheng, 224051, Jiangsu, People's Republic of China.

College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing, 210009, People's Republic of China.

出版信息

Biometals. 2017 Aug;30(4):575-587. doi: 10.1007/s10534-017-0028-8. Epub 2017 Jun 14.

Abstract

Research on copper 1,10-phenanththroline (phen) derivatives continues to attract interest in the context of structure and biological properties. In this paper, two metal complexes [Cu(phen)(μ-Cl)]Cl (1), [Zn(phen)(HO)Cl]Cl·4HO (2) were synthesized and characterized. The crystal structures of 1 and 2 were determined by X-ray diffraction. In order to investigate the biological properties of the prepared complexes, spectroscopic and biological studies were performed. Results of X-ray diffraction showed that 1 and 2 form two types of crystal structures in a given system: dinuclear and mono-nuclear complex. The preliminary study on the DNA cleavage activity has shown that 1 under study behaved as the chemical nucleases. The DNA binding interaction of 1 & 2 with CT-DNA has been investigated by UV-Visible and fluorescence emission spectrometry and the apparent binding constant (K ) values are 5.1 × 10 and 1.2 × 10 M, respectively. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with 1 & 2 showed that the quenching mechanism might be a static quenching procedure with one binding sites for BSA. In addition, the cytotoxicity of 1 in vitro on tumor cells lines (MCF-7, HepG2 and HT29) was examined by MTT and showed better antitumor effect on the tested cells.

摘要

对铜(I)-1,10-菲咯啉(phen)衍生物在结构和生物学性质方面的研究持续受到关注。本文合成并表征了两种金属配合物[Cu(phen)(μ-Cl)]Cl (1)、[Zn(phen)(HO)Cl]Cl·4HO (2)。通过X射线衍射测定了1和2的晶体结构。为了研究所制备配合物的生物学性质,进行了光谱和生物学研究。X射线衍射结果表明,1和2在给定体系中形成两种晶体结构类型:双核和单核配合物。对DNA切割活性的初步研究表明,所研究的1表现为化学核酸酶。通过紫外可见光谱和荧光发射光谱研究了1和2与CT-DNA的DNA结合相互作用,其表观结合常数(K)值分别为5.1×10和1.2×10 M。此外,1和2与牛血清白蛋白(BSA)的荧光光谱表明,猝灭机制可能是对BSA具有一个结合位点的静态猝灭过程。此外,通过MTT法检测了1在体外对肿瘤细胞系(MCF-7、HepG2和HT29)的细胞毒性,结果表明其对受试细胞具有较好的抗肿瘤效果。

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