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铜(II)配合物与抗菌药物氟甲喹:结构与生物学评价。

Copper(II) complexes with antimicrobial drug flumequine: structure and biological evaluation.

机构信息

Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.

出版信息

J Inorg Biochem. 2012 Aug;113:55-65. doi: 10.1016/j.jinorgbio.2012.03.005. Epub 2012 Mar 26.

DOI:10.1016/j.jinorgbio.2012.03.005
PMID:22694822
Abstract

The copper(II) complexes with the first-generation quinolone antibacterial agent flumequine(Hflmq) in the presence or absence of the nitrogen donor heterocyclic ligands 2,2'-bipyridylamine(bipyam), 2,2'-bipyridine(bipy), 1,10-phenanthroline(phen) or pyridine(py) have been synthesized and characterized. Flumequine acts as bidentate ligand coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. The crystal structures of the complexes [Cu(flmq)(bipyam)Cl], [Cu(flmq)(bipy)Cl] and [Cu(flmq)(phen)Cl] have been determined by X-ray crystallography revealing a distorted square pyramidal geometry for Cu(II) atom. The interaction of the complexes with bovine or human serum albumin proteins has been studied by fluorescence spectroscopy revealing their good binding propensity to the proteins with relatively high binding constant values. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA and [Cu(flmq)(2)(py)(2)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide(EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB.

摘要

在存在或不存在氮供杂环配体 2,2'-联吡啶胺(bipyam)、2,2'-联吡啶(bipy)、1,10-菲咯啉(phen)或吡啶(py)的情况下,合成并表征了与第一代喹诺酮类抗菌剂氟甲喹(Hflmq)的铜(II)配合物。氟甲喹作为双齿配体通过吡啶酮氧和羧基氧与 Cu(II)原子配位。配合物[Cu(flmq)(bipyam)Cl]、[Cu(flmq)(bipy)Cl]和[Cu(flmq)(phen)Cl]的晶体结构通过 X 射线晶体学确定,揭示了 Cu(II)原子的扭曲正方形金字塔几何形状。通过荧光光谱研究了配合物与牛或人血清白蛋白蛋白的相互作用,揭示了它们与蛋白质具有良好的结合倾向,具有相对较高的结合常数值。配合物与小牛胸腺 DNA(CT DNA)相互作用的 UV 研究表明,它们与 CT DNA 结合,并且[Cu(flmq)(2)(py)(2)]对 CT DNA 具有最高的结合常数。配合物的循环伏安法表明,在存在 CT DNA 的情况下,配合物可以通过嵌入结合模式与 CT DNA 结合,这也通过 DNA 溶液粘度测量得到了验证。与溴化乙锭(EB)的竞争性研究表明,配合物可以置换 DNA 结合的 EB,表明它们与 DNA 结合具有很强的竞争性与 EB。

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