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镍-喹诺酮相互作用:第 3 部分——抗菌药物氟甲喹的镍(II)配合物。

Nickel-quinolones interaction: part 3--Nickel(II) complexes of the antibacterial drug flumequine.

机构信息

Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, P.O. Box 135, GR-54124 Thessaloniki, Greece.

出版信息

J Inorg Biochem. 2010 Jul;104(7):740-9. doi: 10.1016/j.jinorgbio.2010.03.007. Epub 2010 Mar 24.

DOI:10.1016/j.jinorgbio.2010.03.007
PMID:20403640
Abstract

Nickel(II) complexes with the first-generation quinolone antibacterial agent flumequine in the presence or absence of nitrogen donor heterocyclic ligands (4-benzylpyridine, pyridine, 2,2'-bipyridine or 1,10-phenanthroline) have been structurally characterized by physicochemical and spectroscopic techniques. The experimental data suggest that flumequine acts as deprotonated bidentate ligand coordinated to Ni(II) through the carboxylato and ketone oxygen atoms. The crystal structures of bis(4-benzylpyridine)bis(flumequinato)nickel(II) 2, (2,2'-bipyridine)bis(flumequinato)nickel(II) 4 and (1,10-phenanthroline)bis(flumequinato)nickel(II) 5 have been determined by X-ray crystallography and are the first crystal structures of flumequinato complexes reported. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes bind to CT DNA and bis(aqua)bis(flumequinato)nickel(II) exhibits the highest binding constant to CT DNA. 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. The cyclic voltammograms of the complexes recorded in DMSO solution and in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they bind to CT DNA by the intercalative binding mode. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

摘要

镍(II)配合物与第一代喹诺酮类抗菌药物氟甲喹在存在或不存在氮供杂环配体(4-苄基吡啶、吡啶、2,2'-联吡啶或 1,10-菲咯啉)的情况下,通过物理化学和光谱技术进行了结构表征。实验数据表明,氟甲喹作为去质子双齿配体通过羧基和酮氧原子与 Ni(II)配位。双(4-苄基吡啶)双(氟甲喹酸)镍(II)2、(2,2'-联吡啶)双(氟甲喹酸)镍(II)4 和(1,10-菲咯啉)双(氟甲喹酸)镍(II)5 的晶体结构已通过 X 射线晶体学确定,这是氟甲喹酸配合物的第一个晶体结构报告。配合物与小牛胸腺 DNA(CT DNA)相互作用的紫外研究表明,配合物与 CT DNA 结合,双(水合)双(氟甲喹酸)镍(II)对 CT DNA 具有最高的结合常数。与溴化乙锭(EB)的竞争研究表明,配合物可以置换与 DNA 结合的 EB,表明它们与 DNA 结合具有强烈的竞争与 EB。在 DMSO 溶液中和在 1/2 DMSO/缓冲液(在 pH 7.0 时含有 150 mM NaCl 和 15 mM 三钠柠檬酸盐)溶液中记录的配合物的循环伏安图表明,在存在 CT DNA 的情况下,它们通过嵌入结合模式与 CT DNA 结合。这些配合物与人或牛血清白蛋白蛋白具有良好的结合倾向,具有相对较高的结合常数值。

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