八羟基喹啉铜(Ⅱ)配合物的DNA结合和切割活性及与牛血清白蛋白相互作用（英文）  

DNA binding,DNA cleavage and BSA interaction of a bis-8-hydroxyquinoline copper(Ⅱ) complex

作　　者：陈战芬[1] 张书萍[1] 张健[1] 

机构地区：[1]湖北师范学院化学与化工学院污染物分析与资源化技术湖北省重点实验室稀有金属化学湖北省协同创新中心,湖北黄石435002

出　　处：《化学研究》2015年第4期404-416,共13页Chemical Research

基　　金：The National Natural Science Foundation of China(21301056);the China Postdoctoral Science Foundation(2012M521419)

摘　　要：利用紫外吸收光谱、荧光光谱、圆二色光谱(CD)和琼脂糖凝胶电泳等手段研究了八羟基喹啉铜(Ⅱ)配合物Cu[8-OHQ]2与DNA和蛋白质的相互作用.实验结果表明,在生理条件下,Cu[8-OHQ]2能通过插入方式较强的与CT-DNA结合,诱导DNA构象的改变.其本征结合常数Kb为1.15(±0.01)×105 L/mol,表观结合常数Kapp为4.21×106 L/mol.再者,琼脂糖凝胶电泳实验表明,在生理条件和抗坏血酸(Vc)存在情况下,Cu[8-OHQ]2能有效地将超螺旋pBR322质粒DNA切割成缺刻和线性,甚至降解为小的片断.机理研究表明扩散的·OH,H2O2和1 O2都不是在切割过程中起作用的活性氧物种(ROS);copper-oxo中间体可能是此切割过程中主要的活性氧物种.另外,Cu[8-OHQ]2也能以适中的结合力与牛血清白蛋白(BSA)结合而猝灭BSA内源荧光,猝灭机理为静态猝灭.所有这些结果表明Cu[8-OHQ]2具有作为潜在化疗试剂的生物活性.The interactions between DNA/protein and the bis-8-hydroxyquinoline copper（II）complex,Cu[8-OHQ]2,were investigated under physiological conditions using UV-vis absorption,fluorescence,circular dichroism（CD）,and agarose gel electrophoresis.The experimental results suggest Cu[8-OHQ]2could strongly bind to calf thymus DNA（CT-DNA）through an intercalative mode and induce a remarkable conformational variation of DNA.The intrinsic binding constant Kbof Cu[8-OHQ]2to DNA is 1.15（±0.01）×105 L/mol and the apparent binding constant Kappis 4.21×106 L/mol.Furthermore,agarose gel electrophoresis revealed,in the presence of ascorbic acid（Vc）under nearly physiological conditions,Cu[8-OHQ]2could efficiently cleave the supercoiled pBR322 plasmid DNA into its nicked and linear forms,even degrade into undetectable minor fragments.Mechanism studies demonstrated diffusible·OH,H2O2 and 1 O2 are not the effective reactive oxygen species（ROS）in the cleavage process mediated by the complex and the copper-oxo species might be responsible for the cleavage.Additionally,Cu[8-OHQ]2could also bind to bovine serum albumin（BSA）with a medium affinity and quench the intrinsic fluorescence of BSA through a single static quenching mechanism.All these results suggest that Cu[8-OHQ]2exhibits biological action as a potential chemotherapy agent.

关 键 词：八羟基喹啉铜(Ⅱ)配合物 DNA结合 DNA切割 BSA 

分 类 号：O657.39[理学—分析化学]