2-取代咪唑与去甲斑蝥酸过渡金属配合物的合成、结构及生物活性表征  

Synthesis,structures and biological activity of transition-metal complexes with 2-substitued imidazole and demethyleantharic acid

作　　者：杜芳园[1] 林秋月[1,2] 齐庆远[1] 魏琼[1] 杨立峰[1] 林跃平[1] 

机构地区：[1]浙江师范大学化学与生命科学学院,金华321004 [2]浙江师范大学浙江省固体表面反应化学重点实验室,金华321004

出　　处：《中国科学：化学》2015年第10期1050-1064,共15页SCIENTIA SINICA Chimica

摘　　要：本文以去甲基斑蝥酸（H2DCA）为主要配体，两种2-取代咪唑，即2-甲基咪唑（MeIm）或2-（2’-吡啶基）苯并咪唑（PBIm）为辅助配体，合成了4种过渡金属配合物[Co（Melm）（DCA）（H2O）2]（1）、[Cu（Melm）E（DCA）]2-（H2O）2（2）、[Zn2（Melm）2（DCA）2]n·（H2O）n（3）和[Cu2（PBIm）2-（DCA）2]·（H2O）2（4），其中DCA=去甲基斑蝥酸根、7-氧杂二环[2．2．1]庚烷-2，3-二甲酸根．用元素分析和X-射线单晶衍射法进行了表征．其中配合物1和2分别为六配位和五配位的单核配合物，其中在晶体结构中2为双分子缔合形式：配合物3为四配位和六配位两种配位模式的多核聚合物：配合物4为六配位的双核配合物．通过紫外吸收光谱法、黏度法及琼脂糖凝胶电泳法研究了配合物与DNA的相互作用．结果显示，4种配合物均能以部分插入模式（1-3）和插入模式（4）与DNA发生中等强度的相互作用．在诱导剂H202或V。存在下，4种配合物对超螺旋质粒DNA均有切割作用，并可能为氧化还原作用机制．荧光光谱法研究表明，配合物与牛血清白蛋白fBSA）之间存在强烈的相互作用．配合物能以静态猝灭机理猝灭BSA的荧光．配合物均具有清除HO．自由基的能力．配合物对人体外癌细胞的增殖具有选择性抑制活性．两种铜配合物对人肝癌细胞（SMMC7721）的增殖抑制能力较强，其中配合物4具有更强烈的抗癌活性．Four novel complexes [Co（Melm）（DCA）（H2O）2] （1）, [Cu（Melm）2（DCA）]2-（H2O）2 （2）, [Zn2（Melm）2- （DCA）2]n.（H2O）, （3）, [Cu2（PBIm）2（DCA）2]-（H2O）2 （4） （2-Melm=2-methylimidazole; PBIm=2-（2＇-pyridyl）- benzimidazole; DCA=demethylcantharate） were synthesized and characterized by elemental analysis and X-ray diffraction. Complexes 1 and 2 are mononuclear complexes with six-coordinated and five-coordinated; complex 3 is a multicore polymer with four-coordinated and six-coordinated; complex 4 is a dinuclear complex with six- coordinated. The interaction between complexes and DNA was studied by means of ultraviolet-visible absorption spectra, viscosity measurements and agarose gel electrophoresis. The results showed that the complexes could bind DNA in moderate intensity via partial intercalation （1-3） and intercalation （4）. Under the effect of inducer （H202 or Vc）, four complexes all had cutting effect on superhelix DNA, and oxidation or reduction may be an important mechanism for the cutting effect. The interaction between the complexes and BSA was investigated by fluorescence spectra, and the complexes could quench the fluorescence of BSA strongly through static quenching. The complexes have a more antioxidant system, which can eliminate hydroxyl radical. The results showed that the inhibition effect had selectivity against cancer cells after forming complexes. The antiproliferative activities of two copper complexes had much stronger activity against human hepatoma cells （SMMC7721）. The antiproliferative activities of complex 4 were the most effective against SMMC7721 cells.

关 键 词：甲基咪唑 苯并咪唑 配合物的合成 与DNA的作用 与BSA的作用 体外抗增殖活性 

分 类 号：O641.4[理学—物理化学]