基于两性羧酸配体的Cu(Ⅱ)、Zn(Ⅱ)、Co(Ⅱ)、Mn(Ⅱ)配合物的合成、晶体结构及其与DNA相互作用  

Synthesis,Crystal Structures and DNA Interaction of Cu(Ⅱ),Zn(Ⅱ),Co(Ⅱ),and Mn(Ⅱ) Complexes Derived from Zwitterionic Carboxylate Ligand

作　　者：陈铭臻 陈金香[2] 王若伦[1] 卢钧雄[1] 许雪飞 CHEN Ming-Zhen;CHEN Jin-Xiang;WANG Ruo-Lun;LU Jun-Xiong;XU Xue-Fei(Department of Pharmacy,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,China;NMPA Key Laboratory for Research and Evaluation of Drug Metabolism,Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]广州医科大学附属第二医院药学部,广州510260 [2]南方医科大学药学院,国家药品监督管理局药物代谢研究与评价重点实验室,广东省新药筛选重点实验室,广州510515

出　　处：《无机化学学报》2022年第12期2499-2510,共12页Chinese Journal of Inorganic Chemistry

基　　金：国家自然科学基金(No.21874064,21871203);广东省医学科学技术研究基金(No.A2021267)资助。

摘　　要：以两性羧酸配体溴化N-(4-羧基苄基)异喹啉((HCbiq)Br)合成了4个新的金属配合物:[Cu_(2)(Cbiq)_(4)(H_(2)O)_(2)]Br_(4)·2H_(2)O(1)、[Zn(Cbiq)_(2)(H_(2)O)_(2)]Br_(2)·Cbiq·H_(2)O(2)、[M_(3)(Cbiq)_(8)(μ-OH)_(2)(H_(2)O)_(2)](ClO_(4))_(4)·7H_(2)O(M=Co(3)、Mn(4))。通过单晶X射线衍射、元素分析和红外光谱表征了配合物1~4的结构。配合物1含有一个由4个Cbiq的羧基桥联双核Cu(Ⅱ)的结构,2个Cu(Ⅱ)还分别与一分子水配位。配合物2中,1个Zn(Ⅱ)分别与2个Cbiq的羧基氧原子进行单齿配位,同时还与2个水分子的氧原子进行配位。配合物3和4结构相似,均为三核结构。每2个M(Ⅱ)除了通过2个Cbiq的羧基上的氧进行桥联,还通过一个羟基的氧进行桥联。此外,2个端基的M(Ⅱ)分别与2个Cbiq的羧基进行单齿配位,同时还与一个水分子进行配位。凝胶电泳研究表明,配合物1可能是通过氧化机制在生理条件下有效切割DNA,其最大催化速率常数k_(max)为2.80 h^(-1),米氏常数K_(M)为3.22 mmol·L^(-1)。溴化乙锭(EB)竞争实验表明配合物1具有较强的DNA结合亲和力。采用分子对接模拟计算得到配合物1与DNA的结合自由能为-49.87 kJ·mol^(-1)。Four new metal complexes,namely[Cu_(2)(Cbiq)_(4)(H_(2)O)_(2)]Br_(4)·2H_(2)O(1),[Zn(Cbiq)_(2)(H_(2)O)_(2)]Br_(2)·Cbiq·H_(2)O(2),and [M_(3)(Cbiq)_(8)(μ-OH)_(2)(H_(2)O)_(2)](ClO_(4))_(4)·7H_(2)O(M=Co(3),Mn(4)),were synthesized from the zwitterionic carboxylate ligand N-(4-carboxybenzyl)isoquinolinium bromide((HCbiq)Br)with the corresponding metal salts.All these metal complexes were characterized by single crystal X-ray diffraction,elemental analyses,and IR.In complex 1,the centrosymmetric binuclear Cu(Ⅱ)are bridged by four Cbiq molecules and each Cu(Ⅱ)ion is further coordinated to one water molecule.In complex 2,the center Zn(Ⅱ)ion is coordinated to two unidentate Cbiq molecules and two water molecules.Complexes 3 and 4 have similar structures in which every two M(Ⅱ)ions are bridged by two Cbiq molecules and one hydroxo-O atom and the two peripheric M(Ⅱ)ions are further coordinated to two unidentate Cbiq molecules and one water molecule.Agarose gel electrophoresis(GE)studies on the cleavage of plasmid pBR322 DNA by complexes 1-4 indicated that complex 1 was capable of efficiently cleaving DNA under physiological conditions,most probably via an oxidative mechanism.Kinetic assay of complex 1 afforded the maximal catalytic rate constant k_(max) of 2.80 h^(-1) and Michaelis constant K_(M) of 3.22 mmol·L^(-1).Ethidium bromide(EB)displacement experiments indicated that complex 1 exhibited high DNA binding affinity toward calf‑thymus(CT)DNA.The docking method was used to predict the CT DNA binding affinity of complex 1,with the result that the binding free energy was-49.87 kJ·mol^(-1).

关 键 词：两性羧酸配体 过渡金属配合物 晶体结构 DNA 

分 类 号：O614.121[理学—无机化学] O614.241[理学—化学] O614.812O614.711