Zn^(2+),Cu^(2+)及Ni^(2+)对二甲双胍的配合作用及降血糖活性研究  

Studies on the Structures and Antihyperglycemic Effects of Zn^(2+), Cu ^(2+), Ni^(2+)-Metformin Complexes

作　　者：朱苗力[1] 卢丽萍[1] 杨频[1] 

机构地区：[1]山西大学分子科学研究所化学生物学与分子工程教育部重点实验室,太原030006

出　　处：《化学学报》2004年第8期783-788,共6页Acta Chimica Sinica

基　　金：国家自然科学基金 (No.2 0 1 71 0 31 );山西省青年基金 (No.2 0 0 1 1 0 0 7); 2 0 0 2年山西省归国留学基金资助项目

摘　　要：二甲双胍盐酸盐、硝酸盐及与Zn2 + ,Cu2 + ,Ni2 + 三种金属离子配合物的结构特点、电荷分布和二甲双胍配合物对四氧嘧啶糖尿病小鼠血糖影响的研究表明 :Zn2 + 配合物表现为较为少见的单齿配位 ,而Cu2 + ,Ni2 + 配合物表现为双齿配位 .进一步电荷分布计算发现 ,与端基N原子相比 ,二甲双胍的桥基N原子具有较高的负电荷 .三种金属离子配合物对四氧嘧啶糖尿病小鼠血糖的影响研究显示 ,桥基N配位掩蔽后 ,二甲双胍的降血糖功能丧失 .说明桥基N对二甲双胍的降血糖作用具有重要意义 .The structures and charge distribution as well as antihyperglycemic effects of 1,1-dimethylbiguanide (metformin) metal (Zn 2+, Cu 2+ and Ni 2+) complexes were investigated. Metformin can complex with Zn 2+ at bridging N, forming a rare monodentate complex, but complex with Cu 2+ and Ni 2+ at terminal N atoms, giving rise to bidentate complexes. The charge distribution calculated by DFT and ab initio methods indicates that the bridging N atom has more negative charge than terminal N atoms. The antihyperglycemic effects of metformin metal complexes show that the monodentate complex has no effect and bidentate complexes still keep the activity but less efficient than metformin alone. This result suggests that the bridging N atom of metformin be important for its antihyperglycemic effect.

关 键 词：二甲双胍 配合作用 降血糖活性 铜离子 锌离子 镍离子 电荷分布 金属配合物 糖尿病 

分 类 号：R96[医药卫生—药理学]