Zn2+,Cu2+及Ni2+对二甲双胍的配合作用及降血糖活性研究

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.

Studies on the Structures and Antihyperglycemic Effects of Zn2+,Cu2+,Ni2+-Metformin Complexes

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.