Improvement in the Stability of Gabapentin by the Complexation of Gabapentin with Different Metal Ions: a DFT Study  

作　　者：YANG Li-Xiang LI Dai-Xi LIU Bao-Lin GUO Bai-Song WEI Dong-Qing 杨理想;李代禧;刘宝林;郭柏松;魏东青(Institute of Food Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China;Injection Laboratory, Shanghai Tofflon Science and Technology Co. Ltd., Shanghai 201108, China;State Key Laboratory of Microbial Metabolism, Shanghai Jiaotong University, Shanghai 200240, China)

机构地区：[1]Institute of Food Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China [2]Injection Laboratory, Shanghai Tofflon Science and Technology Co. Ltd., Shanghai 201108, China [3]State Key Laboratory of Microbial Metabolism, Shanghai Jiaotong University, Shanghai 200240, China

出　　处：《Chinese Journal of Structural Chemistry》2019年第5期695-705,667,共12页结构化学（英文）

基　　金：supported by the National Natural Science Fundation of China(No.51776130);the Natural Science Foundation of Shanghai(No.12ZR1420400);Innovation Foundation from the Education Commission of Shanghai City(No.14YZ092)

摘　　要：Gabapentin undergoes intramolecular cyclization by alkylamine nucleophilic attacking on carboxylate carbonyl. And the above self-dehydration condensation can produce gabapentin lactam which has some toxic effects. Therefore, in order to decrease the above subsidiary reaction, the effects of several metal ions on the reaction mechanism and the potential barriers of self-dehydration condensation of gabapentin are analyzed. Each molecular structure of gabapentin in the presence of several metal ions is optimized using the density functional theory(DFT) with B3LYP method at the 6-311+G(d,p) basis set level. And its geometric and thermodynamic parameters are also investigated. The calculated results showed that gabapentin can form stable complexes with divalent metal ions and exhibit the highest affinity for small and highly charged metal cations. The binding ability of these metal ions with gabapentin ranks in an order of Fe^2+>Zn^2+> Mg^2+> Ca^2+> Na^+> K^+. Besides, the potential barriers of subsidiary reaction of gabapentin increase obviously in the presence of several metal ions than that of free gabapentin. This means that the above metal ions can inhibit effectively the intramolecular cyclization of gabapentin.

关 键 词：density functional theory GABAPENTIN potential BARRIER STABILIZATION 

分 类 号：TQ[化学工程]