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.
