关键词: 可乐定, 互变异构, 构象异构, 密度泛函理论方法, 自洽反应场方法

The conformational analysis of the various tautomers of clonidine in both neutral and protonated forms have been investigated using HF/6-31G* method. The conformers located at minima by HF/6-31G* calculation were re-optimized by B3LYP/6-31G** method without any constraints. The B3LYP/6-31G** calculations on the tautomerism of clonidine in an aqueous medium using Onsager solvation theory model have shown that the solvent does not change the relative stability of the individual tautomers of this drug and the neutral molecule of clonidine exists as the more stable imino tautomer in the gas and aqueous phases. The results are in good agreement with available experimental ones. The protonation and solvent effects were examined by analyzing the change of molecular geometric and energy parameters. The mechanism of clonidine conformational isomerization and tautomeric reaction has been studied and the geometric parameters of transition states have been located by B3LYP/6-31G**. In order to evaluate conjugation effects of chlorobenzene on distribution of the clonidine tautomers, we have studied the mechanism of 2-aminoimidazoline tautomeric reaction by B3LYP/6-31G** method.

Key words: clonidine, tautomerization, conformational isomerization, density functional theory method, self-consistent reaction field method