7-硫代鸟嘌呤互变异构体的密度泛函理论计算

Density Functional Theory Calculations on 7-Thioguanine Tautomers

在密度泛函B3LYP/ 6 3 11G 水平下 ,对 14种气相和水相中可能存在的 7 硫代鸟嘌呤异构体进行了几何构型全自由度优化 ,并计算出它们的总能量、焓、熵、吉布斯自由能 .Onsager反应场溶剂模型用于水相的计算 .计算结果表明 ,7 硫代鸟嘌呤在气相中和水相中主要以硫酮形式存在 .在气相中 ,硫酮—N( 6) (H)要比硫酮—N( 4 ) (H)更稳定 ,而在水相中 ,则硫酮—N( 4 ) (H)要比硫酮—N( 6) (H)更稳定 .计算结果同已有实验结果一致 .7 硫代鸟嘌呤互变异构的熵效应小 ,对互变异构平衡没有显著的影响 ,而焓变对互变异构产生了主要的影响 .较详细地讨论了水溶剂化作用对异构体的能量、几何结构、电荷分布和偶极矩的影响 .溶剂化自由能与异构体的偶极矩存在相关性 .

Molecular structures of fourteen 7-thioguanine tautomers were calculated by the B3LYP/6-311G** method, both in the gas and aqueous phases, with full geometry optimization. The Onsager solvate theory model was employed for aqueous solution calculations. The structures, total energy, standard enthalpy, standard entropy and standard free energy were obtained. The calculations show that 7-thioguanine existing as the thione form is the predominant isomers in the gas and aqueous phases. The thione-N (6) (H) isomer is more stable than the thione-N (4) (H) isomer in the gas phase whereas the thione-N (4) ( H) isomer is more stable than the thione-N (6) (H) isomer in the aqueous phase. The results are in good agreement with available experimental results. The entropy effect on the Gibbs free energy of 7-thioguanine base is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant in the determination of tautomeric equilibria. The free energy of solvation is well correlated with the dipole moments of 7-thioguanine tautomers.