2,6-二巯基嘌呤互变异构体热力学稳定性的密度泛函理论研究

Density functional theory investigations of thermodynamic stability of 2,6-dithiopurine tautomers

利用密度泛函(DFT)B3LYP/6-311G(d,p)方法,水相计算采用自洽反应场(SCRF)中的Onsager模型,对气相和水相中可能存在的13种2,6-二巯基嘌呤互变异构体进行了全优化,并计算了各异构体的热力学参数、偶极矩及原子净电荷。计算结果表明,不论是气相还是水相,二硫酮DTP(1,3,7)是最稳定的异构体。溶剂化效应使各异构体的稳定性均增强,偶极矩大者其稳定性显著增大。溶剂化吉布斯自由能与异构体在两相中偶极矩之差存在相关性。二硫酮DTP(1,3,7)在水相中与致癌物BPDE进行亲核取代反应时,二硫酮DTP(1,3,7)中的S10原子优先进攻亲电试剂BPDE.

All the molecular structures of thirteen possible 2,6 -dithlopurine tautomers have been calculated by density functional theory （DFF） method at B3LYP/6 -311G（d,p） level,both in the gas and aqueous phases,wlth full geometry optimization. The Onasoger solvation theory model in the self - consistent reaction field （SCRF） was employed for aqueous solution calculations. The thermodynamic parameters, dipole moments and atomic total charges were obtained at the same level. The calculations show that either in the gas or in the aqueous phases the dithione - N7H is the most stable tautomer. The stabilities of all the tautomers are increased by the solvent and the tautomers which have much larger dipole moments than others are more stable in the aqueous phase. The Gibbs free energy of solvation is well correlated with the differences of the dipole moments between the gas and aqueous phases. When the tautomer DTP（ 1,3,7 ） reacts with the dectrophilic carcinogen BPDE, the atomic S10 of DTP（ 1,3,7） superiorly attacks the BPDE.