Key Laboratory of Space Applied Physics and Chemistry of the Ministry of Education, School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, People's Republic of China.
J Mol Model. 2013 Aug;19(8):3279-305. doi: 10.1007/s00894-013-1858-0. Epub 2013 May 8.
A relative complete study on the mechanisms of the proton transfer reactions of 2-thioxanthine was carried out with density functional theory. The models were designed with monohydrated and dihydrated microsolvent catalyses either with or without the presence of water solvent considered with the polarized continuum model (PCM). A total number of 114 complexes and 67 transition states were found with the B3LYP/6-311+G** calculations. The energies were refined with both B3LYP/aug-cc-pVTZ and PCM-B3LYP/aug-cc-pVTZ methods. The activation energies were reported with respect to the Gibbs free energies obtained in conjunction with the standard statistical thermodynamics. Possible reaction pathways were confirmed with the intrinsic reaction coordinates. Pathways via C8 atom on the imidazole ring, via the bridged C4 and C5 atoms between pyrimidine and imidazole rings and via N, O and S atom on the pyrimidine ring were examined. The results show that the most feasible pathway is the proton transfers within the long range solvent surrounding via the N, O and S atoms in the pyrimidine ring with di-hydrated catalysis: N(7)H + 2H2O → IM89 → IM90 → P13 + 2H2O → IM91 → IM92 → P6 + 2H2O → IM71 → IM72 → P7 + 2H2O → IM107 → IM108 → P18 + 2H2O → IM111 → IM112 → P19 + 2H2O → IM113 → IM114 → P17 + 2H2O → IM105 → IM106 → N(9)H + 2H2O that has the highest energy barrier of 44.0 kJ mol(-1) in the transition of IM89 to IM90 via TS54. The small energy barrier is in good agreement with the experimental observation that 2-TX tautomerizes at room temperature in water. In the aqueous phase, the most stable intermediate is found to be IM21 [N(7)H + 2H2O] and the possible co-existing species are the monohydrated IM1, IM9, IM39 and IM46, and the di-hydrated IM5, IM8, IM13, IM16, IM81, IM89, IM90, IM91 and IM106 complexes that have a relative concentration larger than 10(-6) (1 ppm) with respect to IM21.
采用密度泛函理论对 2-硫代嘌呤质子转移反应的机制进行了相对完整的研究。设计了单水合和双水合微溶剂催化模型，同时考虑了带有极化连续模型（PCM）的水溶剂。使用 B3LYP/6-311+G**计算，共发现 114 个复合物和 67 个过渡态。用 B3LYP/aug-cc-pVTZ 和 PCM-B3LYP/aug-cc-pVTZ 方法对能量进行了细化。根据标准统计热力学，用 Gibbs 自由能得到了活化能。用内禀反应坐标证实了可能的反应途径。研究了通过咪唑环上的 C8 原子、嘧啶环和咪唑环之间的桥接 C4 和 C5 原子以及嘧啶环上的 N、O 和 S 原子的反应途径。结果表明，最可行的途径是在嘧啶环的 N、O 和 S 原子之间通过长程溶剂周围的质子转移，带有双水合催化：N(7)H + 2H2O → IM89 → IM90 → P13 + 2H2O → IM91 → IM92 → P6 + 2H2O → IM71 → IM72 → P7 + 2H2O → IM107 → IM108 → P18 + 2H2O → IM111 → IM112 → P19 + 2H2O → IM113 → IM114 → P17 + 2H2O → IM105 → IM106 → N(9)H + 2H2O，这是在 IM89 到 IM90 过渡中通过 TS54 的最高能量屏障为 44.0 kJ mol(-1)。小的能量势垒与实验观察结果非常吻合，即在室温下 2-TX 在水中发生互变异构。在水相，最稳定的中间体是 IM21[N(7)H + 2H2O]，可能共存的物质是单水合 IM1、IM9、IM39 和 IM46，以及双水合 IM5、IM8、IM13、IM16、IM81、IM89、IM90、IM91 和 IM106 复合物，它们相对于 IM21 的相对浓度大于 10(-6)(1 ppm)。
