7-硫代鸟嘌呤互变异构体的密度泛函理论计算

在密度泛函B3LYP/6-311G^**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.     

6-硫代黄嘌呤互变异构体的密度泛函理论计算

在密度泛函B3LYP/6-311G**水平下,对14种气相和水相中可能存在的6-硫代黄嘌呤异构体进行了几何构型的全自由度优化,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,6-硫代黄嘌呤在气相中和水相中主要以硫酮的形式存在.在气相和水相中,硫酮-N7(H)均比硫酮-N9(H)更稳定.计算结果同已有实验结果一致.6-硫代黄嘌呤异构化的熵效应小,对互变异构平衡几乎没有显著的影响,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.     

2-硫代黄嘌呤互变异构体的密度泛函理论计算

在密度泛函B3LYP/6-311G**水平上,对14种气相和水相中可能存在的2-硫代黄嘌呤互变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,2-硫代黄嘌呤在气相和水相中主要以酮式结构形式存在,与已有实验结果一致.在气相和水相中,酮式结构—N(7)(H)均比酮式结构—N(9)(H)更稳定.2-硫代黄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,而焓变对互变异构却产生了主要的影响.水溶剂化自由能与异构体的气相偶极矩存在相关性.另外,较详细地考察了2-硫代黄嘌呤与6-硫代黄嘌呤的相对稳定性.     

5-氟尿嘧啶和5-氯尿嘧啶及其互变异构体的理论计算研究

采用HF/3-21G方法, 对6种气相和水相中可能存在的5-氟尿嘧啶(和5-氯尿嘧啶)互变异构体进行了构象分析.采用B3LYP/6-311＋G**方法对处于优势构象时的各互变异构体进行了几何全优化, 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, 5-氟尿嘧啶和5-氯尿嘧啶在气相中和水相中主要以双酮形式存在. 5-氟尿嘧啶和5-氯尿嘧啶的熵效应小, 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. 讨论了水溶剂化作用对异构体的能量、电荷分布和偶极矩的影响. 溶剂化自由能与异构体的气相偶极矩存在相关性. 另外, 详细地将5-氟尿嘧啶和5-氯尿嘧啶与尿嘧啶进行了对比, 获得三者最稳定异构体间电子结构异同的有用信息.     

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

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.     

5-氟胞嘧啶互变异构的密度泛函理论计算

采用BH-HLYP/6-311＋G**方法对10种气相和水相中可能存在的5-氟胞嘧啶互变异构体进行了几何全优化, 并计算出它们的总能量和吉布斯自由能. Onsager反应场溶剂模型用于水相的计算. 计算结果表明, 5-氟胞嘧啶在气相中主要以烯醇式-氨基式形式存在, 在水相中主要以酮式-氨基式形式存在. 溶剂化自由能与异构体的气相偶极矩存在相关性．进一步求得互变异构化以及构象异构化和顺反异构化的过渡态, 探讨异构化过程中的几何结构和能量的变化.     

2,6-硫代黄嘌呤质子互变异构反应机理的理论研究

在密度泛函B3LYP/6-311G~(**)理论水平上,对气相和水相中2,6-硫代黄嘌呤各烯醇式与酮式水助质子互变异构体及其过渡态进行几何构型全自由度优化,获得它们在气相和水相中的几何结构和电子结构,PCM反应场溶剂模型用于水相计算.结果显示在气相和水相中,水参与反应降低了互变异构质子迁移的反应活化能,对互变异构质子迁移的反应起到催化作用,但是没有改变各异构体的稳定性顺序,其顺序为W1＞W3＞W2.进一步研究了2,6-硫代黄嘌呤各烯醇式与酮式水助质子互变异构的反应机理,提出了2,6-硫代黄嘌呤各烯醇式与酮式互变异构质子迁移的反应为平面六元环的过渡态结构.探讨了溶剂化效应对互变异构体的几何结构、能量、电荷分布以及互变异构反应活化能的影响等.     

p-羟基苯丙酮酸互变异构反应机理溶剂效应的理论研究

采用密度泛函B3LYP方法,在6-31+G**基组水平上对p-羟基苯丙酮酸质子转移引起的烯醇式-酮式互变异构反应机理进行了计算研究,获得了互变异构过程的反应焓、活化能、活化吉布斯自由能和质子转移反应的速率常数等参数。Onsager反应场溶剂模型用于水相和甲醇相的计算,计算结果表明,p-羟基苯丙酮酸无论在气相还是水相、甲醇相中,其酮式异构体都是最稳定的存在形式,烯醇式异构体也会以一定量共存。气相中孤立分子内质子转移几何构型改变较显著,异构化反应需要较大的活化能,不利于发生质子转移,Onsager模型计算方法对质子转移反应的影响较小。     

胞嘧啶一水复合物质子转移异构化反应机理的理论研究

采用密度泛函B3LYP方法,在6-311＋G＊＊基组水平上对胞嘧啶一水复合物质子转移引起的氨-酮式、氨-烯醇式与亚胺-酮式互变异构反应机理进行了计算研究,获得了互变异构过程的反应焓、活化能、活化吉布斯自由能和质子转移反应速率常数等参数。将Onsager反应场溶剂模型用于水相的计算,结果表明,胞嘧啶一水复合物无论在气相中...     

黄嘌呤及其互变异构体的密度泛函理论研究

嘌呤碱及其衍生物在生物系统中起重要作用。对人具有兴奋和利尿作用的茶碱和咖啡碱就是黄嘌呤的甲基衍生物。黄嘌呤存在多种互变异构体，从理论计算的角度研究这些互变异构体的几何结构、电子结构及相对稳定性，进一步研究溶剂对其结构和性质的影响是有意义旧。密度泛函理论方法既考虑了电子相关，又较其它CI（组态相互作用）或MPn（n级微扰）方法节省机时。其计算结果较好，被广泛应用于研究各种化合物。本文采用密度泛函B3LYP／6—311G方法对14种黄嘌呤可能的互变异构体（见图1），分别在气相和水相中进行几何构型全自由度优化和能量计算，讨论了异构体的相对稳定性，水的溶剂化作用对异构体的能量、几何构型、电荷分布和偶极矩的影响，探讨了溶剂极性对异构体的能量和偶极矩的影响。     

AM1 and PM3 Study of Tautomerism of Hypoxanthine in the Gas and Aqueous Phases

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, dipole moments, and ionization potentials for the eight possible tautomers of hypoxanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimization. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the two keto tautomers H17 and H19 are the predominant species at room temperature in the gas and aqueous phase. However, the tautomer H17 is the more dominant species in gas phase, while the H19 tautomer is the more dominant species in the aqueous phase. Comparison with available experimental data provides support for the results derived from theoretical computations. The entropy effect on the Gibbs free energy of hypoxanthine is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant in the determination of the equilibrium constant.     

Reaction mechanism and tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution: a combined Monte Carlo and quantum mechanics study

A combined Monte Carlo and quantum mechanical study was carried out to analyze the tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution. Second- and fourth-order M?ller-Plesset perturbation theory calculations indicate that in the gas phase thiol (Pym-SH) is more stable than the thione (Pym-NH) by ca. 8 kcal/mol. In aqueous solution, thermodynamic perturbation theory implemented on a Monte Carlo NpT simulation indicates that both the differential enthalpy and Gibbs free energy favor the thione form. The calculated differential enthalpy is DeltaH(SH)(-->)(NH)(solv) = -1.7 kcal/mol and the differential Gibbs free energy is DeltaG(SH)(-->)(NH)(solv) = -1.9 kcal/mol. Analysis is made of the contribution of the solute-solvent hydrogen bonds and it is noted that the SH group in the thiol and NH group in the thione tautomers act exclusively as a hydrogen bond donor in aqueous solution. The proton transfer reaction between the tautomeric forms was also investigated in the gas phase and in aqueous solution. Two distinct mechanisms were considered: a direct intramolecular transfer and a water-assisted mechanism. In the gas phase, the intramolecular transfer leads to a large energy barrier of 34.4 kcal/mol, passing through a three-center transition state. The proton transfer with the assistance of one water molecule decreases the energy barrier to 17.2 kcal/mol. In solution, these calculated activation barriers are, respectively, 32.0 and 14.8 kcal/mol. The solvent effect is found to be sizable but it is considerably more important as a participant in the water-assisted mechanism than the solvent field of the solute-solvent interaction. Finally, the calculated total Gibbs free energy is used to estimate the equilibrium constant.     

On isomers and tautomers of Nitro-1-deazapurine: A DFT study

The 1-deazapurine molecules substituted by the NO₂ group at three different positions of the six-membered ring were subject of computational study performed at the B3LYP/cc-pVTZ level. For each substitution three tautomers were considered. The N3H tautomers are relatively instable in the gas and water phases which is due to significant decrease in aromaticity of the N3H forms. In the gas phase, the equilibria between the N7H and N9H tautomers are determined by a competition of the repulsive and attractive intermolecular interaction of different moieties of Nitro-1-deazapurine. The close neighborhood of the two tertiary N atoms and attractive close neighborhood of the tertiary N atom and the NH group result in preference of the N9H tautomer over the N7H one by ca. 3.5 kcal/mol. By comparing energy of different forms and proposed isodesmic reaction we showed that the Gibbs free energy of the attractive interaction between the NO₂ and HN groups is equal to ca. 1.0 kcal/mol, whereas the repulsive interaction between the NO₂ group and the tertiary N atom of the imidazole is equal to ca. 6.4 kcal/mol. It was shown also that the increase in dipole moment in the water media is the crucial effect influencing the N7H/N9H tautomeric equilibria of Nitro-1-deazapurines. For the three isomers dissolved in water, the two tautomers, N7H and N9H, are predicted to be observed and the former should dominate slightly for the 2-Nitro isomer whereas the latter for the 6-Nitro and 1-Nitro isomers. The NBO analysis showed that the NO₂ group withdraws 0.3 e of the σ-electrons from the pyridine ring of 1-deazapurine and has no influence on the σ-electrons of the imidazole ring. The NBO analysis shows also that the ratio between number of π-electrons which are withdrawed from imidazole vs. pyridine ring is characteristic for position of the substitution. The isodesmic reaction used revealed also that the NO₂ group destabilizes the N3H-1-deazapurine system, whereas it stabilizes the N7H- and N9H-1-deazapurine systems.     

Theoretical study of three predominant tautomers of 2-oxo-6-methylpurine and their two transition state structures

The three predominantly stable tautomers of 2-oxo-6-methylpurine were studied in gas phase and aqueous solution by means of quantum mechanical calculations. Two transition state structures connecting these three tautomeric forms on the free energy surface were determined. The activation free energy for the intramolecular proton transfer in gas phase was calculated to be considerably smaller than the bond energy of either N-H or O-H: 59.01 and 30.37 kcal/mol for N9→N3 and N1→O2, respectively, obtained at the QCISD(T)/6-31G+(d)//MP2(full)/6-31G(d) level of theory.