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.     

尿酸质子转移反应的理论研究I——分子内质子转移研究

使用量子化学中的Hartree-Fock方法和密度泛函理论中的B3LYP方法，分别在3－21G^*和6－31G（d)水平上，计算了尿酸分子从三羰基异构体向三羟基异构体的转化。结果表明，转化过程经历了单羟基和双羟基异构体2种中间物和3种过渡态时的分子内质子转移（IPT），转移中的H原邻近的N，O和C原子形成了具有四元环结构的过渡态。随着IPT的进行，N－H键逐渐被削弱和断裂，O－H键则逐渐生成。3个反应的活化能分别为190.3kJ/mol,181.4kJ/mol和249.9kJ/mol(B3LYP/6-31G(d))。较高的活化能表明在室温下，无催化剂的IPT难以进行。     

方酸构象和振动光谱的从头算研究

在6-31G^*^*水平上对方酸(3, 4-二羟基-3-环丁烯-1, 2-二酮)三种构象异构体进行了SCF计算。结果表明ZZ型异构体最稳定, ZE型次之。用等键反应能量分析方酸的稳定性, 并与苯作比较, 讨论方酸的芳香性。在6-31G水平上计算了方酸三种构象的振动频率。     

ANTA的结构、性质及其互变异构的理论研究

对3-硝基-5-氨基-1,2,4-三唑(ANTA)的三种异构体,1H-ANTA(Ⅰ),2－ANTA(Ⅱ)和4H-ANTA(Ⅲ)在,bainitio-HF/3-21G和DFT-B3LYP/3-21G势能面计算的基础上,进行6-311G^**几何参数全优化,MP2总能量和SCRF溶剂(四氢呋喃)效应计算。以振动分析和统计热力学为基础,作标题物热力学性质以及Ⅰ和Ⅱ之间的互变异构反应计算,求得分子几何,电子结构和300～1000K范围的焓、熵和热容以及Ⅰ和Ⅱ互变异构平衡常数和速率常数。发现在三种异构体中在通常温度下以Ⅱ在气相下最稳定,Ⅰ在溶液中最稳定。低温下难以发生异构化反应,温度可提高Ⅰ与Ⅱ之间的互变速率,在800K时两种异构体在气相中等量共存;大于800K时Ⅰ更为稳定。     

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。     

N8H8环状异构体的结构与稳定性的理论研究

采用密度泛函理论的B3LYP方法在6-311 G**基组水平上对N8H8氮氢环状化合物可能存在的构型进行了几何优化,得到74种稳定异构体,应朋A然键轨道理论NBO和分子中的原子理论AIM分析了这些化合物成键特征和相对稳定性,G3MP2方法汁算了各异构体的能量及生成热.研究结果表明:N原子孤对电子到相邻的氮氮键的超共轭作用是影响氮氮键长变化的丰要因素;N8H8环状异构体的稳定性顺序为:六元环>七元环>八元环,五元环>三元环>四元环,六元环是这些N8H8环状异构体中最稳定的,最不稳定的是四元环,G19是所有环状异构体中能量最低的:M3能量最高,稳定性最差,A7密度最大.     

2-酰基-1,3-环二酮类化合物互变异构的理论计算

采用MP2/6-31+G**//B3LYP/6-31+G**方法,系统地研究了2-酰基-1,3-环二酮类化合物的互变异构性质,探讨了环的饱和性、环的大小、环上杂原子以及溶剂效应对各互变异构体相对稳定性的影响。结果表明:(1)未烯醇化的异构体由于无法形成分子内氢键而具有较高的能量;(2)环上杂原子的推电子效应提高了邻位羰基氧上的负电荷,从而有利于相应环外烯醇式异构体的稳定;(3)对化合物3-酰基-1H-吡啶-2,4-二酮,3-酰基吡喃-2,4-二酮,2-酰基环戊-4-烯-1,3-二酮和3-酰基吡咯-2,4-二酮,由互变异构形成的环的芳香性在各异构体的相对稳定性中扮演着决定性的作用。     

1, 2-二硒方酸气相酸性和芳香性的理论研究

在RHF/6-311G^*^*水平优化得到1,2-二硒方酸(3,4-二羟基-3-环丁烯-1,2-二硒酮)三种平面构象异构体的平衡几何构型。进一步用MP2(full)/6-311G^*//RHF/6-311G^*^*方法计算三种异构体的单点能量,发现ZZ型异构体是能量最低构象,且ZZ和ZE型能量非常接近。用优化的最稳定构象ZZ型异构体在RHF/6-311G^*^*//RHF/6-311G^*^*,RHF/6-311+G^*^*//RHF/6-311+G^*^*,MP2(full)/6-311+G^*^*//RHF/6-311+G^*^*和B3LYP/6-311+G^*^*//B3LYP/6-311+G^*^*水平计算其气相酸性[ΔGⅲ~(~2~9~8~K~)]和同键反应芳香性稳定化能(HASE)。用基团加和法(groupincrementapproach)在RHF/6-311+G^*^*//RHF/6-311+G^*^*和B3LYP/6-311+G^*^*//B3LYP/6-311+G^*^*水平计算其磁化率增量(Λ)。计算结果指出标题化合物的键长发生了平均化,同键反应芳香性稳定化能和磁化率增量均为负值,表明它具有芳香性,实现了标题化合物芳香性的几何、能量和磁性的判定。     

N8H8环状异构体的结构与稳定性的理论研究

采用密度泛函理论的B3LYP方法在6-311＋＋G**基组水平上对N₈H₈氮氢环状化合物可能存在的构型进行了几何优化, 得到74种稳定异构体, 应用自然键轨道理论NBO和分子中的原子理论AIM分析了这些化合物成键特征和相对稳定性, G3MP2方法计算了各异构体的能量及生成热. 研究结果表明: N原子孤对电子到相邻的氮氮键的超共轭作用是影响氮氮键长变化的主要因素; N₈H₈环状异构体的稳定性顺序为: 六元环＞七元环＞八元环, 五元环＞三元环＞四元环, 六元环是这些N₈H₈环状异构体中最稳定的, 最不稳定的是四元环, G19是所有环状异构体中能量最低的; M3能量最高, 稳定性最差, A7密度最大.     

5-醛基-1,2,3-三唑互变异构的理论研究

用密度泛函B3LYP/6-311++G**方法,对气相和水相中的5-醛基-1,2,3-三唑互变异构体进行了几何构型全自由度优化,获得了它们在气相和水相中的几何结构和电子结构.讨论了不同的取代基团和溶剂化效应对互变异构体的几何结构、能量以及互变异构反应活化能的影响.并进一步研究了N1-H、N2-H和N3-H型三唑之间的互变异构机理:(a)分子内质子转移;(b)水助质子转移.计算结果表明,途径(b)所需要的活化能较小,平均为101.31kJ/mol,途径(a)为211.70kJ/mol.     

复合物Ca+-RNA碱基的结构与稳定性

Gas-phase metal ion affinities and optimized structures of RNA nucleic acid bases for the Ca+ were determined at a density functional level employing the hybrid B3LYP exchange correlation potential in connection with the 6-311+G(2df,2p) basis set. All the molecular complexes, obtained by the interaction between several low-lying tautomers of RNA nucleic acid and Ca+ on the different binding sites, were considered. For Cytosine, the most stable complex was obtained starting from the most stable tautomer of the free nucleic acid base tautomers. As to thymine, the bond energy of the ion with the most stable tautomer of the free nucleic acid base is the weakest among the three tautomer’s complexes, and that of the ion with least stable tautomer of the free nucleic acid base is the strongest . Uracil is similar to thymine. The two kinds of relation, bond energy and total energy for the complex, are in disagreement, as the metal affinities of RNA bases for the Ca+ depend on binding sites, and total energy of complex (Ca+-RNA base) relies on all atoms and their relative positions in the complex.     

Tautomerism and infrared spectra of 2-thiopurine: an experimental matrix isolation and theoretical ab initio and density functional theory study

Infrared spectra of 2-thiopurine (2-mercaptopurine, 2-purinethiol ) isolated in low-temperature Ar and N2 matrixes are reported. These spectra indicate that the compound adopts exclusively the thiol N9H tautomeric form. The theoretical calculations of relative energies of 2-thiopurine tautomers have been carried out at the MP4(SDTQ)//HF level using the 6-31G(d,p) basis set. The thiol N9H tautomer was predicted to be the most stable of all isomers of 2-thiopurine. The infrared spectra of the tautomers of 2-thiopurine have been calculated at the DFT(B3LYP)/6-31G(d,p) level. Good agreement between the experimental spectra and the spectra calculated for thiol N9H tautomer supported the identification of the dominant tautomer. It has also allowed for the reliable assignment of the bands observed in the experimental IR spectrum.     

Conformation and tautomerism of the cimetidine molecule: a theoretical study

The cimetidine molecule conformation and tautomer stability was studied at the ab initio HF/6-31G** level and for single point energies at the MP2/6-31G** level. The most stable N3-H cimetidine tautomer was found to be more stable than the most stable N1-H tautomer by ca. 3.7 and 5.0 kcal/mol, at the HF/6-31G** and MP2/6-31G**//HF/6-31G** level, respectively. At the HF/6-31G** level, the most stable N3-H and 1-H forms are stabilized by the intramolecular N3′-H?N1 hydrogen bond and N1-H?N4′, respectively. However, when the correlation effects are included at the MP2/6-31G**//HF/6-31G** level, the most stable N3-H and N1-H tautomers appeared to be folded forms without hydrogen bonds.     

Bond energies and attachments sites of sodium and potassium cations to DNA and RNA nucleic acid bases in the gas phase

Gas-phase metal affinities of DNA and RNA bases for the Na(+) and K(+) ions were determined at density functional level employing the hybrid B3LYP exchange correlation potential in connection with the 6-311+G(2df,2p) basis set. All the molecular complexes, obtained by the interaction between several low-lying tautomers of nucleic acid bases and the alkali ions on the different binding sites, were considered. Structural features of the sodium and potassium complexes were found to be similar except in some uracil and thymine compounds in which the tendency of potassium ion toward monocoordination appeared evident. B3LYP bond energies for both metal ions were in agreement with the available experimental results in the cases of uracil and thymine for which the most stable complex was obtained starting from the most stable tautomer of the free nucleic acid base. For adenine, although the interaction of the ions with the most stable free tautomer generated the least stable molecular complex, the best agreement with experiment was found in just this case. For the remaining cytosine and guanine bases, our calculations indicated that the metal ion affinity value closest to experiment should be determined taking into account the role played by the different tautomers of the free bases with similar energy and all the possible complexes obtained by them.     

Negatively charged xanthine. I. Anions formed by canonical isomers

The possibility of an excess electron binding to canonical isomers of xanthine in the gas phase was studied at the coupled-cluster level with single and double excitations using the 6-31++G** basis sets supplemented with the 4(sp)3d set of diffuse functions. It was found that xanthine should exist in the gas phase as one canonical tautomer while all the other tautomers are not likely to be detected experimentally because of their significant thermodynamic instability. On the other hand, all canonical tautomers (except one) were found to be capable of forming electronically stable anionic states of dipole-bound nature. However, the only thermodynamically stable anion (with vertical electron binding energy estimated to be 0.041 eV) based on xanthine tautomers is the one supported by the most stable neutral species.     

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.     

Evaluation of the origin of conformational and tautomeric preferences in N‐formylformamide – A quantum chemical study

Quantum chemical study of N‐formylformamide (NFF) was carried out at various theoretical levels and the determinate equilibrium conformations were recomputed at the high level ab initio methods such as G2MP2, G2, G3, and complete basis set (CBS)‐QB3. The computational results reveal that the amide resonance and intramolecular hydrogen bonding are two superior factors in determining the most stable conformation of diamide (DA) and amide–imidic (AI) acid tautomers, respectively. The evaluation of hydrogen bond energies predicts that the hydrogen bond (HB( strength of NFF is weaker than the malonaldehyde (MA). But the results of atoms in molecules (AIM(, natural bond orbital (NBO), and geometrical parameters are given a different order, E_HB(NFF) > E_HB(MA). Although the bond average energies of tautomerization process emphasized on more stability of AI tautomer, but our theoretical calculations reveal that the DA conformers are more stable than the AI ones. The population analyses of equilibrium conformations by NBO method also predict that the origin of tautomeric preference is mainly because of the electron delocalization of amide functional group, especially LP(N)→ π*_C?O charge transfer. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

A quantum chemical study of conformational and tautomeric preferences, intramolecular hydrogen bonding and π-electron delocalization on dinitrosomethane; in gas phase and water solution

HF, B3LYP, and MP2 methods with the standard basis set, 6-311++G(d,p), were employed to study various aspects of dinitrosomethane (DNM). These results are compared with the outcomes of G2, G2MP2, G3, and CBS-QB3 methods. In the present study, we first characterized the equilibrium conformations, especially global minima. In general, the nitroso-oxime (NO) tautomers of DNM are stabler than the dioxime and dinitroso ones. Furthermore, it was found that the stablest form of NO tautomer is global minima among the known local minima. Surprisingly, the chelated form of NO tautomer, with O–H···O intramolecular hydrogen bond (IMHB), is less stable than the global minimum. In spite of this instability, we comprehensively studied various aspects of IMHB to evaluate the effect of heteroatom’s (N). The results of open–close and related rotamer models predict that the heteroatoms weaken the hydrogen bond, whereas, the geometric, topologic, and natural bond orbital parameters emphasize on opposite conclusion. The HOMA of aromaticity aromaticity index clearly predicts that the π-electron delocalization of chelated form of NO tautomer is greater than the malonaldehyde. Finally, the solvent effects on the properties of DNM tautomers have been estimated by continuum (PCM, IPCM, and SCIPCM), discrete, and mixed models. Theoretical results clearly show that the potential energy surface of DNM, especially global minima, is strongly affected by the solvent.     

苯甲酰-1,3-环己二酮类化合物互变异构的理论计算

对苯甲酰-1,3-环己二酮的各异构体进行了HF/6-31G＊水平的几何优化,然后对能量低的三酮式和2个顺式烯醇式异构体进行了更广泛的计算,探讨了计算方法、基组大小对异构体相对稳定性的影响。在此基础上,对该类化合物的互变异构化平衡常数、能垒进行了计算,在平衡常数的计算中充分考虑了溶剂的影响并结合实验结果进行了分析。最后,对有代表性的苯环2-位取代衍生物进行了计算,发现互变异构自由能与其HPPD酶抑制活性间存在着较好的相关关系。     

Interaction with glycine increases stability of a mutagenic tautomer of uracil. A density functional theory study

The most stable structures for the gas-phase complexes of minor tautomers of uracil (U) with glycine (G) were characterized at the density functional B3LYP/6-31++G level of theory. These are cyclic structures stabilized by two hydrogen bonds. The relative stability of isolated tautomers of uracil was rationalized by using thermodynamic and structural arguments. The stabilization energies for complexes between the tautomers of U and G result from interplay between the stabilizing two-body interaction energies and destabilizing one-body terms. The latter are related to the energies of (i) tautomerization of the unperturbed moieties and (ii) distortions of the resulting rare tautomers in the complex. The two-body term describes the interaction energy between distorted tautomers. The two-body interaction energy term correlates with perturbations of length of the proton-donor bonds as well as with deprotonation enthalpies and proton affinities of the appropriate monomer sites. It was demonstrated that the relative instability of rare tautomers of uracil is diminished due to their interactions with glycine. In particular, the instability of the third most stable tautomer (U(III)) is decreased from 11.9 kcal/mol for non-interacting uracil to 6.7 kcal/mol for uracil in a complex with the zwitterionic tautomer of glycine. A decrease of instability by 5.2 kcal/mol could result in an increase of concentration of U(III) by almost 5 orders of magnitude. This is the tautomer with proton donor and acceptor sites matching guanine rather than adenine. Moreover, kinetic characteristics obtained for the glycine-assisted conversion of the most stable tautomer of uracil (U(I)) to U(III) indicate that the U(I)<-->U(III) thermodynamic equilibrium could be easily attained at room temperature. The resulting concentration of this tautomer falls in a mutationally significant range.