Computational study of the deamination reaction of cytosine with H2O and OH-

The mechanism for the deamination reaction of cytosine with H(2)O and OH(-) to produce uracil was investigated using ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), and B3LYP/6-31G(d) levels and for anions at the B3LYP/6-31+G(d) level. Single-point energies were also determined at B3LYP/6-31+G(d), MP2/GTMP2Large, and G3MP2 levels of theory. Thermodynamic properties (DeltaE, DeltaH, and DeltaG), activation energies, enthalpies, and free energies of activation were calculated for each reaction pathway that was investigated. Intrinsic reaction coordinate analysis was performed to characterize the transition states on the potential energy surface. Two pathways for deamination with H(2)O were found, a five-step mechanism (pathway A) and a two-step mechanism (pathway B). The activation energy for the rate-determining steps, the formation of the tetrahedral intermediate for pathway A and the formation of the uracil tautomer for pathway B, are 221.3 and 260.3 kJ/mol, respectively, at the G3MP2 level of theory. The deamination reaction by either pathway is therefore unlikely because of the high barriers that are involved. Two pathways for deamination with OH(-) were also found, and both of them are five-step mechanisms. Pathways C and D produce an initial tetrahedral intermediate by adding H(2)O to deprotonated cytosine which then undergoes three conformational changes. The final intermediate dissociates to product via a 1-3 proton shift. Deamination with OH(-), through pathway C, resulted in the lowest activation energy, 148.0 kJ/mol, at the G3MP2 level of theory.     

Mechanistic study of the deamination reaction of guanine: a computational study

The mechanism for the deamination of guanine with H(2)O, OH(-), H(2)O/OH(-) and for GuaH(+) with H(2)O has been investigated using ab initio calculations. Optimized geometries of the reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), B3LYP/6-31G(d), and B3LYP/6-31+G(d) levels of theory. Energies were also determined at G3MP2, G3MP2B3, G4MP2, and CBS-QB3 levels of theory. Intrinsic reaction coordinate (IRC) calculations were performed to characterize the transition states on the potential energy surface. Thermodynamic properties (ΔE, ΔH, and ΔG), activation energies, enthalpies, and Gibbs free energies of activation were also calculated for each reaction investigated. All pathways yield an initial tetrahedral intermediate and an intermediate in the last step that dissociates to products via a 1,3-proton shift. At the G3MP2 level of theory, deamination with OH(-) was found to have an activation energy barrier of 155 kJ mol(-1) compared to 187 kJ mol(-1) for the reaction with H(2)O and 243 kJ mol(-1) for GuaH(+) with H(2)O. The lowest overall activation energy, 144 kJ mol(-1) at the G3MP2 level, was obtained for the deamination of guanine with H(2)O/OH(-). Due to a lack of experimental results for guanine deamination, a comparison is made with those of cytosine, whose deamination reaction parallels that of guanine.     

钠氟类硅烯插入RH键(R=F,OH,NH2,CH3)反应的理论研究

用密度泛函方法研究了钠氟类硅烯插入R_H键(R=F,OH,NH2,CH3)的反应机理.4个反应的机制类似,反应经历了类硅烯的亲电接近、亲核插入和取代三个阶段之后,形成中间络合物,4个反应的势垒分别为0.9,61.7,114.6和190.6kJ/mol(经零点能校正).中间络合物可以解离为取代硅烷和NaF,这是一个无过渡态的过程.反应能分别是-122.6,-96.3,-6.8和50.2kJ/mol.     

DFT studies of the phosphinidene derivative HPNaF and its insertion reaction with R–H(R=F,OH, NH<Subscript>2</Subscript>, CH<Subscript>3</Subscript>)

The formations of the phosphinidene derivative HPNaF and its insertion reactions with R–H (R=F, OH, NH₂, CH₃) have been systematically investigated employing the density functional theory (DFT), such as the B3LYP and MPW1PW91 methods. A comparison with the results of MP2 calculations shows that MPW1PW91 underestimates the barrier heights for the four reactions considered. Similarly, the same is also true for the B3LYP method depending on the selected reactions, but by much less than MPW1PW91, where the barrier heights of the four reactions are 25.2, 85.7, 119.0, and 142.4 kJ/mol at the B3LYP/6-311+G* level of theory, respectively. All the mechanisms of the four reactions are identical to each other, i.e., an intermediate has been located during the insertion reaction. Then, the intermediate could dissociate to substituted phosphinidane(H₂RP) and NaF with a barrier corresponding to their respective dissociation energies. Correspondingly, the reaction energies for the four reactions are −92.2, −68.1, −57.2, and −44.3 kJ/mol at the B3LYP/6-311+G* level of theory, respectively, where both the B3LYP and MPW1PW91 methods underestimate the reaction energies compared with the MP2 results. The linear correlations between the calculated barrier heights and the reaction energies have also been observed. As a result, the relative reactivity among the four insertion reactions should be as follows: H–F > H–OH > H–NH₂ > H–CH₃.     

Computational study of the reactions of SiH3X (X=H, Cl, Br, I) with HCN

Ab initio calculations were carried out for the reactions of silane and halosilanes (SiH3X, X=H, Cl, Br, I) with HCN. Geometries of the reactants, transition states, intermediates and products were optimized at HF, MP2, and B3LYP levels of theory using the 6-31G(d) and 6-31G(d,p) basis sets. Energies were also obtained using G3MP2 and G3B3 levels of theory. Intrinsic reaction coordinate (IRC) calculations were performed to characterize the transition states on the potential energy surface. It was found that HCN can react with silane and halosilanes via three different mechanisms. One involves HX elimination by a one-step pathway producing SiH3CN. The second mechanism consists of H2 elimination, producing SiH2XCN via a one-step pathway or three multiple-step pathways. The third mechanism involves dissociation of SiH3X to various products, which can then react with HCN. Activation energies, enthalpies, and free energies of activation along with the thermodynamic properties (DeltaE, DeltaH, and DeltaG) of each reaction pathway were calculated. The reaction of SiH3X with HCN produce different products depending on substituent X. We have found that the standard 6-31G(d) bromine basis set gave results which were in better agreement with the G3MP2 results than for the Binning-Curtiss basis set. Computed heats of formation (DeltaHf) for SiH3CN, SiH3NC, SiH2ClCN, SiH2BrCN, SiH2ICN, SiHCl, SiHBr, and SiHI were found to be 133.5, 150.8, -34.4, 23.6, 102.4, 48.7, 127.1, and 179.8 kJ mol-1, respectively. From enthalpies calculated at G3MP2, we predict that the DeltaHf for SiH2 to be 262.8 kJ mol-1 compared to the experimental value of 273.8+/-4.2 kJ mol-1.     

乙醇-水分子团簇C2H5OH(H2O)n (n=1-9)稳定结构的量子化学研究

采用密度泛函理论B3LYP方法, 在B3LYP/6-311++G(2d,2p)//B3LYP/6-311++G(d,p)基组水平上对乙醇-水分子团簇(C₂H₅OH(H₂O)_n (n=1-9))的各种性质进行研究, 如: 优化的几何构型、结构参数、氢键、结合能、平均氢键强度、自然键轨道(NBO)电荷分布、团簇的生长规律等. 结果表明, 从二维(2-D)环状结构到三维(3-D)笼状结构的过渡出现在n=5的乙醇-水分子团簇中. 此外, 利用团簇结合能的二阶差分、形成能、能隙等性质, 发现在n=6时乙醇-水分子团簇的最低能量结构稳定性较好, 可能为幻数结构. 最后, 为了进一步探讨氢键本质, 将C₂H₅OH(H₂O)_n (n=2-9)最低能量结构的各种性质与纯水分子团簇(H₂O)_n (n=3-10)比较, 结果表明前者与后者中的水分子之间氢键相似.     

类锗烯H2C=GeLiCl与RH(R=F,OH, NH2)的插入反应

采用DFT B3LYP和QCISD方法研究了不饱和类锗烯H2C=GeLiCl与RH(R=F, OH, NH2)的插入反应. 在B3LYP/6-311+G(d,p)水平上优化了反应势能面上的驻点构型. 结果表明, H2C=GeLiCl与HF、H2O 或NH3发生插入反应的机理相同. QCISD/6-311++G(d,p)//B3LYP/6-311+G(d,p)计算的三个反应的势垒分别为173.53、194.48和209.05 kJ·mol-1, 反应热分别为60.18、72.93和75.34 kJ·mol-1. 相同条件下发生插入反应时, 反应活性顺序都是H—F>H—OH>H—NH2.     

Quantum mechanics study and Monte Carlo simulation on the hydrolytic deamination of 5-methylcytosine glycol

The efficient formation of 5-methylcytosine glycol (mCg) and its facile deamination to thymine glycol (Tg) may account for the prevalent C → T transition mutation found at methylated CpG site (mCpG) in human p53 gene, a hallmark for many types of human tumors. In this work, the hydrolytic deamination of mCg was investigated at the MP2 and B3LYP levels of theory using the 6-311G(d,p) basis set. In the gas phase, three pathways were explored, paths A-C, and it indicates that the direct deamination of mCg with H(2)O by either pathway is unlikely because of the high activation free energies involved in the rate-determining steps, the formation of the tetrahedral intermediate for paths A and B as well as the formation of the Tg tautomer for path C. In aqueous solution, the role of the water molecules in the deamination of mCg with H(2)O was analyzed in two separate parts: the direct participation of one water molecule in the reaction pathway, called the water-assisted mechanism; and the complementary participation of the aqueous solvation. The water-assisted mechanism was carried out for mCg and the cluster of two water molecules by quantum mechanical calculations in the gas phase. This indicates that the presence of the auxiliary water molecule significantly contributes to decreasing all the activation free energies. The bulk solution effect on the water-assisted mechanism was included by free energy perturbation implemented on Monte Carlo simulations, which is found to be substantial and decisive in the deamination mechanism of mCg. In this case, the water-assisted path A is the most plausible mechanism reported for the deamination of mCg, where the calculated activation free energy (22.6 kcal mol(-1) at B3LYP level of theory) agrees well with the experimentally determined activation free energy (24.8 kcal mol(-1)). The main striking results of the present DFT computational study which is in agreement with previous experimental data is the higher rate of deamination displayed by mCg residues with respect to 5-methylcytosine (mC) bases, which supports that the deamination of mCg contributes significantly to the C → T transition mutation at mCpG dinucleotide site.     

The computation of the potential energy surface for H2 + OH → H2O + H using ab initio and density functional theory methods

The reaction energy profile for H₂ + OH → H + H₂O was computed using HF, MP2, MP4, QCISD, G1, G2, and G2MP2 ab initio methods. In addition, the B3LYP, B3P86, B3PW91, BLYP, BP291, and SVWN density functional theory (DFT) methods were also used. All the ab initio methods, with the exception of the G series, produced much higher activation barriers and heats of reaction than the experimental values. On the other hand, the DFT methods produced negative forward and reverse barriers which were too low, with the exception of the hybrid DFT methods. The G2 ab initio method generated energies which deviated from the experimental values by ∼ 1 kcal/mol and therefore should be considered a very accurate computational method. The hybrid DFT methods produced positive forward reaction barriers with energies that were 2–4 kcal/mol lower than the experimental values. The geometries of the transition state and energies computed by the ab initio and DFT methods were compared. These results suggest that, in the hybrid exchange functional, the portion of the Slater exchange term should be increased. This may be the reason why the computed energies were too low. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 62: 639–644, 1997     

AuClx (x=1, 3)催化2-炔丙基苯酮与苯炔环化反应机理

对金属元素Au采用LanL2DZ基组,对非金属元素C,H,O,Cl采用6-31G*和6-311++G**基组,用密度泛函理论的B3LYP、B3PW91、UB3LYP方法和二阶微扰理论MP2方法研究了不同氧化态的金催化剂催化2-炔丙基苯酮与苯炔环化反应的机理.结果表明:在AuCl和AuCl3的作用下,反应均能通过[4+2]和[3+2]途径生成产物.但在AuCl催化下,[4+2]反应途径比[3+2]反应途径具有更低的活化自由能,反应主要通过[4+2]途径进行;而在AuCl3催化下,[4+2]反应途径与[3+2]反应途径的活化自由能相近,反应通过两条途径竞争生成产物.比较AuCl和AuCl3的催化效果发现,不同氧化态的金催化剂改变了反应的机理,该反应的活化自由能在AuCl作用下比在AuCl3作用下低11.18 kJ·mol-1.对于该反应,AuCl表现出了更好的催化活性.这些计算结果和实验现象相吻合.     

OH(3) (-) and O(2)H(5) (-) double Rydberg anions: predictions and comparisons with NH(4) (-) and N(2)H(7) (-)

A low barrier in the reaction pathway between the double Rydberg isomer of OH(3) (-) and a hydride-water complex indicates that the former species is more difficult to isolate and characterize through anion photoelectron spectroscopy than the well known double Rydberg anion (DRA), tetrahedral NH(4) (-). Electron propagator calculations of vertical electron detachment energies (VEDEs) and isosurface plots of the electron localization function disclose that the transition state's electronic structure more closely resembles that of the DRA than that of the hydride-water complex. Possible stabilization of the OH(3) (-) DRA through hydrogen bonding or ion-dipole interactions is examined through calculations on O(2)H(5) (-) species. Three O(2)H(5) (-) minima with H(-)(H(2)O)(2), hydrogen-bridged, and DRA-molecule structures resemble previously discovered N(2)H(7) (-) species and have well separated VEDEs that may be observable in anion photoelectron spectra.     

Theoretical study on the hydrolytic deamination reaction mechanism of guanine and (H2O)n

The hydrolytic deamination reaction mechanism of guanine (G) and (H₂O)n (n = 1–4) has been theoretically investigated, including solvent effects at the B3LYP/6-31G (d,p) and MP2/6-311G (d,p) levels. The results show that the hydrolytic deamination reaction of G involves two steps. In the first step, a tetra-coordinated intermediate is generated by a hydrolysis reaction, and then deamination reaction is carried out. In the second step, the final products form via a hydrogen transfer. For the hydrolytic deamination reaction of guanine and 3H₂O or 4H₂O, only two molecules of water participate in the reaction, and other water molecule make the transition state more stable as a catalyst. The study on the potential energy surface shows that the deamination reaction of G and nH₂O does not take place because of a higher barrier for the opening system, which is in agreement with the experimental result.     

Proton-transfer and H2-elimination reactions of main-group hydrides EH4- (E = B, Al, Ga) with alcohols

The reaction of the isostructural anions of group 13 hydrides EH4- (E = B, Al, Ga) with proton donors of different strength (CH3OH, CF3CH2OH, and CF3OH) was studied with different theoretical methods [DFT/B3LYP and second-order M?ller-Plesset (MP2) using the 6-311++G(d,p) basis set]. The results show the general mechanism of the reaction: the dihydrogen-bonded (DHB) adduct (EH...HO) formation leads through the activation barrier to the next concerted step of H2 elimination and alkoxo product formation. The structures, interaction energies (calculated by different approaches including the energy decomposition analysis), vibrational E-H modes, and electron-density distributions were analyzed for all of the DHB adducts. The transition state (TS) is the dihydrogen complex stabilized by a hydrogen bond with the anion [EH3(eta2-H2)...OR-]. The single exception is the reaction of BH4- with CF3OH exhibiting two TSs separated by a shallow minimum of the BH3(eta2-H2)...OR- intermediate. The structures and energies of all of the species were calculated, leading to the establishment of the potential energy profiles for the reaction. A comparison is made with the mechanism of the proton-transfer reaction to transition-metal hydrides. The solvent influence on the stability of all of the species along the reaction pathway was accounted for by means of polarizable conductor calculation model calculations in tetrahydrofuran (THF). Although in THF the DHB intermediates, the TSs, and the products are destabilized with respect to the separated reactants, the energy barriers for the proton transfer are only slightly affected by the solvent. The dependence of the energies of the DHB complexes, TSs, and products as well as the energy barriers for the H2 release on the central atom and the proton donor strength is also discussed.     

A computational mechanistic study of the deamination reaction of melamine

A detailed computational study of the deamination reaction of melamine by OH^–, n H₂O/OH^–, n H₂O (where n = 1, 2, 3), and protonated melamine with H₂O, has been carried out using density functional theory and ab initio calculations. All structures were optimized at M06/6‐31G(d) level of theory, as well as with the B3LYP functional with each of the basis sets: 6‐31G(d), 6‐31 + G(d), 6‐31G(2df,p), and 6‐311++G(3df,3pd). B3LYP, M06, and ω B97XD calculations with 6‐31 + G(d,p) have also been performed. All structures were optimized at B3LYP/6‐31 + G(d,p) level of theory for deamination simulations in an aqueous medium, using both the polarizable continuum solvation model and the solvation model based on solute electron density. Composite method calculations have been conducted at G4MP2 and CBS‐QB3. Fifteen different mechanistic pathways were explored. Most pathways consisted of two key steps: formation of a tetrahedral intermediate and in the final step, an intermediate that dissociates to products via a 1,3‐proton shift. The lowest overall activation energy, 111 kJ mol^?1 at G4MP2, was obtained for the deamination of melamine with 3H₂O/OH^?.     

水催化2个酯分子相互转化反应的理论研究

从印楝植物内生真菌Phomopsis sp.培养液中分离得到的4-acetoxymultiplolide(1)和1-acetoxymultiplo-lide(2)在室温及水存在下能够相互转化. 提出二者相互转化最可能的4个途径(机理A~D). 在B3LYP/6-311+G(d,p)水平进行气相条件的优化, 结果表明, 无水催化的机理A中TS1和TS2的活化能均显著大于120 kJ/mol, 2个分子水催化的机理D中TS1和TS2的活化能则显著降低. 计算结果显示水的溶剂化效应能进一步降低机理D中TS1和TS2的活化能. 在MP2/6-311++G(2d,2p)//B3LYP/6-311+G(d,p)水平计算了单点能, 得到在水相时机理D中TS1和TS2的活化能分别为106.24和107.37 kJ/mol. 因此, 机理D是化合物1 和2在室温下及水存在时相互转化最可能的途径, 该途径是一种特殊的水催化分子内酯的醇解反应, 也是一种经典的亲核加成反应, 通过一种新的叔醇中间体实现.     

甲醇和氨对腺嘌呤水解脱氨机理的影响(英文)

用密度泛函理论在B3LYP/6-311G(d,p)水平上研究了甲醇和氨辅助的腺嘌呤水解脱氨机理,结果表明该反应首先是在水的亲核进攻下形成一个四面体结构中间体,然后该中间体通过构象变化得到两个不同构象,从而找到两条不同反应路径.在路径a中,辅助分子参与了过渡态的形成,起到转移氢原子的作用;而在路径b中,辅助分子仅作为介质,没有参与过渡态的形成.在氨辅助的情况下,腺嘌呤在亲核反应前发生了胺-亚胺异构化,而在甲醇辅助机理中则未发生该异构化.能量结果表明甲醇辅助腺嘌呤脱氨反应具有与水辅助类似的势垒,而氨辅助反应的势垒则比水辅助的高.     

Rates and mechanism of fluoride and water exchange in UO(2)F(5)(3-) and [UO(2)F(4)(H(2)O)](2-) studied by NMR spectroscopy and wave function based methods

The reaction mechanism for the exchange of fluoride in UO(2)F(5)(3-) and UO(2)F(4)(H(2)O)(2-) has been investigated experimentally using (19)F NMR spectroscopy at -5 degrees C, by studying the line broadening of the free fluoride, UO(2)F(4)(2-)(aq) and UO(2)F(5)(3-), and theoretically using quantum chemical methods to calculate the activation energy for different pathways. The new experimental data allowed us to make a more detailed study of chemical equilibria and exchange mechanisms than in previous studies. From the integrals of the different individual peaks in the new NMR spectra, we obtained the stepwise stability constant K(5) = 0.60 +/- 0.05 M(-1) for UO(2)F(5)(3-). The theoretical results indicate that the fluoride exchange pathway of lowest activation energy, 71 kJ/mol, in UO(2)F(5)(3-) is water assisted. The pure dissociative pathway has an activation energy of 75 kJ/mol, while the associative mechanism can be excluded as there is no stable UO(2)F(6)(4-) intermediate. The quantum chemical calculations have been made at the SCF/MP2 levels, using a conductor-like polarizable continuum model (CPCM) to describe the solvent. The effects of different model assumptions on the activation energy have been studied. The activation energy is not strongly dependent on the cavity size or on interactions between the complex and Na(+) counterions. However, the solvation of the complex and the leaving fluoride results in substantial changes in the activation energy. The mechanism for water exchange in UO(2)F(4)(H(2)O)(2-) has also been studied. We could eliminate the associative mechanism, the dissociative mechanism had the lowest activation energy, 39 kJ/mol, while the interchange mechanism has an activation energy that is approximately 50 kJ/mol higher.     

The mechanism for water exchange in [UO(2)(H(2)O)(5)](2+) and [UO(2)(oxalate)(2)(H(2)O)](2-), as studied by quantum chemical methods.

The mechanisms for the exchange of water between [UO(2)(H(2)O)(5)](2+), [UO(2)(oxalate)(2)(H(2)O)](2)(-)(,) and water solvent along dissociative (D), associative (A) and interchange (I) pathways have been investigated with quantum chemical methods. The choice of exchange mechanism is based on the computed activation energy and the geometry of the identified transition states and intermediates. These quantities were calculated both in the gas phase and with a polarizable continuum model for the solvent. There is a significant and predictable difference between the activation energy of the gas phase and solvent models: the energy barrier for the D-mechanism increases in the solvent as compared to the gas phase, while it decreases for the A- and I-mechanisms. The calculated activation energy, Delta U(++), for the water exchange in [UO(2)(H(2)O)(5)](2+) is 74, 19, and 21 kJ/mol, respectively, for the D-, A-, and I-mechanisms in the solvent, as compared to the experimental value Delta H(++) = 26 +/- 1 kJ/mol. This indicates that the D-mechanism for this system can be ruled out. The energy barrier between the intermediates and the transition states is small, indicating a lifetime for the intermediate approximately 10(-10) s, making it very difficult to distinguish between the A- and I-mechanisms experimentally. There is no direct experimental information on the rate and mechanism of water exchange in [UO(2)(oxalate)(2)(H(2)O)](2-) containing two bidentate oxalate ions. The activation energy and the geometry of transition states and intermediates along the D-, A-, and I-pathways were calculated both in the gas phase and in a water solvent model, using a single-point MP2 calculation with the gas phase geometry. The activation energy, Delta U(++), in the solvent for the D-, A-, and I-mechanisms is 56, 12, and 53 kJ/mol, respectively. This indicates that the water exchange follows an associative reaction mechanism. The geometry of the A- and I-transition states for both [UO(2)(H(2)O)(5)](2+) and [UO(2)(oxalate)(2)(H(2)O)](2-) indicates that the entering/leaving water molecules are located outside the plane formed by the spectator ligands.     

Theoretical studies of the reactions of CF3CHCLOCHF2/CF3CHFOCHF2 with OH radical and Cl atom and their product radicals with OH

The mechanisms and dynamics studies of the OH radical and Cl atom with CF(3)CHClOCHF(2) and CF(3)CHFOCHF(2) have been carried out theoretically. The geometries and frequencies of all the stationary points are optimized at the B3LYP/6-311G(d,p) level, and the energy profiles are further refined by interpolated single-point energies (ISPE) method at the G3(MP2) level of theory. For each reaction, two H-abstraction channels are found and four products (CF(3)CHFOCF(2), CF(3)CFOCHF(2), and CF(3)CHClOCF(2), CF(3)CClOCHF(2)) are produced during the above processes. The rate constants for the CF(3)CHClOCHF(2)/CF(3)CHFOCHF(2) + OH/Cl reactions are calculated by canonical variational transition-state theory (CVT) within 200-2000 K, and the small-curvature tunneling is included. The total rate constants calculated from the sum of the individual rate constants and the branching ratios are in good agreement with the experimental data. The Arrhenius expressions for the reactions are obtained. Our calculation shows that the substitution of Cl by F decreases the reactivity of CF(3)CHClOCHF(2) toward OH and Cl. In addition, the mechanisms of subsequent reactions of product radicals and OH radical are further investigated at the G3(MP2)//B3LYP/6-311G(d,p) level, and the main products are predicted in the this article.