Double Bond Migration Mechanism in Allyl Systems Involving the Hydroxide Ion. 1. Gas-Phase and Born–Onsager Models

The reaction profile of the 1,3-prototropic rearrangement of propene involving the hydroxide ion was studied by the RHF/6-31+G*, MP2/6-31+G*, and B3LYP/6-31+G* ab initio methods within the framework of the gas-phase and Born–Onsager models (the latter including solvent effects). Propene isomerization in the presence of the hydroxide ion in the gas phase may occur with participation of a base proton with the intermediate formation of a water complex of the allyl ion. The transition state energy of this transformation is lower than the total energy of the starting hydroxide ion and propene and much lower than the sum of the energies of the isolated propenide ion and water molecule. An activation barrier arises when the solvent effect is included in calculation within the framework of the Born–Onsager model; the intermediate complex is much less stable than the complex considered in the gas-phase model. As in the latter, the mechanism of multiple bond migration is energetically preferable to the mechanism involving proton transfer to the reaction medium.     

Double Bond Migration Mechanism in Allyl Systems Involving the Hydroxide Ion. 2. Polarizable Continuum Model (PCM)

Isomerization processes of a double bond site in propene and methylthiopropene molecules with the hydroxide ion were studied in the framework of the RHF/6-31+G*, MP2/6-31+G*, and B3LYP/6-31+G* (density functional) ab initio methods. The solvent effect was taken into account using PCM in its IEFPCM and SCIPCM versions. It is shown that to construct a reaction profile for propene rearrangement, it suffices to perform geometry optimization of stationary points within the Born–Onsager model with further refinement of the energy using IEFPCM. The reaction profiles obtained display that the multiple bond migration mechanism involving the hydroxide ion proton is energetically preferable to the two-stage mechanism forming a solvated carbanion for the propene molecule and for the methylthiopropene molecule that forms a much more stable carbanion.     

Multiple bond migration with participation of a protophilic agent

The pathways of migration of the multiple bond in propene and propyne molecules involving the hydroxide ion were investigated by theab initio (RHF/6-31+G^* and MP2/6-31+G^*) methods. Stationary points corresponding to stable complexes between the molecules under study and the hydroxide ion and between corresponding carbanions and water molecule were found on the potential energy surfaces of the proton transfer reactions. In the presence of hydroxide ion, migration of the multiple bond can occur by an “intramolecular” mechanism of the proton transfer involving the proton of hydroxide ion bound in the complex with propene or propyne molecule. For the propene system, such a mechanism seems to be quite realistic and more preferable energetically than a traditional two-stage mechanism with a passage of the proton into the medium. For the system with the triple bond, an equal expenditure of energy is required to follow any mechanism (without taking into account the effects of solvation and the interaction with a cation), whereas the formation of the stable [H₂C=C=CH·H₂O]⁻ complex can prevent further transformations. For Part 1, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 35–41, January, 1999.     

Ab initio study of 2,4-substituted azolidines. II. Amino-imino tautomerism of 2-aminothiazolidine-4-one and 4-aminothiazolidine-2-one in water solution

The relative stabilities of the tautomers of 2-aminothiazolidine-4-one and 4-aminothiazolidine-2-one were calculated at the MP2/6-31+G(d,p) level by considering their mono- and trihydrated complexes. Single-point calculations at the MP4/6-31+G(d,p)//MP2/6-31+G(d,p) level of theory were performed to obtain more accurate energies. The values of proton transfer barriers in the isolated, mono- and trihydrated tautomers of 2-aminothiazolidine-4-one (2AT) and 4-aminothiazolidine-2-one (4AT) were calculated for two different mechanisms of tautomerisation. In the absence of water, the process of proton transfer should not occur. Addition of water molecules decreases the barrier making the process faster, as the participation of two water molecules in a proton transfer reaction is more favorable than the participation of only one water molecule. To estimate the effect of the medium (water) on the relative stabilities of the tautomers of the studied compounds we applied the polarizable continuum model (PCM). (13)C NMR chemical shieldings were calculated using the GIAO approach at MP2/6-31+G(d,p) optimized geometries. HF and the DFT B3LYP functional with 6-31+G(d,p) basis set were employed. The quantum chemical results for the chemical shifts in gas phase and in polar solvents (water and DMSO) were compared with experimental data. TD DFT B3LYP/aug-cc-pVTZ calculations were performed to predict the absorption maxima of tautomers A and B of 2AT and 4AT.     

Theoretical study on the role of cooperative solvent molecules in the neutral hydrolysis of ketene

The results of a theoretical study of the reaction mechanism for the neutral hydration of ketene, H₂C=C=O + (n + 1) H₂O → CH₃COOH + nH₂O (n = 0–4), in solution are presented. All structures were optimized and characterized at the MP2(fc)/6-31 + G* level of theory, and then re-optimized by MP2(fc)/6-311 ++G**, and the effect of the bulk solvent is taken into account according to the conductor-like polarized continuum model (CPCM) using the gas MP2(fc)/6-311 ++G** geometries. Energies were refined for five-water hydration at higher level of theory, QCISD(T)(fc)/6-311 ++G**//MP2(fc)/6-311 ++G**. In the combined supermolecular/continuum model, one water molecule directly attacks the central C-atom, and the other four explicit water molecules are divided into two groups, one acting as catalyst(s) by participating in the proton transfer to reduce the tension of proton transfer ring, and the other being placed near the non-reactive oxygen or carbon atom in order to catalyze the hydration by engaging in hydrogen-bonding to the substrate (the so-called cooperative effect). Between the two possible nucleophilic addition reactions of water molecule, across the C=O bond or the C=C bond, the former one is preferred. Our calculations suggest that the favorable hydrolysis mechanism of ketene involves a sort of eight-membered ring transition structure formed by a three-water proton transfer loop, and a cooperative dimeric water near the non-reactive carbon-atom. The best-estimated in the present paper for the rate-determining barrier in solution, $ \Updelta G_{\text{sol}}^{ \ne } $ (298 K), is about 58 kJ/mol, reasonably close to the available experimental result.     

A Hybrid statistical mechanics—quantum chemical model for proton transfer in 5‐azauracil and 6‐azauracil in water solution

A hybrid statistical physics—quantum‐chemical methodology was implemented to study the water‐assisted intramolecular proton‐transfer processes in 5‐ and 6‐azauracils in aqueous solutions. The solvent effects were included in the model by explicit inclusion of two pairs of water molecules, which model the relevant part of the first hydration shell around the solute. The position of these water molecules was initially estimated by carrying out a classical Metropolis of dilute water solutions of the title compounds and subsequently analyzing solute–solvent intermolecular interactions in the Monte Carlo‐generated configurations. Sequentially to the statistical physics simulation, ab initio quantum mechanical (QM) level of theory was implemented. The effects of the water as solvent (at ab initio QM level) were introduced at two different levels—using solute–solvent clusters (four‐water molecules) and using the same clusters embedded in an external continuum. Full geometry optimizations of these complexes were carried out at MP2/6–31 + G(d, p) and conductor‐polarizable continuum model (C‐PCM)/MP2/6–31 + G(d, p). Single point calculations were performed at CCSD(T)/6–31 + G(d, p)//MP2/6–31 + G(d, p) computational level to obtain more accurate energies. According to our calculations hydrated azauracils should exist in three forms: mainly dioxo form and two hydroxy forms. The calculated proton transfer activation energies for tautomeric reactions of 5‐azauracil and 6‐azauracil show different pictures for these two compounds. According to C‐PCM/MP2/6–31 +G(d, p) data, water‐assisted proton transfer in 5‐azauracil realizes through two parallel reactions: 1,3,5‐triazine‐2,4(1H,3H)‐dione → 6‐hydroxy‐1,3,5‐triazin‐2(1H)‐one and 1,3,5‐triazine‐2,4(1H,3H)‐dione → 4‐hydroxy‐1,3,5‐triazin‐2(1H)‐one. Tautomeric equilibrium in 6‐azauracil in water could occur by two contiguous reactions: 1,2,4‐triazine‐3,5(2H,4H)‐dione → 5‐hydroxy‐1,2,4‐triazin‐3(2H)‐one and 5‐hydroxy‐1,2,4‐triazin‐3(2H)‐one → 3‐hydroxy‐1,2,4‐triazin‐5(2H)‐one. The proton transfer investigated reactions in 5‐ and 6‐azauracils involve concerted atomic movement. © 2015 Wiley Periodicals, Inc.     

MP2 Study on the Proton Transfer Mechanism of Glycine Assisted by Water

The geometries of glycine-nH2O （n = 1-5） complexes and the transition states of proton transfer in glycine-H2O system were calculated at the MP2/6-31＋＋G＊＊//MP2/6-31G＊ level, upon which we discovered the proton transfer mechanisms, including the number of water molecules necessary for the stabilization of zwitterions and the effect of increasing water molecules on the proton transfer. To our interest, we found that only one water molecule can stabilize the zwitterions; in addition, with the increment of water molecules, the activation energy of positive reaction decreases and that of reverse reaction increases gradually. Glycine will be ionized completely while the water molecules reach to a certain number.     

Multiple bond migration with participation of a protophilic agent

Ab initio study of the pathways of migration of the double bond in the 3-methylthioprop-1-ene (1) and 3-methoxyprop-1-ene (2) molecules with participation of hydroxide ion was carried out by the RHF/6-31+G^* and MP2/6-31+G//RHF/6-31+G^* methods. Conformational isomerism of the initial molecules and reaction products was considered. The distinctions are discussed in the spatial and electronic structure of intermediate carbanions stabilized (for1) due to the negative hyperconjugation. Stationary points corresponding to complexes between the molecules under study and the hydroxide ion and between the corresponding carbanion and water molecule were localized on the potential energy surfaces of the proton transfer reactions. For2, the single-stage mechanism of prototropic rearrangement involving the H atom of the hydroxide ions was found to be more energetically preferable than the two-stage mechanism, whereas both mechanisms are expected to be equiprobable for1. For Parts 1–3, see Refs. 1–3. Translated fromIzvestiya Akademii Nauk. Seriya Kimicheskaya, No. 3, pp. 407–413, March, 2000.     

Multiple bond migration with participation of a protophilic agent

The pathways of migration of the double bond in the 1-methoxy-2-propene molecule with participation of a hydroxide ion were investigated by theab initio RHF/6-31+G^* and MP2/6-31+G^* methods. Stationary points corresponding to complexes between the molecule under study and the hydroxide ion and between the corresponding carbanion and a water molecule were found on the potential energy surfaces of the proton transfer reactions. As in the propene molecule, migration of the double bond in the 1-methoxy-2-propene molecule can occur in the gas phase by the mechanism of intramolecular proton transfer involving the proton of the hydroxide ion. Conformational isomerism of the initial molecule and reaction products was considered. The proposed mechanism of 1,3-hydrogen shift involving the proton-containing base suggests the formation of bothE- andZ-products with predominance of the latter irrespective of the nature of the substituent. In this case the direction of multiple bond migration will be completely determined by the energy difference between the initial reagents and final products.     

细胞内第二信使3',5'-环核苷酸酯质子迁移机理的理论研究

应用密度泛函理论B3LYP/6-31G**计算方法对气相中细胞内第二信使3¢,5¢-环核苷酸酯(cAMPm)质子迁移机理进行了理论研究,此外,在相同水平上模拟了水分子作催化剂的反应机理。计算结果表明cAMPm两种构象Bm 和Dm之间的转化经过一个环状过渡态,其中,两分子水参与的H 迁移反应的势能面最低,反应更容易进行。我们的计算结果为研究相关的磷酸二酯的H质子迁移反应提供了理论依据。     

Solvent effects on glycine II. Water-assisted tautomerization

The water-assisted tautomerization of glycine has been investigated at the B3LYP/6-31+G** level using supermolecules containing up to six water molecules as well as considering a 1:1 glycine-water complex embedded in a continuum. The conformations of the tautomers in this mechanism do not display an intramolecular H bond, instead the functional groups are bridged by a water molecule. The replacement of the intramolecular H bond by the bridging water reduces the polarity of the N-H bond in the zwitterion and increases that of the O-H bond in the neutral, stabilizing the zwitterion. Both the charge transfer effects and electrostatic interactions stabilize the nonintramolecularly H-bonded zwitterion conformer over the intramolecularly hydrogen bonded one. The nonintramolecularly H-bonded neutral is favored only by charge transfer effects. Although there is no strong evidence whether the intramolecularly hydrogen bonded or non hydrogen bonded structures are favored in the bulk solution represented as a dielectric continuum, it is likely that the latter species are more stable. The free energy of activation of the water-assisted mechanism is higher than the intramolecular proton transfer channel. However, when the presumably higher conformational energy of the zwitterion reacting in the intramolecular mechanism is taken into account, both mechanisms are observed to compete. The various conformers of the neutral glycine may form via multiple proton transfer reactions through several water molecules instead of a conformational rearrangement.     

Proton affinities of molecules containing nitrogen and oxygen: comparing ab initio and semiempirical results to experiments

We report a comparison of theoretical and experimental proton affinities at nitrogen and oxygen sites within a series of small molecules. The calculated proton affinities are determined using the semiempirical methods AM 1, MNDO , and PM 3; the ab initio Hartree–Fock method at the following basis levels: 3-21G //3-21G , 3-21+G //3-21G , 6-31G *//6-31G *, and 6-31+G (d, p)//6-31G *; and Møller–Plesset perturbation calculations: MP 2/6-31G *//6-31G *, MP 3/6-31G *//6-31G *, MP 2/6-31G +(d, p)//6-31G *, MP 3/6-31G +(d, p)//6-31G *, and MP 4(SDTQ )/6-31G +G (d, p)//6-31G *. The semiempirical methods have more nonsystematic scatter from the experimental values, compared to even the minimal 3-21G level ab initio calculations. The thermodynamically corrected 6-31G *//6-31G * proton affinities provide acceptable results compared to experiment, and we see no significant improvement over 6-31G *//6-31G * in the proton affinities with any of the higher-level calculations. © 1992 John Wiley & Sons, Inc.     

Theoretical study on the hydrogen bonding of five-membered heteroaromatics with water

The hydrogen-bonding ability of five-membered heteroaromatic molecules containing one chalcogen and two heteroatoms with nitrogen in addition to chalcogen, respectively, have been analyzed using density functional and molecular orbital methods through adduct formation with water. The stabilization energies for all the adducts are established at B3LYP/6-31+G* and MP2/6-31+G* levels after correcting for the basis set superposition error by using the counterpoise method and also corrected for zero-point vibrational energies. A natural bond orbital analysis at B3LYP/6-31+G* level and natural energy decomposition analysis at HF/6-31+G* using MP2/6-31+G* geometries have been carried out to understand the nature of hydrogen-bonding interaction in monohydrated heterocyclic adducts. Nucleus-independent chemical shift have been evaluated to understand the correlation between hydrogen bond formation and aromaticity.     

An ab initio quantum chemical study of reaction mechanisms in the C2H2/CH3OH/KOH/DMSO system

An ab initio quantum chemical study (MP2/6-311++G**//B3LYP/6-31+G*) of a number of possible interactions is performed for the gas phase system of acetylene—potassium hydroxide-dimethylsulfoxide(DMSO)—methanol and with regard to the solvent effect within the continuum model. Key structures in the vinylation reaction are shown to be methoxide ion complexes with the alkali metal hydroxide and acetylene molecules. The formation of these complexes results in the activation of the acetylene molecule and an increase in the nucleophilicity of the methoxide ion. In the C₂H₂/CH₃OH/KOH/DMSO reaction system, a proton exchange between the acetylene molecule and the anionic nucleophile ([OH]^- and [CH₃O]^-) is freely performed with the formation of systems with ethynideions, whereas the thermodynamically preferable formation of vinyl alcohol or methyl vinyl ether is determined by a barrier of 20 kcal/mol.     

A computational study of intramolecular proton transfer in gaseous protonated glycine

The minimum energy paths for intramolecular proton transfer between the amino nitrogen and carbonyl oxygen atoms in gaseous protonated glycine were estimated at the Hartree-Fock (HF) and second-order M?ller-Plesset Perturbation (MP2) levels of theory. Potential energy profiles and their associated reactant, transition state, and product species calculated at the MP2/6-31G* level were shown to differ significantly from those obtained at the HF/6-31G* level. Effects of electron correlation and basis functions on the calculated geometries and energies of relevant species were examined at the HF, MP2, MP4, CCSD, and B3LYP levels using the 6-31G*, 6-31G**, 6-31+G**, 6-311+G**, 6-31+G(2d,2p), 6-311+G(3df,2p), cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ basis sets. The HF and MP2 optimized levels with the 6-31G*, 6-31G**, 6-31+G**, and 6-311+G** bases were used to calculate the thermodynamic and kinetic properties of the proton transfer reaction at 298.15 K and 1 atm, which include enthalpy, entropy, Gibbs free energy, equilibrium constant, potential energy barriers, tunneling transmission coefficients, and rate constants. Results indicate that the proton in a carbonyl O-protonated glycine undergoes a rapid migration to the amino nitrogen atom, while the reverse process is extremely unfavorable. The objective of this work is to develop practical theoretical procedures for studying proton transfer reactions in amino acids and peptides and to assemble physical data from these model calculations for future references.     

Mismatch base pairing of the mutagen 8‐oxoguanine and its derivatives with adenine: A theoretical search for possible antimutagenic agents

Molecular geometries of 8‐oxoguanine (8OG), those of its substituted derivatives with the substitutions CH₂, CF₂, CO, CNH, O, and S in place of the N7H7 group, adenine (A), and the base pairs of 8OG and its substituted derivatives with adenine were optimized using the RHF/6‐31+G* and B3LYP/6‐31+G* methods in gas phase. All the molecules and their hydrogen‐bonded complexes were solvated in aqueous media employing the polarized continuum model (PCM) of the self‐consistent reaction field (SCRF) theory using the RHF/6‐31+G* and B3LYP/6‐31+G* methods. The optimized geometrical parameters of the 8OG‐A base pair at the RHF/6‐31+G* and B3LYP/6‐31+G* levels of theory agree satisfactorily with those of an oligonucleotide containing the base pair found from X‐ray crystallography. The pattern of hydrogen bonding in the CF₂‐ and O‐substituted 8OG‐A base pair is of Watson–Crick type and that in the unsubstituted and CH₂‐, CNH‐, and S‐substituted base pairs is of Hoogsteen type. In the CO‐substituted base pair, the hydrogen bonding pattern is of neither Watson–Crick nor Hoogsteen type. The CF₂‐substitution appears to introduce steric hindrance for stacking of DNA bases. On the basis of these results, it appears that among all the substituted 8OG molecules considered here, the O‐substituted derivative may be useful as an antimutagenic drug. It is, however, subject to experimental verification. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

6-甲基-4-羟基嘧啶单体及二聚体激发态质子转移异构化反应及光谱的理论研究

采用ab initio HF理论的组态相关CIS方法和连续溶剂模型PCM, 分别在6-311+G*和6-31G水平上研究了6-甲基-4-羟基嘧啶单体及二聚体激发态质子转移的异构化反应; 对其反应势能面的研究发现, 单体基态和激发态的异构化反应一起可以形成四能级的分子电子体系, 而二聚体的却不能, 由此解释了单体和二聚体的紫外吸收光谱和荧光发射光谱均对应于酮式构型的原因. 利用混合含时密度泛函TD/MPW1PW91理论方法在溶剂存在下计算了标题物质的紫外吸收光谱和荧光发射光谱.     

Theoretical studies on the inactivation mechanism of γ-aminobutyric acid aminotransferase

The inactivation mechanism of γ-aminobutyric acid aminotransferase (GABA-AT) in the presence of γ-vinyl-aminobutyric acid, an anti-epilepsy drug, has been studied by means of theoretical calculations. Density functional theory methods have been applied to compare the three experimentally proposed inactivation mechanisms (Silverman et al., J. Biol. Chem., 2004, 279, 363). All the calculations were performed at the B3LYP/6-31+G(d,p) level of theory. Single point solvent calculations were carried out in water, by means of an integral equation formalism-polarizable continuum model (IEFPCM) at the B3LYP/6-31+G(d,p) level of theory. The present calculations provide an insight into the mechanistic preferences of the inactivation reaction of GABA-AT. The results also allow us to elucidate the key factors behind the mechanistic preferences. The computations also confirm the importance of explicit water molecules around the reacting center in the proton transfer steps.     

Oxo-hydroxy tautomerism of 5-fluorouracil: water-assisted proton transfer

Post-Hartree-Fock ab initio quantum chemical calculations were performed for 5-fluorouracil in the gas phase and in a three-water cluster. Full geometry optimizations of the 5-fluorouracil-water complexes were carried out at the MP2/6-31+G(d,p) level of theory. MP4/6-31+G(d,p)//MP2/6-31+G(d,p) and MP4/6-31++G(d,p)//MP2/6-31+G(d,p) single-point calculations were performed to obtain more accurate energies. In water solution, 5-fluorouracil exists mainly in the 2,4-dioxo form (A). We propose that the populations of the 2-hydroxy-4-oxo (B) and 4-hydroxy-2-oxo (D) tautomers are 1 x 10(-4)% and 3.9 x 10(-8)%, respectively, on the basis of the relative stabilities of the tautomers calculated at the MP4/6-31++G(d,p)//MP2/6-31+G(d,p) level of theory. A profound difference between isolated and hydrated 5-fluorouracil is noted for the height of the tautomerization barrier. In the absence of water, the process of proton transfer is very slow. The addition of water molecules decreases the barrier by 2.3 times, making the process much faster. The minimum energy path (MP2/6-31+G(d,p)) for water-assisted proton transfer in trihydrated 5-fluorouracil was followed. CNDO/S-CI calculations predict singlet pi-pi(*) electron transitions at 312 nm for B and at 318 nm for D. The fluorescence spectrum of 5-fluorouracil in water confirms the presence of the hydroxy tautomer.     

Ab initio study of gas phase and water-assisted tautomerization of maleimide and formamide

Maleimide serves as an important starting material in the synthesis of drugs and enzyme inhibitors. In the present paper, knowing the importance of tautomerization in maleimide for its drug action, potential energy surface of maleimide is studied and its tautomerization has been discussed and compared with tautomerization of formamide. Gas phase tautomerization of maleimide requires large amount of energy (23·21 kcal/mol) in comparison to formamide (15·05 kcal/mol) at HF/6-31+G* level. Thus making the proton transfer reaction a difficult process in gas phase. Water molecule lowers the energy barrier of tautomerization thus facilitating the tautomerization of maleimide to 5-hydroxy-pyrrol-2-one. Water assisted tautomerization of maleimide requires 19·60 kcal/mol energy at HF/6-31+G* and 17·63 kcal/mol energy at B3LYP/6-31+G* level, a decrease of 3·61 and 5·96 kcal/mol over gas phase tautomerization. Whereas, tautomerization of formamide requires 14·16 and 12·84 kcal/mol energy, a decrease of 0·89 and 2·01 kcal/mol energy over gas phase tautomerization at HF/6-31+G* and B3LYP/6-31+G* level, respectively. Water-assisted tautomerization in maleimide and formamide showed that difference in energy barrier reduces to 2·83 kcal/mol from 10·41 kcal/mol (in gas phase) at B3LYP level, which resulted that maleimide readily undergoes tautomerization in water molecule.