Conductor-like Polarizable Continuum Model Research Articles

Identification of initial decomposition reactions in liquid-phase HMX using quantum mechanics calculations

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine, (HMX), also known as octogen, is a commonly used ingredient in solid propellants and explosives. As a result, many experimental and theoretical studies have investigated HMX to elucidate its liquid-phase and gas-phase decomposition behavior. In various experimental efforts, including both fast and slow thermolysis, the results indicate that ring opening occurs very early due to the presence of carbon-containing species, such as HCN, H2CO, HNCO, CO and CO2. After a lengthy search using quantum mechanics, ring-opening and subsequent reactions have been identified which may occur in both liquid and gas phases. Two existing pathways – 1) HONO elimination and 2) NNO2 homolysis – are re-examined for liquid-phase decomposition, and early ring-opening reactions have been identified. Three additional pathways – 1) reaction with NO and formation of ONTNTA, 2) prompt oxidation via HONO and ONNO2 addition, and 3) hydrogen abstraction via NO2– are also identified along with early ring-opening reactions in each pathway. The proposed pathways for decomposition of HMX are similar to that of RDX presented earlier [37]. The quantum mechanics calculations are performed using density functional theory (DFT) at the B3LYP/6-311 + + G(d,p) level. Conductor-like Polarizable Continuum Model (CPCM) is used to account for solvation effects with water as solvent within the Gaussian program package. Intrinsic reaction coordinate calculations have also been performed to verify that the reactants are indeed connected to the expected products. Similar to RDX, HONO elimination appears to be the initiation reaction followed by early ring-opening reactions. Results also indicate simultaneous formation of formaldehyde and N2O from early ring-opening reactions. Competing bimolecular reactions with NO2, HONO and ONNO2 are also investigated in the liquid phase, which explain the experimentally observed autocatalytic behavior. These reactions can assist in the development of a detailed liquid-phase chemical kinetics mechanism of nitramine propellants containing RDX and HMX.

Theoretical Studies on the Aminolysis Mechanism of Methomyl: Effect of the Catalysis to the Reaction of Carbamate with Ammonia

AbstractThe aminolysis mechanisms of methomyl are systematically investigated through the M06‐2X/6‐311++G(d,p) and MP2/6‐311+G(d,p) methods. The uncatalyzed, base‐catalyzed and water‐catalyzed aminolysis processes are also taken into consideration together with the concerted, BAC2 (a stepwise channel through a neutral tetrahedral intermediate) and E1cB (a stepwise mechanism via an isocyanate intermediate) pathways. The solvent effects are discussed in detail by using the CPCM (conductor‐like polarized continuum model) with the M06‐2X/6‐311++G(d,p) method. The computational values provide convincing evidence that three alternative pathways possess similar energy barriers for the uncatalyzed aminolysis. It can be concluded that the base‐catalyzed and water‐catalyzed aminolysis processes are more favorable compared with the uncatalyzed reaction. Concerning the base‐catalyzed process, the E1cB pathway is preferable to other channels. However, the water‐catalyzed aminolysis is dominated by the BAC2 mechanism. In a word, the aminolysis reactions in solution could readily occur and the solvent effects do not remarkably alter the mechanism.

New Methods of Esterification of Nanodiamonds in Fighting Breast Cancer-A Density Functional Theory Approach.

The use of nanodiamonds as anticancer drug delivery vehicles has received much attention in recent years. In this theoretical paper, we propose using different esterification methods for nanodiamonds. The monomers proposed are 2-hydroxypropanal, polyethylene glycol, and polyglicolic acid. Specifically, the hydrogen bonds, infrared (IR) spectra, molecular polar surface area, and reactivity parameters are analyzed. The monomers proposed for use in esterification follow Lipinski’s rule of five, meaning permeability is good, they have good permeation, and their bioactivity is high. The results show that the complex formed between tamoxifen and nanodiamond esterified with polyglicolic acid presents the greatest number of hydrogen bonds and a good amount of molecular polar surface area. Calculations concerning the esterified nanodiamond and reactivity parameters were performed using Density Functional Theory with the M06 functional and the basis set 6–31G (d); for the esterified nanodiamond–Tamoxifen complexes, the semi-empirical method PM6 was used. The solvent effect has been taken into account by using implicit modelling and the conductor-like polarizable continuum model.

Substituent and Solvent Effects on the Electronic and Structural Properties of Silacyclopropylidenoids

The isomeric structures, energies, and properties of the substituted silacyclopropylidenoids, SiC<sub>2</sub>H<sub>3</sub>RLiBr (R= –H, –CH<sub>3</sub>, –SiH<sub>3</sub>, –CN, –OH, –NH<sub>2</sub>), were studied by <em>ab initio</em> calculations at the MP2/6-311+G(d,p) level of theory. The calculations indicate that each of SiC<sub>2</sub>H<sub>3</sub>RLiBrs for R= –H, –CH<sub>3</sub>, –SiH<sub>3</sub>, –CN, –OH, –NH<sub>2 </sub>has three stationary structures: silacyclopropylidenoid (<strong>S</strong>), tetrahedral (<strong>T1</strong> or <strong>T2</strong>), and inverted (<strong>I</strong>). The conductor–like polarizable continuum model (CPCM) using various solvents (dimethyl sulfoxide (ε = 46.7), acetone (ε = 21.0), tetrahydrofuran (ε = 7.5), and diethyl ether (ε = 4.3)) has been applied to compute single point energies for title molecules. In addition, the molecular electrostatic potential maps, natural bond orbitals, and the frontier molecular orbitals of substituted silacyclopropylidenoids were calculated.

Activation barriers for methylation of DNA bases by dimethyl sulfate

The SN2 transition states of the methylation reaction of DNA bases with dimethyl sulfate were examined employing DFT/ M06-2X/6-31+G∗ and DFT/B3LYP-D3/6-311+G (2df, 2p) levels of theory. Solvation effects were examined using the conductor-like polarizable continuum model (CPCM). Calculation results and feedback from electrostatic potential maps show that in water, charge separation lowers the activation barriers relative to the gas phase for the reactions at N7 of guanine, N3 of adenine and cytosine. Also, the reaction at the O6 site of guanine is governed by steric interference and exhibits a higher activation barrier in water.

Antimicrobial activities, DNA interactions, spectroscopic (FT-IR and UV-Vis) characterizations, and DFT calculations for pyridine-2-carboxylic acid and its derivates

In this paper, pyridine- 2- carboxylic acid, also known as picolinic acid (pic), and its two derivate, 4- methoxy-pyridine- 2- carboxylic acid (4-Mpic) and 4- chloro-pyridine- 2- carboxylic acid (4-Clpic) have been characterized by FT-IR and UV-Vis spectroscopy techniques as well as DFT calculations. B3LYP level of Density Functional Theory (DFT) method was used to obtain ground state geometries, vibration wavenumbers, first order hyperpolarizabilities and molecular electrostatic potential (MEP) surfaces for pic, 4Clpic and 4Mpic. The electronic absorption wavelengths and HOMO-LUMO energies were investigated by time dependent B3LYP (TD-B3LYP) level with the conductor-like polarizable continuum model (CPCM). The effects of Cl atom and OCH3 group on HOMO-LUMO energy gaps and first order hyperpolarizability parameters of pic, 4Clpic and 4Mpic molecules were examined. All molecules were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against yeast strains by using minimal inhibitory concentration method (MIC). All compounds (pic, 4Mpic and 4Clpic) have been found to be very active against to the Gram (+) and Gram (−) bacteria. The DNA interactions of pic, 4Clpic and 4Mpic were analyzed by molecular docking simulations, and the interaction of the 4Mpic molecule with DNA is found to be higher than 4Clpic and pic.

TD-DFT Study on Thiacalix[4]arene, the Receptor of a Fluorescent Chemosensor for Cu2.

The electronic and spectral properties of p-tert-butylthiacalix[4]arene (TCA) and its Cu2+ complexes (CuTCA and Cu2TCA) were characterized by time-dependent density functional theory (TD-DFT). Geometries of TCA, CuTCA, and Cu2TCA were optimized at the CAM-B3LYP/6-31+G(d,p) level of theory in water using the conductor-like polarizable continuum model. The absorption spectra of TCA, CuTCA, and Cu2TCA were demonstrated by TD-DFT method. The quenching mechanism of perylene as the fluorophore of a chemosensor based on thiacalix[4]arene was discussed. The addition of Cu2+ to TCA introduced a series of low-lying excited states involving copper d orbitals. The overlap between absorption of TCA complexes and emission of perylene indicated that the quenching of perylene fluorescence is due to fluorescence resonance energy transfer.

An integrated theoretical and experimental investigation of insensitive munition compounds adsorption on cellulose, cellulose triacetate, chitin and chitosan surfaces

This manuscript reports results of combined computational chemistry and batch adsorption investigation of insensitive munition compounds, 2,4-dinitroanisole (DNAN), triaminotrinitrobenzene (TATB), 1,1-diamino-2,2-dinitroethene (FOX-7) and nitroguanidine (NQ), and traditional munition compound 2,4,6-trinitrotoluene (TNT) on the surfaces of cellulose, cellulose triacetate, chitin and chitosan biopolymers. Cellulose, cellulose triacetate, chitin and chitosan were modeled as trimeric form of the linear chain of 4C1 chair conformation of β-d-glucopyranos, its triacetate form, β-N-acetylglucosamine and D-glucosamine, respectively, in the 1➔4 linkage. Geometries were optimized at the M062X functional level of the density functional theory (DFT) using the 6-31G(d,p) basis set in the gas phase and in the bulk water solution using the conductor-like polarizable continuum model (CPCM) approach. The nature of potential energy surfaces of the optimized geometries were ascertained through the harmonic vibrational frequency analysis. The basis set superposition error (BSSE) corrected interaction energies were obtained using the 6-311G(d,p) basis set at the same theoretical level. The computed BSSE in the gas phase was used to correct interaction energy in the bulk water solution. Computed and experimental results regarding the ability of considered surfaces in adsorbing the insensitive munitions compounds are discussed.

Insight into substituent effects on the hydrolysis of amidines by a microhydration model

The hydrolysis of substituted amidines XN′=CH–N(Y)2 (X = alkyl, nucleoside, aryl; Y = methyl, benzyl) is studied by use of computational techniques. For each substituted system, two possible pathways, N′-Path and N-Path, are considered, in which the proton transfer to N′ and N, respectively, after the nucleophilic attack of H2O to C=N′ double bond. The geometry optimizations of the stationary states are carried out to map out the hydrolysis pathways at the density functional theory B3LYP/6-311+G(d,p) level. Single-point MP2 calculations (MP2/6-311++G(d,p)//B3LYP/6-311+G(d,p)) are performed to obtain more credible energy information. A microhydration surrounding is constructed to describe the effect of water molecules in the first hydration shell on the energy barrier from radial distribution functions, g(R). The bulk solvent effects are examined by using the conductor-like polarizable continuum model (CPCM). The calculated results indicate that the hydrolysis of N,N-disubstituted formamidines is more favored for Y = methyl than for Y = benzyl. Furthermore, for N′-substituted formamidines, the hydrolysis reactivity increases in the following order: X = aryl < X = nucleoside < X = alkyl. In addition, the substituent effects on the proton transfer manner after the nucleophilic attack of H2O to C=N′ double bond are discussed. The preference of proton transfer to N′ or N atom depends on the different nucleophilicity of each nitrogen atom bearing different substituents in the intermediate (IM). Our computational results are in agreement with the available experimental conclusion and will allow for a better understanding of the hydrolysis mechanism of amidines.

Computational assisted electrochemical studies for 1,4-diazabicyclo[2,2,2]octane determination at multiwalled carbon nanotube paste electrode

A multiwalled carbon nanotube-modified carbon paste electrode (MWCNT-PE) was used for determination of 1,4-diazabicyclo[2,2,2]octane (DABCO or TEDA) in 0.1 M phosphate buffer solutions (pH 10.25). Cyclic voltammetry(CV) and differential pulse voltammetry (DPV) techniques were used to investigate the electrocatalytic oxidation of DABCO at the surface of modified electrode. The results shown that the oxidation peak current of DABCO at the surface of MWCNT-PE was 2.40 times larger than that at the bare electrode. The experimental formal redox potential (E°') of DABCO was obtained 986 mV versus SHE (Standard Hydrogen Electrode). Density functional theory (DFT) method at B3LYP/6-311++G** level of theory and a conductor-like Polarizable Continuum Model (CPCM) was used to calculate the E°' values. The highest occupied molecular orbital (E HOMO), lowest unoccupied molecular orbital (E LUMO) and some thermodynamic parameters such as Gibbs free energy of DABCO and its oxidation forms were calculated. Both direct and indirect methods were used to calculate the theoretical standard electrode potential for DABCO and the results were found to be in good agreement with the experimental values.

Hydrolysis theory based on density functional studies for cytotoxic Pt(II) and Pd(II) complexes with benzimidazole derivative

The hydrolysis processes of cytotoxic Pt(II) and Pd(II) complexes bearing benzimidazole moieties were explored combining density functional theory with conductor-like polarisable continuum model (CPCM) approach. Pentacoordinated transition state (TS) structures as well as the other stationary points for two distinct paths were optimized and characterized. The computed potential energy surfaces reveal the rate-limiting step as the second aquation, suggesting that the monohydrated complex is most likely to react with the DNA bases. The results give detailed energy profiles for the hydrolysis mechanism, which may assist in understanding the interaction of such anticancer agents with their ultimate cellular target.

Electroanalytical Measurement of TEDA (Triethylenediamine) in the Masks of War

In this paper, for the first time, the electroanalytical study of Triethylenediamine, TEDA was done on a typically graphene modified carbon paste electrode (Gr/CPE) in pH=10.5 of phosphate buffer solutions (PBS). The surface morphology of the bare and modified electrodes was characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The electro-oxidation of TEDA was investigated at the surface of modified electrode. The results revealed that the oxidation peak current of TEDA at the surface of Gr/CPE is 2.70 times than that shown at bare-CPE. A linear calibration plot was observed in the range of 1.0 to 202.0 ppm. In this way, the detection limit was found to be 0.18 ppm. The method was then successfully applied to determination of TEDA in aqueous samples obtained from two kinds of activated carbon from the masks of war. On the other hand, density functional theory (DFT) method at B3LYP/6-311++G** level of theory and a conductor-like Polarizable Continuum Model (CPCM) was used to calculate the pKa values of TEDA. The energies of lowest unoccupied molecular orbital (ELUMO) and highest occupied molecular orbital (EHOMO), gap energy (ΔE) and some thermodynamic parameters such as Gibbs free energy of TEDA and its conjugate acid (HT+) were calculated. The results of calculated pKa were found to be in good agreement with the experimental values. Keywords: TEDA, Graphene, Differential pulse voltammetry, War mask, Acidity constant, Density functional theory

Quantum mechanics investigation of initial reaction pathways and early ring-opening reactions in thermal decomposition of liquid-phase RDX

Cyclotrimethylene trinitramine (RDX) is a commonly used ingredient in solid propellants and explosives. As a result, RDX has been the subject of many experimental and theoretical investigations to elucidate its liquid-phase and gas-phase decomposition. In our experimental effort involving Fourier Transform Infrared (FTIR) spectroscopy and time-of-flight mass spectrometry (ToFMS) of fast thermolysis of RDX, the results indicate that ring-opening occurs very early due to the presence of carbon-containing species among the detected gas-phase species, such as HCN, H2CO, CO and CO2. Two existing pathways – 1) HONO elimination and 2) NNO2 homolysis – are re-examined for liquid-phase decomposition and early ring-opening reactions have been identified after a lengthy search using quantum mechanics. Three additional pathways – 1) reaction with NO and formation of ONDNTA, 2) prompt oxidation via HONO and ONNO2 addition, and 3) hydrogen abstraction via NO2– are also identified along with early ring-opening reactions in each pathway. The quantum mechanics investigation is based on using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. The liquid-phase studies use the Conductor-like Polarizable Continuum Model (CPCM) for solvation with water as solvent within the Gaussian program package. Intrinsic reaction coordinate calculations have also been performed to verify that the reactants indeed are connected to the expected products. Results explain the mechanistic details of the formation of early carbon containing species, simultaneous formation of formaldehyde and N2O, as well as the formation of minor species such as HNCO and HOCN. Proposed reactions can account for the experimentally observed autocatalytic behavior and can assist in the development of a detailed chemical kinetics mechanism of nitramine propellants containing RDX and possibly HMX.

Effective Polarization in Pairwise Potentials at the Graphene-Electrolyte Interface.

At the graphene-electrolyte interface, the polarizability of both the surface and the solution plays a major role in defining the interfacial structure and dynamics of the ions. Current molecular models predict different ion adsorption behavior at the interface depending on whether surface or solution polarization is included in the model. Here, we propose a simple method to parametrize the ion-carbon interaction from density functional theory, implicitly modeling the solution using the conductor-like polarizable continuum model. The new model simultaneously takes into account the polarizability of both the graphene sheet and the solution without the need to use time-consuming polarizable potentials and can predict the ion adsorption trend so far only achievable using first-principles simulations. Simulations performed with 1 M electrolyte solutions of different ions show that cations are strongly adsorbed onto the graphene surface with a trend (Li+ < Na+ < K+) opposite to that predicted by the gas-phase calculations and different from that obtained from the single-ion simulations.

Prediction of 1H NMR chemical shifts for clusters of imidazolium-based ionic liquids.

Nuclear magnetic resonance (NMR) has been widely used to elucidate the bulk structure of ionic liquids. In this work, we calculated 1H NMR chemical shifts of 1-ethyl-3-methylimidazolium (C2mim+) ionic liquids combined with various anions such as chloride (Cl), tetrafluoroborate (BF4), hexafluorophosphate (PF6), acetate (OAc), trifluoroacetate (TFA), and dicyanamide (DCA). The previously established level of theory, HF/6-311G+(3df,2p), was used for the accurate prediction of NMR chemical shifts both in gas phase and in solvents with varying dielectric constant such as CHCl3 and ethanol. The following factors affecting the predicted proton chemical shifts were considered. Firstly, ionic clusters consisting of 2, 8 and 16 ion pairs were optimized to model interionic interactions present in the bulk of ionic liquids. In larger clusters the distribution of the calculated chemical shifts of individual protons in the C2mim+ cation was examined with respect to the position of the cation in the cluster. We further confirmed that electronic properties of ionic liquids such as magnetic shielding had local nature, thus allowing us to accurately predict proton NMR chemical shifts of ionic liquids from relatively small-sized clusters. Secondly, solvent effects in single ion pairs as well as larger ionic clusters were accounted through a Conductor-like Polarisable Continuum Model (CPCM). Solvent effects generated through a dielectric constant of either chloroform or ethanol were found to be important in single ion pairs due to improved description of interionic distances. With increasing cluster size the difference between gas-phase and CPCM optimized structures became minimal, thus resulting in similar values for calculated 1H NMR chemical shifts. We also established that the model size that produced the best results for imidazolium ionic liquids strongly depended on the anion type. Strongly coordinating anions such as chloride and acetate require calculations of clusters consisting of at least 8 ion pairs, whereas weakly coordinating anions produce excellent accuracy for single ion pairs optimized in the presence of solvent. The polarity of the solvent was found to play a minor role.

Theoretical study on the investigation of antioxidant properties of some hydroxyanthraquinones

ABSTRACTAnthraquinones are located in an important class of natural compounds having antioxidant properties. Quantum chemical calculations based on the density functional theory were employed to study the relationship between the structure and the antioxidant activity of four hydroxyanthraquinones. The solvation effects on the antioxidant activity were taken into account by using the conductor-like polarisable continuum model with different dielectric constants (ε = 2.25, C6H6; ε = 78.39, H2O). The three antioxidant action mechanisms, hydrogen atom transfer (HAT), single electron transfer-proton transfer and sequential proton loss electron transfer (SPLET) were elucidated. The reaction enthalpies related to the steps in these mechanisms were computed in gas phase and solvents. The calculated results are in line with experimental values. The results showed that HAT was the most favourable mechanism for describing the antioxidant activity of hydroxyanthraquinones in the gas phase and in benzene, whereas in aqueous solution, SPLET represented the most thermodynamically plausible reaction pathway.

A DFT Approach to the Mechanistic Study of Hydrozone Hydrolysis.

Hydrazone chemistry is widely utilized in biomedical field as a means of bioconjugation protocol, especially in drug delivery field due to pH labile nature of this linkage. In the light of kinetics studies, the generally accepted mechanism for the hydrolysis of hydrazones involves two main steps, namely, nucleophilic addition of water molecule to the hydrazone molecule to form carbinolamine intermediate and subsequent decomposition of this intermediate into the hydrazine and aldehyde/ketone moieties. Hydrolysis of hydrazones is catalyzed in the acidic environments and is thought to proceed through several proton transfer steps. To the best of our knowledge, in the literature no detailed theoretical study has been reported related to the mechanism of hydrolysis. In this study, we evaluated the proposed mechanism with DFT calculations with M06-2X functional at the 6-311+g(d,p) level including conductor-like polarizable continuum model solvation model. We also analyzed possible proton transfer pathways and assessed energetics of each step.

A machine learning correction for DFT non-covalent interactions based on the S22, S66 and X40 benchmark databases.

Background Non-covalent interactions (NCIs) play critical roles in supramolecular chemistries; however, they are difficult to measure. Currently, reliable computational methods are being pursued to meet this challenge, but the accuracy of calculations based on low levels of theory is not satisfactory and calculations based on high levels of theory are often too costly. Accordingly, to reduce the cost and increase the accuracy of low-level theoretical calculations to describe NCIs, an efficient approach is proposed to correct NCI calculations based on the benchmark databases S22, S66 and X40 (Hobza in Acc Chem Rev 45: 663–672, 2012; Řezáč et al. in J Chem Theory Comput 8:4285, 2012).ResultsA novel type of NCI correction is presented for density functional theory (DFT) methods. In this approach, the general regression neural network machine learning method is used to perform the correction for DFT methods on the basis of DFT calculations. Various DFT methods, including M06-2X, B3LYP, B3LYP-D3, PBE, PBE-D3 and ωB97XD, with two small basis sets (i.e., 6-31G* and 6-31+G*) were investigated. Moreover, the conductor-like polarizable continuum model with two types of solvents (i.e., water and pentylamine, which mimics a protein environment with ε = 4.2) were considered in the DFT calculations. With the correction, the root mean square errors of all DFT calculations were improved by at least 70 %. Relative to CCSD(T)/CBS benchmark values (used as experimental NCI values because of its high accuracy), the mean absolute error of the best result was 0.33 kcal/mol, which is comparable to high-level ab initio methods or DFT methods with fairly large basis sets. Notably, this level of accuracy is achieved within a fraction of the time required by other methods. For all of the correction models based on various DFT approaches, the validation parameters according to OECD principles (i.e., the correlation coefficient R2, the predictive squared correlation coefficient q2 and q_{cv}^{2} from cross-validation) were >0.92, which suggests that the correction model has good stability, robustness and predictive power.ConclusionsThe correction can be added following DFT calculations. With the obtained molecular descriptors, the NCIs produced by DFT methods can be improved to achieve high-level accuracy. Moreover, only one parameter is introduced into the correction model, which makes it easily applicable. Overall, this work demonstrates that the correction model may be an alternative to the traditional means of correcting for NCIs.Graphical abstractA machine learning correction model efficiently improved the accuracy of non-covalent interactions(NCIs) calculated by DFT methods. The application of the correction model is easy and flexible, so it may be an alternative correction means for NCIs by first-principle calculations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-016-0133-7) contains supplementary material, which is available to authorized users.

Quantum chemical approach for condensed-phase thermochemistry (III): Accurate evaluation of proton hydration energy and standard hydrogen electrode potential

Gibbs free energy of hydration of a proton and standard hydrogen electrode potential were evaluated using high-level quantum chemical calculations. The solvent effect was included using the cluster-continuum model, which treated short-range effects by quantum chemical calculations of proton–water complexes, and the long-range effects by a conductor-like polarizable continuum model. The harmonic solvation model (HSM) was employed to estimate enthalpy and entropy contributions due to nuclear motions of the clusters by including the cavity–cluster interactions. Compared to the commonly used ideal gas model, HSM treatment significantly improved the contribution of entropy, showing a systematic convergence toward the experimental data.

Theoretical studies on the hydrolysis mechanism of acetamiprid

The possible hydrolysis mechanisms for acetamiprid (AAP) with H3O+, H2O and OH− in the gas phase were studied by employing the B3LYP/6-311+G(d,p) and MP2/6-311+G(d,p) levels. In each case, two different pathways were taken into account in our calculations. Moreover, the solvent effect of water was estimated at the B3LYP/6-311+G(d,p) level by using the conductor-like polarizable continuum model (CPCM). The calculated results clearly showed that hydrolysis of AAP with OH− could readily take place in comparison with hydrolysis with H3O+, H2O. The most favorable pathway in the gas phase is the proton transfer toward the N atom in the single bond of AAP in the hydrolysis with OH−. The solvent effect does not significantly change the conclusion. The free energy barrier height of 25.74 kcal/mol (107.6 kJ/mol) is in excellent agreement with the available experimental value (106.3 kJ/mol).