Remote substituent effects on N-X (X = H,F, Cl,CH3, Li) bond dissociation energies in para-substituted anilines

UB3LYP/6-311++g**//UB3LYP/6-31+g* and ROMP2/6-311++g**//UB3LYP/6-31+g* methods were used to calculate (i) N-X bond dissociation energies (BDE) in 4-YC6H4NH-X and (ii) N-H BDEs in 4-YC6H4NU-H, where Y = H, Me, OCH3, SMe, NH2, NMe2, SiMe3, F, Cl, CN, COOH, CF3, and NO2, X = H, CH3, F, Cl, and Li, and U = H, F, and CH(3). It was found that N-H BDEs of 4-YC6H4NH2 have a positive correlation with the substituent sigma(p+) constants. The slope (rho+) is about 3.0-4.3 kcal/mol, which is in good agreement with the experimental results. It was also found that the substituent effects on N-X BDEs of 4-YC6H4NH-X change considerably when X changes. rho(+)values for N-CH3, N-F, N-Cl, and N-Li BDEs were calculated to be 3.1-4.6, 1.3-1.9, 1.8-2.6, and 4.9-6.8 kcal/mol, respectively. The reason for the variation of substituent effects was proposed to be the ground-state effect, i.e., the interaction between the intact NH-X moiety and the parasubstituents. Finally, alpha-substitution was found to be able to significantly change the substituent effects. rho(+)values for N-H BDEs of 4-C6H4NCH3(-)H and 4-C6H4NF-H are 2.5-4.0 and 1.7-1.9 kcal/mol, respectively.     

Computational investigation of the weakly bound dimers HOX...SO(3) (X = F, Cl, Br)

The electronic structure and thermochemical stability of the HOX-SO(3) (X = F, Cl, Br) complexes is studied using second-order M?ller-Plesset perturbation theory (MP2). The calculated dissociation energies of the HOF-SO(3), HOCl-SO(3), and HOBr-SO(3) complexes are 5.43, 6.02, and 5.98 kcal mol(-1) at MP2/6-311++G(3df,3pd) level, respectively. Anharmonic OH stretching frequencies of the HOX (X = F, Cl, Br) moieties along with the frequency shifts upon complex formation are calculated at the MP2/6-311++G(2df,2p) level. AIM and NBO analyses were also performed. Theoretical data strongly encourage performing of matrix-isolation studies of the title complexes and their spectroscopic identification.     

Conformational equilibria of trans -3-X-cyclohexanols (X = Cl, Br, CH3 and OCH3). A low temperature NMR study and theoretical calculations

The integration of 1H and 13C NMR spectra, at - 90 degrees C in CS2/CD2Cl2 (9:1), for the trans-3-chlorocyclohexanol (1), trans-3-bromocyclohexanol (2), and trans-3-methoxycyclohexanol (4) showed that the equatorial-axial (ea) conformer occurs as ca 63, 63, and 69% in the conformational equilibrium, respectively. This corresponds to the following DeltaG(ea-ae) values (from (1)H spectrum): - 0.32 +/- 0.01, - 0.32 +/- 0.04, - 0.48 +/- 0.05 kcal mol(-1); and to (from 13C spectrum): - 0.31 +/- 0.04, - 0.35 +/- 0.05, and - 0.44 +/- 0.01 kcal mol(-1), respectively, in very good agreement within both series. Thus, although bromine is bulkier than chlorine, the 1,3-diaxial steric effects are similar in these equilibria. However, the integration of (1)H NMR spectrum for the trans-3-methylcyclohexanol (3) gave 90% of the 3ae conformer in the equilibrium, at - 90 degrees C on CS2/CD2Cl2 (9:1), corresponding to a DeltaG(ea-ae) value of 1.31 +/- 0.02 kcal mol(-1). The values obtained through the additivity rule, with data from monosubstituted cyclohexanes (DeltaG(Ad) = DeltaG(X) + DeltaG(OH)), for compounds 1, 2, and 4 (-0.37 +/- 0.15, - 0.34 +/- 0.09, and - 0.46 +/- 0.04 kcal mol(-1), respectively) are in very good agreement with the experimental values, but it is significantly smaller for compound 3 (0.79 +/- 0.02 kcal mol(-1)). Theoretical calculations through different levels of theory (HF/6-311 + g**, B3LYP/6-311 + g**, MP2/6-31 + g**, and CBS-4M) showed that CBS-4M is the best method for the study of conformational equilibria for these systems, since it provides DeltaG(ea-ae) values similar to the experimental values.     

Quantum theory of atoms in molecules charge-charge flux-dipole flux models for the infrared intensities of X(2)CY (X = H, F, Cl; Y = O, S) molecules

The molecular dipole moments, their derivatives, and the fundamental IR intensities of the X2CY (X = H, F, Cl; Y = O, S) molecules are determined from QTAIM atomic charges and dipoles and their fluxes at the MP2/6-311++G(3d,3p) level. Root-mean-square errors of +/-0.03 D and +/-1.4 km mol(-1) are found for the molecular dipole moments and fundamental IR intensities calculated using quantum theory of atoms in molecules (QTAIM) parameters when compared with those obtained directly from the MP2/6-311++G(3d,3p) calculations and +/-0.05 D and 51.2 km mol(-1) when compared with the experimental values. Charge (C), charge flux (CF), and dipole flux (DF) contributions are reported for all the normal vibrations of these molecules. A large negative correlation coefficient of -0.83 is calculated between the charge flux and dipole flux contributions and indicates that electronic charge transfer from one side of the molecule to the other during vibrations is accompanied by a relaxation effect with electron density polarization in the opposite direction. The characteristic substituent effect that has been observed for experimental infrared intensity parameters and core electron ionization energies has been applied to the CCFDF/QTAIM parameters of F2CO, Cl2CO, F2CS, and Cl2CS. The individual atomic charge, atomic charge flux, and atomic dipole flux contributions are seen to obey the characteristic substituent effect equation just as accurately as the total dipole moment derivative. The CH, CF, and CCl stretching normal modes of these molecules are shown to have characteristic sets of charge, charge flux, and dipole flux contributions.     

Structures of protonated arginine dimer and bradykinin investigated by density functional theory: further support for stable gas-phase salt bridges

The gas-phase structures and energetics of both protonated arginine dimer and protonated bradykinin were investigated using a combination of molecular mechanics with conformational searching to identify candidate low-energy structures, and density functional theory for subsequent minimization and energy calculations. For protonated arginine dimer, a good correlation (R = 0.88) was obtained between the molecular mechanics and EDF1 6-31+G* energies, indicating that mechanics with MMFF is suitable for finding low-energy conformers. For this ion, the salt-bridge or ion-zwitterion form was found to be 5.7 and 7.2 kcal/mol more stable than the simple protonated or ion-molecule form at the EDF1 6-31++G** and B3LYP 6-311++G** levels. For bradykinin, the correlation between the molecular mechanics and DFT energies was poor (R = 0.28), indicating that many low-energy structures are likely passed over in the mechanics conformational searching. This result suggests that structures of this larger peptide ion obtained using mechanics calculations alone are not necessarily reliable. The lowest energy structure of the salt-bridge form of bradykinin is 10.6 kcal/mol lower in energy (EDF1) than the lowest energy simple protonated form at the 6-311G* level. Similarly, the average energy of all salt-bridge structures investigated is 13.6 kcal/mol lower than the average of all the protonated forms investigated. To the extent that a sufficient number of structures are investigated, these results provide some additional support for the salt-bridge form of bradykinin in the gas phase.     

Gas phase SN2 reactions of halide ions with trifluoromethyl halides: front- and back-side attack vs. complex formation

Density functional theory computations and pulsed-ionization high-pressure mass spectrometry experiments have been used to explore the potential energy surfaces for gas-phase S(N)2 reactions between halide ions and trifluoromethyl halides, X(-) + CF(3)Y --> Y(-) + CF(3)X. Structures of neutrals, ion-molecule complexes, and transition states show the possibility of two mechanisms: back- and front-side attack. From pulsed-ionization high-pressure mass spectrometry, enthalpy and entropy changes for the equilibrium clustering reactions for the formation of Cl(-)(BrCF(3)) (-16.5 +/- 0.2 kcal mol(-1) and -24.5 +/- 1 cal mol(-1) K(-1)), Cl(-)(ICF(3)) (-23.6 +/- 0.2 kcal mol(-1)), and Br(-)(BrCF(3)) (-13.9 +/- 0.2 kcal mol(-1) and -22.2 +/- 1 cal mol(-1) K(-1)) have been determined. These are in good to excellent agreement with computations at the B3LYP/6-311+G(3df)//B3LYP/6-311+G(d) level of theory. It is shown that complex formation takes place by a front-side attack complex, while the lowest energy S(N)2 reaction proceeds through a back-side attack transition state. This latter mechanism involves a potential energy profile which closely resembles a condensed phase S(N)2 reaction energy profile. It is also shown that the Cl(-) + CF(3)Br --> Br(-) + CF(3)Cl S(N)2 reaction can be interpreted using Marcus theory, in which case the reaction is described as being initiated by electron transfer. A potential energy surface at the B3LYP/6-311+G(d) level of theory confirms that the F(-) + CF(3)Br --> Br(-) + CF(4) S(N)2 reaction proceeds through a Walden inversion transition state.     

A new scheme for determining the intramolecular seven-membered ring N-H...O=C hydrogen-bonding energies of glycine and alanine peptides

In this paper a new scheme was proposed to calculate the intramolecular hydrogen-bonding energies in peptides and was applied to calculate the intramolecular seven-membered ring N-H...O=C hydrogen-bonding energies of the glycine and alanine peptides. The density-functional theory B3LYP6-31G(d) and B3LYP6-311G(d,p) methods and the second-order Moller-Plesset perturbation theory MP26-31G(d) method were used to calculate the optimal geometries and frequencies of glycine and alanine peptides and related structures. MP26-311++G(d,p), MP26-311++G(3df,2p), and MP2/aug-cc-pVTZ methods were then used to evaluate the single-point energies. It was found that the B3LYP6-31G(d), MP26-31G(d), and B3LYP6-311G(d,p) methods yield almost similar structural parameters for the conformers of the glycine and alanine dipeptides. MP2/aug-cc-pVTZ predicts that the intramolecular seven-membered ring N-H...O=C hydrogen-bonding strength has a value of 5.54 kcal/mol in glycine dipeptide and 5.73 and 5.19 kcal/mol in alanine dipeptides, while the steric repulsive interactions of the seven-membered ring conformers are 4.13 kcal/mol in glycine dipeptide and 6.62 and 3.71 kcal/mol in alanine dipeptides. It was also found that MP26-311++G(3df,2p) gives as accurate intramolecular N-H...O=C hydrogen-bonding energies and steric repulsive interactions as the much more costly MP2/aug-cc-pVTZ does.     

Estimation on the intramolecular 10-membered ring N-H...O=C hydrogen-bonding energies in glycine and alanine peptides

Computation of accurate intramolecular hydrogen-bonding energies for peptides is of great importance in understanding the conformational stabilities of peptides and developing a more accurate force field for proteins. We have proposed a method to determine the intramolecular seven-membered ring N-H...O=C hydrogen-bonding energies in glycine and alanine peptides. In this article, the method is further applied to evaluate the intramolecular 10-membered ring N-H...O=C hydrogen-bonding energies in peptides. The optimal structures of the intramolecular 10-membered ring N-H...O=C hydrogen bonds in glycine and alanine tripetide molecules are obtained at the MP2 level with 6-31G(d), 6-31G(d,p), and 6-31+G(d,p) basis sets. The intramolecular 10-membered ring N-H...O=C hydrogen-bonding energies are then evaluated based on our method at the MP2/6-311++G(3df,2p) level with basis set superposition error correction. The intramolecular 10-membered ring N-H...O=C hydrogen-bonding energies are calculated to be in the range of -6.84 to -7.66, -4.44 to -4.98, and -6.95 to -7.88 kcal/mol. The method is also applied to estimate the individual intermolecular hydrogen-bonding energies in the dimers of amino-acetaldehyde, 2-amino-acetamide, formamide, and oxalamide, each dimer having two identical intermolecular hydrogen bonds. According to our method, the individual intermolecular hydrogen-bonding energies in the four dimers are calculated to be -1.77, -1.67, -6.35, and -4.82 kcal/mol at the MP2/6-311++G(d,p) level, which are in good agreement with the values of -1.84, -1.72, -6.23, and -4.93 kcal/mol predicted by the supermolecular method.     

CH_2X(X=H,FCI)与臭氧反应机理的最子化学研究

用量化学UMP2方法，在6-311++G**基组水平上研究了CH_2X(X=H,FCI)与臭氧反 应机理，全参数优化了反应过程中反应物、中间体、过渡态和产物的内何构型，在 UQCISD（T）/6-311++G**水平上计算了它们的能量，并对它们进行了振动分析，以 确定中间体和过渡态的直实性。从CH_2X(X=H,FCI)与O_3的反应机理的研究结果看 ，它们与O_3反应的活性都比较强，相对而言，活性大小顺序为CH_2F＞CH_3＞ CH_2CI，也就是说，CH_2F自由基与臭氧间的反应活性最强，对大气臭氧的损耗将 是最大的。同时研究还发现CH_2X(X=H,FCI)系列自由基与O_3的反应都是强放热反 应。     

Nucleofugality of phenyl and methyl carbonates

A series of X,Y-substituted benzhydryl phenyl carbonates 1 and X,Y-substituted benzhydryl methyl carbonates 2 were subjected to solvolysis in different methanol/water, ethanol/water, and acetone/water mixtures at 25 degrees C. The LFER equation, log k = sf(Ef + Nf), was used to derive the nucleofuge-specific parameters (Nf and sf) for phenyl carbonate (1LG) and methyl carbonate (2LG) leaving groups in a given solvent in SN1 type reaction. Kinetic measurements showed that phenyl carbonates solvolyze one order of magnitude faster than methyl carbonates. Optimized geometries of 1LG and 2LG at B3LYP/6-311G(d,p), B3LYP/6-311++G(d,p), and MP2(full)/6-311++G(d,p) levels revealed that negative charge delocalization in carbonate anions to all three oxygen atoms occurs due to negative hyperconjugation. Phenyl carbonate (1LG) is a better leaving group (Nf = -0.84 +/- 0.07 in 80% v/v aq EtOH) than methyl carbonate 2LG (Nf = -1.84 +/- 0.07 in 80% v/v aq EtOH) because of more pronounced negative hyperconjugation, which is characterized with a more elongated RO-C bond and more increased RO-C-CO angle in 1LG than in 2LG. Calculated affinities of benzhydryl cation toward methyl and phenyl carbonate anions (DeltaDeltaEaff = 11.7 kcal/mol at the B3LYP/6-311++G(d,p) level and DeltaDeltaEaff = 2.7 kcal/mol at the PCM-B3LYP/6-311++G(d,p) level in methanol, respectively) showed that 1LG is more stabilized than 2LG, which is in accordance with greater solvolytic reactivity of 1 than 2.     

Polarization Effects for Hydrogen-Bonded Complexes of Substituted Phenols with Water and Chloride Ion

Variations in hydrogen-bond strengths are investigated for complexes of nine para-substituted phenols (XPhOH) with a water molecule and chloride ion. Results from ab initio HF/6-311+G(d, p) and MP2/6-311+G(d, p)//HF/6-311+G(d, p) calculations are compared with those from the OPLS-AA and OPLS/CM1A force fields. In the OPLS-AA model, the partial charges on the hydroxyl group of phenol are not affected by the choice of para substituent, while the use of CM1A charges in the OPLS/CM1A approach does provide charge redistribution. The ab initio calculations reveal a 2.0-kcal/mol range in hydrogen-bond strengths for the XPhOH?OH(2) complexes in the order X = NO(2) > CN > CF(3) > Cl > F > H >OH >CH(3) > NH(2). The pattern is not well-reproduced with OPLS-AA, which also compresses the variation to 0.7 kcal/mol. However, the OPLS/CM1A results are in good accord with the ab initio findings for both the ordering and range, 2.3 kcal/mol. The hydrogen bonding is, of course, weaker with XPhOH as acceptor, the order for X is largely inverted, and the range is reduced to ca. 1.0 kcal/mol. The substituent effects are found to be much greater for the chloride ion complexes with a range of 11 kcal/mol. For quantitative treatment of such strong ion-molecule interactions the need for fully polarizable force fields is demonstrated.     

Conformational studies in the cyclohexane series. 2. Phenylcyclohexane and 1-methyl-1-phenylcyclohexane

The structures and relative energies of the conformers of phenylcyclohexane, and 1-methyl-1-phenylcyclohexane have been calculated at theoretical levels including HF/6-31G, B3LYP/6-311G, MP2/6-311G, MP2/6-311(2df,p), QCISD/6-311G, and QCISD/6-311G(2df,p). The latter gives conformational enthalpy (DeltaH degrees ), entropy (DeltaS degrees ), and free energy (DeltaG degrees ) values for phenylcyclohexane that are in excellent agreement with the experimental data. The calculations for 1-methyl-1-phenylcyclohexane find a free energy difference of 1.0 kcal/mol at -100 degrees C, favoring the conformation having an axial phenyl group, that is in only modest agreement with the experimental value of 0.32 +/- 0.04 kcal/mol. The origin of the phenyl rotational profiles for the conformers of phenylcyclohexane and 1-methyl-1-phenylcyclohexane is discussed.     

Off-center oxygen-arene interactions in solution: a quantitative study

[reaction: see text] Triptycenes with C1-MeO/RCOO (R = H, Me, Et, i-Pr, CF3) and C9-XC6H4CH2 (X = Me, H, F, CN, CF3) have been prepared to determine lone pair-arene interactions in the off-center configuration. The ratios of the syn and anti conformers were determined by low-temperature NMR spectroscopy. The syn conformer allows the attached arene and the MeO/ester to interact with each other while the anti conformer does not. The free energies of interaction have been derived from the syn/anti ratios. Compound 7 in the ester series with X = H and R = CF3 is the only compound that shows a slightly repulsive interaction (0.08 kcal/mol). Compound 2e in the MeO series with X = CF3 exhibits an attractive interaction (-0.47 +/- 0.05 kcal mol). All other compounds show smaller attractive interactions.     

A computational study of conformational interconversions in 1,4-dithiacyclohexane (1,4-dithiane)

Ab initio molecular orbital theory with the 6-31G(d), 6-31G(d,p), 6-31+G(d), 6-31+G(d,p), 6-31+G(2d,p), 6-311G(d), 6-311G(d,p), and 6-311+G(2d,p) basis sets and density functional theory (BLYP, B3LYP, B3P86, B3PW91) have been used to locate transition states involved in the conformational interconversions of 1,4-dithiacyclohexane (1,4-dithiane) and to calculate the geometry optimized structures, relative energies, enthalpies, entropies, and free energies of the chair and twist conformers. In the chair and 1,4-twist conformers the C-Hax and C-Heq bond lengths are equal at each carbon, which suggest an absence of stereoelectronic hyperconjugative interactions involving carbon-hydrogen bonds. The 1,4-boat transition state structure was 9.53 to 10.5 kcal/mol higher in energy than the chair conformer and 4.75 to 5.82 kcal/mol higher in energy than the 1,4-twist conformer. Intrinsic reaction coordinate (IRC) calculations showed that the 1,4-boat transition state structure was the energy maximum in the interconversion of the enantiomers of the 1,4-twist conformer. The energy difference between the chair conformer and the 1,4-twist conformer was 4.85 kcal/mol and the chair-1,4-twist free energy difference (deltaG degrees (c-t)) was 4.93 kcal/mol at 298.15 K. Intrinsic reaction coordinate (IRC) calculations connected the transition state between the chair conformer and the 1,4-twist conformer. This transition state is 11.7 kcal/mol higher in energy than the chair conformer. The effects of basis sets on the 1,4-dithiane calculations and the relative energies of saturated and unsaturated six-membered dithianes and dioxanes are also discussed.     

Origin of the SN2 benzylic effect

The S N2 identity exchange reactions of the fluoride ion with benzyl fluoride and 10 para-substituted derivatives (RC6H 4CH 2F, R = CH3, OH, OCH 3, NH2, F, Cl, CCH, CN, COF, and NO2) have been investigated by both rigorous ab initio methods and carefully calibrated density functional theory. Groundbreaking focal-point computations were executed for the C6H5CH 2F + F (-) and C 6H 5CH2Cl + Cl (-) SN2 reactions at the highest possible levels of electronic structure theory, employing complete basis set (CBS) extrapolations of aug-cc-pV XZ (X = 2-5) Hartree-Fock and MP2 energies, and including higher-order electron correlation via CCSD/aug-cc-pVQZ and CCSD(T)/aug-cc-pVTZ coupled cluster wave functions. Strong linear dependences are found between the computed electrostatic potential at the reaction-center carbon atom and the effective SN2 activation energies within the series of para-substituted benzyl fluorides. An activation strain energy decomposition indicates that the SN2 reactivity of these benzylic compounds is governed by the intrinsic electrostatic interaction between the reacting fragments. The delocalization of nucleophilic charge into the aromatic ring in the SN2 transition states is quite limited and should not be considered the origin of benzylic acceleration of SN2 reactions. Our rigorous focal-point computations validate the benzylic effect by establishing SN2 barriers for (F (-), Cl (-)) identity exchange in (C6H5CH2F, C6H 5CH2Cl) that are lower than those of (CH3F, CH3Cl) by (3.8, 1.6) kcal mol (-1), in order.     

HCHO+X(X=F、Cl、Br)的反应机理

采用CCSD/6-311++G(d,p)//B3LYP/6-311++G(d,p)方法研究了HCHO与卤素原子X(X=F、Cl、Br)的反应机理. 计算结果表明, 卤素原子X(X=F、Cl、Br)主要通过直接提取HCHO中的H原子生成HCO+HX(X=F、Cl、Br). 另外还可以生成稳定的中间体, 中间体再通过卤原子夺氢和氢原子直接解离两个反应通道分别生成HCO+HX(X=F、Cl、Br)和H+XCHO(X=F、Cl、Br). 其中卤原子夺氢通道为主反应通道, HCO和HX(X=F、Cl、Br)为主要的反应产物; 且三个反应的活化能均较低, 说明此类反应很容易进行, 计算结果与实验结果符合很好. 电子密度拓扑分析显示, 在HCHO+X反应通道(b)中出现了T型结构过渡态, 结构过渡态(STS)位于能量过渡态(ETS)之后. 并且按F、Cl、Br的顺序, 结构过渡态出现得越来越晚.     

Energetic preferences for alpha,beta versus beta,gamma unsaturation

Density functional theory has been applied at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level to examine the energetics of alpha,beta- versus beta,gamma-unsaturation for some common organic functional groups. Specifically, the relative stabilities of allyl-X (H2C=CHCH2X) and 1-propenyl-X (H3CCH=CHX) isomers have been computed for X = methyl, vinyl, phenyl, formyl, acetyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, sulfamoyl, and methoxysulfonyl, and the results are compared to available experimental data. The intrinsic preference of 3 kcal/mol for the 1-propenyl isomer when X = CH3 is exceeded by 2-4 kcal/mol for first-row conjugating groups, but it is not met for the sulfur-containing groups. In particular, alpha,beta-unsaturation is favored by less than 1 kcal/mol for the sulfone and sulfonamide analogues, while it is preferred by 8 kcal/mol for the vinyl-substituted case. Detailed structural results and torsional energy profiles are also reported.     

Polarizable model potential function for nucleic acid bases

A polarizable model potential (PMP) function for adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) is developed on the basis of ab initio molecular orbital calculations at the MP2/6-31+G* level. The PMP function consists of Coulomb, van der Waals, and polarization terms. The permanent atomic charges of the Coulomb term are determined by using electrostatic potential (ESP) optimization. The multicenter polarizabilities of the polarization term are determined by using polarized one-electron potential (POP) optimization in which the electron density changes induced by a test charge are target. Isotropic and anisotropic polarizabilities are adopted as the multicenter polarizabilities. In the PMP calculations using the optimized parameters, the interaction energies of Watson-Crick type A-T and C-G base pairs were -15.6 and -29.4 kcal/mol, respectively. The interaction energy of Hoogsteen type A-T base pair was -17.8 kcal/mol. These results reproduce well the quantum chemistry calculations at the MP2/6-311++G(3df,2pd) level within the differences of 0.6 kcal/mol. The stacking energies of A-T and C-G were -9.7 and -10.9 kcal/mol. These reproduce well the calculation results at the MP2/6-311++G (2d,2p) level within the differences of 1.3 kcal/mol. The potential energy surfaces of the system in which a sodium ion or a chloride ion is adjacent to the nucleic acid base are calculated. The interaction energies of the PMP function reproduced well the calculation results at the MP2/6-31+G* or MP2/6-311++G(2d,2p) level. The reason why the PMP function reproduces well the high-level quantum mechanical interaction energies is addressed from the viewpoint of each energy terms.     

Ab initio studies of the conformations of ethynyl formate, cyano formate and related ethynyl and cyano compounds

The optimized geometries, relative free energies and related thermodynamic properties, harmonic frequencies, and dipole moments have been calculated at the HF and MP2 levels for ethynyl formate (1a), ethynyl acetate (1b), cyano formate, HCO₂CN (1c), cyano acetate (1d), S-ethynyl thioformate (2a), S-ethynyl thioacetate (2b), S-cyano thioformate (2c), S-cyano thioacetate (2d), N-ethynylformamide (3a), N-ethynylacetamide (3b), N-cyanoformamide (3c), and N-cyanoacetamide (3d) with the gaussian 98 program. For ethynyl formate, the calculation for 25 °C at the MP2/6-311++G(df,pd) level predicts that the Z isomer is more stable by 1.23 kcal/mol. For S-ethynyl thioformate, calculations at the MP2/6-311++G(2d,2p) level predict that the E isomer is favored by 0.71 kcal/mol at 25 °C. The E isomers of N-ethynylformamide and N-ethynylacetamide were found at all levels to be more stable than the Z isomers at 25 °C. For cyano formate and cyano acetate, calculations at the MP2/6-311++G(df,pd) level predict that the Z isomers are more stable at 25 °C by 1.50 and 2.72 kcal/mol, respectively. At this level and temperature, the Z isomers of 2c, 2d, 3c, and 3d are predicted to have free energies of 0.46, −0.07, 1.22, and 2.28 kcal/mol, respectively, relative to the E conformations. Z to E free-energy barriers at 25 °C of 8.63, 10.64, 17.63, 7.39, and 14.03 kcal/mol were calculated for 1a, 2a, 3a, 1c, and 3c at the HF/6-311G(d,p) level, and at the HF/6-311+G(d,p) level, the free-energy barrier for 2c was 7.08 kcal/mol.     

Assessment of density functionals with long‐range and/or empirical dispersion corrections for conformational energy calculations of peptides

Density functionals with long‐range and/or empirical dispersion corrections, including LC‐ωPBE, B97‐D, ωB97X‐D, M06‐2X, B2PLYP‐D, and mPW2PLYP‐D functionals, are assessed for their ability to describe the conformational preferences of Ac‐Ala‐NHMe (the alanine dipeptide) and Ac‐Pro‐NHMe (the proline dipeptide) in the gas phase and in water, which have been used as prototypes for amino acid residues of peptides. For both dipeptides, the mean absolute deviation (MAD) is estimated to be 0.22–0.40 kcal/mol in conformational energy and 2.0–3.2° in torsion angles ? and ψ using these functionals with the 6‐311++G(d,p) basis set against the reference values calculated at the MP2/aug‐cc‐pVTZ//MP2/aug‐cc‐pVDZ level of theory in the gas phase. The overall performance is obtained in the order B2PLYP‐D ≈ mPW2PLYP‐D > ωB97X‐D ≈ M06‐2X > MP2 > LC‐ωPBE > B3LYP with the 6–311++G(d,p) basis set. The SMD model at the M06‐2X/6‐31+G(d) level of theory well reproduced experimental hydration free energies of the model compounds for backbone and side chains of peptides with MADs of 0.47 and 4.3 kcal/mol for 20 neutral and 5 charged molecules, respectively. The B2PLYP‐D/6‐311++G(d,p)//SMD M06‐2X/6‐31+G(d) level of theory provides the populations of backbone and/or prolyl peptide bond for the alanine and proline dipeptides in water that are consistent with the observed values. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010