Theoretical and vibrational study of the conformation of 2-methoxy- 1,2-diphenylethanone.

The conformation and vibrational properties of 2-methoxy-1,2-diphenylethanone (MDPE) are investigated in the gas phase and in organic solvents. Ab initio calculations carried out at the B3LYP/6-31G(d) level demonstrate that three stable conformers having cisoid, skewed and transoid structures are present in the gas phase. In the gas phase, the conformers are separated by a low energy barrier and their relative energies do not differ by more than 7.2 kJ mol (-1) Like in crystalline MDPE 'Acta Crystallogr. Sect. C 44 (1988) 894', weak CH...O hydrogen bonds are present in the cisoid conformation. The IR and Raman spectra of solid MDPE are discussed. Several vibrational modes are split in organic solvents. A comparison between the theoretical data and the experimental dipole moments indicates that two conformers are present in solution, the population of the cisoid form increasing with the permittivity of the medium.     

Ab initio studies of aspartic acid conformers in gas phase and in solution

Systematic and extensive conformational searches of aspartic acid in gas phase and in solution have been performed. For the gaseous aspartic acid, a total of 1296 trial canonical structures and 216 trial zwitterionic structures were generated by allowing for all combinations of internal single-bond rotamers. All the trial structures were optimized at the B3LYP/6-311G* level and then subjected to further optimization at the B3LYP/6-311++G** level. A total of 139 canonical conformers were found, but no stable zwitterionic structure was found. The rotational constants, dipole moments, zero-point vibrational energies, harmonic frequencies, and vertical ionization energies of the canonical conformers were determined. Single-point energies were also calculated at the MP2/6-311++G** and CCSD/6-311++G** levels. The equilibrium distributions of the gaseous conformers at various temperatures were calculated. The proton affinity and gas phase basicity were calculated and the results are in excellent agreement with the experiments. The conformations in the solution were studied with different solvation models. The 216 trial zwitterionic structures were first optimized at the B3LYP/6-311G* level using the Onsager self-consistent reaction field model (SCRF) and then optimized at the B3LYP/6-311++G** level using the conductorlike polarized continuum model (CPCM) SCRF theory. A total of 22 zwitterions conformers were found. The gaseous canonical conformers were combined with the CPCM model and optimized at the B3LYP/6-311++G** level. The solvated zwitterionic and canonical structures were further examined by the discrete/SCRF model with one and two water molecules. The incremental solvation of the canonical and zwitterionic structures with up to six water molecules in gas phase was systematically examined. The studies show that combining aspartic acid with at least six water molecules in the gas phase or two water molecules and a SCRF solution model is required to provide qualitatively correct results in the solution.     

Theoretical and experimental study of valence photoelectron spectrum of D,L-alanine amino acid

In this work, the He-I (21.218 eV) photoelectron spectrum of D,L-alanine in the gas phase is revisited experimentally and theoretically. To support the experiment, the high level ab initio calculations were used to calculate and assign the photoelectron spectra of the four most stable conformers of gaseous alanine, carefully. The symmetry adapted cluster/configuration interaction (SAC-CI) method based on single and double excitation operators (SD-R) and its more accurate version, termed general-R, was used to separately calculate the energies and intensities of the ionization bands of the L- and D-alanine conformers. The intensities of ionization bands were calculated based on the monopole approximation. Also, natural bonding orbital (NBO) calculations were employed for better spectral band assignment. The relative electronic energy, Gibbs free energy, and Boltzmann population ratio of the conformers were calculated at the experimental temperature (403 K) using several theoretical methods. The theoretical photoelectron spectrum of alanine was calculated by summing over the spectra of individual D and L conformers weighted by different population ratios. Finally, the population ratio of the four most stable conformers of alanine was estimated from the experimental photoelectron spectrum using theoretical calculations for the first time.     

Hydration of cyclohexylamines: CPCM calculation of hydration Gibbs energy of the conformers

This work presents a theoretical study on the hydration of cyclohexylamine and isomers of cyclohexyldiamine. All possible conformers were fully optimized in solution using the conductor-like polarizable continuum model (CPCM) and density functional theory. Values of the Gibbs energy of solvation, its respective contributions (electrostatic, nonelectrostatic and conformational change), and the relative Gibbs energy of the conformers in aqueous solution and gas phase are reported. From these values and the Boltzmann populations of the conformers in both phases, the weighted mean values of DeltaG(solv) for the compounds are calculated. Three structural features were found to be important for the hydration of these compounds: the distance between the two NH2 groups (proximity disfavors hydration), their position relative to the ring (equatorial is preferred over axial), and the orientation of the nitrogen lone-pairs (gauche is more favorable to hydration than trans). In the particular case of vicinal cyclohexyldiamines, in addition to these two factors, the relative orientation of one group to the other should also be taken into account.     

Why do GroEL Ions Exhibit Two Gas Phase Conformers?

The reasons for the existence of two gas phase conformers for electrosprayed ions of the large tetradecameric protein complex GroEL are considered. Key features are that: (1) both conformers extrapolate to very similar cross sections in the limit of zero charge; (2) both conformers supercharge above the maximum value permitted by the Rayleigh criterion; and (3) one of the conformers supercharges substantially more than the other. We hypothesize that the supercharging observed is associated to the approximately cylindrical shape of GroEL in aqueous solution, enabling accumulation of extra charge on either one or two of its bases when they intersect the evaporating drop surface. The two conformers would then correspond to cases when either one or the two bases of the cylinder carry extra charge. Apparently, the conformer symmetrically (doubly) supercharged on both ends is Coulombically stretched, therefore exhibiting a mobility different from the conformer asymmetrically supercharged only on one end. Several general consequences follow. First, non-spherical proteins may generally be charged above the usual Rayleigh limit. Second, we confirm the previously advanced but contentious notion that gas phase protein ions are readily compacted or stretched away from their crystal structure by capillary and Coulombic forces during the electrospraying process.     

Spectroscopic and theoretical investigation of (R)-3-methylcyclopentanone. The effect of solvent and temperature on the distribution of conformers

Temperature-dependent electronic circular dichroism (CD) spectra are reported for (R)-(+)-3-methylcyclopentanone (R3MCP) in 34 solvents. Analysis of these data yielded the enthalpy and entropy differences between axial methyl and equatorial methyl conformers, the dominant conformers for R3MCP. The weakly absorbing n-->pi* transition exhibited a decrease in lambdamax as the solvent polarity increased. Vibrational CD fine structure of the n-->pi* transition was observed in the gas phase in addition to several of the solvents. Vapor-phase CD spectra were compared to both the solution-phase spectra and theoretical calculations of the axial and equatorial methyl conformers. Optical rotation (OR) measurements for R3MCP in cyclohexane solution in the visible region showed excellent agreement with OR DFT calculations of the equatorial and axial methyl conformers. Density functional calculations with B3LYP and the 6-13G* and aug-cc-pVDZ basis sets, which incorporate the solvent dielectric constant, yielded trends in thermodynamic quantities as a function of polarity and solvent dipole moments that are only weakly or not observed in experiments.     

Ab initio conformational maps in the gas phase and aqueous solution for a prototype of the glycosidic linkage

Ab initio conformational maps for methoxyethoxymethane (MEM) in both the gas phase and aqueous solution have been constructed using two different approaches. The results obtained allow us to conclude that a rigid conformational map is able to predict the regions of the minima, in the potential energy surface of MEM, in full agreement with those found in the relaxed conformational map, in both phases studied. This is a good indication that ab initio rigid conformational maps may be reliably used to sort the stablest conformers of disaccharides in aqueous solution. Besides that, in the MEM case, the solvation effects do not give rise to any new local minimum in its potential energy surface, but just change the relative energies of the stablest conformers found in the gas phase. This may be an indication that even in aqueous solution the anomeric effect is still the determinant effect defining the conformation of the molecule.Proceedings of the 11th International Congress of Quantum Chemistry satellite meeting in honor of Jean-Louis Rivail     

Quantum mechanical study of the syn-anti isomerisation of 2-tellurophenecarboaldehyde: vive la différence

The syn- and anti-conformers of 2-tellurophenecarboaldehyde are studied in the gas phase. A transition state is also modelled for the syn-anti isomerisation. Computations are done using different methods namely HF, DFT/B3LYP, MP2 and CCSD(T). The basis set used for all atoms is 6-311++G(d,p) except that LanL2DZ ECP is used for tellurium atom only. The optimised molecular structures and related structural parameters of these conformers are reported. The energy differences between the syn- and anti-conformers, associated rotational barriers and thermodynamic parameters are derived from the computations. The infrared frequencies of these conformers are also reported with appropriate assignments. This study is extended to include solvent effect and the conformers are fully optimised (DFT/B3LYP) using the integral equation formalism in the Polarisable Continuum model. In the gas phase, the theoretical rate constant for the unimolecular conversion, anti conformer to transition state, is reported for the first time; DFT/B3LYP (4.82×10(30) s(-1)) and MP2 (7.81×10(30) s(-1)). It is found that the structures are not much affected by the solvents but energy difference increases and rotational barrier decreases. The results indicate that there is a close agreement with the predictions from the different theoretical methods. The results obtained are critically analysed and compared with the furan, thiophene and selenophene analogues. A major factor affecting conformational preference and the mole fraction is the charge on the chalcogen heteroatom in the ring. An interesting outcome of this work is that in both the gas phase and solutions, the syn conformer is more stable and exists almost exclusively.     

A density functional theory study on pelargonidin

A complete conformational analysis on the isolated and polarizable continuum model (PCM) modeled aqueous solution cation, quinonoidal, and anion forms of pelargonidin, comprising the diverse tautomers of the latter forms, was carried out at the B3LYP/6-31++G(d,p) level. The results indicate that the most stable conformer of cationic and quinonoidal forms of pelargonidin are completely planar in the gas phase, whereas that of the anionic form is not planar. In contrast, PCM calculations show that the plane of the B ring is slightly rotated with regard to the AC bicycle in the most stable conformer of the cation and quinonoidal form. The most stable conformers of the cation, both in gas phase and aqueous solution, display anti and syn orientations for, respectively, C2-C3-O-H and C6-C5-O-H dihedral angles, whereas syn and anti orientation of hydroxyls at 7 and 4' positions are nearly isoenergetic. The most stable tautomer of quinonoidal pelargonidin is obtained by deprotonating hydroxyl at C5 in gas phase but at C7 according to PCM. Also, the most stable tautomer of the anion is different in gas phase (hydrogens are abstracted from hydroxyls at C5 and C4') and PCM simulation (C3 and C5). Tautomeric equilibria affect substantially the geometries of the AC-B backbone providing bond length variations that basically agree with the predictions of the resonance model. Most of the conformers obtained display an intramolecular hydrogen bond between O3 and H6'. Nevertheless, this interaction is not present in the most stable anions. Ionization potentials and O-H bond dissociation energies computed for the most stable conformers of cation, quinonoidal, and anion forms are consistent with an important antioxidant activity.     

Computational study on the properties and structure of methyl lactate

A theoretical study on the properties and molecular level structure of the very important green solvent methyl lactate is carried out in the gas phase and methanol and water solutions, with the solvent treated both explicitly and as a continuum. Torsional barriers giving rise to different conformers by rotation of the hydroxyl and methyl groups were analyzed using density functional theory (DFT) to establish the most stable conformer both in gas phase and solution. DFT computations on lactate dimers were also done to study short-range features, and the effect of the surrounding solvent on intra- and intermolecular hydrogen bonding was analyzed according to the polarizable continuum model approach. We have also studied lactate/water and lactate/methanol small clusters together with the corresponding binding energies. Moreover, classical molecular dynamics simulations (MD) were carried out to study medium- and large-range effects at lower computational cost. MD simulations at different pressure and temperature conditions on pure lactate were carried out, and mixtures with water and methanol of different compositions were also studied. Structural information, analyzed through the radial distribution functions, together with dynamic aspects of pure and mixed fluids were considered. The intramolecular hydrogen bonding ability of methyl lactate together with the possibility of homo- and hetero-intermolecular association determines the behavior of this molecule in pure fluids or in mixed.     

Quantum-chemical calculations of the relative stability of the keto-enol tautomers of 5-chlorouracyl

Relative energies (by MP4(SQTQ)/def2-TZVPP) for 13 tautomeric conformers of 5-chlorouracyl in the gas phase and in solution with consideration of nonspecific solvation in water are calculated. The geometrical parameters of the calculated conformers are analyzed. A stability series of tautomers with respect to the diketo form is obtained. It is shown that nonspecific solvation leads to changes in the stability series.     

Structure of isolated tryptophyl-glycine dipeptide and tryptophyl-glycyl-glycine tripeptide: ab initio SCC-DFTB-D molecular dynamics simulations and high-level correlated ab initio quantum chemical calculations

The tryptophyl-glycine (Trp-Gly) and tryptophyl-glycyl-glycine (Trp-Gly-Gly) peptides have been studied by means of molecular dynamic simulations combined with high-level correlated ab initio quantum chemical and statistical thermodynamic calculations. The lowest energy conformers were localized in the free energy surface. The structures of the different Trp-Gly and Trp-Gly-Gly conformers coexisting in the gas phase have been for the first time reported and their scaled theoretical IR spectra unambiguously assigned and compared with previous gas-phase experimental results. Common geometrical features have been systematically observed for the sequence Trp, Trp-Gly, and Trp-Gly-Gly. In addition, the peptide backbone of Trp-Gly-Gly has been compared with that of the previously studied Phe-Gly-Gly (Reha, D. et. al. Chem. Eur. J. 2005, 11, 6803). From the observed systematic structural behavior between these peptide analogues, it is expected that the gas-phase conformers of other similar aromatic small peptides would present equivalent geometries. The DFT methodology failed to describe the potential energy surface of the studied peptides since the London dispersion energy (not covered in DFT) plays a significant role in the stabilization of most stable conformers.     

Tautomer selective photochemistry in 1-(tetrazol-5-yl)ethanol

A combined matrix isolation FTIR and theoretical DFT/B3LYP/6-311++G(d,p) study of the molecular structure and photochemistry of 1-(tetrazol-5-yl)ethanol [1-TE] was performed. The potential energy surface landscapes of the 1H and 2H tautomers of the compound were investigated and the theoretical results were used to help characterize the conformational mixture existing in equilibrium in the gas phase prior to deposition of the matrices, as well as the conformers trapped in the latter. In the gas phase, at room temperature, the compound exists as a mixture of 12 conformers (five of the 1H tautomer and seven of the 2H tautomer). Upon deposition of the compound in an argon matrix at 10 K, only three main forms survive, because the low barriers for conformational isomerization allow extensive conformational cooling during deposition. Deposition of the matrix at 30 K led to further simplification of the conformational mixture with only one conformer of each tautomer of 1-TE surviving. These conformers correspond to the most stable forms of each tautomer, which bear different types of intramolecular H-bonds: 1H-I has an NH···O hydrogen bond, whereas 2H-I has an OH···N hydrogen bond. Upon irradiating with UV light (λ > 200 nm), a matrix containing both 1H-I and 2H-I forms, an unprecedented tautomer selective photochemistry was observed, with the 2H tautomeric form undergoing unimolecular decomposition to azide + hydroxypropanenitrile and the 1H-tautomer being photostable.     

Calculation of relative energies of permethylated oligosilane conformers in vapor and in alkane solution

The geometries of 35 conformers of Me(SiMe2)nMe (n = 4, 1; n = 5, 2; n = 6, 3; n = 7, 4) were optimized at the MP2/VTDZ level, and CCSD(T) single-point calculations were done at three MP2/VTDZ conformer geometries of 1. The relative ground-state energies of the conformers of 1-4 in the gas phase were obtained from the MP2/VTDZ electronic energy, zero-point vibrational energy, and thermal corrections at 0, 77, and 298 K. Relative energies in an alkane solvent at 77 and 298 K were obtained by the addition of solvation energies, obtained from the SM5.42R model. The calculated energies of 26 of the conformers (n = 4-6) have been least-squares fitted to a set of 15 additive increments associated with each Si-Si bond conformation and each pair of adjacent bond conformations, with mean deviations of 0.06-0.20 kcal/mol. An even better fit for the energies of 24 conformers (mean deviations, 0.01-0.09 kcal/mol) has been obtained with a larger set of 19 increments, which also contained contributions from selected combinations of conformations of three adjacent bonds. The utility of the additive increments for the prediction of relative conformer energies in the gas phase and in solution has been tested on the remaining nine conformers (n = 6, 7). With the improved increment set, the average deviation from the SM5.42R//MP2 results for solvated conformers at 298 K was 0.18 kcal/mol, and the maximum error was 0.98 kcal/mol.     

Quantum-chemical study of tautomers of reduced forms of anthraquinone

The quantum-chemical method B3LYP/6-311G(d,p) was used to calculate structural parameters of four conformers of 9,10-dihydroxyanthracene, two conformers of 9-hydroxyanthrone, and the corresponding anions, dianion, and radical anion. The energy of 9,10-dihydroxyanthracene in a gas phase is higher and in aqueous solution lower than the energy of 9-hydroxyanthrone. The dianion can exist exclusively in a polarizable medium.     

Computational study on hydrolysis of cefotaxime in gas phase and in aqueous solution

We are presenting a theoretical study of the hydrolysis of a β‐lactam antibiotic in gas phase and in aqueous solution by means of hybrid quantum mechanics/molecular mechanics potentials. After exploring the potential energy surfaces at semiempirical and density functional theory (DFT) level, potentials of mean force have been computed for the reaction in solution with hybrid PM3/TIP3P calculations and corrections with the B3LYP and M06‐2X functionals. Inclusion of the full molecule of the antibiotic, Cefotaxime, in the gas phase molecular model has been demonstrated to be crucial since its carboxylate group can activate a nucleophilic water molecule. Moreover, the flexibility of the substrate implies the existence of a huge number of possible conformers, some of them implying formation of intramolecular hydrogen bond interaction that can determine the energetics of the conformers defining the different states along the reaction profile. The results show PM3 provides results that are in qualitative agreement with DFT calculations. The free energy profiles show a step‐wise mechanism that is kinetically determined by the nucleophilic attack of a water molecule activated by the proton transfer to the carboxylate group of the substrate (the first step). However, since the main role of the β‐lactamase would be reducing the free energy barrier of the first step, and keeping in mind the barrier obtained from second intermediate to products, population of this second intermediate could be significant and consequently experimentally detected in β‐lactamases, as shown in the literature. © 2012 Wiley Periodicals, Inc.     

Conformations, energies, and intramolecular hydrogen bonds in dicarboxylic acids: implications for the design of synthetic dicarboxylic acid receptors

The various conformers of the dicarboxylic acids HO2C--(CH2)n--CO2H, n = 1-4, were obtained using density functional methods (DFT), both in the gas phase and in the aqueous phase using a polarized continuum model (PCM). Several new conformers were identified, particularly for the two larger molecules glutaric (n = 3) and adipic acid (n =4). The PCM results show that the stability of most conformers were affected, many becoming unstable in the aqueous phase; and the energy ordering of conformers is also different. The results suggest that conformational preferences could be important in determining the design and stability of appropriate synthetic receptors for glutaric and adipic acid. Geometry changes between gas and aqueous phases were most marked in those conformers containing an intramolecular hydrogen bond. Additional calculations have probed the strength of intramolecular hydrogen bonds in these dicarboxylic acids. In the cases of glutaric and adipic acid, the strength of the intramolecular hydrogen bond were estimated to be around 28-29 kJ/mol, without any vibrational energy correction. The intramolecular hydrogen bond energies in malonic and succinic acid were also estimated from the calculated H-bond distances using an empirical relationship. Intramolecular H-bond redshifts of 170-250 cm(-1) have been estimated from the results of the harmonic frequency analyses.     

Conformational search for zwitterionic leucine and hydrated conformers of both the canonical and zwitterionic leucine using the DFT-CPCM model

The stable conformations for zwitterionic leucine have been searched for in solution as well as in gas phase. A total of 54 trial structures were generated by considering possible combinations of single bond rotamers. It is observed that zwitterions are not stable in gas phase. In order to investigate the zwitterions of leucine in solution, the calculations for all trial structures of zwitterions were performed initially at the PM3 level and 14 the lowest energy structures were reoptimized at the B3LYP/6-311G(d) level using the CPCM model. Seven of these conformers of zwitterionic leucine were found to be stable in solution. The five most stable conformers were then reoptimized at the B3LYP/6-311++G(d, p) level. The energy ordering of the canonical leucine(neutral) conformers were also considered on the basis of single point energy calculations at the B3LYP/6-311++G(d, p) level using the CPCM model. The chemical hardness, chemical potential, vertical ionization energy and vertical electron affinity were calculated for a few of the most stable canonical leucine and its zwitterions in solution. The effects of explicit addition of water molecules (microsolvation) on the structure and the energy of both canonical and zwitterionic conformers of leucine were investigated. It is noted that in gas phase, the singly and doubly hydrated canonical (neutral) forms are more stable than their zwitterionic counterparts. The solvated zwitterions and canonical structures of leucine were further investigated using the discrete/SCRF model with zero, one and two water molecules. In solution, the continuum solvent model shows that the bare zwitterionic form is more stable than the bare canonical form by 1.6 kcal/mol. This energy separation is increased to 3.8 and 4.8 kcal/mol with inclusion of one and two water molecules, respectively. The optimized structural parameters for the most stable zwitterionic leucine with zero, one and two water molecules in solution were compared with those reported for l-leucine crystal, which shows a close agreement between the optimized geometrical parameters of the zwitterionic leucine with two water molecules in solution with the experimental geometrical parameters for l-leucine crystal. It is also observed that when the structures of zwitterions with one and two explicit water molecules are optimized in solution, the geometrical parameters and their relative energies are found to be appreciably modified. We have also calculated the vibrational spectra of the most stable solvated zwitterionic leucine as well as for the most stable structure of zwitterionic leucine with one and two water molecules in solution.     

Conformational properties of penicillins: quantum chemical calculations and molecular dynamics simulations of benzylpenicillin

Herein, we present theoretical results on the conformational properties of benzylpenicillin, which are characterized by means of quantum chemical calculations (MP2/6-31G* and B3LYP/6-31G*) and classical molecular dynamics simulations (5 ns) both in the gas phase and in aqueous solution. In the gas phase, the benzylpenicillin conformer in which the thiazolidine ring has the carboxylate group oriented axially is the most favored one. Both intramolecular CH. O and dispersion interactions contribute to stabilize the axial conformer with respect to the equatorial one. In aqueous solution, a molecular dynamics simulation predicts a relative population of the axial:equatorial conformers of 0.70:0.30 in consonance with NMR experimental data. Overall, the quantum chemical calculations as well as the simulations give insight into substituent effects, the conformational dynamics of benzylpenicillin, the frequency of ring-puckering motions, and the correlation of side chain and ring-puckering motions.