Gas phase and water solution conformational analysis of the herbicide diuron (DCMU): an ab initio study

In the present work, the conformational equilibrium for the herbicide diuron (DCMU) has been investigated using high level ab initio calculations. The solvent effect was included through two different continuum models: (1) the real cavity IPCM method and (2) the standard dipole Onsager model SCRF. The effect due to solute-solvent hydrogen-bond interactions was analyzed considering a hybrid discreet-continuum model. At the Hartree-Fock level, the gas phase results showed that only the trans forms (A and B) are present in the equilibrium mixture, with the relative concentrations found to be 33% (A) and 67% (B) (HF/6-311+G**//6-31G**). When the electronic correlation effect is included (MP2/6-31G*//HF/6-31G*), a relative stabilization of the cis forms was observed, with the conformational distribution calculated as 38% (A), 50% (B), 6% (C) and 6% (D). The trans conformations were found to be completely planar, which has been considered to be a prerequisite for the herbicide binding. In water solution, the trans conformation A should be the most abundant conformer, the IPCM and SCRF values being ca. 100% and ca. 85% respectively. The IPCM calculations with the isodensity level set to 0.0005 present a conformational distribution close to that obtained from the hybrid model [92% (A) and 8% (B)], which has been considered our best solvent approach. Regarding the biological action of urea-type herbicides, the results presented here are important, because some QSAR studies have suggested that the partition coefficient is related to the herbicide activity, so the conformational equilibrium may play a role in the biological action. Received: 23 February 1998 / Accepted: 28 May 1998 / Published online: 19 August 1998     

Infrared, and Raman spectra, conformational stability, normal coordinate analysis, ab initio calculations, and vibrational assignment of 1-chlorosilacyclobutane

The infrared spectra (3500–40 cm⁻¹) of gaseous and solid and the Raman spectra (3500–30 cm⁻¹) of liquid and solid 1-chlorosilacyclobutane, c-C₃H₆SiClH, have been obtained. Both the axial and equatorial conformers with respect to the chlorine atom have been identified in the fluid phases. Variable temperature (−105 to −150°C) studies of the infrared spectra of the sample dissolved in liquid krypton have been carried out. From these data, the enthalpy difference has been determined to be 211±17 cm⁻¹ (2.53±0.21 kJ/mol), with the equatorial conformer being the more stable form and the only conformer remaining in the annealed solid. At ambient temperatures, approximately 26% of the axial conformers are present in the vapor phase. A complete vibrational assignment is proposed for the equatorial conformer, and many of the fundamentals of the axial conformers have also been identified. The vibrational assignments are supported by normal coordinate calculations utilizing ab initio force constants. Complete equilibrium geometries, conformational stabilities, harmonic force fields, infrared intensities, Raman activities, and depolarization ratios have been determined for both rotamers by ab initio calculations employing the 6-31G(d) basis set at the levels of restricted Hartree–Fock (RHF) and/or Moller–Plesset (MP) to second order. Structural parameters have also been obtained using MP2/6-311+G(d,p) ab initio calculations. The r₀ parameters for both conformers are obtained from a combination of the ab initio predicted values and the twelve previously reported microwave rotational constants. The results are discussed and compared to those obtained for some similar molecules.     

Experimental and theoretical multiple kinetic isotope effects for an SN2 reaction. An attempt to determine transition-state structure and the ability of theoretical methods to predict experimental kinetic isotope effects

The secondary alpha-deuterium, the secondary beta-deuterium, the chlorine leaving-group, the nucleophile secondary nitrogen, the nucleophile (12)C/(13)C carbon, and the (11)C/(14)C alpha-carbon kinetic isotope effects (KIEs) and activation parameters have been measured for the S(N)2 reaction between tetrabutylammonium cyanide and ethyl chloride in DMSO at 30 degrees C. Then, thirty-nine readily available different theoretical methods, both including and excluding solvent, were used to calculate the structure of the transition state, the activation energy, and the kinetic isotope effects for the reaction. A comparison of the experimental and theoretical results by using semiempirical, ab initio, and density functional theory methods has shown that the density functional methods are most successful in calculating the experimental isotope effects. With two exceptions, including solvent in the calculation does not improve the fit with the experimental KIEs. Finally, none of the transition states and force constants obtained from the theoretical methods was able to predict all six of the KIEs found by experiment. Moreover, none of the calculated transition structures, which are all early and loose, agree with the late (product-like) transition-state structure suggested by interpreting the experimental KIEs.     

Direct ab initio dynamics study on the rate constants and kinetic isotope effect for the reactions of H atoms with GeDn(CH3)4-n (n = 1-4)

Direct ab initio dynamic calculations are performed on the reactions of atomic hydrogen with GeD(n)(CH(3))(4-n) (n = 1-4) over the temperature range 200-2000 K at the PMP4SDTQ/6-311 +G(3df,2p)//MP2/6-31 +G(d) (for n = 2-4) and G2//MP2/6-31 +G(d) (for n = 1) levels. The corresponding k(H)/k(D) ratios are then calculated in order to determine the kinetic isotope effect for the four reactions. For the simplest GeD(4) +H reaction, the only one that has available experimental data, the calculated canonical variational transition state theory incorporates small-curvature tunneling correction (CVT/SCT) thermal rate constants, and the k(H)/k(D) values are in good agreement with the experimental values within the experimental temperature range 293-550 K. For the four GeD(n)(CH(3))(4-4) (n = 1-4) reactions, the variational effect is small over the whole temperature range, whereas the small-curvature effect is important in the lower temperature range. Finally, the overall rate constants are fitted to the three-parameter expression over the whole temperature range 200-2000 K as 5.8 x 10(8)T(1.68)exp(-929/T), 1.7 x 10(8)T(1.80)exp(-691/T), 2.58 x 10(8)T(1.71)exp(-706/T), and 1.0 x 10(7)T(2.08)exp(-544/T) cm(3) mol(-1) s(-1) for the n = 4, 3, 2, and 1 reactions. Our work may represent the first theoretical study of the kinetic isotope effect for the H-attack on the G-H bonding.     

Molecular structure and conformational analysis of chiral alcohols. Application to the enantioselectivity study of lipases

The molecular structures of the chiral compounds 1-phenylethanol, 2-hexanol and 1-phenylethanol acetate have been studied theoretically by ab initio methods. Conformational analysis and electronic structure studies have been carried out with these molecules at STO-3G^* and 6-31G^* basis sets. For the study of the interaction of lipases with substrates, a simplified model of the tetrahedral intermediate has been calculated at the 6-31G^*//4-31G^* level. Molecular mechanics simulations of the interaction of these compounds with the lipases of Candida rugosa, Pseudomonas cepacia and Rhizomucor miehei have been used to study the enantioselectivity of these lipases in the transesterification reaction of the chiral alcohols. The theoretical results have been compared with experimental data and good agreement was observed. It can be concluded that the enantioselectivity of these lipases is controlled by the formation of a tetrahedral intermediate, whereas Michaelis complex formation has a much lower significance.     

Infrared and Raman spectra, conformational stability, ab initio calculations of structure, and vibrational assignment of 2-hexyne

The infrared spectra (3500–50 cm⁻¹) of the gas and solid and the Raman spectra (3500–50 cm⁻¹) of the liquid and solid have been recorded for 2-hexyne, CH₃–CC–CH₂CH₂CH₃. Variable temperature studies of the infrared spectrum (3500–400 cm⁻¹) of 2-hexyne dissolved in liquid krypton have also been recorded. Utilizing four anti/gauche conformer pairs, the anti(trans) conformer is found to be the lower energy form with an enthalpy difference of 74±8 cm⁻¹ (0.88±0.10 kJ/mol) determined from krypton solutions over the temperature range −105 to −150 °C. At room temperature it is estimated that there is 42% of the anti conformer present. Equilibrium geometries and energies of the two conformers have been determined by ab initio (HF and MP2) and hybrid DFT (B3LYP) methods using a number of basis sets. Only the HF and DFT methods predict the anti conformer as the more stable form as found experimentally. A vibrational assignment is proposed based on the force constants, relative intensities, depolarization ratios from the ab initio and DFT calculations and on rotational band contours obtained using the calculated equilibrium geometries. From calculated energies it is shown that the CH₃ group exhibits almost completely free rotation which is in agreement with the observation of sub-band structure for the degenerate methyl vibrations from which values of the Coriolis coupling constants, ζ, have been determined. The results are compared to similar properties of some corresponding molecules.     

Infrared and Raman spectra, conformational stability, normal coordinate analysis, ab initio calculations, and vibrational assignment of 1-fluoro-1-methylsilacyclobutane

The infrared (3500–40 cm⁻¹) spectra of gaseous and solid 1-fluoro-1-methylsilacyclobutane, c-C₃H₆SiF(CH₃), have been recorded. Additionally, the Raman spectrum (3500–30 cm⁻¹) of the liquid has been recorded and quantitative depolarization values have been obtained. Both the axial and equatorial (with respect to the methyl group) conformers have been identified in the fluid phases. Variable temperature (−55–−100°C) studies of the infrared spectra of the sample dissolved in liquid xenon have been carried out. From these data, the enthalpy difference has been determined to be 267±10 cm⁻¹ (3.19±0.12 kJ mol⁻¹), with the axial conformer being the more stable form and the only conformer remaining in the polycrystalline solid. A complete vibrational assignment is proposed for the axial conformer and many of the fundamentals for the equatorial conformer have also been identified. The vibrational assignments are supported by normal coordinate calculations utilizing ab initio force constants. Complete equilibrium geometries have been determined for both rotamers by ab initio calculations employing the 6-31G* and 6-311++G** basis sets at the levels of restricted Hartree–Fock (RHF) and/or Moller–Plesset (MP) to second order. The results are discussed and compared to those obtained for some similar molecules.     

Electronic structure and conformational properties of (carboxy-alkenyl)-phosphonic acids

The general conformational properties and electronic structure of (carboxy-alkenyl)-phosphonic derivatives were determined at RHF/STO-3G^* level. In all the series, low rotation barriers were found for the two C=C/P=O conformers. In the compounds in which the interactions between the carboxylic and phosphonic moieties are smaller, the most stable conformers are the C=C/P=O s-cis ones. In most of the conformers, the C=C/C=O system presents the disposition s-cis. The Z-(2-carboxy-vinyl) and Z-(2-carboxy-propenyl) phosphonic acids present intramolecular hydrogen bonds, existing in at least four conformer with internal hydrogen bonds. These last compounds were more rigorously studied at RHF/3-21G^* and RHF/6-31G^** levels. The most stable conformer shows a trans structure for the C=C/P=O angle, with an intramolecular hydrogen bond located between the hydroxylic hydrogen of phosphonic group and the carbonyl oxygen of carboxylic moiety. A secondary conformer is found with a double intramolecular hydrogen bond between two hydroxylic hydrogens of the phosphonic moiety and the oxygen of carboxylic bond. Another secondary conformer appears with an intramolecular hydrogen bond between the oxygen of the phosphoryl bond and the hydroxylic hydrogen of the carboxylic group. A study of the topology of charge densities is carried out. This analysis reveals bonds with an ionic participation. A very weak π conjugation, variable with the conformers, is found in the C=C/P=O system, as well as a strongly polarized P=O partial triple bond. The intramolecular hydrogen bonds give rise to cyclic structures.     

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     

Vibrational spectra, conformations, ab initio calculations and vibrational assignments of 3-pentyn-2-ol

The infrared spectra of 3-pentyn-2-ol, CH₃CCCH(OH)CH₃, have been recorded as a vapour and liquid at ambient temperature, as a solid at 78 K in the 4000–50 cm⁻¹ range and isolated in an argon matrix at ca. 5 K. Infrared spectra of the solid phase at 78 K were obtained before and after annealing to temperatures of 120 and 130 K. The IR spectra of the solid were quite similar to that of the liquid.

Raman spectra of the liquid were recorded at room temperature and at various temperatures between 295 and 153 K. Spectra of an amorphous and annealed solid were recorded at 78 K. In the variable temperature Raman spectra, some bands changed in relative intensity and were interpreted in terms of conformational equilibria between the three possible conformers. Complete assignments were made for all the bands of the most stable conformer in which OH is oriented anti to C₁(a_Me). From various bands assigned to a second conformer in which OH is oriented anti to H_gem(a_H), the conformational enthalpy differences was found to be between 0.4 and 0.8 kJ mol⁻¹. The highest energy conformer with OH anti to C₃(a_C) was not detected.

Quantum-chemical calculations have been carried out at the MP2 and B3LYP levels with a variety of basis sets. Except for small basis set calculations for which the a_H conformer had slightly lower energy, all the calculations revealed that a_Me was the low energy conformer. The B3LYP/cc-pVTZ calculations suggested the a_Me conformer as more stable by 0.8 and 8.3 kJ mol⁻¹ relative to a_H an a_C, respectively. Vibrational wavenumbers and infrared and Raman band intensities for two of the three conformers are reported from B3LYP/cc-pVTZ calculations.     

Theoretical investigation into the influence of conformational equilibria on the water-exchange process in magnetic resonance imaging contrast agents

The conformational behavior in aqueous solution of four complexes of the Eu(III) ion with bis (R–amide) derivatives (R=H, methyl, ethyl, butyl) of diethylentriamine pentacetate ligands has been characterized at the ab initio level to rationalize the experimentally observed influence of alkyl substituents on the rate of the exchange process of the water molecule coordinated to the ion with the bulk water. Calculations were performed in vacuo and for aqueous solution, the latter by using the polarizable continuum model. Geometry optimizations provide, for each system, four isomers as stable conformations, all presenting a distorted tricapped trigonal prism coordination geometry around the ion. No significant influence of the alkyl substitution on the coordination geometry, nor on the europium–water distance, was observed. Moreover, increasing the length of the alkyl chain had no significant effect on the relative isomer population in solution. Thus, these results lead us to suppose that other effects, like those deriving from lateral chain folding in solution, should be considered to explain the increased rate of the water-exchange process with alkyl chain lengthening.Contribution to the Jacopo Tomasi Honorary Issue     

On the vibrational spectra and conformational stability of 1,1-dimethylhydrazine from temperature dependent FT-IR spectra of krypton solutions and ab initio calculations

Variable temperature (−105 to −150 °C) studies of the infrared spectra (3500–400 cm⁻¹) of 1,1-dimethylhydrazine, (CH₃)₂NNH₂, in liquid krypton have been carried out. No convincing spectral evidence could be found for the trans conformer which is expected to be at least 600 cm⁻¹ less stable than the gauche form. The structural parameters, dipole moments, conformational stability, vibrational frequencies, and infrared and Raman intensities have been predicted from MP2/6-31G(d) ab initio calculations. The predicted infrared and Raman spectra are compared to the experimental ones. The adjusted r₀ parameters from MP2/6-311+G(d,p) calculations are compared to those reported from an electron diffraction study. The energy differences between the gauche and trans conformers have been obtained from MP2 ab initio calculations as well as from density functional theory by the B3LYP method calculations from a variety of basis sets. All of these calculations indicate an energy difference of 650–900 cm⁻¹ with the B3LYP calculations predicted the larger values. The potential function governing the conformational interchange has been predicting from both types of calculations and comparisons have been made. The barrier to internal rotation by the independent rotor model of the inner methyl group is predicted to have a value of 1812 cm⁻¹ and that of the outer one of 1662 cm⁻¹ from ab initio MP2/6-31G(d) calculations. These values agree well with the experimentally determined values of 1852±16 and 1558±12 cm⁻¹, respectively, from a fit of the torsional transitions with the coupled rotor model. For the coupled rotor model the predicted V′₃₃ (sin 3τ₀ sin 3τ₁ term) value which ranged from 190 to 232 cm⁻¹ is in reasonable agreement with the experimental value of 268±3 cm⁻¹ but the predicted V₃₃ (cos 3τ₀ cos 3τ₁ term) value of −73 to −139 cm⁻¹ is 25% smaller and of the opposite sign of the experimental value of 333±22 cm⁻¹. These theoretical and spectroscopy results are compared to similar quantities of some corresponding molecules.     

Primary kinetic isotope effect in the nitrosation of 1,3- dialkylureas

In the nitrosation mechanism of 1,3 dialkylureas, the existence of protonic transfer to the solvent as a rate-limiting step was confirmed when a primary kinetic isotope effect was observed in these reactions.     

Hyperconjugation as it affects conformational analysis

A primer for the qualitative identification and quantitative analysis of hyperconjugative delocalization is presented. The particular focus is upon the influence of hyperconjugation as it affects conformational analysis. Computational methodologies are illustrated within the context of several diverse molecular systems: anomeric and reverse anomeric effects in 2-tetrahydropyranosylammonium, generalized anomeric effects in phosphorus-stabilized carbanions, and hyperconjugative effects in phosphorus- and silicon-based trigonal bipyramids. Hyperconjugation is shown to compete with apicophilicity in the final examples. Although the latter influence has long been accounted for in traditional conformational analysis of trigonal bipyramidal systems, the former has been less appreciated.     

Comparison of conformer distributions in the crystalline state with conformational energies calculated by ab initio techniques

Summary The conformational preferences of 12 molecular substructures in the crystalline state have been determined and compared with those predicted for relevant model compounds by ab initio molecular orbital calculations. Least-squares regression shows that there is a statistically significant correlation between the crystal-structure conformer distributions and the calculated potential-energy differences, even though the calculations relate to a gas-phase environment. Torsion angles associated with high strain energy (>1 kcal mol^-1) appear to be very unusual in crystal structures and, in general, high-energy conformers are underrepresented in crystal structures compared with a gas-phase, room-temperature Boltzmann distribution. It is concluded that crystal packing effects rarely have a strong systematic effect on molecular conformations. Therefore, the conformational distribution of a molecular substructure in a series of related crystal structures is likely to be a good guide to the corresponding gas-phase potential energy surface.     

Conformational Analysis of 2,2′-bifuran: Correlated High-level Ab initio and DFT Results

The torsional potential for inter-ring rotation in 2,2′-bifuran has been systematically tackled using highly accurate ab initio calculations as well as cost-effective DFT methods. The successful convergence of the ab initio results allowed to confirm the presence of a shallow gauche minimum in the torsional potential curve. The standard DFT methods failed to capture such a tiny energy barrier but, interestingly, the results could be remarkably improved by a mixture of wavefunction and DFT energies in a multi-coefficient fashion; thus, accurate DFT-based and ab initio reference data also become available. Since the experimental evaluation of torsional potentials faces quantitative problems, the outcome of high-level theoretical calculations is expected to be reliably used in further investigation on structure and conformational distribution of this system.     

Solid state and theoretical evaluation of β-fluoroethyl esters indicate a fluorine-ester gauche effect

Single crystal X-ray diffraction studies and a theoretical analysis indicate a preferred conformation for O-β-fluoroethyl esters, where the CF and CO(CO) bonds are gauche rather than anti to each other. The OCCF dihedral angles for three compounds and five independent structures indicate a range of only 63.4-69.6°. Evaluation of a rotational energy profile around this bond in a model system (β-fluoroethyl acetate) predicted a similar dihedral angle and the gauche conformation to be the minimum on the rotational energy profile. High level ab initio calculations measured the gauche conformer to be 0.95 kcal mol⁻¹ lower in energy than the anti conformer and application of a solvation model further increased this differential to 1.6 kcal mol⁻¹, consistent with a previous solution state (NMR) evaluation of this system.