Ab initio optical rotatory dispersion and electronic circular dichroism spectra of (S)-2-chloropropionitrile

Coupled-cluster and density-functional methods have been used to determine specific rotations and electronic circular dichroism (ECD) rotational strengths for (S)-2-chloropropionitrile. Coupled-cluster specific rotations using both the length- and velocity-gauge representations of the electric-dipole operator, computed with basis sets of triple-zeta quality containing up to 326 functions, compare very well with recently reported gas-phase cavity-ring-down polarimetry data. ECD rotational strengths for the six lowest-lying excited states are found to vary in sign, and the second excited state, which has a larger rotational strength than the first by a factor of 4, was found to yield a much larger contribution (by a factor of 10) to the overall negative specific rotation observed both experimentally and theoretically. However, both valence and Rydberg states appear to make substantial contributions to the total rotation, often of opposite sign from the converged/linear-response result. Furthermore, the sum-over-states approach was found to be inadequate for reproducing the specific rotations derived from the linear-response approach, even when 100 excited states (well beyond the estimated ionization limit) were included in the summation. Density-functional specific rotations using the B3LYP functional with basis sets of quadruple-zeta quality containing up to 588 functions are found to be too large compared to experiment by approximately a factor of 2. This error appears to be related to both the underestimation of the electronic excitation energies, as well as concomitant overestimation of the corresponding ECD rotational strengths. Although earlier studies reported good agreement between density-functional specific rotations and experiment when electric-field-dependent functions were used in conjunction with a double-zeta-quality basis set, the results reported here, which are near the basis-set limit, suggest that this agreement may be fortuitous.     

Optical rotatory dispersion of 2,3-hexadiene and 2,3-pentadiene

The specific rotation of (P)-2,3-hexadiene (1) was measured as a function of wavelength for the gas phase, the neat liquid, and solutions. There was a surprisingly large difference between the gas phase and condensed phase values. The specific rotation was calculated using B3LYP and CCSD, and the difference in energy between the three low energy conformers was estimated at the G3 level. The Boltzmann-averaged CCSD-calculated rotations using the gauge independent velocity gauge representation, as well as the B3LYP values, are in agreement with the gas-phase experimental values. In order to avoid possible problems associated with the conformers of 1, 2,3-pentadiene (2) also was examined. Here again, there was a large difference between the gas-phase and condensed-phase specific rotations, with the CCSD velocity gauge (and B3LYP) results being close to the gas-phase experimental values. The possibility that 2,3-pentadiene could be distorted on going from the gas to liquid phase, thereby accounting for the effect of phase on the specific rotation, was examined via a Monte Carlo statistical mechanics simulation. No effect on the geometry was found. Specific rotations of 1 found in solutions were similar to those for the liquid phase, indicating that the phase difference was not due to association.     

Pseudohelical and helical primary structures of 1,2-spiroannelated four- and five-membered rings: syntheses and chiroptical properties

The pseudohelical hydrocarbons (R)-6, (S)-7, and (R)-8 and the helical hydrocarbon (P)-9, formally derived from the helical hydrocarbon (P)-4 by stepwise replacement of each of the four-membered rings by a five-membered ring, have been prepared. Their optical rotations vary systematically, both in magnitude and sign. Of the extremes, (P)-4 represents the usual case of a right-handed dextrorotatory helix, while (P)-9 represents the unusual case of a right-handed levorotatory helix. To rationalize these facts, DFT calculations of the rotatory power of (P)-helices of three-, four-, and five-membered rings have been performed. The results show a very good agreement with the experimental data for the rigid helices of three-membered rings and always show the correct sign and order of magnitude for the flexible helices of four- and five-membered rings for which Boltzmann-averaged optical rotations of up to six conformers had to be used. Within the conformers of the latter, a set of large dihedral angles for the bonds of the inner sphere correspond to a high specific rotation, and a set of small dihedral angles correspond to a low specific rotation. As a consequence, the Boltzmann-averaged values markedly depend on the geometry and weight of the conformers involved.     

Conformational analysis of jet-cooled tryptophan analogs and Histamine using the MM3(94) force field: Comparison with experiment

MM3(94) has been used to predict the conformers of nitrogen-containing aromatic heterocycles with polar aliphatic sidechains. Computations were done for cases in which experimental gas-phase rotational constants have been determined and include histamine and analogs of tryptophan. The agreement with experiment for the tryptophan analogs is better than earlier MM2(87) computations but still not complete. A fairly good match can be made to experimental rotational constants of four histamine conformers, but other conformers are also predicted that may not be important experimentally. A comparison can be made with ab initio calculations undertaken for histamine. Similar structures were generally predicted, but there were significant discrepancies with MM3 in relative conformer energies. © 1995 by John Wiley & Sons, Inc.     

Chiroptical properties of (R)-3-chloro-1-butene and (R)-2-chlorobutane

Coupled cluster and density functional models of specific rotation and vacuum UV (VUV) absorption and circular dichroism spectra are reported for the conformationally flexible molecules (R)-3-chloro-1-butene and (R)-2-chlorobutane. Coupled cluster length- and modified-velocity-gauge representations of the Rosenfeld optical activity tensor yield significantly different specific rotations for (R)-3-chloro-1-butene, with the latter providing much closer comparison (within 3%) to the available gas-phase experimental data at 355 and 633 nm. Density functional theory overestimates the experimental rotations for (R)-3-chloro-1-butene by approximately 80%. For (R)-2-chlorobutane, on the other hand, all three models give reasonable comparison to experiment. The theoretical specific rotations of the individual conformers of (R)-3-chloro-1-butene are much larger than those of (R)-2-chlorobutane, in disagreement with previous studies of the temperature dependence of the experimental rotations in solution. Simulations of VUV absorption and circular dichroism spectra reveal large differences between the coupled cluster and density functional excitation energies and the rotational strengths. However, while these differences lead to very different specific rotations for (R)-3-chloro-1-butene, they have much less impact on the computed specific rotations for (R)-2-chlorobutane. In addition, the coupled cluster VUV absorption spectrum of (R)-2-chlorobutane compares well to experiment.     

Coexistence of 1,3-butadiene conformers in ionization energies and Dyson orbitals

The minimum-energy structures on the torsional potential-energy surface of 1,3-butadiene have been studied quantum mechanically using a range of models including ab initio Hartree-Fock and second-order M?ller-Plesset theories, outer valence Green's function, and density-functional theory with a hybrid functional and statistical average orbital potential model in order to understand the binding-energy (ionization energy) spectra and orbital cross sections observed by experiments. The unique full geometry optimization process locates the s-trans-1,3-butadiene as the global minimum structure and the s-gauche-1,3-butadiene as the local minimum structure. The latter possesses the dihedral angle of the central carbon bond of 32.81 degrees in agreement with the range of 30 degrees-41 degrees obtained by other theoretical models. Ionization energies in the outer valence space of the conformer pair have been obtained using Hartree-Fock, outer valence Green's function, and density-functional (statistical average orbital potentials) models, respectively. The Hartree-Fock results indicate that electron correlation (and orbital relaxation) effects become more significant towards the inner shell. The spectroscopic pole strengths calculated in the Green's function model are in the range of 0.85-0.91, suggesting that the independent particle picture is a good approximation in the present study. The binding energies from the density-functional (statisticaly averaged orbital potential) model are in good agreement with photoelectron spectroscopy, and the simulated Dyson orbitals in momentum space approximated by the density-functional orbitals using plane-wave impulse approximation agree well with those from experimental electron momentum spectroscopy. The coexistence of the conformer pair under the experimental conditions is supported by the approximated experimental binding-energy spectra due to the split conformer orbital energies, as well as the orbital momentum distributions of the mixed conformer pair observed in the orbital cross sections of electron momentum spectroscopy.     

Empirical methods for computing molecular partition coefficients: II. Inclusion of conformational flexibility within fragment–based approaches

A novel algorithm for computing the water/1-octanol partition coefficient, log P , of conformationally flexible molecules, has been investigated using calculations upon a number of uncharged, linear dipeptides. In this method (which appears to be the first to consider explicitly the effects of the population of accessible conformational minima in both phases), the partition coefficient for each dipeptide was calculated from the overall energy change associated with moving the relevant gas-phase conformational distribution into water and into 1-octanol. These energies were computed using solvation contributions based upon the solvent accessible molecular surface area and two sets of empirical parameters. In these initial studies, gas-phase conformational minima were generated using systematic search methods. While the standard error in the computed log P values was disappointing, reasonable agreement was observed between calculated and experimental log P values for the set of model dipeptides, especially when specific hydration interactions involving polar fragments were correctly included in the empirical solvation term. These results indicate that the physical basis of many correction factors employed in the ClogP algorithm for computing log P probably arise from neglect of the redistribution of conformer populations as flexible molecules partition between water and 1-octanol.     

Conformational analysis of N-Boc-N,O-isopropylidene-α-serinals. A combined DFT and NMR study

This work describes an extensive conformational analysis of Garner's aldehyde and its α-methylated homologue—two important chiral building blocks that are widely used in organic synthesis. A combination of density-functional theory and NMR spectroscopy confirmed the existence of a dynamic equilibrium between two possible conformers of the carbamate group in these compounds. The calculated properties such as conformer populations and rotational barriers around the (CO)-N bond are in good agreement with the experimental values. Finally, the dipole moments of the molecules appear to be a decisive factor in the stabilization of the conformers in solution.     

Role of electron-driven proton-transfer processes in the excited-state deactivation of the adenine-thymine base pair

Exploratory electronic structure calculations have been performed with the CC2 (simplified singles and doubles coupled-cluster) method for two conformers of the adenine (A)-thymine (T) base pair, with emphasis on excited-state proton-transfer reactions. The Watson-Crick conformer and the most stable (in the gas-phase) conformer of the A-T base pair have been considered. The equilibrium geometries of the ground state and of the lowest excited electronic states have been determined with the MP2 (second-order M?ller-Plesset) and CC2 methods, respectively. Vertical and adiabatic excitation energies, oscillator strengths, and dipole moments of the excited states are reported. Of particular relevance for the photochemistry of the A-T base pair are optically dark (1)pipi* states of charge-transfer character. Although rather high in energy at the ground-state equilibrium geometry, these states are substantially lowered in energy by the transfer of a proton, which thus neutralizes the charge separation. A remarkable difference of the energetics of the proton-transfer reaction is predicted for the two tautomers of A-T: in the Watson-Crick conformer, but not in the most stable conformer, a sequence of conical intersections connects the UV-absorbing (1)pipi* state in a barrierless manner with the electronic ground state. These conical intersections allow a very fast deactivation of the potentially reactive excited states in the Watson-Crick conformer. The results provide evidence that the specific hydrogen-bonding pattern of the Watson-Crick conformer endows this structure with a greatly enhanced photostability. This property of the Watson-Crick conformer of A-T may have been essential for the selection of this species as carrier of genetic information in early stages of the biological evolution.     

Conformation effects on the electronic structures of beta-alanine

Ten low-lying conformers of beta-alanine have been studied by the hybrid density functional B3LYP/aug-cc-pVDZ method. Energetic extrapolation calculations at the MP3 and MP4(SDQ) levels of theory and the theoretical photoelectron spectra simulated with the electron propagation theory demonstrate that there are at least three gauche conformers (G1, G2, and G3) in gas-phase experiments. The calculated ionization potentials are in good agreement with the experimental data available in the literature. Natural bond orbital and atoms-in-molecules analyses exhibit a remarkable influence on the molecular electronic structures by the strong intramolecular hydrogen bonding O-H...N in the neutral conformer G2. Remarkable internal rotations of the COOH group are found in the cationic G1+ and G3+ with respect to the neutral conformers. A distonic [NH3+-(CH2)2-COO*] radical can be formed through the spontaneous intramolecular proton transfer in G2+. A novel intramolecular hydrogen bonding, C-H...O, is found in the anti A1+ cation.     

Internal rotation in peroxynitrous acid (ONOOH)

Using higher levels of wave-function-based electronic structure theory than previously applied, as well as density functional theory (B-LYP and B3-LYP functionals), all theoretical models conclude that three ONOOH conformers are stationary point minima, in disagreement with some of the previous studies that we survey. In order of increasing energy, these are the cis-cis, cis-perp, and trans-perp conformers. Basis sets including diffuse functions seem to be needed to obtain a qualitatively correct representation of the internal rotation potential energy surface at higher levels of theory. Internal rotation about the peroxide bond involving the cis-cis, cis-gauche transition structure (TS), cis-perp, and cis-trans TS conformers is studied in detail. To help ascertain the relative stability of the cis-perp conformer, multireference configuration interaction energy calculations are carried out, and rule of thumb estimates of multireference character in the ground-state wave functions of the ONOOH conformers are considered. CCSD(T)/aug-cc-pVTZ physical properties (geometries, rotational constants, electric dipole moments, harmonic vibrational frequencies, and infrared intensities) are compared with the analogous experimental data wherever possible, and also with density functional theory. Where such experimental data are nonexistent, the CCSD(T) and B3-LYP results are useful representations. For example, the electric dipole moment |mu(e)| of the cis-cis conformer is predicted to be 0.97+/-0.03 D. CCSD(T) energies, extrapolated to the aug-cc-pVNZ limit, are employed in isodesmic reaction schemes to derive zero Kelvin heats of formation and bond dissociation energies of the ONOOH stationary point minima. In agreement with recent gas-phase experiments, the peroxide bond dissociation energies of the cis-cis and trans-perp conformers are calculated as 19.3+/-0.4 and 16.0+/-0.4 kcalmol, respectively. The lowest energy cis-cis conformer is less stable than nitric acid by 28.1+/-0.4 kcalmol at 0 K.     

Photoionization of epichlorohydrin enantiomers and clusters studied with circularly polarized vacuum ultraviolet radiation

The photoionization of enantiomerically pure epichlorohydrin (C(3)H(5)OCl) has been studied using linearly and circularly polarized vacuum ultraviolet synchrotron radiation. The threshold photoelectron spectrum was recorded and the first three bands assigned using molecular orbital calculations for the expected conformers, although uncertain experimental conformer populations and an anticipated breakdown in Koopmans' theorem leave some ambiguity. Measurements of the photoelectron circular dichroism (PECD) were obtained across a range of photon energies for each of these bands, using electron velocity map imaging to record the angular distributions, during which a record PECD chiral asymmetry factor of 32% was observed. A comparison with calculated PECD curves clarifies the assignment achieved using ionization energies alone and further suggests a likely relative population of the conformers. Threshold photoelectron-photoion coincidence methods were used to study the ionic fragmentation of epichlorohydrin. Fragment ion appearance energies show nonstatistical behavior with clear indications that the cationic epoxide ring is unstable and lower energy decay channels proceeding via ring breaking are generally open. Extensive neutral homochiral clusters of epichlorohydrin may be formed in supersonic molecular beam expansions seeded in Ar. Electron angular distribution measurements made in coincidence with dimer and trimer ions are used to effect an examination of the PECD associated with ionization of size-selected neutral cluster species, and these results differ clearly from PECD of the neutral monomer. The shifted ionization thresholds of the n-mers (n = 2, ..., 7) are shown to follow a simple linear relationship, but under intense beam expansion conditions the monomer deviates from this relationship, and the monomer electron spectra tail to below the expected monomer adiabatic ionization potential (IP). PECD measurements made in coincidence with monomer ions obtained under different beam expansion conditions were used to identify unambiguously a contribution from dissociative photoionization of larger clusters to the monomer parent mass ion yield above and below its adiabatic IP.     

Electron propagator theory study of N-/O-methylglycine conformers

The low-lying conformers of N-/O-methylglycine are studied by ab initio calculations at the B3LYP, MP3, and MP4(SDQ) levels of theory with the aug-cc-pVDZ basis set. The conformers having the intramolecular hydrogen bonds N-H...O=C or O-H...N are more stable than the others. Vertical ionization energies for the valence molecular orbitals of each conformer predicted with the electron propagator theory in the partial third-order quasiparticle approximation are in good agreement with the experimental data available in the literatures. The relative energies of the conformers and comparison between the simulated and the experimental photoelectron spectra demonstrate that there are at least three and two conformers of N- and O-methylglycine, respectively, in the gas-phase experiments. The intramolecular hydrogen bonding O-H...N effects on the molecular electronic structures are discussed for the glycine methyl derivatives, on the basis of the ab initio electronic structure calculations, natural orbital bond, and atoms-in-molecules analyses. The intramolecular hydrogen bonding O-H...N interactions hardly affect the electronic structures of the O-NH2-CH2-C(=O)-O-CH3 and alpha-methylated NH2-CH2-C(CH3)OOH conformers, while the similar intramolecular interactions lead to the significantly lower-energy levels of the highest occupied molecular orbitals for the N-(CH3-NH-CH2-COOH) and beta-methylated (NH2-CH2-CH2-COOH) conformers.     

Probing the influence of solvent effects on the conformational behavior of 1,3-diazacyclohexane systems

The conformational behavior of a 1,3-diazacyclohexane system has been investigated using the DFT B3LYP/6-311+G** level of theory. The structural parameters and relative energies predicted that anomeric effects are operative in the conformations of 1,3-diazacyclohexane. The stability of conformers predicted in the solvent continuum model (water and acetonitrile) is similar to the gas-phase results. The explicit water molecules stabilized the least-stable conformer, and the predictive trend is opposite to that of the gas-phase results. The stability of the conformers in the gas phase is a compromise between avoiding repulsions and maximizing hyperconjugative stabilization. The NBO analysis suggests that the interactions of explicit solvent molecules with 1,3-diazacyclohexane conformers attenuate the anomeric stabilization. The hydrogen-bonding interactions of explicit solvent molecules with 1,3-diazacyclohexane swamped the anomeric effects to alter the conformational stability compared to the gas-phase and solvent continuum model studies.     

Absolute configuration of conformationally flexible cis-dihydrodiol metabolites by the method of confrontation of experimental and calculated electronic CD spectra and optical rotations

We have determined the absolute configurations of conformationally flexible cis-dihydrodiol metabolites (cis-1,2-dihydroxy-3,5-cyclohexadienes), bearing different substituents (e.g., Br, F, CF3, CN, Me) in 3- and 5-positions, by the method of confrontation of experimental and calculated electronic CD spectra and optical rotations. Convergent results were obtained by both methods in eight out of ten cases. For the difficult cases, where either conformer population and/or chiroptical properties (calculated rotational strengths of the long-wavelength Cotton effect or optical rotations) of contributing conformers remain inconclusive, the absolute configuration could still be correctly assigned based on one of the biased properties (either ECD or optical rotation). This approach appears well-suited for a broad spectrum of conformationally flexible chiral molecules.     

Comparison of time-dependent density-functional theory and coupled cluster theory for the calculation of the optical rotations of chiral molecules

A comparison of the abilities of time-dependent density-functional theory (TDDFT) and coupled cluster (CC) theory to reproduce experimental sodium D-line specific rotations for 13 conformationally rigid organic molecules is reported. The test set includes alkanes, alkenes, and ketones with known absolute configurations. TDDFT calculations make use of gauge-including atomic orbitals and give origin-independent specific rotations. CC rotations are computed using both the origin-independent dipole-velocity and origin-dependent dipole-length representations. The mean absolute deviations of calculated and experimental rotations are of comparable magnitudes for all three methods. The origin-independent DFT and CC methods give the same sign of [alpha]D for every molecule except norbornanone. For every large-rotation ketone and alkene for which DFT and CC yield the incorrect sign as compared to liquid-phase experimental data, the corresponding optical rotatory dispersion (ORD) curve is bisignate, suggesting that the two models cannot reliably reproduce the relative excitation energies and antagonistic rotational strengths of multiple competing electronic states that contribute to the total long-wavelength rotation. Several potential sources of error in the theoretical treatments are considered, including basis set incompleteness, vibrational and temperature effects, electron correlation, and solvent effects.     

Conformations of allyl amine: theory vs experiment

The relative stabilities of the five conformers of allyl amine, a medium-size aliphatic molecule, were estimated by applying ab initio quantum mechanical methods at several levels of theory. The second-order M?ller-Plesset perturbation method (MP2), quadratic configuration interaction including single and double excitations (QCISD), coupled-cluster with single and double excitations (CCSD) and CCSD plus perturbative triple excitations [CCSD(T)] were applied. The Dunning correlation consistent basis sets (through aug-cc-pVQZ and cc-pV5Z) were employed. The MP2 energies relative to the energy of the cis-trans conformer reported here appear to approach the basis set limit. The predicted allyl amine conformer energies approaching the Hartree-Fock basis set limit are 158 cm-1 (cis-gauche), -5 cm-1 (gauche-trans), and -146 cm-1 (gauche-gauche). The same three relative energies near the MP2 basis set limit are 135, 103, and 50 cm-1, respectively. The analogous energies deduced from experiment are 173 +/- 12, 92 +/- 8, and 122 +/- 5 cm-1. The theoretical results obtained in the present study suggest that satisfactory predictions of the conformer energetics of allyl amine may be achieved only by theoretical methods that incorporate consideration of correlation effects in conjunction with large basis sets. Evaluation of the zero-point vibrational energy corrections is critical, due to the very small classical energy differences between the five conformers of allyl amine. Agreement between theory and experiment for the gauche-gauche conformational energy remains problematical.     

Substituted profanes: VII The vibrational spectra and conformations of 1,2,3-trichloro- and 1,2,3-tribromopropane

The infrared, far-infrared and Raman spectra of 1,2,3-trichloro- and 1,2,3-tribromopropane were recorded in the liquid state, in polar and non-polar solvents and in the crystalline state at low temperature. Crystals were formed under ca. 20 kbar pressure at ambient temperature and the infrared spectra recorded. Dipole measurements were carried out in CCl₄ and C₆H₆ solutions.The existence of three or possibly four conformers in the liquids at room temperature was verified. Combined with independent electron diffraction measurements of the vapours, the spectra demonstrated an anti-gauche conformer (relative to the halogens) to be present in the low temperature and high pressure crystals of both compounds. This conformer was not the one suggested by earlier authors. The C-halogen stretching vibrations for the conformers do not agree with the predicted values.     

Hydrogen-bonding interactions in acetic acid monohydrates and dihydrates by density-functional theory calculations

Equilibrium structures and the respective binding energies of acetic acid monohydrates and dihydrates have been determined by density-functional theory calculations with different basis sets, including 6-31+G(3d,p), 6-311++G(d,p), and 6-311++G(3df,3pd). Given that the C=O and OH groups in acetic acid provide the predominant hydrogen-bonding interactions with water, six stable conformer structures have been found each for the monohydrate and syn-dihydrate. Of the three syn- and three anti-conformers of acetic acid with water, the most stable monohydrate structure is found to be that of the syn-conformer bonding with water in a cyclic double H-bonded geometry. Similarly, the syn-conformer bonding with two water molecules in a cyclic double H-bonded geometry has also been determined to be the most stable among the six plausible structures for the syn-dihydrate. Frequency analysis of the stable conformers has been performed and the vibrational spectra of the most stable monohydrate and dihydrate structures are compared with the experimental gas-phase and matrix data. Furthermore, the calculated binding energies between an acetic acid and a water molecule for both monohydrate and dihydrate are larger than that between two water molecules, which supports our recent experimental observation of coevaporation of acetic acid with water upon annealing acetic acid on ice.     

13-methyl-2,6-dithia[7]metacyclophane: a useful molecule to connect VT NMR results and structure with calculations

Ground state energies (DFT) and 1H and 13C NMR chemical shifts are calculated for the conformers of 13-methyl-2,6-dithia[7]metacyclophane (1), and the results are compared with X-ray structural data and variable-temperature NMR data, including the determination of the activation barrier. Calculations predict the correct low energy conformer with good agreement with chemical shifts, bond distances, and angles. VT NMR data for the 10-tert-butyl-substituted derivative 2 indicate that it undergoes the same conformational equilibria as 1. This paper should enhance the confidence that organic chemists have in calculations to satisfactorily predict conformer energies.