Analysis of the Conformational Composition of 2-Alkyl-4-phenyl-1,3,2-oxazaborinanes

The empirical MM2 and semiempirical AM1 methods were used to calculate the energy of model 2-methyl-4-phenyl-1,3,2-oxazaborinane with full optimization of the molecular geometry. Comparison of the experimental coupling constants for the 2-isobutyl analog and calculated coupling constants as well as the data for the relative energy of the individual conformers indicated that these compounds form a multicomponent equilibrium system containing sofa and a family of half-chair forms.     

Gas-Phase Conformational Map of the Amino Acid Isovaline

Four conformers of the non-proteinogenic α-amino acid isovaline, vaporized by laser ablation, are characterized by Fourier-transform microwave techniques in a supersonic expansion. The comparison between the experimental rotational and ¹⁴N nuclear quadrupole coupling constants and the ab initio calculated ones provides conclusive evidence for the identification of the conformers. The most stable species is stabilized by an N−H⋅⋅⋅O =C intramolecular hydrogen bond and a cis-COOH interaction, whereas the higher-energy conformers exhibit an N⋅⋅⋅H−O intramolecular hydrogen bond and trans-COOH, as in other aliphatic amino acids. The spectroscopic data herein reported can be used for the astrophysical purpose in a possible detection of isovaline in space.     

Modelling zwitterions in solution: 3-fluoro-γ-aminobutyric acid (3F-GABA)

The conformations and relative stabilities of folded and extended 3-fluoro-γ-aminobutyric acid (3F-GABA) conformers were studied using explicit solvation models. Geometry optimisations in the gas phase with one or two explicit water molecules favour folded and neutral structures containing intramolecular NH···O-C hydrogen bonds. With three or five explicit water molecules zwitterionic minima are obtained, with folded structures being preferred over extended conformers. The stability of folded versus extended zwitterionic conformers increases on going from a PCM continuum solvation model to the microsolvated complexes, though extended structures become less disfavoured with the inclusion of more water molecules. Full explicit solvation was studied with a hybrid quantum-mechanical/molecular-mechanical (QM/MM) scheme and molecular dynamics simulations, including more than 6000 TIP3P water molecules. According to free energies obtained from thermodynamic integration at the PM3/MM level and corrected for B3LYP/MM total energies, the fully extended conformer is more stable than folded ones by about -4.5 kJ mol(-1). B3LYP-computed (3)J(F,H) NMR spin-spin coupling constants, averaged over PM3/MM-MD trajectories, agree best with experiment for this fully extended form, in accordance with the original NMR analysis. The seeming discrepancy between static PCM calculations and experiment noted previously is now resolved. That the inexpensive semiempirical PM3 method performs so well for this archetypical zwitterion is encouraging for further QM/MM studies of biomolecular systems.     

Rationalizing nuclear overhauser effect data for compounds adopting multiple-solution conformations

An algorithm is described for refining the populations of a set of multiple-solution conformers using experimental nuclear Overhauser effects (nOes). The method is based upon representing the effective relaxation matrix for the set of interconverting proposed conformers as a linear combination of relaxation matrices (LCORMs) due to each conformer. The conformer population derivative of the nOe is derived from a Taylor series expression for the calculated nOe. This derivative may then be used in a standard nonlinear least-squares refinement procedure. The LCORM nOe procedure is tested using a monosaccharide system, 1-O-methyl-α-L -iduronate, that is known to exhibit conformational variability. The measured nOes for this system are used to refine the populations of a set of three static conformers, namely, the ¹C₄, ⁴C₁, and ²S₀ ring conformers. The populations thus derived are compared to those previously obtained using nuclear magnetic resonance proton-proton coupling constant information. Two possible extensions to the method are discussed: The first uses combined nOe and coupling constant data while the second removes the restrictions that the conformers used for fitting be rigid entities. © 1994 by John Wiley & Sons, Inc.     

An ab initio study on the torsional surface of alkanes and its effect on molecular simulations of alkanes and a DPPC bilayer

Energies of 119 conformations of normal alkanes from butane to heptane were calculated at approximately the CCSD(T)/cc-pVQZ level. Energies of gauche (g) conformers relative to trans (t) decrease as chain length increases. In what is termed the "positive pentane effect", adjacent gauche conformers of the same sign are stabilized compared to nonadjacent conformers; e.g., for hexane the energies of tgt, tgg, and gtg are 0.600, 0.930, and 1.18 kcal/mol, respectively. Torsional terms in the CHARMM27 (C27) force field were fit to the calculated QM energies to yield a revised potential, C27r. Molecular dynamics simulations of normal alkanes (heptane, decane, tridecane, and pentadecane) with C27r yield higher populations of gauche states, increased transition rates, and improved agreement with experiment as compared to C27. In addition, C27r simulations of a hydrated DPPC lipid bilayer yield improved agreement with the experimental NMR deuterium order parameters for the aliphatic chain ends.     

Diastereomer configurations from joint experimental-computational analysis

The potential of the approach combining nuclear magnetic resonance (NMR) spectroscopy, relaxed grid search (RGS), molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations for the determination of diastereomer configurations is demonstrated using four diastereomers of a trisubstituted epoxide. Since the change in configuration of the chiral center is expected to change the distribution of conformer populations (including those of side-chain rotamers), changes in NMR parameters [chemical shifts, J couplings, and nuclear Overhauser effects (NOEs)] are expected. The method therefore relies on (1) identification of possible conformations in each diastereomer using relaxed grid search analysis and MD simulations; (2) geometry optimizations of conformers selected from step (1), followed by calculations of their relative energies (populations) using QM methods; (3) calculations of averaged NMR parameters using QM methods; (4) matching calculated and experimental values of NMR parameters of diastereomers. The diastereomer configurations are considered resolved, if three NMR parameters different in nature, chemical shifts, J couplings, and NOEs, are in agreement. A further advantage of this method is that full structural and dynamics characterization of each of the diastereomers is achieved based on the joint analysis of experimental and computational data.     

Prediction of microscopic protonation constants of polybasic molecules via computational methods: A complete microequilibrium analysis of spermine

For the first time, a simple methodology is reported for theoretical calculation of microscopic protonation constants of polybasic molecules in solution. Density functional theory study was used for complete microequilibrium analysis of spermine, H₂N(CH₂)₃NH(CH₂)₄NH(CH₂)₃NH₂, a linear tetraamine with 16 known microspecies. A general thermodynamic cycle is proposed to calculate protonation microconstants of polybasic molecules using calculated micro‐ΔG values in aqueous solution. The microscopic protonation constants were determined with considering both the most abundant and most stable conformers for all microspecies. The results show that the microscopic protonation constants derived from the most abundant conformers (i.e., linear conformers in which the intramolecular hydrogen bonding does not exist) are in good agreement with the corresponding available experimental data. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Conformational studies of 1,2,3-trichloro- and 1,2,3-tribromopropane by nuclear magnetic resonance spectroscopy: attractive parallel (1:3) halogen-hydr

Analysis of the NMR spectra of 1,2,3-trichloropropane and 1,2,3-tribromopropane in various media shows the most stable conformer to be AG_-. The populations of several conformera have been estimated by using pure trans and gauche coupling constants obtained from closely similar molecules. The calculated populations found in non-polar solvents agree well with those obtained by electron diffraction studies in the gas phase. It is suggested that the AG_- form is stabilised relative to AG₊ by the former having two parallel (1:3) halogen-hydrogen attractions against one in the AG₊ form. Comparison is made to related molecules where the most stable conformers also have the greatest number of parallel (1:3) halogen-hydrogen interactions.     

Pentafluorobutane; an example of long-range five bond H?F coupling

The complete analysis of the spectrum of 2,2,4,4,4-pentafluoro-n-butane is reported. From the sum of the vicinal proton-fluorine coupling constants an estimate of the conformational energy has been obtained and successively the long-range coupling of the individual conformers has been calculated.     

The conformers of phenylglycine

The neutral form of the unnatural amino acid phenylglycine was vaporized by laser ablation, and the presence of two conformers was detected in a supersonic expansion by Fourier transform microwave spectroscopy. Both conformers were unequivocally identified by comparison of their experimental rotational and quadrupole coupling constants with those calculated ab initio. The most stable conformer is stabilized by intramolecular hydrogen bonds N-H...O=C, N-H...pi (with the closest C-C bond in the aromatic ring), and a cis-COOH interaction. The other conformer exhibits a O-H...N hydrogen bond between the hydrogen atom of the hydroxyl group and the lone pair at the nitrogen atom.     

Structural and vibrational study of the tautomerism of histamine free-base in solution

Infrared and Raman spectroscopy in H(2)O and D(2)O and quantum Density Functional calculations were used to determine the structure of histamine free-base in aqueous solution. A quantum mechanical study of the tautomeric equilibrium of histamine free-base in solution was performed at the 6-311G level. Electronic correlation energies were included by using the hybrid functional B3LYP. The solvent was simulated as a continuum characterized by a dielectric constant, and the quantum system (solute) was placed in an ellipsoidal cavity. Solute-solvent electrostatic interaction was calculated by means a multipolar moment expansion introduced in the Hamiltonian. Four relevant histamine conformations were optimized by allowing all the geometrical parameters to vary independently, which involved both the gauche-trans and the N3H-N1H tautomerisms. The calculated free energies predicted N3H-gauche as the most stable one of histamine free-base in solution. The order of stability is here completely altered with respect to previous results in gas phase, which presented the N1H-gauche conformer as the most stable structure. Our results also differ from previous Monte Carlo simulations, which obtained the N3H-trans conformer as the most stable in solution, although in this case, the histamine structures were kept frozen to the gas-phase geometry. Vibrational spectroscopy results support theoretical ones. Quadratic force fields for the four histamine conformers were achieved under the same calculation methodology. Previously, a general assignment of the infrared and Raman spectra of histamine free-base was proposed for solutions in both natural and heavy water. This allowed us to compare the experimental set of both wavenumbers and infrared intensities with the calculated ones. The lowest quadratic mean wavenumber deviation was obtained for the N3H-gauche conformer, in agreement with the free-energy calculations. Calculated infrared intensities were also compared to the experimental intensities, supporting this conformer as the relevant structure of histamine free-base in solution. It was then selected for a complete vibrational dynamics calculation, starting with a low-level scaling procedure to fit the set of calculated wavenumbers to the experimental values. The results were presented in terms of quadratic force constants, potential energy distribution, and normal modes.     

Conformational analysis of furanose rings with PSEUROT: parametrization for rings possessing the arabino,lyxo, ribo,and xylo stereochemistry and application to arabinofuranosides

The solution conformation of a furanose ring can be assessed through PSEUROT analysis of three-bond (1)H-(1)H coupling constants ((3)J(HH)) of the ring hydrogens. For each coupling constant, PSEUROT requires two parameters, A and B, which are used to translate the H[bond]C[bond]C[bond]H dihedral angle predicted from the (3)J(HH) into an endocyclic torsion angle from which the identity of the conformers can be determined. In this paper, we have used density functional theory methods to generate a family of envelope conformers for methyl furanosides 1-8. From these structures, A and B were calculated for each H[bond]C[bond]C[bond]H fragment. In turn, the values of these parameters for the arabinofuranose ring were used in PSEUROT calculations to determine the conformers populated by monosaccharides 1 and 2 as well as the furanose rings in oligosaccharides 9-15. The results of these analyses are consistent with the low-energy conformers identified from previous computational and X-ray crystallographic studies of 1 and 2.     

Cumulative reaction probabilities: A comparison between quasiclassical and quantum mechanical results

This article presents a quasiclassical trajectory (QCT) method for determining the cumulative reaction probability (CRP) as a function of the total energy. The method proposed is based on a discrete sampling using integer values of the total and orbital angular momentum quantum numbers for each trajectory and on the development of equations that have a clear counterpart in the quantum mechanical (QM) case. The calculations comprise cumulative reaction probabilities at a given total angular momentum J, as well as those summed over J. The latter are used to compute QCT rate constants. The method is illustrated by comparing QCT and exact QM results for the H+H2, H+D2, D+H2, and H+HD reactions. The agreement between QCT and QM results is very good, with small discrepancies between the two data sets indicating some genuine quantum effects. The most important of these involves the value of the CRP at low energies which, due to the absence of tunneling, is lower in the QCT calculations, causing the corresponding rate constants to be smaller. The second is the steplike structure that is clearly displayed in the QM CRP for J = 0, which is much smoother in the corresponding QCT results. However, when the QCT density of reactive states, i.e., the derivatives of the QCT CRP with respect to the energy, is calculated, a succession of maxima and minima is obtained which roughly resembles those found in the QM calculations, although the latter are considerably sharper. The analysis of the broad peaks in the QCT density of reactive states indicates that the distributions of collision times associated with the maxima are somewhat broader, with a tail extending to larger collision times, than those associated with the minima. In addition, the QM and QCT dynamics of the isotopic variants mentioned above are compared in the light of their CRPs. Issues such as the compliance of the QCT CRP with the law of microscopic reversibility, as well as the similarity between the CRPs for ortho and para species in the QM and QCT cases, are also addressed.     

Rotational isomerism as studied by nuclear quadrupole coupling.: Theoretical and experimental 14NX tensors for hydrazine,methylhydrazine, and 1,2-dimethylhydrazine

The nuclear quadrupole coupling constants of the ¹⁴N nuclei for hydrazine, the inner and outer conformers of methylhydrazine, and the inner-outer and the outer-outer conformers of 1,2-dimethylhydrazine are calculated by an ab initio SCF method, and also by a CI calculation for hydrazine. The results are compared with available experimental values. Characteristic dependence of the X tensors on the conformational structure is demonstrated. An application of theoretical hyperfine structures to a spectral analysis is discussed.     

Molecular structure and conformational composition of 1,3-dihydroxyacetone studied by combined analysis of gas-phase electron diffraction data, rotational constants, and results of theoretical calculations. Ideal gas thermodynamic properties of 1,3-dihydroxyacetone

The molecular structure of 1,3-dihydroxyacetone (DHA) has been studied by gas-phase electron diffraction (GED), combined analysis of GED and microwave (MW) data, ab initio, and density functional theory calculations. The equilibrium re structure of DHA was determined by a joint analysis of the GED data and rotational constants taken from the literature. The anharmonic vibrational corrections to the internuclear distances (re-ra) and to the rotational constants (B(i)e-B(i)0) needed for the estimation of the re structure were calculated from the B3LYP/cc-pVTZ cubic force field. It was found that the experimental data are well reproduced by assuming that DHA consists of a mixture of three conformers. The most stable conformer of C2v symmetry has two hydrogen bonds, whereas the next two lowest energy conformers (Cs and C1 symmetry) have one hydrogen bond and their abundance is about 30% in total. A combined analysis of GED and MW data led to the following equilibrium structural parameters (re) of the most abundant conformer of DHA (the uncertainties in parentheses are 3 times the standard deviations): r(C=O)=1.215(2) A, r(C-C)=1.516(2) A, r(C-O)=1.393(2) A, r(C-H)=1.096(4) A, r(O-H)=0.967(4) A, angleC-C=O=119.9(2) degrees, angleC-C-O=111.0(2) degrees, angleC-C-H=108.2(7) degrees, angleC-O-H=106.5(7) degrees. These structural parameters reproduce the experimental B(i)0 values within 0.05 MHz. The experimental structural parameters are in good agreement with those obtained from theoretical calculations. Ideal gas thermodynamic functions (S degrees (T), C degrees p(T), and H degrees (T)-H degrees (0)) of DHA were calculated on the basis of experimental and theoretical molecular parameters obtained in this work. The enthalpy of formation of DHA, -523+/-4 kJ/mol, was calculated by the atomization procedure using the G3X method.     

Conformational study of 2-phenylethylamine by molecular-beam Fourier transform microwave spectroscopy

The conformational preferences of the simplest amine neurotransmitter 2-phenylethylamine have been investigated using molecular beam Fourier transform microwave (MB-FTMW) spectroscopy. Two new conformers have been observed together with the two previously reported by Godfrey et al. [J. Am. Chem. Soc., 1995, 117, 8204]. The (14)N nuclear quadrupole hyperfine structure has been resolved for all four conformers. Comparison of the experimental rotational and quadrupole coupling constants with those calculated theoretically provides a conclusive test for the identification of all conformers. The two most stable conformers present a gauche (folded) disposition of the alkyl-amine chain and are stabilised by a weak NH...pi interaction between the amino group and the aromatic ring. The other two conformers show an anti (extended) arrangement of the alkyl-amine chain. Tunnelling splittings have been observed in the spectrum of one of the anti conformers. The post expansion relative abundances in the supersonic jet have been also investigated and related to the conformer energies.     

The coupling constant polarizability and hyperpolarizabilty of 1J(NH) in N-methylacetamide, and its application for the multipole spin-spin coupling constant polarizability/reaction field approach to solvation

We present a benchmark study of a combined multipole spin-spin coupling constant (SSCC) polarizability/reaction field (MJP/RF) approach to the calculation of both specific and bulk solvation effects on SSCCs of solvated molecules. The MJP/RF scheme is defined by an expansion of the SSCCs of the solvated molecule in terms of coupling constant dipole and quadrupole polarizabilities and hyperpolarizabilities derived from single molecule ab initio calculations. The solvent electric field and electric field gradient are calculated based on data derived from molecular dynamics (MD) simulations thereby accounting for solute-solvent dynamical effects. The MJP/RF method is benchmarked against polarizable QM/MM calculations for the one-bond N-H coupling constant in N-methylacetamide. The best agreement between the MJP/RF and QM/MM approaches is found by truncating the electric field expansion in the MJP/RF approach at the linear electric field level. In addition, we investigate the sensitivity of the results due to the choice of one-electron basis set in the ab initio calculations of the coupling constant (hyper-)polarizabilities and find that they are affected by the basis set in a way similar to the coupling constants themselves.     

Experimental and theoretical differential cross sections for the N(2D) + H2 reaction

In this paper, we report a combined experimental and theoretical study on the dynamics of the N(2D) + H2 insertion reaction at a collision energy of 15.9 kJ mol(-1). Product angular and velocity distributions have been obtained in crossed beam experiments and simulated by using the results of quantum mechanical (QM) scattering calculations on the accurate ab initio potential energy surface (PES) of Pederson et al. (J. Chem. Phys. 1999, 110, 9091). Since the QM calculations indicate that there is a significant coupling between the product angular and translational energy distributions, such a coupling has been explicitly included in the simulation of the experimental results. The very good agreement between experiment and QM calculations sustains the accuracy of the NH2 ab initio ground state PES. We also take the opportunity to compare the accurate QM differential cross sections with those obtained by two approximate methods, namely, the widely used quasiclassical trajectory calculations and a rigorous statistical method based on the coupled-channel theory.     

1H NMR spectra of butane‐1,4‐diol and other 1,4‐diols: DFT calculation of shifts and coupling constants

The proton nuclear magnetic resonance (NMR) spectra of butane‐1,4‐diol, pentane‐1,4‐diol, (S,S)‐hexane‐2,5‐diol, 2,5‐dimethylhexane‐2,5‐diol and cyclohexane‐1,4‐diols (cis and trans) in benzene and some other solvents have been analysed. The conformer distribution and the NMR shifts of these diols in benzene have been computed on the basis of the density functional theory, the solvent being included by means of the integral‐equation‐formalism polarizable continuum model implemented in Gaussian 09. Relative Gibbs energies of all conformers are calculated at the Perdew, Burke and Ernzerhof (PBE)0/6‐311+G(d,p) level and NMR shifts by the gauge‐including atomic orbital method with the PBE0/6‐311+G(d,p) geometry and the cc‐pVTZ basis set. Vicinal three‐bond coupling constants for the acyclic diols are calculated from the relative conformer populations, the geometries and generalized Karplus equations developed by Altona's group; these correlate well with the experimental values. The solvent dependence of coupling constants for butane‐1,4‐diol is attributed to conformational change. Coupling constants for the rigid cyclohexane‐1,4‐diols do not change with solvent and are readily explained in terms of their geometries. The NMR shifts of hydrogen‐bonded protons in individual conformers of alkane‐1,n‐diols show a very rough correlation with the OH···OH distances. The computed overall NMR shifts for CH protons in 1,2‐diols, 1,3‐diols and 1,4‐diols are systematically high but correlate very well with the experimental values, with a gradient of 1.07 ± 0.01; those for OH protons correlate less well. Copyright © 2014 John Wiley & Sons, Ltd.     

1,3-Diaxial steric effects and intramolecular hydrogen bonding in the conformational equilibria of new cis-1,3-disubstituted cyclohexanes using low temperature NMR spectra and theoretical calculations

The conformational equilibria of 3-X-cyclohexanol [X=F (1), Cl (2), Br (3), I (4), Me (5), NMe(2) (6) and MeO (7)] and of 3-X-methoxycyclohexane [X=F (8), Cl (9), Br (10), I (11), Me (12), NMe(2) (13) and MeO (14)] cis isomers were determined from low temperature NMR spectra and PCMODEL calculated coupling constants. The energy differences between aa and ee conformers were obtained from these data (DeltaG(J)(av) and DeltaG(PC)(av), respectively) and also by the additivity principle from data for the monosubstituted cyclohexanes (DeltaG(Ad)). H-1 and H-3 hydrogen vicinal coupling constants and DeltaG(J)(av) values showed that the diequatorial conformer is predominant in the conformational equilibrium of the compounds studied at low temperature. However, DeltaG(PC)(av) data show that compounds 6 and 7 constitute an exception, since they are almost equally populated by ee and aa at room temperature, due to stabilization of their aa conformer by an intramolecular hydrogen bond. DeltaG(Ad) values, obtained according to the additivity principle, show a better agreement for compounds 2 and 3, since the 1,3-diaxial steric effect is counterbalanced by the formation of an intramolecular hydrogen bond (IAHB). For the remaining compounds, DeltaG(Ad) values underestimate the energy differences, since the 1,3-diaxial steric effect, between X and OH or OCH(3), is absent in the monosubstituted compounds used as references. Moreover, the DeltaG(PC)(av), calculated from the coupling constants, obtained through the PCMODEL program, are rather smaller than the DeltaG(J)(av) values, since the program does not have parameters for the effect, observed in this report, of a substituent at gamma position on coupling constants values for the hydrogen under consideration.