Ab Initio Studies of the Exocyclic Hydroxymethyl Rotational Surface in α- d -Glucopyranose (original) (raw)
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The Journal of Physical Chemistry, 1995
An ab initio study of the conformational behavior of aand ,!%glycosidic linkages has been carried out on axial and equatorial 2-methoxytetrahydropyrans as models. The geometry of the conformers about the glycosidic C-0 bond was determined by gradient optimization at the SCF level using the 4-21G and 6-31G* basis sets and at the second-order Moller-Plesset level using the MP2/6-31G* basis set. The potential of rotation has been calculated using 4-21G, 6-31G*, 6-31+G*, MP2/6-31G*, and 6-31 l++G** basis sets. At all levels of theory, both axial and equatorial forms prefer the GT conformation around the C-0 glycosidic bond. Conformational changes in bond lengths and angles at the anomeric center also display significant variations with computational methods, but structural trends are in fair agreement with experiment. The correction for the effect of zero-point energy, thermal energy, and entropy on the axial-equatorial energy difference at the 6-31G* level is-0.63 kcal/mol. After these corrections to the energy difference calculated at the 6-31G* level, the axial form is favored by 0.84 kcaymol, in reasonable agreement with experimental values of AG = 0.7-0.9 kcaymol estimated for nonpolar solvents. Solvent effects reduce this energy difference; in the extreme case of water, a value of 0.24 kcal/mol was obtained. Complete torsional profiles have been obtained for rotation about the glycosidic C-0 bond in eleven solvents, and the calculated energy differences are in fair agreement with experimental data on 2-alkoxytetrahydropyrans in solutions. The MM3 (6 = 1.5) force field reproduces the 6-31G* a b initio energy difference reasonably well, but barrier heights are in poor agreement with the ab initio data. The calculated energies and geometries provide an essential set of data for the parametrization of the behavior of acetal fragments in molecular mechanical force fields for carbohydrates.
Relative stability of alternative chair forms and hydroxymethyl conformations of ��-D-glucopyranose
1995
The relative energies of two hydroxymethyl conformers for each of the two chair forms (4C 1 and aC 4) of /3-D-glucose were calculated at much more complete levels of quantum mechanical (QM) electronic structure theory than previously, and relative free energies in solution were calculated by adding vibrational, rotational, and solvent effects. The gas-phase results are based on very large basis sets (up to 624 contracted basis functions), and the coupled cluster method for electron correlation. Solvation Model 4 was used to calculate the effects of hydration or nonpolar solvation. Molecular mechanics (MM) and QM electronic structure theory have been applied to analyze the factors contributing to the relative energies of these conformers. Relative energies varied widely (up to 35 kcal/mol) depending on theoretical level, and several levels of theory predict the experimentally unobserved 1C 4 ring conformation to be the lower in energy. The highest level calculations predict the 4C 1 chair to be lower in free energy by about 8 kcal/mol, and we also find that the gauche + (gt) conformer of 4C 1 is lower than the trans (tg) conformer. Low-energy structures optimized by either quantum mechanical or molecular mechanical methods were commonly characterized by multiple intramolecular hydrogen bonds. Superior hydrogen bonding geometries are available in the 1C 4 chair, but are counteracted by increased steric repulsions between axial substituents; MM calculations also indicate increased torsional strain in the IC 4 chair. Manifestations of greater steric strain in the calculated 1C 4 structures compared to the 4C~ structures include longer ring bonds, a larger bond angle at the ring oxygen atom, and * Corresponding authors. 0008-6215/95/$09.50 © 1995 Elsevier Science Ltd. All rights reserved SSDI 0008-6215(95)00175-1 220 S.E. Barrows et aL / Carbohydrate Research 276 (1995) smaller puckering amplitudes. The MM and QM 4C 1 structures compare well with each other and with available X-ray diffraction data. The largest discrepancies between the two kinds of models occur for geometric parameters associated with the anomeric center --the QM structure agrees better with experiment. Greater differences between QM and MM structures are observed for 1C 4 structures, especially in the relative orientations of hydroxyl groups serving as hydrogen bond acceptors. In water, the 4C~ chairs are better solvated than the 1C 4 chairs by about 5 to 9 kcal/mol because of both larger polarization free energies and improved hydrogen bonding interactions with the first solvation shell. In (a hypothetical) n-hexadecane solution, the 4C 1 chairs are better solvated by about 2 to 4 kcal/mol both because of larger polarization free energies and because the larger solvent accessible surface areas of the 4C 1 conformers allow increased favorable dispersion interactions. The differential polarization free energies are associated primarily with the hydroxyl groups; the greater steric congestion in the ~C 4 chairs reduces opportunities for favorable dielectric screening.
Journal of the American Chemical Society Jacs, 2004
The R-anomer energy difference and the stability of 10 rotamers of counterclockwise D-glucopyranose were studied in vacuo and in aqueous solution at the B3LYP/6-31+G(d,p) level. To obtain the solute charge distribution and the solvent structure around it, we used the averaged solvent electrostatic potential from molecular dynamics method, ASEP/MD, which alternates molecular dynamics and quantum mechanics calculations in an iterative procedure. The main characteristics of the anomeric equilibrium, both in vacuo and in solution, are well reproduced. The relative stability of the different anomers is related to the availability of the free pairs of electrons in the anomeric oxygen to interact with the water molecules. The influence of solvation in the conformer equilibrium is also analyzed.
Journal of the American Chemical Society, 2004
The R-anomer energy difference and the stability of 10 rotamers of counterclockwise D-glucopyranose were studied in vacuo and in aqueous solution at the B3LYP/6-31+G(d,p) level. To obtain the solute charge distribution and the solvent structure around it, we used the averaged solvent electrostatic potential from molecular dynamics method, ASEP/MD, which alternates molecular dynamics and quantum mechanics calculations in an iterative procedure. The main characteristics of the anomeric equilibrium, both in vacuo and in solution, are well reproduced. The relative stability of the different anomers is related to the availability of the free pairs of electrons in the anomeric oxygen to interact with the water molecules. The influence of solvation in the conformer equilibrium is also analyzed.
Journal of Molecular Structure: THEOCHEM, 1997
An ab initio study of the conformational behavior of aglycon O-C glycosidic bonds and rotameric distribution in Omethylated carbohydrates has been carried out on axial and equatorial 1,2-, 1,3and 1 $dimethoxytetrahydropyran as models. The geometry of the conformers about the C(aglycon)-O(glycosidic) bond (q-type) in 12 models was determined by gradient optimization at the SCF level using split valence 6-3lG* basis sets. The potential of rotation has been calculated using 6-3 lG* and 63 I + G* basis sets. At all levels of theory, both axial and equatorial forms prefer the GT or TG conformers around the C-O glycosidic bond over the GG conformer. Exceptions are models of (I -2) linkages with the equatorial anomeric methoxyl group (E2A and E2E), where the TG conformer is not present. Calculated potential energy profiles show high flexibility within a 1.5 kcal mol-' low energy region that is 180" wide. The glycosidic bond angle C 1 -Oi-Ci depends on the torsion angle \k and assumes values in the interval from 115" to 125". 0 1997 Elsevier Science B.V.
J Mol Struc Theochem, 1997
An ab initio study of the conformational behavior of aglycon OC glycosidic bonds and rotameric distribution in O-methylated carbohydrates has been carried out on axial and equatorial 1,2-, 1,3- and 1,4-dimethoxytetrahydropyran as models. The geometry of the conformers about the C(aglycon)O(glycosidic) bond (Ψ-type) in 12 models was determined by gradient optimization at the SCF level using split valence 6-31G∗ basis sets. The potential of rotation has been calculated using 6-31G∗ and 631 + G∗ basis sets. At all levels of theory, both axial and equatorial forms prefer the GT or TG conformers around the CO glycosidic bond over the GG conformer. Exceptions are models of (1 → 2) linkages with the equatorial anomeric methoxyl group (E2A and E2E), where the TG conformer is not present. Calculated potential energy profiles show high flexibility within a 1.5 kcal mol−1 low energy region that is 180 ° wide. The glycosidic bond angle ClOiCi depends on the torsion angle Ψ and assumes values in the interval from 115 ° to 125 °.
Carbohydrate Research, 1988
Presented herein are potential-energy functions for the two side chains of a methyl ether of D-lyxo-2-hexulose, namely, 6O-methyl-/3-D, a model for /3+tagatofuranose 6-phosphate. The methyl ether was chosen because, sterically, it is a good model of the phosphate, and yet it does not introduce the overwhelming complexity of phosphorus .d orbitals into the calculations. The original minimum-energy structure for this molecule was obtained by using an empirical program, developed by Warshel, Lifson, and Karpl~, which determined that the 'T3(D) conformation is a minimum-energy structure; this was verified by our ub inifio calculations. However, substantial differences were found in the minimum potential-energy s&uctures of the two exocyclic groups. The equilibrium rotational orientation of each of these groups was then calculated. The results indicated that rotamers of angles 195" (for G2) and 65" (for C-5) are very minor components. The calculations indicated that the molecule should mainly exist in two equal proportions as the two rotamers, one having angles of 295" (for G2) and 290" (for C5) and the other, angles of 75" (for C-2) and 290" (for G5). All ab titio calculations were performed by using mod&d versions of the Gaussian-70 and Gaussian-76 programs at the STO-3G level. lNTBODUCl'ION Ketohexose &phosphates are ubiquitous intermediates and regulators of carbohydrate metabolism1 that exist in anomeric equilibria in solution2J. Because *To whom CorreBpondence should be addremd. fJoow321w 03.50 Q 1988 Elsevier Science Publishers B.V.
The Journal of Physical Chemistry, 1994
A b initio calculations have been carried out on model compounds for the pyranose halides 2-fluoro-and 2-chlorotetrahydropyran with either an axially or an equatorially oriented halogen atom. Energy minimization has been carried out at the STO-3G. 3-21G, 6-3 lG, 6-3 1G*, 6-31+G*, and MP2/6-3 lG* levels. The optimized geometries were used to calculate the energy difference between the axial and equatorial conformers with STO-3G, 3-21G, 4-31G, 6-31G, 6-31G*, 6-31G**, 6-31+G*, 6-311G*, 6-31+G**, 6-31 l++G**, and MP2/ 6-31G* basis sets. Large differences in C-Hal bond lengths and 0-C-Hal bond angles were found between the axial and equatorial conformers. After including the zero-point energy, thermal energy, entropy, and MP3 electron correlation corrections to energy differences calculated at 6-3 1 1 ++G**//6-3 1 +G* basis set, these calculations favored the axial conformers by 2.4 and 2.5 kcal/mol. Solvent effects considerably reduce this energy difference; in the extreme case, in water, values of 0.5 and 1.5 kcal/mol were obtained for fluoro and chloro derivatives, respectively. The magnitude of the anomeric effect depends on the solvent and was estimated to be in the range 0.9-2.8 kcal/mol for the fluoro and 2.3-3.1 kcal/mol for the chloro forms. On the basis of these results, we suggest that the 6-31+G*//6-31G* procedure is suitable for calculations of the geometry and the conformational energies of carbohydrate molecules. The calculated energies and geometries provide additional data which should prove useful in the reparametrization of existing force fields to better reproduce the behavior of C-O-Hal systems.
The Journal of Physical Chemistry B, 1997
An ab initio study of the conformational behavior of Rand -anomeric linkages in C-, N-, and S-glycosyl compounds has been carried out on axially and equatorially 2-substituted derivatives (2-ethyl, 2-methylamino, 2-thiomethyl, and 2-methylammonio) of tetrahydropyran as models. The geometry of the conformers about the anomeric C-X bond was determined by gradient optimization at the SCF level using the 6-31G* basis set. The potential of rotation has been calculated using the 6-31G* and 6-31+G* basis sets. Vibrational frequencies were calculated at the 6-31G* level and used to evaluate zero-point energies, thermal energies, and entropies for minima. Variations in calculated valence geometries for the compounds, display structural changes distinctive for the anomeric and exo-anomeric effects. Differences between bond lengths and bond angles for different conformers correlate with the importance of the lone pair delocalization interactions. The calculated conformational equilibria have been used to estimate the magnitudes of the anomeric, reverse anomeric, and exo-anomeric effects. It was found that the anomeric effect decreases in the following order: chlorine > methoxy ∼ fluorine > thiomethyl > methylamino > ethyl > methylammonio, with the methylamino, ethyl, and methylammonio groups exhibiting reverse anomeric effects. The sc preference of the methyl group over the ap orientation around the C1-C bond in 2-ethyltetrahydropyran is assumed to be entirely on basis of steric interactions. The exo-anomeric effect is expected to be present when the preference for the sc conformation is larger than that for the ethyl group. Thus, the exo-anomeric effect decreases in the order methoxy ∼ methylamino > thiomethyl. The methylammonio group does not show an exo-anomeric effect.
Journal of Computational Chemistry, 1995
A b initio molecular orbital calculations have been carried out on over 50 model organic molecules and ions to provide the data necessary in the determination of torsional parameters for a force field involving polypeptides. The rotational energy profiles were obtained at the HF/6-31G*//HF/6-31G* level. The results were supported, in many cases, by full geometry optimizations and with consideration of correlation corrections at the MP2 level. With the exception of the dihedral angle being studied, all of the molecules were fully optimized with C, symmetry.