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An exhaustive search approach was used to establish all possible rotamers of α- and β-D-galactopyranose using DFT at the B3LYP/6-311+G** and M06-2X/6-311+G** levels, both in vacuum calculations, and including two variants of continuum solvent models as PCM and SMD to simulate water solutions. Free energies were also calculated. MM3 was used as the starting point for calculations, using a dielectric constant of 1.5 for vacuum modeling, and 80 for water solution modeling. For the vacuum calculations, out of the theoretically possible 729 rotamers, only about a hundred rendered stable minima, highly stabilized by hydrogen bonding and scattered in a ca. 14 kcal/mol span. The rotamer with a clockwise arrangement of hydrogen bonds was the most stable for the α-anomer, whereas that with a counterclockwise arrangement was the most stable for the β-anomer. Free energy calculations, and especially solvent modeling, tend to flatten the potential energy surface. With PCM, the total range of energies was reduced to 9–10 kcal/mol (α-anomer) or 7–8 kcal/mol (β-anomer). These figures fall to 4.5–6 kcal/mol using SMD. At the same time, the total number of possible rotamers increases dramatically to about 300 with PCM, and to 400 with SMD. Both models show a divergent behavior: PCM tends to underestimate the effect of solvent, thus rendering as the most stable many common rotamers with vacuum calculations, and giving underestimations of populations of β-anomers and gt rotamers in the equilibrium. On the other hand, SMD gives a better estimation of the solvent effect, yielding correct populations of gt rotamers, but more β-anomers than expected by the experimental values. The best agreement is observed when the functional M06-2X is combined with SMD. Both DFT models show minimal geometrical differences between the optimized conformers. © 2017 Elsevier Ltd


Documento: Artículo
Título:Exhaustive rotamer search of the 4C1 conformation of α- and β-D-galactopyranose
Autor:Del Vigo, E.A.; Marino, C.; Stortz, C.A.
Filiación:Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Consejo Nacional de Investigaciones Científicas y Técnicas, Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), Departamento de Química Orgánica, Pab. 2, Ciudad Universitaria, Buenos Aires, 1428, Argentina
Palabras clave:Conformation; Density functional theory; Exhaustive search; Galactose; Rotamer; Solvent model; Chemical bonds; Conformations; Density functional theory; Free energy; Quantum chemistry; Solvents; Divergent behaviors; Exhaustive search; Experimental values; Free-energy calculations; Galactose; Geometrical differences; Rotamers; Solvent model; Hydrogen bonds; galactopyranose; galactose; unclassified drug; galactose; solvent; Article; calculation; chemical structure; conformation; density functional theory; dielectric constant; energy; hydrogen bond; priority journal; rotamer; solvation; solvent effect; vacuum; X ray diffraction; chemistry; conformation; molecular model; quantum theory; stereoisomerism; Carbohydrate Conformation; Galactose; Models, Molecular; Quantum Theory; Solvents; Stereoisomerism
Página de inicio:136
Página de fin:147
Título revista:Carbohydrate Research
Título revista abreviado:Carbohydr. Res.
CAS:galactose, 26566-61-0, 50855-33-9, 59-23-4; Galactose; Solvents


  • Pérez, S., Theoretical aspects of oligosaccharide conformation (1993) Curr. Opin. Struct. Biol., 3 (5), pp. 675-680
  • French, A.D., Brady, J.W., (1989) ACS Symp. Ser., 430, pp. 1-19
  • Mayes, H.B., Broadbelt, L.J., Beckham, G.T., How sugars pucker: electronic structure calculations map the kinetic landscape of five biologically paramount monosaccharides and their implications for enzymatic catalysis (2014) J. Am. Chem. Soc., 136 (3), pp. 1008-1022
  • Cosenza, V.A., Navarro, D.A., Stortz, C.A., DFT/PCM theoretical study of the conversion of methyl 4-O-methyl-α-d-galactopyranoside 6-sulfate and its 2-sulfated derivative into their 3,6-anhydro counterparts (2016) Carbohydr. Res., 426, pp. 15-25
  • Melberg, S., Rasmussen, K., Conformations of disaccharides by empirical force-field calculations: Part I, β-maltose (1979) Carbohydr. Res., 69 (1), pp. 27-38
  • French, A.D., Comparisons of rigid and relaxed conformational maps for cellobiose and maltose (1989) Carbohydr. Res., 188, pp. 206-211
  • Imberty, A., Tran, V., Pérez, S., Relaxed potential energy surfaces ofN-linked oligosaccharides: the mannose-α(1 → 3)-mannose case (1990) J. Comput. Chem., 11 (2), pp. 205-216
  • Tvaroška, I., Kožar, T., Hricovíni, M., (1989) ACS Symp. Ser., 430, pp. 162-176
  • Ha, S.N., Madsen, L.J., Brady, J.W., Conformational analysis and molecular dynamics simulations of maltose (1988) Biopolymers, 27 (12), pp. 1927-1952
  • Martín-Pastor, M., Espinosa, J.F., Asensio, J.L., Jiménez-Barbero, J., A comparison of the geometry and of the energy results obtained by application of different molecular mechanics force fields to methyl α-lactoside and the C-analogue of lactose (1997) Carbohydr. Res., 298 (1-2), pp. 15-49
  • Koča, J., Pérez, S., Imberty, A., (1995) J. Comput. Chem., 16, pp. 296-310
  • Engelsen, S.B., Koca, J., Braccini, I., Hervé du Penhoat, C., Pérez, S., Travelling on the potential energy surfaces of carbohydrates: comparative application of an exhaustive systematic conformational search with an heuristic search (1995) Carbohydr. Res., 276 (1), pp. 1-29
  • Homans, S.W., Forster, M., Application of restrained minimization, simulated annealing and molecular dynamics simulations for the conformational analysis of oligosaccharides (1992) Glycobiology, 2 (2), pp. 143-151
  • Ott, K.-H., Meyer, B., (1996) Carbohydr. Res., 281, pp. 11-34
  • Schmidt, R.K., Karplus, M., Brady, J.W., The anomeric equilibrium ind-xylose: free energy and the role of solvent structuring (1996) J. Am. Chem. Soc., 118 (3), pp. 541-546
  • Plazinski, W., Drach, M., Plazinska, A., Ring inversion properties of 1→2, 1→3 and 1→6-linked hexopyranoses and their correlation with the conformation of glycosidic linkages (2016) Carbohydr. Res., 423, pp. 43-48
  • Plazinski, W., Plazinska, A., Drach, M., Acyclic forms of aldohexoses and ketohexoses in aqueous and DMSO solutions: conformational features studied using molecular dynamics simulations (2016) Phys. Chem. Chem. Phys. PCCP, 18 (14), pp. 9626-9635
  • Ardèvol, A., Biarnés, X., Planas, A., Rovira, C., The conformational free-energy landscape of β-D-mannopyranose: evidence for a (1)S(5) → B(2,5) → (O)S(2) catalytic itinerary in β-mannosidases (2010) J. Am. Chem. Soc., 132 (45), pp. 16058-16065
  • Polavarapu, P.L., Ewig, C.S., Ab Initio computed molecular structures and energies of the conformers of glucose (1992) J. Comput. Chem., 13 (10), pp. 1255-1261
  • Cramer, C.J., Truhlar, D.G., Quantum chemical conformational analysis of glucose in aqueous solution (1993) J. Am. Chem. Soc., 115 (13), pp. 5745-5753
  • Zuccarello, F., Buemi, G., A theoretical study of d-glucose, d-galactose, and parent molecules: solvent effect on conformational stabilities and rotational motions of exocyclic groups (1995) Carbohydr. Res., 273 (2), pp. 129-145
  • Stortz, C.A., (1998) An. Asoc. Quim. Argent., 86, pp. 94-103
  • Rahal-Sekkal, M., Sekkal, N., Kleb, D.C., Bleckmann, P., (2002) J. Comput. Chem., 24, pp. 806-818
  • Momany, F.A., Appell, M., Willett, J.L., Schnupf, U., Bosma, W.B., DFT study of alpha- and beta-D-galactopyranose at the B3LYP/6-311++G** level of theory (2006) Carbohydr. Res., 341 (4), pp. 525-537
  • Sturdy, Y.K., Skylaris, C.K., Clary, D.C., Torsional anharmonicity in the conformational analysis of beta-D-galactose (2006) J. Phys. Chem. B, 110 (8), pp. 3485-3492
  • Jockusch, R.A., Talbot, F.O., Simons, J.P., Sugars in the gas phase (2003) Phys. Chem. Chem. Phys., 5 (8), pp. 1502-1507
  • Çarçabal, P., Jockusch, R.A., Hünig, I., Snoek, L.C., Kroemer, R.T., Davis, B.G., Gamblin, D.P., Simons, J.P., (2005) J. Am. Chem. Soc., 127, pp. 11414-11425
  • Allinger, N.L., Yuh, Y.H., Lii, J.H., Molecular mechanics. The MM3 force field for hydrocarbons. 1 (1989) J. Am. Chem. Soc., 111 (23), pp. 8551-8566
  • Allinger, N.L., Rahman, M., Lii, J.H., (1990) J. Am. Chem. Soc., 112, pp. 8293-8307
  • Becke, A.D., Density-functional thermochemistry. III. The role of exact exchange (1993) J. Chem. Phys., 98 (7), pp. 5648-5652
  • Zhao, Y., Truhlar, D.G., The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals (2008) Theor. Chem. Acc., 120 (1-3), pp. 215-241
  • Tomasi, J., Mennucci, B., Cammi, R., Quantum mechanical continuum solvation models (2005) Chem. Rev., 105 (8), pp. 2999-3093
  • Marenich, A.V., Cramer, C.J., Truhlar, D.G., Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions (2009) J. Phys. Chem. B, 113 (18), pp. 6378-6396
  • Stortz, C.A., Comparative performance of MM3(92) and two TINKER MM3 versions for the modeling of carbohydrates (2005) J. Comput. Chem., 26 (5), pp. 471-483
  • Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Fox, D.J., Gaussian 09, Revision C.01 (2009), Gaussian, Inc. Wallingford CT; Csonka, G.I., French, A.D., Johnson, G.P., Stortz, C.A., Evaluation of density functionals and basis sets for carbohydrates (2009) J. Chem. Theory Comput., 5 (4), pp. 679-692
  • Ohanessian, J., Gillier-Pandraud, H., (1976) Acta Cryst. B, 32, pp. 2810-2813
  • Kouwijzer, L.C.E., van Eijck, V.P., Kooijman, H., Kroon, J., (1995) Acta Cryst. B, 51, pp. 209-220
  • Csonka, G.I., Ángyán, J.G., The origin of the problems with the PM3 core repulsion function (1997) J. Mol. Struct. Theochem., 393 (1-3), pp. 31-38
  • Longchambon, F., Ohanessian, J., Avenel, D., Neuman, A., (1975) Acta Cryst. B, 31, pp. 2623-2627
  • Kinoshita, M., (2003) Molecular Theory of Solvation, pp. 101-168. , F. Hirata Kluwer Dordrecht
  • Ohrui, H., Nishida, Y., Higuchi, H., Hori, H., Meguro, H., The preferred rotamer about the C5—C6bond ofD-galactopyranoses and the stereochemistry of dehydrogenation byD-galactose oxidase (1987) Can. J. Chem., 65 (6), pp. 1145-1153
  • Bock, K., Thøgersen, H., (1983) Annu. Rep. NMR Spectrosc., 13, pp. 1-57
  • Bock, K., Duus, J.Ø., (1994) J. Carbohydr. Chem., 13, pp. 513-543
  • Thibadeau, C., Stenutz, R., Hertz, B., Klepach, T., Zhao, S., Wu, Q., Carmichael, I., Serianni, A.S., (2004) J. Am. Chem. Soc., 126, pp. 15668-15685
  • Wang, C., Ying, F., Wu, W., Mo, Y., How solvent influences the anomeric effect: roles of hyperconjugative versus steric interactions on the conformational preference (2014) J. Org. Chem., 79 (4), pp. 1571-1581
  • Zhu, Y., Zajicek, J., Serianni, A.S., Acyclic forms of [1-(13)C]aldohexoses in aqueous solution: quantitation by (13)C NMR and deuterium isotope effects on tautomeric equilibria (2001) J. Org. Chem., 66 (19), pp. 6244-6251
  • Schnupf, U., Willett, J.L., Momany, F., DFTMD studies of glucose and epimers: anomeric ratios, rotamer populations, and hydration energies (2010) Carbohydr. Res., 345 (4), pp. 503-511
  • Tvaroska, I., Taravel, F.R., Utille, J.P., Carver, J.P., Quantum mechanical and NMR spectroscopy studies on the conformations of the hydroxymethyl and methoxymethyl groups in aldohexosides (2002) Carbohydr. Res., 337 (4), pp. 353-367
  • Stenutz, R., Carmichael, I., Widmalm, G., Serianni, A.S., Hydroxymethyl group conformation in saccharides: structural dependencies of (2)J(HH), (3)J(HH), and (1)J(CH) spin-spin coupling constants (2002) J. Org. Chem., 67 (3), pp. 949-958
  • Juaristi, E., Antúnez, S., Conformational analysis of 5-substituted 1,3-dioxanes. 6. Study of the attractive gauche effect in O-C-C-O segments (1992) Tetrahedron, 48 (29), pp. 5941-5950
  • Rao, V.S.R., Qasba, P.K., Balaji, P.V., Chandrasekaran, R., Conformation of Carbohydrates (1998), Hardwood Academic Publishers Amsterdam 359 pp


---------- APA ----------
Del Vigo, E.A., Marino, C. & Stortz, C.A. (2017) . Exhaustive rotamer search of the 4C1 conformation of α- and β-D-galactopyranose. Carbohydrate Research, 448, 136-147.
---------- CHICAGO ----------
Del Vigo, E.A., Marino, C., Stortz, C.A. "Exhaustive rotamer search of the 4C1 conformation of α- and β-D-galactopyranose" . Carbohydrate Research 448 (2017) : 136-147.
---------- MLA ----------
Del Vigo, E.A., Marino, C., Stortz, C.A. "Exhaustive rotamer search of the 4C1 conformation of α- and β-D-galactopyranose" . Carbohydrate Research, vol. 448, 2017, pp. 136-147.
---------- VANCOUVER ----------
Del Vigo, E.A., Marino, C., Stortz, C.A. Exhaustive rotamer search of the 4C1 conformation of α- and β-D-galactopyranose. Carbohydr. Res. 2017;448:136-147.