DFT Conformational Studies of a-Maltotriose UDO SCHNUPF,1 JULIOUS L. WILLETT,1 WAYNE B. BOSMA,2 FRANK A. MOMANY1 1Plant Polymer Research, National Center for Agricultural Utilization Research, ARS, USDA, 1905 N. University Street, Peoria, Illinois 61604 2Department of Chemistry and Biochemistry, Bradley University, Peoria, Illinois 61625 Received 26 July 2007; Revised 3 October 2007; Accepted 10 October 2007 DOI 10.1002/jcc.20872 Published online 10 December 2007 in Wiley InterScience (www.interscience.wiley.com). Abstract: Recent DFT optimization studies on a-maltose improved our understanding of the preferred conforma- tions of a-maltose. The present study extends these studies to a-maltotriose with three a-D-glucopyranose residues linked by two a-[1?4] bridges, denoted herein as DP-3’s. Combinations of gg, gt, and tg hydroxymethyl groups are included for both ‘‘c’’ and ‘‘r’’ hydroxyl rotamers. When the hydroxymethyl groups are for example, gg-gg-gg, and the hydroxyl groups are rotated from all clockwise, ‘‘c’’, to all counterclockwise, ‘‘r’’, the minimum energy positions of the bridging dihedral angles (/H and wH) move from the region of conformational space of (2, 2), relative to (08,08), to a new position defined by (1, 1). Further, it was found previously that the relative energies of a-maltose gg-gg-c and ‘‘r’’ conformations were very close to one another; however, the DP-3’s relative energies between hydroxyl ‘‘c’’ or ‘‘r’’ rotamers differ by more than one kcal/mol, in favor of the ‘‘c’’ form, even though the lowest energy DP-3 conformations have glycosidic dihedral angles similar to those found in the a-maltose study. Prelimi- nary solvation studies using COSMO, a dielectric solvation method, point to important solvent contributions that reverse the energy profiles, showing an energy preference for the ‘‘r’’ forms. Only structures in which the rings are in the chair conformation are presented here. q 2007 Wiley Periodicals, Inc. J Comput Chem 29: 1103–1112, 2008 Key words: conformation; DFT; B3LYP/6-31111G**; a-maltotriose; COSMO Introduction groups relative to the ring hydroxyl group’s direction and found these factors to be important in determining the preferred con- a-maltotriose is the second most abundant fermentable sugar in formation at the glycosidic bonds. Because of this, it becomes brewer’s wort and, due to incomplete fermentation, causes qual- important to study larger systems to note how the dihedral 1–3 ity and economic problems in the beer and wine industry. angles (/H, wH) of the optimized conformers, which direct the This sugar is of structural interest, being a repeating unit of pul- overall three-dimensional structure, change with chain length. lulan,4 a linear homopolysaccharide of glucose made up of a- In the work presented here, rigorous DFT optimization stud- (1?6) linked maltotriose units. Many uses for this carbohydrate ies at the B3LYP/6-31111G** level of theory have been car- or its derivatives can be found, for example in the inhibition of ried out on a-maltotriose (with a degree of polymerization of specific enzymes,5 as well as use in spectroscopic examination three residues, denoted as DP-3) conformers in vacuo and with of size effects as the carbohydrate chain length increases.6 solvent contributions, looking specifically at the question of the Although many empirical computational structural studies have effect of ‘‘c’’ (clockwise) and ‘‘r’’ (reverse clockwise) hydroxyl been carried out on the conformational properties of carbohy- rotamers and hydroxymethyl conformations on glycosidic (/H, drates, in particular starch and model amylose fragments (see wH) dihedral angle values. Applying a dielectric solvation ref. 7 for lists of earlier computational studies), DFT studies on carbohydrates are recent additions to this extensive list of stud- ies.7–19 To date, high quality computational DFT studies have This article contains supplementary material available via the Internet at not, to our knowledge, been applied to linear amylose fragments http://www.interscience.wiley.com/jpages/0192-8651/suppmat larger than maltose outside of our laboratory. Further, there have Names are necessary to report factually on available data; however, the been few accounts outside of our DFT work7,8 on the direction USDA neither guarantees nor warrants the standard of the product, and of the hydroxyl groups and their role in determining the dihedral the use of the name by USDA implies no approval of the product to the angles at the glycosidic bridge between residues. Our recent a- exclusion of others that may also be suitable maltose7 studies examined the orientation of the hydroxymethyl Correspondence to: F. A. Momany; e-mail: [email protected] q 2007 Wiley Periodicals, Inc. 1104 Schnupf et al. • Vol. 29, No. 7 • Journal of Computational Chemistry ab ab bc bc Table 1. Glycosidic Dihedral Angles (/H, wH) and (/H, wH), Relative Dipole Moments (Debye), and Relative Energies (kcal/mol) of DP-3 Amylose Fragments. DE Dipole a ab ab bc bc Structure (kcal/mol) moment /H wH /H wH gg(g1)-gg(g1)-gg(g1)-c 0.27 3.7 28.0 218.1 28.0 219.4 gg(g1)-gg(g1)-gg(g1)-r 1.29 10.2 0.9 15.2 3.1 16.1 gt(g2)-gt(g2)-gt(g2)-c 3.09 6.9 28.1 224.3 28.5 225.6 gt(g2)-gt(g2)-gt(g2)-r 4.15 7.3 3.3 16.3 1.2 14.1 gg(g1)-gt(g2)-gg(g1)-c 0.12 4.7 28.9 217.9 210.4 215.9 gg(g1)-gt(g2)-gg(g1)-r 1.93 8.7 23.8 13.3 23.4 9.3 gt(g2)-gg(g1)-gg(g1)-c 1.07 5.5 210.5 218.0 27.6 217.6 gt(g2)-gg(g1)-gg(g1)-r 1.01 8.2 23.5 9.6 2.5 16.0 gg(g1)-gg(g1)-gt(g2)-c 0.58 3.4 27.7 218.4 29.0 220.1 gg(g1)-gg(g1)-gt(g2)-r 2.25 10.0 0.9 15.4 24.3 12.9 gg(g1)-gt(g2)-gt(g2)-c 1.39 5.3 28.6 220.1 28.3 224.7 gg(g1)-gt(g2)-gt(g2)-r 3.65 8.9 24.0 12.9 2.9 15.4 gt(g2)-gg(g1)-gt(g2)-c 1.42 5.2 210.6 218.1 28.8 221.8 gt(g2)-gg(g1)-gt(g2)-r 2.16 8.2 23.2 9.7 23.4 14.0 gt(g2)-gt(g2)-gg(g1)-c 1.86 6.7 28.5 223.0 210.6 215.3 gt(g2)-gt(g2)-gg(g1)-r 2.29 6.8 2.3 15.5 25.5 7.4 tg(t)-tg(g1)-tg(g1)-c 4.58 6.8 27.6 22.9 26.1 0.2 tg(g1)-tg(g1)-tg(g1)-r 4.21 6.0 1.8 15.8 2.0 16.4 tg(t)-gt(g2)-gg(g1)-c 0.00 5.8 29.1 218.5 210.8 216.6 tg(g1)-gt(g2)-gg(g1)-r 1.93 6.8 22.0 15.7 23.9 9.2 tg(t)-gg(g1)-gg(g1)-c 0.12 5.0 28.2 221.3 27.9 221.3 tg(g1)-gg(g1)-gg(g1)-r 1.10 8.0 1.2 16.7 2.3 16.1 tg(t)-gg(g1)-gt(g2)-c 0.51 4.9 27.8 220.5 29.0 221.2 tg(g1)-gg(g1)-gt(g2)-r 2.21 8.0 3.4 17.6 22.8 14.6 tg(t)-gt(g2)-gt(g2)-c 1.29 6.5 28.6 218.9 28.3 225.1 tg(g1)-gt(g2)-gt(g2)-r 3.75 7.4 22.4 15.4 2.2 15.4 aB3LYP/6-31111G** electronic energy of lowest energy conformer, (tg(t)-gt(g2)-gg(g1)-c) 5 21198104.158 kcal/mol. method, COSMO,20 to selected DP-3 conformations, is found to Computational Methodology reverse the energy preference by favoring the ‘‘r’’ conformers over the ‘‘c’’ forms. It is of further interest to examine the dif- Generation of Starting Conformations ferences between maltose7,8 conformations and larger amylose fragments, in order to examine longer range contributions to the Starting conformations are generated using in-house empirical energetic stability and favored conformations. Optimized DP-3 potentials21 and InsightII/Discover software.22 To obtain cover- structures in which the central residue is in a boat or skew con- age of the many different conformations, we have chosen to formation will be presented elsewhere. include all of the low energy combinations of the gg and gt ab ab bc bc Table 2. Glycosidic Dihedral Angles (/H, wH) and (/H, wH), Relative Dipole Moments (Debye), and Relative Energies (kcal/mol) of DP-3 Amylose Fragments Optimized with COSMO. DE Dipole a ab ab bc bc Structure (kcal/mol) moment /H wH /H wH gg(g1)-gg(g1)-gg(g1)-c 1.74 4.2 28.1 25.8 29.0 27.8 gg(g1)-gg(g1)-gg(g1)-r 0.00 12.2 23.1 12.2 24.0 11.0 gt(g2)-gt(g2)-gt(g2)-c 2.05 9.4 28.0 212.2 28.5 211.4 gt(g2)-gt(g2)-gt(g2)-r 1.08 8.3 21.7 11.0 22.3 10.0 tg(t)-tg(g1)-tg(g1)-c 5.81 9.6 22.8 6.2 22.4 7.8 tg(g1)-tg(g1)-tg(g1)-r 3.37 7.0 1.5 14.1 2.0 14.0 aB3LYP/6-31111G** electronic energy of lowest energy conformer, (gg(g1)-gg(g1)-gg(g1)-r) 521198139.937 kcal/mol.