DFT study of α- and β-D-galactopyranose at the B3LYP/6-311++G** level of theory

Forty-one conformations of alpha- and beta-(D)-galactopyranose were geometry optimized using the B3LYP density functional and 6-311 double dagger double dagger G** basis set. Full geometry optimization was performed on different ring geometries and different hydroxymethyl rotamers (gg/gt/tg). Analytically derived Hessians were used to calculate zero point energy, enthalpy, and entropy. The lowest energy and free-energy conformation found is the alpha-gg-C-4(1)-c chair conformation, which is of lower electronic and free energy than the lowest energy alpha-D-glucopyranose conformer because of favorable hydrogen-bonding interactions. The in vacuo calculations showed considerable (similar to 2.2 kcal/mol) energetic preference for the alpha over the beta anomer for galactopyranose in both the C-4(1) and C-1(4) chair conformations. Results are compared to glucopyranose and mannopyranose calculations in vacuo. Boat and skew-boat forms were found that remained stable upon gradient optimization, although many starting conformations moved to other boat forms upon optimization. As with glucopyranose and mannopyranose, the orientation and interaction of the hydroxyl groups make the most significant contributions to the conformation-energy relationship in vacuo. (c) 2005 Elsevier Ltd. All rights reserved.