DFT study of α- and β-d-galactopyranose at the B3LYP/6-311++G** level of theory Original Research Article

Forty-one conformations of α- and β-d-galactopyranose were geometry optimized using the B3LYP density functional and 6-311++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 α-gg-4C1-c chair conformation, which is of lower electronic and free energy than the lowest energy α-d-glucopyranose conformer because of favorable hydrogen-bonding interactions. The in vacuo calculations showed considerable (∼2.2 kcal/mol) energetic preference for the α over the β anomer for galactopyranose in both the 4C1 and 1C4 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.