B3LYP/6-311++G** study of α- and β-d-glucopyranose and 1,5-anhydro-d-glucitol: 4C1 and 1C4 chairs, 3,OB and B3,O boats, and skew-boat conformations Original Research Article

Geometry optimization, at the B3LYP/6-311++G** level of theory, was carried out on 4C1 and 1C4 chairs, 3,OB and B3,O boats, and skew-boat conformations of α- and β-d-glucopyranose. Similar calculations on 1,5-anhydro-d-glucitol allowed examination of the effect of removal of the 1-hydroxy group on the energy preference of the hydroxymethyl rotamers. Stable minimum energy boat conformers of glucose were found, as were stable skew boats, all having energies ranging from ∼4–15 kcal/mol above the global energy 4C1 chair conformation. The 1C4 chair electronic energies were ∼5–10 kcal/mol higher than the 4C1 chair, with the 1C4 α-anomers being lower in energy than the β-anomers. Zero-point energy, enthalpy, entropy, and relative Gibbs free energies are reported at the harmonic level of theory. The α-anomer 4C1 chair conformations were found to be ∼1 kcal/mol lower in electronic energy than the β-anomers. The hydroxymethyl gt conformation was of lowest electronic energy for both the α- and β-anomers. The glucose α/β anomer ratio calculated from the relative free energies is 63/37%. From a numerical Hessian calculation, the tg conformations were found to be ∼0.4–0.7 kcal/mol higher in relative free energy than the gg or gt conformers. Transition-state barriers to rotation about the C-5–C-6 bond were calculated for each glucose anomer with resulting barriers to rotation of ∼3.7–5.8 kcal/mol. No energy barrier was found for the path between the α-gt and α-gg B3,O boat forms and the equivalent 4C1 chair conformations. The α-tg conformation has an energy minimum in the 1S3 twist form. Other boat and skew-boat forms are described. The β -anomer boats retained their starting conformations, with the exception of the β-tg-3,OB boat that moved to a skew form upon optimization.