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

Thirty-five conformations of α- and β-d-mannopyranose, the C-2 substituted epimer of glucopyranose, were geometry optimized using the density functional (B3LYP), and basis set (6-311++G**). Full geometry optimization was performed on the hydroxymethyl rotamers (gg/gt/tg) and an analytical hessian program was used to calculate the harmonic vibrational frequencies, zero point energy, enthalpy, and entropy. The lowest energy conformation investigated is the β-tg in the 4C1 chair conformation. The in vacuo calculations showed little energetic preference for either the α or β anomer for mannopyranose in the 4C1 chair conformation. Results are compared to similar glucopyranose calculations in vacuo where the α anomer is ∼1 kcal/mol lower in electronic energy than the β anomer. In the case of the generally higher energy 1C4 chair conformations, one low-energy, low-entropy β-gg-1C4 chair conformation was identified that is within ∼1.4 kcal/mol of the lowest energy 4C1 conformation of mannopyranose. Other 1C4 chair conformations in our investigation are ∼2.9–7.9 kcal/mol higher in overall energy. Many of the 3,OB, B3,O, 1,4B, and B1,4 boat forms passed through transitions without barriers to 1S3, 5S1, 1S5 skew forms with energies between ∼3.6 and 8.9 kcal/mol higher in energy than the lowest energy conformation of mannopyranose. Boat forms were found that remained stable upon gradient optimization. As with glucopyranose, the orientation and interaction of the hydroxy groups make a significant contribution to the conformation/energy relationship in vacuo.