B3LYP/6-311++G** study of monohydrates of α- and β-d-glucopyranose: hydrogen bonding, stress energies, and effect of hydration on internal coordinates Original Research Article

Twenty-six monohydrates of α- and β-d-glucopyranose were studied using gradient methods at the B3LYP/6-311++G** level of theory. Geometry optimization was carried out with the water molecules at different configurations around the glucose molecule. A new nomenclature for hydrated carbohydrates was developed to describe the water configurations. Zero-point vibrational energy, enthalpy, entropy, and relative free energy were obtained using the harmonic approximation. Hydrogen-bond energies for the monohydrates range from ∼−5 to −12 kcal/mol, and the average relative free energy is ∼5 kcal/mol. The 1-hydroxy position is the most energetically favored site for hydration, and the region between the two and three positions is the next-most favored site. A water molecule approaching α-d-glucose between the 1- and 2-hydroxy positions pulls the 2-hydroxyl hydrogen atom away from the 1-hydroxy oxygen atom, thus increasing the hydrogen-bond length and also increasing the α-d-glucose energy. The increase in energy that occurs with a similar interaction on the β-anomer is much less effective since the hydrogen bond is much longer. Using the calculated free energies of all 26 configurations, the anomer population (α/β) increases in the β-anomer population relative to the in vacuo case by ∼10% at the expense of the α-anomer, giving an (α/β) ratio of ∼50/50. This result arises from entropy contributions favoring the β-anomer more than the α-anomer. From analysis of donor and acceptor hydrogen-bond lengths, excellent correlation is found between the DFT calculated distances and those taken from carbohydrate structures in the Cambridge Crystallographic Data Bank.