DFT optimization and DFT-MD studies of glucose, ten explicit water molecules enclosed by an implicit solvent, COSMO

DFT optimization and DFT-MD studies are carried out on α/β-glucose surrounded by ten explicit water molecules and the glucose/water super-molecule completely enclosed by an implicit solvation model, COSMO. A set of twenty one starting configurations of the explicit waters were first optimized empirically with the AMB06C/TIP3P force field, and further optimized using a reduced basis set (B3LYP/4-31G) on the sugar carbon atoms and the larger B3LYP/6-31+G* level on all other atoms. Glucose hydroxymethyl conformations included gg, gt, and tg forms, with the hydroxyl group’s conformations counter clockwise, ‘r’, and clockwise, ‘c’, forms. The empirical force field optimized configurations were in general agreement with the DFT results in hydrogen bonding distances from glucose to water molecules, but not in such good agreement in water molecule orientation, a result of lack of lone-pair orientation within the TIP3P force field. The individual energies of all components of the super-molecule complex (i.e. water–water, water–glucose), with and without COSMO, allows analysis of the hydration and interaction energies. Examination of the hydroxyl and hydroxymethyl low energy conformations suggests that the hydrated configurations with gg-r and gg-c conformers are preferred in water. DFT-MD is carried out on all configurations leading to understanding of the lifetimes of water molecule contact with glucose. The results suggest that no water molecule remains at any one specific site around glucose for a significant time, water molecules migrating off and moving around the molecule within several picoseconds.