Quantum Chemical Conformational Analysis of Glucose in Aqueous Solution

We have calculated the aqueous solvation effects on the anomeric and conformational equilibria of D-glucopyranose using a quantum chemical solvation model based on a continuum treatment of dielectric polarization and solvent accessible surface area. The solvation model puts the relative ordering of the hydroxymethyl conformers in line with the experimentally determined ordering of populations. Our calculations indicate that the anomeric equilibrium is controlled primarily by effects that are also present in the gas-phase potential energy function, that the gauche/trans O-C(6)-C(5)-O hydroxymethyl conformational equilibrium is dominated by favorable solute-solvent hydrogen bonding interactions, and that other rotameric equilibria are controlled mainly by dielectric polarization of the solvent. The description of the aqueous free energy changes of the latter require at least a distributed monopole representation since they do not correlate with overall dipole moment. We also find evidence for intra-glucose hydrogen bond conjugation in aqueous solution.