Predicting carbohydrate chain and heterocyclic ring coupling constants in monosaccharides using gmmx conformational searching 1

Abstract

The gmmx global searching program was applied to D-glucitol and α- and β- D-glucopyranose to predict the 3 J HH nuclear magnetic resonance (NMR) coupling constants, which were then compared with the experimental NMR values determined in aqueous solution. The conformational search was conducted using the technique of mixed combination Monte Carlo movements of atom coordinates and bond rotations, with the best coupling constants determined with the hydrogen bonding function turned off and the dielectric constant set between 4.0 and 5.0. The gmmx Boltzmann averaged coupling constants for D-glucitol were found to fit with a root-mean-square (rms) deviation of 1.3 Hz compared with a molecular dynamics rms value of 1.9 Hz. For α- and β- D-glucopyranose, the coupling constants were found to fit the experimental NMR values with an rms of 0.7 Hz including the values for the hydroxymethyl group. The conformations of the lowest energy structures were found and compared with X-ray crystal structures. The lowest energy 4C 1 and 1C 4 conformers for both α- and β- D-glucopyranose were studied, with the 1C 4 reverse-chair conformations for α- and β- D-glucopyranose found to be 5.0 and 5.9 kcal mol −1 higher respectively than the 4C 1 structures. The relative energy of the α- D-glucopyranose 1C 4 conformer agreed with that found by MM3, but the β- D-glucopyranose 1C 4 conformer had a lower relative energy and a different hydroxyl group configuration than that found by a number of other computational methods.