Ring inversion properties of 1→2, 1→3 and 1→6-linked hexopyranoses and their correlation with the conformation of glycosidic linkages

Enhanced-sampling molecular dynamics simulations performed within the GROMOS 56a6(CARBO_R) force field were applied in order to elucidate ring-inversion properties of hexopyranose residues in a chain for the case of alpha(1 -> n) and beta(1 -> n) glycosidic linkages (n = 2, 3 or 6). The results indicate that ring-inversion free energies calculated for residues in a chain are weakly correlated with those of corresponding monomers, except of the case of 1 -> 6 linkages. This, in combination with the results for O-1-methyl-hexopyranosides (Plazinski et al, 2016), suggests that both the type of functionalization (glycolysation vs. methylation) and the topology of glycosidic linkage play an important role in possible alterations of the hexopyranose ring flexibility. Additionally, the correlation of the ring shape with the preferred geometry of glycosidic linkages was investigated. The linkages of the 1 -> 2, 1 -> 3 and 1 -> 6 types do not follow the trend found in the case of the 1 -> 4 linkages, i.e. there is no correlation between the range of changes in the glycosidic linkage conformation and the topological orientation of the glycosidic oxygen atoms. Overall, the ring shape affects the glycosidic linkages of the 1 -> 6 type to the least extent in comparison to the remaining ones. (C) 2016 Elsevier Ltd. All rights reserved.