Relation between the Δ2 effect and the solution conformational entropy of aldohexoses and select methyl glycosides

Configurational differences between monosaccharides directly impact properties such as cryoprotectant ability and binding selectivity. Here, we examine how diastereomeric differences among select aldohexoses and methyl glycosides affect the flexibility of the sugars in solution. Our analysis takes advantage of the entropic nature of the separation in size-exclusion chromatography (SEC). Particular attention is given to the influence of the Δ2 effect, the greater destabilization of the pyranose ring conformation when the hydroxyl group at carbon 2 (C2) is in the axial position, on solution conformational entropy (ΔS) in aqueous solvent as well as in N,N-dimethyl acetamide (DMAc) and in DMAc/LiCl. For example, the rankings of the ΔS values of mannose and talose in water, relative to the other aldohexoses examined, can be directly attributed to the influence of the Δ2 effect. As part of this study, we have also investigated how the pyranose:furanose and α:β ratios affect the relative flexibilities of the sugars in solution. Several differences, not all of which we are currently able to explain, are noted between the behavior of the sugars in aqueous versus organic solvent.