Solvent-Dependent Conformational Diversity of Polysaccharide-Based Chiral Selectors

The chromatographic separation of pharmaceutically relevant enantiomers is an important clinical and economical issue. A popular class of chiral stationary phases used for this purpose employs polysaccharide-based chiral selectors. In the present work, the structure and dynamics of two representative polysaccharide-based chiral selectors, amylose tris(3,5-dimethylphenylcarbamate) and cellulose tris(3,5-dimethylphenylcarbamate) were studied, using explicit solvent molecular dynamics. The conformational ensemble emerging from this work is substantially more disordered than what is often assumed in the literature. We show that existing nuclear Overhauser effect spectroscopy (NOESY) results on an amylose tris(3,5-dimethylphenylcarbamate) substituted disaccharide are compatible with an equilibrium between two major conformations. While longer oligomers are substantially more constrained due to steric crowding, there is still considerable conformational flexibility in our simulations, even more so in more polar solvent mixtures that are representative for reversed-phase liquid chromatography conditions. Either way, we conclude that explicitly accounting for the conformational freedom of polysaccharide-based selectors will be important for future studies aimed at predicting enantioselectivity.