Chiral recognition mechanism of acyloin-containing chiral solutes by amylose tris[(S)-α-methylbenzylcarbamate]

Although polysaccharide sorbents have been widely used for chiral separations, the recognition mechanisms have not been fully elucidated. In this study, we focus on one important commercial sorbent, amylose tris[(S)-α-methylbenzylcarbamate] (AS) sorbent. Four solutes containing acyloin, O=C - C - OH, which has a hydroxyl group in the α-position of a carbonyl group, were studied: ethyl lactate (EL), methyl mandelate (MM), benzoin (B), and pantolactone (PL). The observed retention factors (k_R and k_S) and enantioselectivities (α = k_R/ k_S) were determined in n-hexane and in hexane-isopropanol (IPA) solutions. Infrared (IR) spectroscopy and density functional theory (DFT) simulations of the interactions of these solutes with the side chains of the polymer led to a general hypothesis for the chiral recognition mechanism for these solutes: A strong H-bond forms as the primary (or "leading") nonenantioselective interaction (or "anchor" point) between the solute OH group of each enantiomer and the sorbent C=O group. A weaker H-bond forms preferably for the R enantiomer between the solute C=O groups and the sorbent NH groups. The S enantiomer is prevented from forming such a bond for steric restrictions. A third interaction might involve the O groups of the phenyl groups of the solutes. IR spectroscopy shows evidence of an intramolecular H-bond for all four solutes. The retention factors were found to increase with increasing strength of the intermolecular H-bond and with decreasing strength of the intramolecular H-bond. The enantioselectivities were found to correlate with the molecular rigidity or flexibility, as determined from the distribution of the torsion angles of the acyloin group. The enantioselectivity was higher for the more rigid molecules. Simulations of left-handed AS with 200 n-hexane molecules indicated no effect of hexane on the H-bonds in AS. Monte Carlo (MC) and molecular dynamics (MD) "docking" simulations of AS with these solutes revealed certain chiral cavities that can lead to chiral discrimination. The results support the proposed mechanism.