(395ao) Chiral Recognition Mechanism of Amide-Containing Chiral Solutes By Amylose Tris[(S)-Alpha-Methylbenzylcarbamate] Sorbent

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)-alpha-methylbenzylcarbamate] sorbent, or AS. Four solutes were studied: ethyl lactate (EL), methyl mandelate (MM), benzoin (B), and pantolactone (PL),  which have the same two key functional groups attached to the asymmetric carbon, O=C-C-OH. Each enantiomer pair of these solutes can be well separated by AS. The retention factors k_R and k_S and enantioselectivities (S= k_R/ k_S) were determined in n-hexane. Infrared spectroscopy (IR) data for polymer-solute,  Density Functional Theory (DFT) simulations of the interactions of these solutes with the side chains of the polymer,  and Monte Carlo (MC) and MD simulations lead to the following general hypothesis for the chiral recognition mechanism for these four molecules. First, a strong H-bond forms between the solute OH groups for each enantiomer and the sorbent C=O groups as the leading interaction, or “anchor” point. Then, a weaker H-bond forms between the solute C=O groups and the sorbent NH groups only for the R-enantiomer, but not for the S-enantiomer, which is prevented for steric restrictions. A third synergistic interaction may involve the C-O-C groups of the R-enantiomers of EL and PL with the sorbent NH groups, or the phenyl groups of the R-enantiomers of MM and B with the sorbent phenyl groups. Moreover, IR shows evidence of an intra H-bond for all four solutes, supported by DFT simulations. The retention factors increase with increasing strength of the inter H –bond, and decreasing strength of the intra H-bond. The intra H-bond strength correlates with the O=C-C-OH group molecular flexibility, as determined from a novel method involving the distribution of torsion angles of this group. The distributions were quantified with molecular dynamics simulations of the solute structure. Moreover, the retention factor and enantioselectivity increase with increasing molecular rigidity, which appears to facilitate the formation of the third synergistic interactions in the R-enantiomers. MD simulations of a left-handed 12-mer AS polymer rod model revealed that the polymer has orderly “grooves” and cavities. Simulations of AS with 200 n-hexane molecules indicate no effect of n-hexane on H-bonds in AS. Monte Carlo (MC) and MD “docking” simulations reveal certain chiral cavities which can lead to chiral discrimination. Molecular rigidity hinders the formation of strong intra H-bond and facilitates the formation of the synergistic third interactions in the R-enantiomers. Strong intra H-bond and molecular flexibility, on the other hand, hinder the formation of the three synergistic interactions in the R-enantiomers. The results support the proposed general mechanism.