Molecular dynamics simulations of the chiral recognition mechanism for a polysaccharide chiral stationary phase in enantiomeric chromatographic separations

Abstract

We use explicit-solvent fully atomistic molecular dynamics (MD) simulations, permitting all the interactions between the atoms constituting the polymeric chiral stationary phase (CSP), the solvent molecules and the drug molecule enantiomers, to better understand the chiral recognition mechanism that makes chromatographic separation possible. Using amylose tris(3,5-dimethylphenyl carbamate) (ADMPC) as prototype, three solvent systems, and ten racemates as solutes, we seek a molecular dynamics average quantity that could serve as a metric that predicts which of the two enantiomers will elute first and also correlates with the ratio of retention times for enantiomers. To better understand the molecular dynamic chiral recognition that provides the discrimination which results in the separation of enantiomers by high performance liquid chromatography, we examine the differences in hydrogen bonding lifetimes in various donor–acceptor pairs between the drugs and the ADMPC, and map out the differences in ring-ring interactions between the drugs and the ADMPC. Several MD average quantities related to hydrogen-bonding lifetimes correlate with the ratio of retention times for the enantiomers. One of these quantities provides a prediction of the correct elution order 90% of the time, and the ratios of these quantities for the enantiomers provide linear correlation (0.85 coefficient) with experimental separation factors.