Molecular dynamics simulations of chiral recognition of drugs by amylose polymers coated on amorphous silica

Fully atomistic molecular dynamics (MD) simulation is a useful tool to provide molecular-level understanding of the chiral recognition. MD can predict which enantiomer elutes first, and provide an estimate of experimental separation factors under a given set of conditions in chiral high-performance liquid chromatography (HPLC). Here, we consider a commonly used chiral stationary phase (CSP), that is, amylose tris(3,5-dimethylphenyl carbamate) (ADMPC) on amorphous silica, in the presence of a commonly used solvent system, that is, heptane/IPA (90:10 by volume) for the separation of four sets of enantiomers, namely, flavanone, trans-stilbene oxide, tetramisole and naringenin. We obtain the correct elution order in all cases. The estimates for separation factors found by analyses of the hydrogen bonding lifetime distributions are in the correct order of magnitude in all cases except trans stilbene, where the interactions between enantiomer and CSP are not strongly dominated by hydrogen-bonding interactions.