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

Abstract

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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Chiral separation
• molecular dynamics
• enantiomers
• HPLC
• amylose tris(3,5-dimethylphenyl carbamate)

Acknowledgements

The authors dedicate this paper to the many accomplishments of Mike Klein to the field. SM fondly remembers meeting him as a graduate student at Cornell when he gave a seminar there and proudly describing their new Quaternion method for molecular dynamics (Was then at the National Research Council of Canada). Along with SM, CJJ and XW have greatly benefited for the insight provided by him in many of his publications.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the US National Science Foundation (under grant CBET 1545560), and grant from the Eppley Foundation for Research.