Investigation of the mechanism of enantioseparation of some drug compounds by considering the mobile phase in HPLC by molecular dynamics simulation

J Mol Model. 2019 Sep 3;25(9):297. doi: 10.1007/s00894-019-4184-3.

Abstract

The separation mechanism of chiral drugs in high-pressure liquid chromatography is yet ambiguous. Computational chemistry helps to gain insights about chiral drug separations. The interaction between the 13 drug enantiomers and cellulose tris (3, 5-dimethyl phenyl carbamate) (chiral cel OD) as chiral stationary phase in 3 mobile phases was assayed by AutoDock and LAMMPS simulations. It is found that not only the structure of 2 enantiomers but also the mobile phase has an important role in enantioseparations and sometimes may invert the elution order. The molecular dynamics simulation is a comprehensive method that can be used to investigate the chiral drug enantioseparation mechanism in HPLC.

Keywords: Docking; Drug enantiomers; Elution order; Mobile phase effect; Molecular dynamics simulation (MD).

MeSH terms

  • Anticonvulsants / chemistry
  • Anticonvulsants / isolation & purification*
  • Cellulose / analogs & derivatives*
  • Cellulose / chemistry
  • Chromatography, High Pressure Liquid / methods
  • Esters / chemistry
  • Esters / isolation & purification*
  • Ethanol / chemistry
  • Ethanol / isolation & purification*
  • Humans
  • Hydrogen Bonding
  • Imidazoles / chemistry
  • Imidazoles / isolation & purification*
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Naphthalenes / chemistry
  • Naphthalenes / isolation & purification*
  • Phenylcarbamates / chemistry*
  • Quantum Theory
  • Solutions
  • Stereoisomerism
  • Thermodynamics

Substances

  • Anticonvulsants
  • Esters
  • Imidazoles
  • Naphthalenes
  • Phenylcarbamates
  • Solutions
  • cellulose tris-3,5-dimethylphenyl-carbamate
  • Ethanol
  • Cellulose