Enantioseparation, quantification, molecular docking and molecular dynamics study of five β-adrenergic blockers on...

Enantioseparation of five β-adrenergic blockers was studied using two mobile phases on a cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux-Cellulose-2) chiral column in normal phase mode. The first mobile phase composed of n-hexane: ethanol: diethylamine 60: 40: 0.1 by volume has successfully resolved the chromatographic peaks of three pairs of β-adrenergic blockers namely, bisoprolol, carvedilol and atenolol. A mixture of n-hexane: ethanol: diethyl amine 75: 25: 0.1 by volume was used as the second mobile phase to separate the four pairs of enantiomers, metoprolol, carvedilol, nebivolol and atenolol with high resolution values. The mobile phases were pumped at a flow rate 1 mL/min with column temperature 25 °C using a UV detector at 230 nm. Molecular docking simulations of the five pairs of enantiomers was carried out in the cavities of the chiral stationary phase to gain a better understanding of the interaction between analyte enantiomers and chiral stationary phase and to better understand the mechanism of chiral recognition. According to the results, hydrogen bond interactions and π-π- interactions were the main types of interaction involved in the chiral recognition. Molecular dynamics simulation was performed to investigate the solvent effect on the interaction of the five pair of enantiomers in the chiral stationary phase cavity under dynamic conditions.