Abstract
Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins (CDs) as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD) exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the –OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy.
Highlights
Introduction βAdrenergic antagonists are effectively used for the treatment of hypertension, prevention of anginal attacks, suppression of cardiac arrhythmia, prevention of myocardial infarction and possibly, amelioration of congestive heart failure [1]
The type of CD plays an important role in enantiomeric separation by cyclodextrin-capillary zone electrophoresis
CM-β-CD was chosen for the optimization of the separation
Summary
All CE experiments were performed on an HP3D CE system from Agilent Technologies (Palo Alto, CA, USA) with an online diode-array detector. Instrument control and data acquisition were performed by the HP3D CE ChemStation software [29]. An uncoated fused-silica capillary with a total length of. (Yongnian Optical Fiber Plant, Hebei, China) was used as the separation column. The new capillary column was rinsed with methanol for. 5 min, and conditioned with background electrolyte (BGE) for 15 min. Between each run, it was treated with 0.1 M NaOH for 4 min, water for 2 min, and running BGE for 4 min. The detection wavelength was 214 nm and the column temperature was kept at 20 °C. 828 pH meter with a precision of 0.01 pH units (Thermo Electron, Milford, MA, USA) was used for pH measurement
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