Int. J. Mol. Sci. 2012, 13(1), 710-725; doi:10.3390/ijms13010710
Article

Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis

1 School of Pharmacy, Second Military Medical University, Shanghai 200433, China 2 Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Second Military Medical University, Shanghai 200433, China
* Author to whom correspondence should be addressed.
Received: 9 November 2011; in revised form: 13 December 2011 / Accepted: 31 December 2011 / Published: 11 January 2012
(This article belongs to the Section Molecular Recognition)
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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.
Keywords: molecular docking; cyclodextrin; β-adrenergic antagonists; capillary electrophoresis; chiral recognition mechanism

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MDPI and ACS Style

Li, W.; Liu, C.; Tan, G.; Zhang, X.; Zhu, Z.; Chai, Y. Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis. Int. J. Mol. Sci. 2012, 13, 710-725.

AMA Style

Li W, Liu C, Tan G, Zhang X, Zhu Z, Chai Y. Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis. International Journal of Molecular Sciences. 2012; 13(1):710-725.

Chicago/Turabian Style

Li, Wuhong; Liu, Changhai; Tan, Guangguo; Zhang, Xinrong; Zhu, Zhenyu; Chai, Yifeng. 2012. "Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis." Int. J. Mol. Sci. 13, no. 1: 710-725.

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