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

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 com...

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Autores principales: Li, Wuhong, Liu, Changhai, Tan, Guangguo, Zhang, Xinrong, Zhu, Zhenyu, Chai, Yifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269715/
https://www.ncbi.nlm.nih.gov/pubmed/22312281
http://dx.doi.org/10.3390/ijms13010710
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author Li, Wuhong
Liu, Changhai
Tan, Guangguo
Zhang, Xinrong
Zhu, Zhenyu
Chai, Yifeng
author_facet Li, Wuhong
Liu, Changhai
Tan, Guangguo
Zhang, Xinrong
Zhu, Zhenyu
Chai, Yifeng
author_sort Li, Wuhong
collection PubMed
description 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.
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spelling pubmed-32697152012-02-06 Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis Li, Wuhong Liu, Changhai Tan, Guangguo Zhang, Xinrong Zhu, Zhenyu Chai, Yifeng Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2012-01-11 /pmc/articles/PMC3269715/ /pubmed/22312281 http://dx.doi.org/10.3390/ijms13010710 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Li, Wuhong
Liu, Changhai
Tan, Guangguo
Zhang, Xinrong
Zhu, Zhenyu
Chai, Yifeng
Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis
title Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis
title_full Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis
title_fullStr Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis
title_full_unstemmed Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis
title_short Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis
title_sort molecular modeling study of chiral separation and recognition mechanism of β-adrenergic antagonists by capillary electrophoresis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269715/
https://www.ncbi.nlm.nih.gov/pubmed/22312281
http://dx.doi.org/10.3390/ijms13010710
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