title: Molecular Dynamics Simulation and NMR Investigation of the Association of the β-Blockers Atenolol and Propranolol with a Chiral Molecular Micelle.
abstract: Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two β-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S)-propranolol associated more strongly with the molecular micelle than (R)-propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies.
authors.affiliation: Department of Chemistry, Carthage College, 2001 Alford Park Drive, Kenosha, WI 53140.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Morris
authors.affiliation: Department of Physical and Environmental Sciences, Texas A&M University-Corpus Christi, 6300 Ocean Drive, Corpus Christi, TX 78412.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Billiot
authors.affiliation: Department of Physical and Environmental Sciences, Texas A&M University-Corpus Christi, 6300 Ocean Drive, Corpus Christi, TX 78412.
authors.forename: Fereshteh H
authors.initials: FH
authors.lastname: Billiot
authors.affiliation: Department of Chemistry, Carthage College, 2001 Alford Park Drive, Kenosha, WI 53140.
authors.forename: Charlene B
authors.initials: CB
authors.lastname: Hoffman
authors.affiliation: Department of Chemistry, Carthage College, 2001 Alford Park Drive, Kenosha, WI 53140.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Gladis
authors.affiliation: Office of Naval Research, 875 North Randolph Street, Arlington, VA 22203.
authors.forename: Kenny B
authors.initials: KB
authors.lastname: Lipkowitz
authors.affiliation: Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059.
authors.forename: William M
authors.initials: WM
authors.lastname: Southerland
authors.affiliation: Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059.
authors.forename: Yayin
authors.initials: Y
authors.lastname: Fang
keywords: Molecular dynamics simulation; NMR; chiral recognition