title: A comprehensive study of the enantioseparation of chiral drugs by cyclodextrin using capillary electrophoresis combined with theoretical approaches.
abstract: Four chiral drugs were enantioseparated by native beta-cyclodextrin (β-CD) and negatively charged carboxymethyl-beta-cyclodextrin (CM-β-CD) using capillary electrophoresis coupled with electrochemiluminescence detection (CE-ECL). Using 50 mM pH 5.5 Tris-H3PO4 with 10 mM CM-β-CD as a running buffer, high resolution efficiency could be obtained. With the help of isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and molecular modeling, the chiral recognition mechanism was comprehensively investigated. Thermodynamic parameters data from ITC revealed that CM-β-CD exhibited stronger binding affinity with analytes than β-CD, and that the driving forces of CM-β-CD responsible for chiral recognition were mainly electrostatic interactions between negatively charged CM-β-CD and positively charged analytes. In addition, from both a macroscopic and microscopic point of view, the results of NMR and molecular modeling investigation adequately confirm the conclusion by comparing the stereochemical structures of complexes. Combination of ITC, NMR and molecular modeling techniques not only can assist CE to investigate the chiral discrimination mechanism, but also can predict and guide CE enantioseparation efficiency conversely.
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012, Jilin, China. Electronic address: luoquan@jlu.edu.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, China. Electronic address: youty@ciac.jl.cn.
authors.forename: Tianyan
authors.initials: T
authors.lastname: You
mesh_terms: D000420:Albuterol / Q000032:analysis* / Q000737:chemistry; D001592:Benzyl Alcohols / Q000032:analysis* / Q000737:chemistry; D019075:Electrophoresis, Capillary; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013015:Sotalol / Q000032:analysis* / Q000737:chemistry; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D001592:Benzyl Alcohols; D047392:beta-Cyclodextrins; C523155:2-amino-1-phenylethanol; D013015:Sotalol; C031215:betadex; D000420:Albuterol
keywords: Capillary electrophoresis chiral separation; Chiral drug; Isothermal titration calorimetric; Molecular modeling; Nuclear magnetic resonance spectroscopy