A comprehensive study of the enantioseparation of chiral drugs by cyclodextrin using capillary electrophoresis combined with theoretical approaches

Four chiral drugs were enantioseparated by native beta-cyclodextrin (beta-CD) and negatively charged carboxymethyl-beta-cyclodextrin (CM-beta-CD) using capillary electrophoresis coupled with electro-chemiluminescence detection (CE-ECL). Using 50 mM pH 5.5 Tris-H3PO4 with 10 mM CM-beta-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-beta-CD exhibited stronger binding affinity with analytes than beta-CD, and that the driving forces of CM-beta-CD responsible for chiral recognition were mainly electrostatic interactions between negatively charged CM-beta-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. (C) 2015 Elsevier B.V. All rights reserved.