Baseline separation of ten new, substituted [1-(imidazo-1-yl)-1-phenylmethyl)] benzothiazolinone and benzoxazolinone derivatives with one chiral center was achieved using cyclodextrin-capillary zone electrophoresis (CD-CZE). A method for the enantiomeric resolution of these compounds was developed using neutral CDs (native alpha-, beta-, gamma-CDs or alpha-, beta-, gamma-hydroxypropyl (HP)-CDs) as chiral selectors. Operational parameters including the nature and concentration of the chiral selectors, pH, ionic strength, organic modifiers, temperature, and applied voltage were investigated. The use of neutral CDs provides enantiomeric resolution by inclusion of compounds in the CD cavity. The HP-alpha-CD and HP-beta-CD were found to be the most effective complexing agents and allowed efficient enantiomeric resolutions. Optimal separation of N-imidazole derivatives was obtained using 50 mM phosphate buffer at pH 2.5 containing either HP-alpha-CD or HP-beta-CD (7.5-12.5 mM) at 25 degrees C, with an applied field of 0.50 kV.cm(-1) giving resolution factors Rs superior to 1.70 with migration times of the second enantiomer less than 13 min. The same enantiomer migration order observed for all molecules can be related to a close interaction mechanism with CDs. The influence of structural features of the solutes on Rs and tm was studied. The lipophilic character (log kw) of the solutes and the apparent and averaged association constants of inclusion complexes for four compounds with the six different CDs led us to rationalize the enantioseparation mechanisms. The conclusions were corroborated with reversed-phase high-performance liquid chromatography (HPLC) on chiral stationary phases (CSPs) based on CDs.

No abstract

No abstract

No abstract

No abstract

No abstract

In this study, baseline separation of the stereoisomers of six tetrahydronaphthalenic derivatives (agonists and antagonists for the melatonin (N-acetyl-5-methoxytryptamin) binding sites) was successfully achieved using CE and CDs as chiral selectors. The method for the simultaneous chiral separation of the four stereoisomers uses a capillary dynamically coated with polyethylene oxide and a dual CD system. Optimisation was performed first upon the constituents of the CD system, by varying neutral and anionic CD type, size and concentration, at first in mono-CD systems and subsequently in dual neutral/anionic CD systems. Once these characteristics of the dual CD system were established, operational parameters such as voltage and temperature were then optimised. Under the optimal conditions (i.e. 1.5% w/v of highly S-beta-CD and 10 mM of gamma-CD in 25 mM phosphate buffer (pH 2.5) as the BGE, separation voltage 20 kV and a temperature of 25 degrees C), complete resolution of the six molecules was accomplished. Preliminary results for repeatability and the migration order of the optimised method are described.

Baseline separation of ten new substituted [1-(imidazo-1-yl)-1-phenylmethyl)] benzothiazolinone and benzoxazolinone derivatives, with one chiral center, was achieved by CD-EKC using highly sulfated CDs (alpha, beta, gamma highly S-CDs) as chiral selectors. The influence of the type and concentration of the chiral selectors on the enantioseparations was investigated. The highly S-CDs exhibit a very high enantioselectivity power since they allow excellent enantiomeric resolutions compared to those obtained with the neutral CDs. The enantiomers were resolved with analysis times inferior to 2.5 min and resolution factors R(s) of 3.73, 3.90, 1.40, and 4.35 for compounds 1, 2, 3, and 5, respectively, using 25 mM phosphate buffer at pH 2.5 containing either highly S-alpha-CD, highly S-beta-CD, and highly S-gamma-CD (3 or 4% w/v) at 298 K, with an applied field of 0.30 kV/cm. The determination of the enantiomer migration order for the various analytes and the study of the analyte structure-enantioseparation relationships display the high contribution of the interactions between the analytes phenyl ring and the CDs to the enantiorecognition process. The thermodynamic study of the analyte-CD affinities permits us to improve our knowledge about the enantioseparation mechanism.