Enantioseparation of chiralN-imidazole derivatives by electrokinetic chromatography using highly sulfated cyclodextrins: Mechanism of enantioselective recognition

Abstract

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.

Enantioselective separation of azole compounds by EKC. Reversal of migration order of enantiomers with CD concentration

“…As it can be observed in Table 1, the highest analyte-CD interactions (i.e., the highest apparent binding constant values) were not related to the highest enantioselectivities, fact that has already been reported for other azole derivatives with neutral and highly sulfated CDs [32,33]. Thus, TM-b-CD was the best chiral selector for the separation of the enantiomers of ketoconazole, terconazole, and bifonazole.…”

“…This supposition was supported by previous works where the relation between the structure and enantioseparation of different N-imidazole derivatives was studied by using neutral CDs or anionic highly sulfated CDs [32][33][34]. In order to calculate the apparent analyte-CD binding constants for the six compounds studied in this work with three neutral b-CDs (b-CD, HP-b-CD, and TM-b-CD), the mobilities of the enantiomers of each compound were measured at different concentrations of chiral selector.…”

Chiral capillary electrophoretic determination of the enantiomeric purity of homocamptothecin derivatives, promising antitumor topoisomerase I inhibitors, using highly sulfated CDs and fluorescence detection

“…For example, the migration times of the second migrating enantiomer are equal to 17.65 and 3.52 min with highly S-b-CD for 1 and 2, respectively. This is probably the result of additional electrostatic interactions or ion-pairing between cationic compound 2 and highly S-CD [31].…”

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…Migration orders were correlated to analyte affinity for the selector. In a different study, the chiral recognition mechanism between a negatively charged CD (HS-CDs) and cationic enantiomers (benzothiazolinone and benzoxazolinone derivatives) was investigated [94]. The fact that analyte structure has a major impact on complex formation was confirmed.…”