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

Abstract

The enantioselective separation of a group of six weak base azole compounds was achieved in this work using EKC with three neutral b-CDs as chiral selectors. The native b-CD and two other b-CD derivatives with different types and positions of the substituents on the CD rim ((2-hydroxy)propyl-b-CD (HP-b-CD) and heptakis-2,3,6-tri-O-methyl-b-CD (TM-b-CD)) were employed. Apparent binding constants for each pair compound-CD were determined in order to study analyte-CD interactions. The best enantiomeric resolutions for miconazole, econazole, and sulconazole were observed with HP-b-CD whereas for the separation of the enantiomers of ketoconazole, terconazole, and bifonazole, TM-b-CD was the best chiral selector. The enantioseparations obtained were discussed on the basis of the structure of the compounds taking into account that inclusion into the hydrophobic CD cavity occurred through the phenyl ring closer to the azole group. In addition, a change in the migration order for the enantiomers of two of the compounds studied (ketoconazole and terconazole) with the concentration of HP-b-CD was observed for the first time.

About the role of enantioselective selector–selectand interactions and the mobilities of diastereomeric associates in enantiomer separations using CE

“…The reversal of enantiomer migration order for the enantiomers of KC had been observed in a previous study by Castro-Puyana et al [23]. One of the goals in the present study was to confirm this effect for TC.…”

“…In addition, the data of these experiments should be used for CE determination of enantioselective binding constants and diastereoselective mobilities of the temporary associates. The reversal of the order of migration of the enantiomers, depending on the concentration of HP-b-CD as previously observed [23], was confirmed for both analytes (Figs. 5A and B).…”

“…Recently, Castro-Puyana et al reported a reversal of the enantiomer migration order of the chiral antimycotic drugs ketoconazole (KC) and terconazole (TC) depending on the concentration of the chiral selector, 2-hydroxypropyl-b-CD, (HP-b-CD) [23]. In the present study, the mechanism of the above-mentioned phenomenon has been studied by the combined use of CE and NMR spectroscopy.…”

The role of cyclodextrins in chiral capillary electrophoresis

“…However, minor peak first enantiomer migration order overcomes this difficulty. CE and mostly CD selectors offer much more possibility for minor first migration order than other chromatographic modes: using various selectors with opposite selectivity [31,56,62]; changing the ionization state of selector or selectands [63]; elimination or reversal of EOF [63]; an increase in the concentration of chiral selector [29,30,97]; addition of achiral surfactant [64]. Changing of chirality of selector cannot be applied in the case of CD-type selectors, in spite of being a common practice in amino acid-based selectors [3].…”

Enantiomeric separation of glycidyl tosylate by CE: Application to the study of catalytic asymmetric epoxidation of allyl alcohol

“…However, in the few last years, CE has become a very interesting alternative for chiral analysis because it offers advantages such as high-peak efficiency, faster method development, lower consumption of solvents and reagents and a great variety of chiral selectors [14][15][16][17]. CDs are the most important chiral selectors used in CE because there are commercially available CDs of various ring sizes as well as derivatized CDs with higher solubilities in aqueous solvents than the native CDs [18][19][20][21][22]. Using chiral CE, Morante-Zarcero et al [23] optimized the first method for the separation of phenylglycidol enantiomers in asymmetric epoxidation process.…”