Enantioseparation of aromatic α-hydroxycarboxylic acids: The application of a dinuclear Cu2(II)-β-cyclodextrin complex as a chiral selector in high speed counter-current chromatography compared with native β-cyclodextrin

Abstract

The use of a dinuclear Cu2(II)-β-cyclodextrin complex (Cu2-β-CyD) as a chiral selector (CS) was successfully applied to chiral high speed counter-current chromatography (HSCCC) for the enantioseparation of aromatic α-hydroxycarboxylic acids. α-cyclohexylmandelic acid (CHMA) as a case was studied to optimize the separation temperature, the pH value of the aqueous phase, and the concentration of the chiral selector, which were comparatively studied between Cu2-β-CyD and native β-cyclodextrin (β-CyD) as CSs. The thermodynamic parameters of the formation of the complex between the enantiomers and the CSs were obtained, and the complex formation constants between the enantiomers and Cu2-β-CyD or β-CyD were determined using induced circular dichroism technology. The results indicate that Cu2-β-CyD can remarkably improve the enantioseparation compared with β-CyD, mainly due to the ion-pairing interactions between the deprotonation of carboxyl group of CHMA and the Cu(II) ion of Cu2-β-CyD. Five of other aromatic α-hydroxycarboxylic acids were also enantioseparated successfully by HSCCC using Cu2-β-CyD as a CS.