Use of a zwitterionic cyclodextrin as a chiral agent for the separation of enantiomers by capillary electrophoresis

Abstract

The purity and enantioselectivity of a novel chiral agent, the zwitterionic mono-(6-delta-glutamylamino-6-deoxy)-beta-cyclodextrin (beta-CD-Glu), were studied by capillary electrophoresis. Chiral separation of the enantiomers of chlorthalidone was obtained at pH 2.3, a pH at which beta-CD-Glu is partially protonated. Comparison with the cationic mono-(6-amino-6-deoxy)-beta-cyclodextrin (beta-CD-NH2) enantioselectivity clearly shows that the greater the difference in mobility between the free analyte and the analyte-cyclodextrin complex, the better the resolution. Hydrobenzoin enantiomers were separated at pH 11.2, a pH at which beta-CD-Glu is anionic. Under these conditions, the migration order was opposite to that observed in the presence of beta-CD-NH2 at pH 2.3. When no separation was obtained directly with beta-CD-Glu, a dual cyclodextrin system was developed. Carprofen enantiomers were resolved at pH 2.3 in the presence of a beta-CD-Glu/trimethyl-beta-cyclodextrin (TM-beta-CD) system in which the charged CD confers a non-zero mobility to the analyte, while the neutral CD allows chiral recognition.

Chiral separation by chromatographic and electromigration techniques. A Review

“…Two new amphoteric CD derivatives, mono-(6-glutamylamino-6-deoxy)-b-CD (Glu-b-CD) and AM-b-CD of undefined structure have recently been introduced and shown to be applicable to neutral, acidic and basic compounds [368,366].…”

Chiral separations by capillary electrophoresis: Recent developments and applications

“…Only two different zwitterionic CDs are described so far for CE enantioseparations [20], namely a CD containing 2-hydroxypropyltrimethylammonium chloride (degree of substitution, DS = 2.0) as well as sodium acetate (DS = 2.0) as substituents [48] and glutamylamino-b-CD [49].…”

Chiral separations in capillary electrophoresis

“…CZE separations of acylated dipeptide stereoisomers [158] or nonsteroidal anti-inflammatory drugs [159] are made easier by mixtures of neutral and charged cyclodextrins. Histamine-modified b-cyclodextrins were used for separation of dansyl derivatives of amino acids [160]; zwitterionic cyclodextrin served as the chiral agent in separation of chlorthalidone [161]. Anionic and cationic derivatives of b-cyclodextrin were used in micellar separations of neutral barbiturates, chorthalidone, terbutaline, warfarin, salbutamol and brompheniramide [162].…”