Histamine-modified cationic beta-cyclodextrins as chiral selectors for the enantiomeric separation of hydroxy acids and carboxylic acids by capillary electrophoresis.
The enantiomeric separation of alpha-hydroxy acids and carboxylic acids was successfully performed by using 6-deoxy-6-N-histamino-beta-cyclodextrin (CD-hm), a monosubstituted positively charged beta-cyclodextrin (beta-CD) bearing a histamine moiety linked to the C6 of a glucose unit in the upper CD rim via the amino group. Good results were obtained at a low selector concentration (1 mM). The number of positive charges on the upper rim may be modulated as a function of pH, because of the different pKa of the amino and the imidazolyl groups, and was found to affect both the enantioselectivity and resolution factors. With the analogous 6-deoxy-[4-(2-aminoethyl)imidazolyl]-beta-cyclodextrin (CD-mh) bearing the histamine moiety linked to the C6 via the imidazolyl group, very poor results were obtained, showing that the proximity of the positive charge to the cavity plays an important role in the enantiomeric recognition. The complexation mode was studied by electrospray ionization-mass spectrometry (ESI-MS) and two-dimensional nuclear magnetic resonance (2-D NMR) ROESY experiments: the recognition model is consistent with an inclusion complexation of the aromatic ring of the analyte within the CD cavity coupled to electrostatic interactions between the carboxylate and the protonated amino group of the cyclodextrin.
Galaverna
G
G
Dipartimento di Chimica Organica e Industriale, Università di Parma, Italy.
Corradini
R
R
Dossena
A
A
Marchelli
R
R
D002264:Carboxylic Acids / Q000302:isolation & purification*; D002412:Cations; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006632:Histamine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006880:Hydroxy Acids / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013237:Stereoisomerism; D047392:beta-Cyclodextrins
D002264:Carboxylic Acids; D002412:Cations; D003505:Cyclodextrins; D006880:Hydroxy Acids; D047392:beta-Cyclodextrins; D006632:Histamine; C031215:betadex