Capillary electrophoresis, nuclear magnetic resonance and mass spectrometry studies of opposite chiral recognition of chlorpheniramine enantiomers with various cyclodextrins

Markedly different chiral separation abilities were observed for native β‐cyclodextrin (β‐CD), carboxymethyl‐β‐CD (CM‐β‐CD) and heptakis (2,3,6‐tri‐O‐methyl)‐β‐CD (TM‐β‐CD) towards the enantiomers of (±)‐chlorpheniramine ((±)‐CHL) in capillary electrophoresis (CE). Native β‐CD afforded almost baseline enantioseparation at a concentration of 18 mg/mL, whereas only 1 mg/mL solution of CM‐β‐CD was required for adequate enantioseparation. TM‐β‐CD allowed the nearly baseline enantioseparation only at a concentration as high as 80 mg/mL. Moreover, the migration order of (±)‐CHL in the presence of TM‐β‐CD was opposite to that with β‐CD and CM‐β‐CD. 1H and 13C‐NMR spectroscopy and electrospray ionization mass spectrometry (ESI‐MS) have been used in order to obtain preliminary information about the stoichiometry and the binding constants in the intermolecular diastereomeric complexes of (±)‐CHL with these CDs.