Separation of brompheniramine enantiomers by capillary electrophoresis and study of chiral recognition mechanisms of cyclodextrins using NMR-spectroscopy, UV spectrometry, electrospray ionization mass spectrometry and X-ray crystallography

Opposite migration order was observed for the enantiomers of brompheniramine {N-[3-(4-bromphenyl)-3-(2-pyridyl)propyl]-N,N-dimethylamine} (BrPh) in capillary electrophoresis (CE) when native β-cyclodextrin (β-CD) and heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD) were used as chiral selectors. NMR spectrometry was applied in order to obtain information about the stoichiometry, binding constants and structure of the selector-selectand complexes in solution. The data were further confirmed by UV spectrometry and electrospray ionization mass spectrometry. The structure of the complexes in the solid state was determined using X-ray crystallography performed on the co-crystals precipitated from the 1:1 aqueous solution of selector and selectand. This multiple approach allowed an elucidation of the most likely structural reason for a different affinity (binding strength) of BrPh enantiomers towards β-CD and TM-β-CD. However, the question about a force responsible for the opposite affinity pattern of BrPh enantiomers towards these CDs could not be answered definitely. Copyright (C) 2000 Elsevier Science B.V.