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

• Published in: Journal of Chromatography A 2000-04, Vol.875 (1), p.471-484
• Main Authors: Chankvetadze, Bezhan, Burjanadze, Naira, Pintore, Giorgio, Bergenthal, Dieter, Bergander, Klaus, Mühlenbrock, Christoph, Breitkreuz, Jörg, Blaschke, Gottfried
• Format: Article
• Language: English
• Subjects: Brompheniramine; Brompheniramine - chemistry; Brompheniramine - isolation & purification; Crystallography, X-Ray; Cyclodextrins; Cyclodextrins - chemistry; Electrophoresis, Capillary - methods; Molecular Structure; Spectrum Analysis - methods; Stereoisomerism
• ISSN: 0021-9673
• DOI: 10.1016/S0021-9673(00)00153-9

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.