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 beta-cyclodextrin (beta-CD) and heptakis(2,3,6-tri-O-methyl)-beta-CD (TM-beta-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 beta-CD and TM-beta-CD. However, the question about a force responsible for the opposite affinity pattern of BrPh enantiomers towards these CDs could not be answered definitely.
Chankvetadze
B
B
Institute of Pharmaceutical Chemistry, University of Münster, Germany.
Burjanadze
N
N
Pintore
G
G
Bergenthal
D
D
Bergander
K
K
Mühlenbrock
C
C
Breitkreuz
J
J
Blaschke
G
G
D001977:Brompheniramine / Q000737:chemistry / Q000302:isolation & purification*; D018360:Crystallography, X-Ray; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D015394:Molecular Structure; D013057:Spectrum Analysis / Q000379:methods; D013237:Stereoisomerism
D003505:Cyclodextrins; D001977:Brompheniramine