Mechanistic study of enantiomeric recognition with native γ-cyclodextrin by capillary electrophoresis, reversed-phase liquid chromatography, nuclear magnetic resonance spectroscopy, electrospray mass spectrometry and circular dichroism techniques

Abstract

The possible mechanisms for the chiral recognition of 2( S)-(3,5-bis-trifluoromethyl-phenyl)-2-[3( S)-(4-fluorophenyl)-4-(1H-[1,2,4]triazol-3-ylmethyl)-morpholin-2( R)-yloxy]-ethanol (compound A) and its enantiomer with native γ-cyclodextrin (γ-CD) were investigated using capillary electrophoresis (CE), reversed-phase liquid chromatography (RPLC), proton ( 1H), fluorine ( 19F) and carbon ( 13C) nuclear magnetic resonance spectroscopy (NMR), electrospray mass spectrometry (ESI-MS) and circular dichroism (CD). All experiments provided clear evidence of the formation of diastereomeric complexes between the enantiomers and γ-CD. Proton, fluorine and carbon NMR spectra suggested that both aromatic rings, with mono-fluoro and bis-tri-fluoro functional groups, on the guest molecule were partially included into the cavity of the γ-CD. ESI-MS spectra indicated that the diastereomeric complexes have a 1:1 stoichiometric ratio. The binding constants of the diastereomeric complexes obtained by CE, RPLC and CD were compared. The effects of the γ-CD concentration, organic modifiers and temperature on the CE-chiral separation were also investigated.