Mechanistic study of enantiomeric recognition with native gamma-cyclodextrin by capillary electrophoresis, reversed-phase liquid chromatography, nuclear magnetic resonance spectroscopy, electrospray mass spectrometry and circular dichroism techniques.
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 gamma-cyclodextrin (gamma-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 gamma-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 gamma-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 gamma-CD concentration, organic modifiers and temperature on the CE-chiral separation were also investigated.
Zhou
Lili
L
Merck Research Laboratories, Merck and Co. Inc., P.O. Box 2000, RY818-C213, Rahway, NJ 07065, USA. lili_zhou@merck.com
Thompson
Richard
R
Reamer
Robert A
RA
Miller
Carrie
C
Welch
Chris
C
Ellison
Dean K
DK
Wyvratt
Jean M
JM
D002853:Chromatography, Liquid / Q000379:methods*; D002942:Circular Dichroism / Q000379:methods*; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D047408:gamma-Cyclodextrins
D003505:Cyclodextrins; D047408:gamma-Cyclodextrins; C023792:gamma-cyclodextrin