Chromatographic and spectroscopic studies on the chiral recognition of sulfated beta-cyclodextrin as chiral mobile phase additive enantiomeric separation of a chiral amine.
A fast enantiomeric separation of a chiral aromatic amine was achieved, using ultra high pressure liquid chromatography and highly sulfated beta-cyclodextrin (S-beta-CD) as a chiral additive in the mobile phase. The stationary phase consisted of a core-shell support with a particle size of 2.7mum. Under these conditions the base-line separation was obtained within 2.5min. The influence of the concentration of the additive, along with the thermodynamics of the separation, was studied. Vibrational circular dichroism (VCD) spectroscopy was applied to assess the absolute configuration of the two enantiomeric analytes, as well as the interaction of these enantiomers with the S-beta-CD. The VCD results revealed that S-beta-CD undergoes a temperature-induced conformational change. Further, VCD experiments indicate that the interactions of the two enantiomers with the S-beta-CD occur through an inclusion of the aromatic part of the analyte, as well as through electrostatic interaction between the protonated amine and the sulfate groups located at the narrow part of the S-beta-CD. Molecular mechanics calculations performed according to the VCD results are consistent with experimental data, providing further evidence of these interactions.
Ma
Shengli
S
Chemical Development Department, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877-0368, USA.
Shen
Sherry
S
Haddad
Nizar
N
Tang
Wenjun
W
Wang
Jing
J
Lee
Heewon
H
Yee
Nathan
N
Senanayake
Chris
C
Grinberg
Nelu
N
D000588:Amines / Q000737:chemistry / Q000302:isolation & purification*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000588:Amines; D047392:beta-Cyclodextrins; C031215:betadex