TY - JOUR
T1 - Enantiodifferentiation of chiral baclofen by β-cyclodextrin using capillary electrophoresis
T2 - A molecular modeling approach
AU - Suliman, Fakhreldin O.
AU - Elbashir, Abdalla A.
PY - 2012/7/18
Y1 - 2012/7/18
N2 - Using capillary electrophoresis baclofen (BF) enantiomers were separated only in the presence of β-cyclodextrin (βCD) as a chiral selector when added to the background electrolyte. Proton nuclear magnetic resonance and electrospray ionization mass spectrometry (ESI-MS) techniques were used to determine the structure of the BF-βCD inclusion complexes. From the MS data BF was found to form a 1:1 complex with α- and βCD, while the NMR data suggest location of the aromatic ring of BF into the cyclodextrin cavity. A molecular modeling study, using the semiempirical PM6 calculations was used to investigate the mechanism of enantiodifferentiation of BF with cyclodextrins. Optimization of the structures of the complexes by PM6 method indicated that separation is obtained in the presence of β-CD due to a large binding energy difference (ΔΔE) of 46.8 kJ mol-1 between S-BF-βCD and R-BF-βCD complexes. In the case of αCD complexes ΔΔE was 1.3 kJ mol-1 indicating poor resolution between the two enantiomers. Furthermore, molecular dynamic simulations show that the formation of more stable S-BF-βCD complex compared to R-BF-β-CD complex is primarily due to differences in intermolecular hydrogen bonding.
AB - Using capillary electrophoresis baclofen (BF) enantiomers were separated only in the presence of β-cyclodextrin (βCD) as a chiral selector when added to the background electrolyte. Proton nuclear magnetic resonance and electrospray ionization mass spectrometry (ESI-MS) techniques were used to determine the structure of the BF-βCD inclusion complexes. From the MS data BF was found to form a 1:1 complex with α- and βCD, while the NMR data suggest location of the aromatic ring of BF into the cyclodextrin cavity. A molecular modeling study, using the semiempirical PM6 calculations was used to investigate the mechanism of enantiodifferentiation of BF with cyclodextrins. Optimization of the structures of the complexes by PM6 method indicated that separation is obtained in the presence of β-CD due to a large binding energy difference (ΔΔE) of 46.8 kJ mol-1 between S-BF-βCD and R-BF-βCD complexes. In the case of αCD complexes ΔΔE was 1.3 kJ mol-1 indicating poor resolution between the two enantiomers. Furthermore, molecular dynamic simulations show that the formation of more stable S-BF-βCD complex compared to R-BF-β-CD complex is primarily due to differences in intermolecular hydrogen bonding.
KW - Baclofen
KW - Capillary electrophoresis
KW - Chiral separation
KW - Molecular modeling
KW - PM6
KW - β-Cyclodextrin
UR - http://www.scopus.com/inward/record.url?scp=84861823774&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861823774&partnerID=8YFLogxK
U2 - 10.1016/j.molstruc.2012.03.055
DO - 10.1016/j.molstruc.2012.03.055
M3 - Article
AN - SCOPUS:84861823774
SN - 0022-2860
VL - 1019
SP - 43
EP - 49
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
ER -