Enantiodifferentiation of chiral baclofen by 尾-cyclodextrin using capillary electrophoresis: A molecular modeling approach

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• 作者：FakhrEldin O. Suliman^a ; ^{fsuliman@squ.edu.om} ; Abdalla A. Elbashir^b
• 关键词：Chiral separation ; Capillary electrophoresis ; Baclofen ; Molecular modeling ; PM6 ; 尾-Cyclodextrin
• 刊名：Journal of Molecular Structure
• 出版年：2012
• 期刊代码：62_00222860
• 类别：ch
• 出版时间：18 July, 2012
• 卷：1019
• 期：Complete
• 页码：43-49
• 文件大小：920 K

摘要

Using capillary electrophoresis baclofen (BF) enantiomers were separated only in the presence of 尾-cyclodextrin (尾CD) 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-尾CD inclusion complexes. From the MS data BF was found to form a 1:1 complex with 伪- and 尾CD, 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 尾-CD due to a large binding energy difference (螖螖E) of 46.8 kJ mol^鈭? between S-BF-尾CD and R-BF-尾CD complexes. In the case of 伪CD complexes 螖螖E was 1.3 kJ mol^鈭? indicating poor resolution between the two enantiomers. Furthermore, molecular dynamic simulations show that the formation of more stable S-BF-尾CD complex compared to R-BF-尾-CD complex is primarily due to differences in intermolecular hydrogen bonding.