Jin L J, Li S F
Department of Chemistry, National University of Singapore, Kent Ridge Crescent, Singapore.
J Chromatogr B Biomed Sci Appl. 1998 Apr 24;708(1-2):257-66. doi: 10.1016/s0378-4347(97)00640-3.
The enantiomeric separation of some racemic anti-histamines and anti-malarials, namely (+/-)-pheniramine, (+/-)-brompheniramine, (+/-)-chlorpheniramine, (+/-)-doxylamine, and (+/-)-chloroquine, was investigated by capillary zone electrophoresis. The enantiomeric separation of five compounds was obtained by addition of approximately 7 mM (1%, w/v) sulfated-beta-cyclodextrin into the buffer as a chiral selector. The effects of sulfated-beta-cyclodextrin concentration and buffer pH on migration and resolution are discussed. Two other cyclodextrins, carboxyethylated-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin were also investigated. Four of the racemic compounds were resolved using 14 mM (2%, w/v) carboxyethylated-beta-cyclodextrin while 28 mM (4%, w/v) hydroxypropyl-beta-cyclodextrin resolved only two of them. It was found that the type of substituent and the degree of substitution on the rim of the CD structure played an important role in enhancing the chiral recognition. Cyclodextrins with negatively charged substituents and higher degree of substitution on the rim of the structure proved to give better resolution to the cationic racemic compounds compared with cyclodextrin with neutral substituents. This is due to the countercurrent mobility of the negatively charged cyclodextrin relative to the cationic analytes thus allowing for a smaller difference in interaction constants to achieve a successful resolution of enantiomers. Furthermore, lower concentrations of negatively charged cyclodextrins were necessary to achieve the equivalent resolutions as compared with the neutral ones.
采用毛细管区带电泳法研究了一些外消旋抗组胺药和抗疟药，即（±）-苯海拉明、（±）-溴苯那敏、（±）-氯苯那敏、（±）-多西拉敏和（±）-氯喹的对映体分离。通过在缓冲液中加入约7 mM（1%，w/v）硫酸化β-环糊精作为手性选择剂，实现了这五种化合物的对映体分离。讨论了硫酸化β-环糊精浓度和缓冲液pH对迁移和分离度的影响。还研究了另外两种环糊精，即羧乙基化β-环糊精和羟丙基β-环糊精。使用14 mM（2%，w/v）羧乙基化β-环糊精拆分了四种外消旋化合物，而28 mM（4%，w/v）羟丙基β-环糊精仅拆分了其中两种。研究发现，CD结构边缘的取代基类型和取代度在增强手性识别方面起着重要作用。与具有中性取代基的环糊精相比，结构边缘带有负电荷取代基且取代度较高的环糊精对阳离子外消旋化合物具有更好的分离效果。这是由于带负电荷的环糊精相对于阳离子分析物的逆流迁移，从而使得相互作用常数的差异更小，以实现对映体的成功拆分。此外，与中性环糊精相比，实现等效分离所需的带负电荷环糊精浓度更低。
