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手性拆分 12 对对映异构体通过毛细管电泳使用七(2,3-二乙酰基-6-磺酸钠基)-β-环糊精作为手性选择剂和通过计算方法阐明手性识别机制。

Chiral separation of 12 pairs of enantiomers by capillary electrophoresis using heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin as the chiral selector and the elucidation of the chiral recognition mechanism by computational methods.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, P. R. China.

School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, P. R. China.

出版信息

J Sep Sci. 2017 Jul;40(14):2999-3007. doi: 10.1002/jssc.201700137.

DOI:10.1002/jssc.201700137
PMID:28544353
Abstract

Chiral separation of 12 pairs of basic analyte enantiomers including oxybutynin, bambuterol, tradinterol, clenbuterol, clorprenaline, terbutaline, tulobuterol, citalopram, phencynonate, fexofenadine, salbutamol, and penehyclidine was conducted by capillary electrophoresis using a single-isomer anionic β-cyclodextrin derivative, heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin as the chiral selector. Parameters influencing separation were studied, including background electrolyte pH, heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin concentration, buffer concentration, and separation voltage. A background electrolyte consisting of 50 mM Tris-H PO and 6 mM heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin at pH 2.5 was found to be highly efficient for the separation of most enantiomers, with other conditions of normal polarity mode at 10 kV, detection wavelength of 210 nm using hydrodynamic injection for 3 s. Under the optimal conditions, baseline resolution (>1.50) for 11 pairs of enantiomers and somewhat lower resolution for penehyclidine enantiomers (1.17) were generated. Moreover, the possible mechanism of separation of clenbuterol, oxybutynin, salbutamol, and penehyclidine was investigated using a computational modeling method.

摘要

采用单一对映体阴离子β-环糊精衍生物,即七(2,3-二乙酰基-6-磺酸钠基)-β-环糊精作为手性选择剂,通过毛细管电泳对手性分离了 12 对碱性分析物对映体,包括奥昔布宁、班布特罗、特拉特洛尔、克仑特罗、氯苯丙胺、特布他林、妥布特罗、西酞普兰、苯环壬酯、非索非那定、沙丁胺醇和苯海索。研究了影响分离的参数,包括背景电解质 pH 值、七(2,3-二乙酰基-6-磺酸钠基)-β-环糊精浓度、缓冲液浓度和分离电压。发现 50 mM Tris-H3PO4 和 6 mM 七(2,3-二乙酰基-6-磺酸钠基)-β-环糊精的背景电解质在 pH 2.5 时非常有效地分离大多数对映体,其他条件为正常极性模式,分离电压为 10 kV,210 nm 检测波长,采用 3 s 的液压进样。在最佳条件下,可产生 11 对对映体的基线分离(>1.50),对苯海索对映体的分离度稍低(1.17)。此外,还使用计算建模方法研究了克仑特罗、奥昔布宁、沙丁胺醇和苯海索分离的可能机制。

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