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由于桥联双β-环糊精的协同包结作用和独特的多重识别功能已被广泛地用作人工模拟酶,本文尝试用桥联双β-环糊精作固定相配体,开发其手性分离功能.采用3-异氰酸丙基三乙氧基硅烷偶联剂连续反应法,首先将(6-氧-对甲苯磺酰)-β-环糊精键合到有序介孔SBA-15硅胶表面,然后与(6-乙二胺-6-去氧)-β-环糊精反应,制备一种新型的乙二胺桥联双β-环糊精键合SBA-15液相色谱手性固定相(BCDSP).采用质谱、红外光谱、元素分析、热重分析和透射电镜等进行结构表征.在极性有机溶剂模式下,评价了新固定相的基本色谱性能,并用于β-受体阻滞剂对映体的拆分.考察了流动相中有机溶剂、三乙胺、冰醋酸改性剂用量和柱温对手性分离的影响.基于优化的色谱条件,采用双β-环糊精键合固定相成功地拆分了常用的14种β-受体阻滞剂药物对映体,其中普萘洛尔的分离度可达到2.18,卡维地洛的分离度可达到2.01,分析时间一般为10~20 min,取得了较高的分离效率.为比较研究,还制备了一种单β-环糊精固定相(CDSP),结果发现双β-环糊精键合相可拆分14种β-受体阻滞剂,而在优化的条件下单β-环糊精键合相仅能部分拆分4种β-受体阻滞剂,且前者的分离度明显优于后者.基于实验数据对双β-环糊精和单β-环糊精固定相的分离机理的异同点展开讨论.一方面包结作用和氢键作用在桥联双β-环糊精键合相的手性分离中占重要地位,与常见的单β-环糊精固定相相似;另一方面桥联双β-环糊精固定相拥有自身的特点,两个β-环糊精腔体存在协同作用,相应于它的模拟酶功能,协同作用不仅扩大了空间识别域,还提高了立体选择性,基于双腔体的包结作用和乙二胺桥键的氢键作用等增强了固定相的手性识别能力,加上有序的SBA-15能加快传质,使得BCDSP具有较好的手性色谱性能,拥有更广泛的拆分对象、更高的分离度和更短的分析时间.新固定相的制备方法简便,手性分离功能强,色谱性能稳定,且制备成本较低.这类桥联双β-环糊精键合有序介孔SBA-15新型的快速分离材料在手性药物质量监控和药代动力学研究中存在良好的应用前景.
Because of the synergistic inclusion effect of bridged bis-β-cyclodextrin and its unique multiple recognition function, it has been widely used as an artificial mimic enzyme. In this paper, we attempted to develop a chiral separation using bridged β-cyclodextrin as a stationary phase ligand (6-O-tosyl) -β-cyclodextrin was first bound to the ordered mesoporous SBA-15 using a 3-isocyanatopropyltriethoxysilane coupling agent continuous reaction Silica gel surface and then reacted with (6-ethylenediamine-6-deoxy) -β-cyclodextrin to prepare a novel ethylenediamine bridged bis-β-cyclodextrin-bonded SBA-15 liquid chromatography hand The stationary phase (BCDSP) was characterized by mass spectroscopy, infrared spectroscopy, elemental analysis, thermogravimetric analysis and transmission electron microscopy, etc. The basic chromatographic properties of the new stationary phase were evaluated in a polar organic solvent mode and applied to β- The enantiomeric separation of blockers was investigated.The effects of organic solvents, triethylamine, glacial acetic acid modifier and column temperature on the chiral separation were investigated.According to the optimized chromatographic conditions, Fine bond stationary phase successfully split the commonly used 14 kinds of β-blockers drug enantiomers, of which propranolol can reach 2.18 resolution, For the comparative study, a single β-cyclodextrin stationary phase (CDSP) was also prepared, and it was found that the double β - cyclodextrin bonded phase can be split 14 kinds of β-blockers, and in the optimized conditions, single β-cyclodextrin bonding phase can only be partially split four kinds of β-blockers, And the resolution of the former is obviously better than the latter.The dissertation discusses the similarities and differences of the separation mechanism between β-cyclodextrin and β-cyclodextrin stationary phase based on the experimental data.On the one hand, Β-Cyclodextrin bonded phase chiral separation occupies an important position, and similar to the common single β-cyclodextrin stationary phase; on the other hand, bridged β-cyclodextrin stationary phase has its own characteristics, The two β-cyclodextrin cavities have a synergistic effect, corresponding to its mimic enzyme function, and the synergism not only expands the space recognition domain but also enhances the stereoselectivity, based on the dual chamber inclusion and ethylenediamine bridge Hydrogen bonds and other enhance the chiral recognition ability of the stationary phase, coupled with orderly SBA-15 can speed up the mass transfer, making BCDSP Chiral chromatography has better performance , Has a wider range of split objects, higher resolution and shorter analysis time.New stationary phase preparation method is simple, strong chiral separation, chromatographic performance and stability, and the preparation cost is low.This type of bridged double β-Cyclodextrin-Ordered Mesoporous SBA-15 The new rapid separation material has good application prospects in the monitoring of chiral drug quality and pharmacokinetics.