Zhang Qiaoxuan, Guo Jialiang, Xiao Yuan, Crommen Jacques, Jiang Zhengjin
Department of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine & New Drug Research, Jinan University, Guangzhou, China.
Department of Laboratory Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
J Sep Sci. 2015 Jun;38(11):1813-21. doi: 10.1002/jssc.201500124. Epub 2015 Apr 10.
To further evaluate the feasibility and applicability of the one-pot strategy in monolithic column preparation, two novel β-cyclodextrin-functionalized organic polymeric monoliths were prepared using two β-cyclodextrin derivatives, i.e. mono(6-amino-6-deoxy)-β-cyclodextrin and heptakis(6-amino-6-deoxy)-β-cyclodextrin. In this improved method, mono(6-amino-6-deoxy)-β-cyclodextrin or heptakis(6-amino-6-deoxy)-β-cyclodextrin reacted with glycidyl methacrylate to generate the corresponding functional monomers and were subsequently copolymerized with ethylene dimethacrylate. The polymerization conditions for both monoliths were carefully optimized to obtain satisfactory column performance with respect to column efficiency, reproducibility, permeability, and stability. The obtained poly(glycidyl methacrylate-mono(6-amino-6-deoxy)-β-cyclodextrin-co-ethylene dimethacrylate) and poly(glycidyl methacrylate-heptakis(6-amino-6-deoxy)-β-cyclodextrin-co-ethylene dimethacrylate) monoliths exhibited a uniform structure, good permeability, and mechanical stability as indicated by scanning electron microscopy and micro-high-performance liquid chromatography experimental results. Because of the probable existence of multi-glycidyl methacrylate linking spacers on the poly(glycidyl methacrylate-heptakis(6-amino-6-deoxy)-β-cyclodextrin-co-ethylene dimethacrylate) monolith, the effect of the ratio of glycidyl methacrylate/heptakis(6-amino-6-deoxy)-β-cyclodextrin was especially studied, and satisfactory reproducibility could still be achieved by strictly controlling the composition of the polymerization mixture. To investigate the effect of the degree of amino substitution of β-cyclodextrin on column performance, a detailed comparison of the two monoliths was also carried out using series of analytes including small peptides and chiral acids. It was found that the β-cyclodextrin-functionalized monolith with mono-glycidyl methacrylate linking spacers demonstrated better chiral separation performance than that with multi-glycidyl methacrylate linking spacers.
为了进一步评估一锅法策略在整体柱制备中的可行性和适用性，使用两种β-环糊精衍生物，即单（6-氨基-6-脱氧）-β-环糊精和七（6-氨基-6-脱氧）-β-环糊精，制备了两种新型的β-环糊精功能化有机聚合物整体柱。在这种改进的方法中，单（6-氨基-6-脱氧）-β-环糊精或七（6-氨基-6-脱氧）-β-环糊精与甲基丙烯酸缩水甘油酯反应生成相应的功能单体，随后与二甲基丙烯酸乙二酯共聚。对两种整体柱的聚合条件进行了仔细优化，以获得在柱效、重现性、渗透性和稳定性方面令人满意的柱性能。扫描电子显微镜和微高效液相色谱实验结果表明，所制备的聚（甲基丙烯酸缩水甘油酯-单（6-氨基-6-脱氧）-β-环糊精-二甲基丙烯酸乙二酯）和聚（甲基丙烯酸缩水甘油酯-七（6-氨基-6-脱氧）-β-环糊精-二甲基丙烯酸乙二酯）整体柱具有均匀的结构、良好的渗透性和机械稳定性。由于聚（甲基丙烯酸缩水甘油酯-七（6-氨基-6-脱氧）-β-环糊精-二甲基丙烯酸乙二酯）整体柱上可能存在多个甲基丙烯酸缩水甘油酯连接间隔基，特别研究了甲基丙烯酸缩水甘油酯/七（6-氨基-6-脱氧）-β-环糊精比例的影响，通过严格控制聚合混合物的组成仍可实现令人满意的重现性。为了研究β-环糊精的氨基取代度对柱性能的影响，还使用包括小肽和手性酸在内的一系列分析物对两种整体柱进行了详细比较。结果发现，具有单甲基丙烯酸缩水甘油酯连接间隔基的β-环糊精功能化整体柱比具有多个甲基丙烯酸缩水甘油酯连接间隔基的整体柱表现出更好的手性分离性能。
