College of Chemistry, Nanchang University, Nanchang 330031, China.
College of Chemistry, Nanchang University, Nanchang 330031, China.
J Chromatogr A. 2020 May 24;1619:460937. doi: 10.1016/j.chroma.2020.460937. Epub 2020 Jan 30.
An ethylenediamine dicarboxyethyl diacetamido-bridged bis(β-cyclodextrin) was firstly synthesized through the reaction of 6-deoxy-6-amino-β-cyclodextrin (NH-CD) with ethylenediaminetetraacetic dianhydride. Then it was bonded onto the surface of silica gel SBA-15 to obtain an ethylenediamine dicarboxyethyl diacetamido-bridged bis(β-CD)-bonded chiral stationary phase (EBCDP). The structures of the bridged bis(β-CD) and EBCDP were characterized by infrared spectroscopy, mass spectrometry, elemental analysis and thermogravimetric analysis, accordingly. The chiral chromatographic performances of EBCDP were systematically evaluated by separating 28 racemic analytes in the reversed-phase or polar organic mode, including eight flavanones, eight bolckers, five dansyl-amino acids, three DL-amino acids and four other common drugs. As a result, the relatively high enantioselectivity of EBCDP was observed in comparison with a native β-CD-CSP (CDSP). All selected analytes were separated on EBCDP, of which 20 analytes had resolutions up to baseline, 2'-hydroxyflavanone and arotinolol had resolutions up to 4.35 and 2.05 in about 30 min, respectively, whereas CDSP only separated 11 analytes with low resolutions (0.551.69). Moreover, EBCDP was able to utilize the complexation of the bridging linker (ethylenediamine dicarboxyethyl diamide group, EDTA-based) to realize direct separations of DL-amino acids with a mobile phase containing copper ion (Cu), which was similar to the chiral ligand exchange chromatography. Unlike the native cyclodextrin with small cavity (242 Å), the bridged bis(β-CD) combined two β-CD units with a bridging linker, having a well-organized "pseudo-cavity" as an organic whole to encapsulate more analytes, which made EBCDP have broad-spectrum applications in chiral separations.
一种乙二胺二羧酸二乙酯二乙酰氨基桥联双（β-环糊精）首先通过 6-脱氧-6-氨基-β-环糊精（NH-CD）与乙二胺四乙酸二酐的反应合成。然后将其键合到硅胶 SBA-15 表面上，得到乙二胺二羧酸二乙酯二乙酰氨基桥联双（β-CD）键合手性固定相（EBCDP）。通过红外光谱、质谱、元素分析和热重分析对桥联双（β-CD）和 EBCDP 的结构进行了表征。通过在反相或极性有机模式下分离 28 种外消旋分析物，系统地评价了 EBCDP 的手性色谱性能，包括八种黄烷酮、八种阻滞剂、五种丹磺酰基氨基酸、三种 DL-氨基酸和四种其他常见药物。结果表明，与天然β-CD-CSP（CDSP）相比，EBCDP 具有较高的对映选择性。所有选定的分析物都在 EBCDP 上分离，其中 20 种分析物的分辨率达到基线，2'-羟基黄烷酮和阿罗洛尔的分辨率分别达到 4.35 和 2.05，约 30 分钟，而 CDSP 仅分离 11 种分辨率低（0.55-1.69）的分析物。此外，EBCDP 能够利用桥接连接体（乙二胺二羧酸二乙酯二酰胺基，基于 EDTA）的络合作用，实现含有铜离子（Cu）的流动相直接分离 DL-氨基酸，类似于手性配体交换色谱。与具有小空腔（~242 Å）的天然环糊精不同，桥联双（β-CD）结合了两个β-CD 单元和一个桥接连接体，具有一个组织良好的“拟空腔”作为一个整体来包裹更多的分析物，这使得 EBCDP 在手性分离中有广泛的应用。
