基于环糊精本征识别能力的手性色谱介质点击制备及应用

引用本文: 陈明, 靳晓宁, 马骁飞, 王勇. 基于环糊精本征识别能力的手性色谱介质点击制备及应用[J]. 色谱, 2020, 38(11): 1270-1280. doi: 10.3724/SP.J.1123.2020.02011 shu

Citation: CHEN Ming, JIN Xiaoning, MA Xiaofei, WANG Yong. Click preparation and application of chiral stationary phase based on intrinsic recognition ability of cyclodextrin[J]. Chinese Journal of Chromatography, 2020, 38(11): 1270-1280. doi: 10.3724/SP.J.1123.2020.02011 shu

基于环糊精本征识别能力的手性色谱介质点击制备及应用

天津大学理学院, 天津 300350

通讯作者: 王勇, E-mail:wangyongtju@tju.edu.cn

基金项目:
国家自然科学基金（21922409，21976131，21575100）；天津应用基础与先进技术研究计划（18JCZDJC37500，17JCYBJC20500）.

摘要: 目前环糊精（CD）手性固定相（CSP）的研究大多集中于对CD或桥联臂进行功能衍生引入更多作用位点以提升手性拆分能力，鲜有能够反映天然CD本征识别能力的CSP的研究报道，该文通过"巯基-烯"点击化学反应合成了结构明确可控的单（6-巯基-6-去氧）-β-环糊精手性固定相（CSP1），其最大限度地保留了天然CD的本征结构，且桥联臂无识别作用位点，固体核磁共振（¹³C SSNMR）和红外光谱（FTIR）的表征结果证明了CSP1的成功制备，元素分析结果表明，与双键功能化硅胶相比，CSP1的C、H、N的百分含量均得到了提高，计算得出CSP1的表面CD固载量为0.82 μmol/m²。采用高效液相色谱反相模式对50多种手性对映体包括异（口恶）唑啉、手性交酯、手性酮、黄烷酮以及丹磺酰氨基酸等进行了手性拆分，充分考察了天然CD的本征手性识别能力，结果表明CD的本征识别能力比较有利于异（口恶）唑啉类样品中含有两个疏水苯环基团Ph-Ph类样品的分离，对于其他几类样品仅利于部分样品的分离。同时与前期制备的功能三唑桥联CD-CSP及咪唑嗡桥联CD-CSP在同一色谱条件下进行了结果比对，结果证明样品的分离过程除了与手性介质的结构有关外，还与样品分子的结构有很大关系，对桥联臂进行功能改性可提升对部分对映体的选择性，但同时会小幅损失CD的本征手性识别能力。对于环糊精本征识别能力易于分离的样品，在设计手性介质时，其桥联臂不需要任何官能团，这为CD固定相结构的设计提供了有益参考。

关键词:

English

Click preparation and application of chiral stationary phase based on intrinsic recognition ability of cyclodextrin

School of Science, Tianjin University, Tianjin 300350, China

Corresponding author: WANG Yong, wangyongtju@tju.edu.cn

Received Date: 18 February 2020
Fund Project:
National Natural Science Foundation of China (Nos. 21922409, 21976131, 21575100)

Abstract: Most of the studies on cyclodextrin (CD)-based chiral stationary phase (CSP) have focused on the functional derivatization of CD or the bridging arms to introduce more interaction sites and thus improve the chiral resolution ability. At present, there are only a few reports on CSP that can reflect the intrinsic recognition ability of natural CD. In this study, a mono(6-mercapto-6-deoxy)-β-CD CSP (CSP1) with a clear and controllable structure was synthesized by the "thiol-ene" click reaction. CSP1 retained the intrinsic structure of natural CD to the maximum extent, and the bridge arm had no recognition site. The results of ¹³C solid-state nuclear magnetic resonance (SSNMR) and Fourier transform infrared (FTIR) analyses confirmed the successful preparation of CSP1. Elemental analysis results showed that compared with double-bond functionalized silica, the percentages of C, H, and N in CSP1 increased, and the calculated CD loading of CSP1 was 0.82 μmol/m². Reversed-phase high performance liquid chromatography was performed for the chiral resolution of more than 50 chiral enantiomers, including isoxazoline, chiral lactide, chiral ketone, flavone, and dansyl amino acid. This fully demonstrated the intrinsic chiral recognition ability of natural CD, and the results showed that the intrinsic recognition ability of cyclodextrin was more conducive to the separation of Ph-Ph samples containing two hydrophobic benzene ring groups in the isoxazoline samples. For the Ph-Py and Ph-OPr samples, the separation effect was not satisfactory. The separation results for the Ph-Py samples were not ideal because the outer hydroxyl group of cyclodextrin could form a hydrogen bond with the pyridine nitrogen, thus hindering the inclusion and the separation effect. This eventually led to poor separation of the enantiomers. While the pyrrolidone group in the Ph-OPr sample could also form a good inclusion complex with cyclodextrin, its higher polarity weakened the inclusion effect compared to that for benzene rings, thus leading to poor chirality separation results. For chiral lactides, the intrinsic recognition ability of CD was good only for the separation of some samples. In the separation of chiral ketones, large steric hindrance effect inhibited the intrinsic recognition ability of CD, and the separation effect of such samples on CSP1 was not ideal. External functional groups were required in some cases to further regulate the chiral recognition performance. The molecular structure of dansyl amino acids played an important role in the separation effect, in addition to the intrinsic recognition ability of CD. The number of side chains in the substituent also affected the quality of separation. Lengthening the side chain or increasing the hydrophobicity could effectively improve the separation efficiency. The separation effect of flavanone samples on CSP1 was ordinary. The substituent positions also affected the separation effect. In order to further explore the intrinsic recognition ability of CD, the functional triazole-bridged CD-CSP (CSP2) and imidazole-bridged CD-CSP (CSP3) (the surface CD loadings of CSP2 and CSP3 were 0.51 μmol/m² and 0.46 μmol/m², respectively) prepared earlier were selected and compared under the same chromatographic conditions. The results showed that the separation of the sample was related not only to the structure of the chiral medium but also to the structure of the sample molecules. Functional modification of the bridge arm could improve the selectivity of some enantiomers, but would also cause partial loss of the intrinsic chiral recognition ability of CD. For samples with the intrinsic recognition ability of CD to facilitate separation, no functional group had to be added to the bridge arm when designing a chiral medium. This study provides a useful reference for the design of CD-based CSPs.

Key words:

cyclodextrin
/ click chemistry
/ high performance liquid chromatography (HPLC)
/ chiral recognition

1. [1] Herrera B A, Bruna T C, Sierpe R A, et al. Carbohyd Polym, 2020:115865
2. [2] Wang Q, Liu Z X, Zhang Y M, et al. Science in China:Chemistry, 2019, 49(11):1343 王倩, 柳志学, 张瀛溟, 等. 中国科学:化学, 2019, 49(11):1343
3. [3] Zheng Z, Chen X J, Zhao L, et al. Chinese Journal of Chromatography, 2017, 35(3):286 郑振, 陈秀娟, 赵亮, 等. 色谱, 2017, 35(3):286
4. [4] Shuang Y Z, Wang H, Zhang T C, et al. Chinese Journal of Chromatography, 2020, 38(4):464 双亚洲, 王惠, 张天赐, 等. 色谱, 2020, 38(4):464
5. [5] Tang J, Pang L, Zhou J, et al. Anal Chim Acta, 2016, 946:96
6. [6] Chen J, Shi H. Chinese Journal of Chromatography, 2017, 35(12):1229 陈娇, 石浩. 色谱, 2017, 35(12):1229
7. [7] Fujimura K, Ueda T, Ando T. Anal Chem, 1983, 55(3):446
8. [8] Shuang Y, Liao Y, Wang H, et al. Chirality, 2020, 32(2):168
9. [9] He X L, Tan T W, Janson J C. Chinese Journal of Chromatography, 2003(6):610 贺湘凌, 谭天伟, Janson J C. 色谱, 2003(6):610
10. [10] Zhang L, Wong Y C, Chen L, et al. Tetrahedron Lett, 1999, 40(9):1815
11. [11] Li L, Zhang M, Wang Y, et al. J Sep Sci, 2016, 39(21):4136
12. [12] Wu Q, Dong S Q, Zhang X, et al. Chinese Journal of Analysis Laboratory, 2016, 35(4):492 武琪, 董树清, 张霞, 等. 分析试验室, 2016, 35(4):492
13. [13] Zhang Y, Guo Z, Ye J, et al. J Chromatogr A, 2008, 1191(1/2):188
14. [14] Guo Z, Jin Y, Liang T, et al. J Chromatogr A, 2009, 1216(2):257
15. [15] Ai F, Li L, Ng S C, et al. J Chromatogr A, 2010, 1217(48):7502
16. [16] Tang J, Zhang S, Lin Y, et al. Sci Rep-UK, 2015, 5:11523
17. [17] Lin Y, Zhou J, Tang J, et al. J Chromatogr A, 2015, 1406:342
18. [18] Tang X, Li X, Sun Y, et al. J Sep Sci, 2018, 41(13):2710
19. [19] Li M, De P, Gondi S R, et al. J Polym Sci Pol Chem, 2008, 46(15):5093
20. [20] Yao X, Tan T T Y, Wang Y. J Chromatogr A, 2014, 1326:80
21. [21] Yao X, Zheng H, Zhang Y, et al. Anal Chem, 2016, 88(9):4955
22. [22] Li X X.[MS Dissertation]. Tianjin:Tianjin University, 2018 李晓旋.[硕士学位论文]. 天津:天津大学, 2018
23. [23] Gong Y, Wang Y, Zhao W T, et al. J Chem Res, 2013, 37(8):499
24. [24] Gong J, Wan Q, Kang Q. Adv Synth Catal, 2018, 360(21):4031
25. [25] Gong J, Wan Q, Kang Q. Org Lett, 2018, 20(11):3354
26. [26] Martinelli J, Thangavel K, Tei L, et al. Chem-Eur J, 2014, 20(35):10944
27. [27] Wang Y, Chen H, Xiao Y, et al. Nat Protoc, 2011, 6(7):935
28. [28] Li X, Jin X, Yao X, et al. J Chromatogr A, 2016, 1467:279

扫一扫看文章

计量

PDF下载量: 6
文章访问数: 753
HTML全文浏览量: 103

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

基于环糊精本征识别能力的手性色谱介质点击制备及应用

通讯作者: 王勇, E-mail:wangyongtju@tju.edu.cn

English

Click preparation and application of chiral stationary phase based on intrinsic recognition ability of cyclodextrin

Corresponding author: WANG Yong, wangyongtju@tju.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

基于环糊精本征识别能力的手性色谱介质点击制备及应用

通讯作者: 王勇, E-mail:wangyongtju@tju.edu.cn

English

Click preparation and application of chiral stationary phase based on intrinsic recognition ability of cyclodextrin

Corresponding author: WANG Yong, wangyongtju@tju.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

文章相关

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs