利用非共价复合物实现对布洛芬分子的手性分析

引用本文: 古连城, 周爱南, 陈新, 吴芳玲, 李建其, 余绍宁, 周鸣飞, 丁传凡. 利用非共价复合物实现对布洛芬分子的手性分析[J]. 分析化学, 2021, 49(1): 95-102. doi: 10.19756/j.issn.0253-3820.201477 shu

Citation: GU Lian-Cheng, ZHOU Ai-Nan, CHEN Xin, WU Fang-Ling, LI Jian-Qi, YU Shao-Ning, ZHOU Ming-Fei, DING Chuan-Fan. Chiral Analysis of Ibuprofen through Non-covalent Complexes[J]. Chinese Journal of Analytical Chemistry, 2021, 49(1): 95-102. doi: 10.19756/j.issn.0253-3820.201477 shu

利用非共价复合物实现对布洛芬分子的手性分析

古连城 ^1, ,
周爱南 ^2, ,
陈新 ^1, ,
吴芳玲 ^3, ,
李建其 ^{2,
,} ,
余绍宁 ^3, ,
周鸣飞 ^1, ,
丁传凡 ^{3,
,}

1.
复旦大学化学系, 上海 200438;
2.
上海医药工业研究院, 上海 200040;
3.
宁波大学材料科学与化学工程学院, 质谱技术与应用研究院, 宁波 315211

通讯作者: 李建其,E-mail:lijianqb@126.com; 丁传凡,E-mail:dingchuanfan@nbu.edu.cn

基金项目:
国家自然科学基金项目（Nos.21773035，21803013）资助。

摘要: 手性药物的检测对于深入了解药物作用机理具有十分重要的意义。布洛芬（Ibuprofen）是常用的临床消炎药物，具有R型和S型两种构型，但其消炎作用却几乎全部由S-布洛芬所提供。本研究建立了一种区分布洛芬手性的方法，将布洛芬对映体与γ-环糊精及BaCl₂混合，得到系列非共价复合物，利用捕集离子淌度质谱（Trapped ion mobility spectrometry-time-of-flight mass spectrometry，TIMS-TOF MS）测量各物质的离子淌度（Ion moboility）。采用TIMS-TOF MS成功分离了非对映体离子[γ-CD+R-Ibuprofen+Ba（BaCl）-H]²⁺与[γ-CD+S-Ibuprofen+Ba（BaCl）-H]²⁺，碰撞截面的差值高达0.07 nm²。此外，实验结果表明，一系列[γ-CD+S-Ibuprofen+Ba（BaCl）-H]²⁺的离子淌度谱峰强度分数与其摩尔分数呈线性关系。本方法无需对样品分子进行前处理或化学衍生化，可以快速、高效地分析手性分子。

关键词:

English

Chiral Analysis of Ibuprofen through Non-covalent Complexes

1.
Department of Chemistry, Fudan University, Shanghai 200433, China;
2.
Shanghai Institute of Pharmaceutical Industry, Shanghai 200240, China;
3.
School of Material Science and Chemical Engineering, Institute of Mass Spectrometry, Ningbo University, Ningbo 315211, China

Corresponding author: LI Jian-Qi, ; DING Chuan-Fan,

Received Date: 07 August 2020
Revised Date: 13 November 2020
Fund Project:
Supported by the National Natural Science Foundation of China (Nos.21773035, 21803013).

Abstract: The recognition and discrimination of chirality is of great significance for further understanding the pharmaceutical mechanism of chiral drugs. Ibuprofen is a well-popular clinically used anti-inflammatory drug in the world. However, in R-ibuprofen and S-ibuprofen enantiomers, only S-ibuprofen is responsible for the anti-inflammatory effects. In this work, a novel discrimination method for chiral ibuprofen was investigated. A stoichiometric R- and S-Ibuprofen were mixed with γ-cyclodextrin and barium chloride to obtain the noncovalent complexes in methanol aqueous solution, and the ion mobility of the complexes was measured by trapped ion mobility spectrometry-time-of-flight mass spectrometry (TIMS-TOF-MS). The formed diastereomeric ions of[γ-CD+R-ibuprofen+Ba(BaCl)-H]²⁺ and[γ-CD+S-ibuprofen+Ba(BaCl)-H]²⁺ were successfully separated in ion mobility spectra and the collision cross section difference (ΔCCS) reached 0.07 nm².Additionally, the experimental data indicated that the fractions of mobility peak intensities for[γ-CD+S-ibuprofen+Ba(BaCl)-H]²⁺ and their molar fractions exhibited a great linear relationship. Due to that no complicate pre-treatment or chemical derivation was needed, this method could discriminate chiral molecules rapidly and efficiently.

Key words:

Ibuprofen
/ γ-Cyclodextrins
/ Barium chloride
/ Non-covalent complex
/ Chiral analysis
/ Trapped ion mobility spectrometry-time-of-flight mass spectrometry

1. [1]
  HARE P, GILAV E. Science, 1979, 204(4398):1226-1228.
2. [2]
  GLAVIN D P, BURTON A S, ELSILA J E, APONTE J C, DWORKIN J P. Chem. Rev., 2020, 120(11):4660-4689.
3. [3]
  BOESL U, KARTOUZIAN A. Annu. Rev. Anal. Chem., 2016, 9(18):343-364.
4. [4]
  ROCCO A, ATURKI Z, FANALI S. TrAC-Trends Anal.Chem., 2013, 52:206-225.
5. [5]
  CHOUINARD C D, NAGY G, WEBB I K, GARIMELLA S V, BAKER E S, IBRAHIM Y M, SMITH R D. Anal. Chem., 2018, 90(18):11086-11091.
6. [6]
  WNENDT S, ZWINGENBERGER K. Nature, 1997, 385(6614):303-304.
7. [7]
  TAO W A, GOZZO F C, COOKS R G. Anal. Chem., 2001, 73(8):1692-1698.
8. [8]
  NGUYEN L A, HE H, PHAM-HUY C. Int. J. Biomed. Sci., 2006, 2(2):85-100.
9. [9]
  SANGANYADO E, LU Z, FU Q, SCHLENK D, GAN J. Water Res., 2017, 124:527-542.
10. [10]
  IZQUIERDO S, AGUILERA J, BUSCHMANN H H, GARCÍA M, TORRENS A, ORTUÑO R M. Tetrahedron:Asymmetry, 2008, 19(6):651-653.
11. [11]
  HAN D Q, YAO Z P. TrAC-Trends Anal. Chem., 2020, 123:115763.
12. [12]
  SCRIBA G K. Chromatographia, 2012, 75(15-16):815-838.
13. [13]
  SCRIBA G K. TrAC-Trends Anal. Chem., 2019, 119:115628.
14. [14]
  XU Xu, CHEN Gang, LIU Hao. Chin. J. Chromatogr., 2020, 38(10):1154-1169. 许旭, 陈钢, 刘浩. 色谱, 2020, 38(10):1154-1169.
15. [15]
  ZHANG J T, WANG H Y, ZHANG X, ZHANG F, GUO Y L. Catal. Sci. Technol., 2016, 6(17):6637-6643.
16. [16]
  RAINSFORD K. Inflammopharmacology, 2009, 17(6):275-342.
17. [17]
  CARVALHO P, CASS Q, CALAFATTI S, CONTESINI F, BIZACO R. Braz. J. Chem. Eng., 2006, 23(3):291-300.
18. [18]
  PÉREZ-MÍGUEZ R, BRUYNEEL B, CASTRO-PUYANA M, MARINA M L, SOMSEN G W, DOMÍNGUEZ-VEGA E. Anal. Chem., 2019, 91(5):3277-3285.
19. [19]
  BHUSHAN R, BRVCKNER H. Amino acids, 2004, 27(3-4):231-247.
20. [20]
  AYON N J, SHARMA A D, GUTHEIL W G. J. Am. Soc. Mass Spectrom., 2018, 30(3):448-458.
21. [21]
  SZABÓ Z I, SZÖCS L, HORVÁTH P, KOMJÁTI B, NAGY J, JÁNOSKA Á, MUNTEAN D L, NOSZÁL B, TÓTH G. J. Sep. Sci., 2016, 39(15):2941-2949.
22. [22]
  LI J, LIU R, WANG L, LIU X, GAO H. Chirality, 2019, 31(3):236-247.
23. [23]
  LV Na, ZHENG Yong-Yong, LI Jian-Qi, PAN Ting-Ting, CHU Yan-Qiu, ZHOU Ming-Fei, DING Chuan-Fan. Chin. J. Anal. Chem., 2009, 37(2):199-204. 吕娜, 郑永勇, 李建其, 潘婷婷, 储艳秋, 周鸣飞, 丁传凡. 分析化学, 2009, 37(2):199-204.
24. [24]
  SZEJTLI J. Chem. Rev., 1998, 98(5):1743-1754.
25. [25]
  CRINI G. Chem. Rev., 2014, 114(21):10940-10975.
26. [26]
  LEBRILLA C B. Acc. Chem. Res., 2001, 34(8):653-661.
27. [27]
  RAMIREZ J, AHN S, GRIGOREAN G, LEBRILLA C B. J. Am. Chem. Soc., 2000, 122(29):6884-6890.
28. [28]
  FERNANDEZ-LIMA F, KAPLAN D, PARK M. Rev. Sci. Instrum., 2011, 82(12):126106.
29. [29]
  RIDGEWAY M E, LUBECK M, JORDENS J, MANN M, PARK M A. Int. J. Mass spectrom., 2018, 425(22-35):22-35.
30. [30]
  HERNANDEZ D R, DEBORD J D, RIDGEWAY M E, KAPLAN D A, PARK M A, FERNANDEZ-LIMA F. Analyst, 2014, 139(8):1913-1921.
31. [31]
  DOMALAIN V, TOGNETTI V, HUBERT-ROUX M, LANGE C M, JOUBERT L, BAUDOUX J, ROUDEN J, AFONSO C. J. Am. Soc. Mass Spectrom., 2013, 24(9):1437-1445.
32. [32]
  HADAVI D, DE LANGE E, JORDENS J, MENGERINK YNZE, CUYCKENS F, HONING M. Rapid Commun. Mass Spectrom., 2019, 33(49-59):49-59.
33. [33]
  DODDS J N, MAY J C, MCLEAN J A. Anal. Chem., 2017, 89(1):952-959.
34. [34]
  DODDS J N, MAY J C, MCLEAN J A. Anal. Chem., 2017, 89(22):12176-12184.

扫一扫看文章

计量

PDF下载量: 17
文章访问数: 1943
HTML全文浏览量: 484

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

利用非共价复合物实现对布洛芬分子的手性分析

通讯作者: 李建其,E-mail:lijianqb@126.com; 丁传凡,E-mail:dingchuanfan@nbu.edu.cn

English

Chiral Analysis of Ibuprofen through Non-covalent Complexes

Corresponding author: LI Jian-Qi, ; DING Chuan-Fan,

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

利用非共价复合物实现对布洛芬分子的手性分析

通讯作者: 李建其,E-mail:lijianqb@126.com; 丁传凡,E-mail:dingchuanfan@nbu.edu.cn

English

Chiral Analysis of Ibuprofen through Non-covalent Complexes

Corresponding author: LI Jian-Qi, ; DING Chuan-Fan,

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