Advertisement

Evaluation of an ionic liquid chiral selector based on clindamycin phosphate in capillary electrophoresis

  • Xiaofei Ma
  • Yingxiang DuEmail author
  • Xinqi Zhu
  • Zijie Feng
  • Cheng Chen
  • Jiangxia Yang
Research Paper
  • 15 Downloads

Abstract

Recently, increasing attention has been given to the research on chiral ionic liquids (CILs) in chiral separation field; however, only a few literatures focus on the exploration of CILs as the sole chiral selector. In this study, an ionic liquid chiral selector based on antibiotic, namely tetramethylammonium clindamycin phosphate (TMA-CP), was originally synthesized and subsequently utilized for enantioseparation in capillary electrophoresis (CE). Remarkably improved separations of eight racemic analytes were achieved in TMA-CP system in contrast to the clindamycin phosphate (CP) system. The optimal separation conditions were determinated by systematic experiments on several crucial parameters including the type and proportion of organic modifier, CIL concentration, buffer pH, and applied voltage. Additionally, molecular modeling with AutoDock was applied to probe into the chiral recognition mechanism of the ionic liquid chiral selectors, which well corresponded with the experimental results. It is the first time that antibiotic-based ionic liquid was exploited as favorable sole chiral selector in CE, and this strategy has paved a new way for development of novel ionic liquids chiral selectors based on antibiotics.

Graphical abstract

Keywords

Ionic liquids Clindamycin phosphate Capillary electrophoresis Enantioseparation Molecular docking 

Notes

Funding information

This work was supported by the Project of National Natural Science Foundation of China (No.: 81373378) and the Natural Science Foundation of Jiangsu Province (Program No.: BK20150697).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1967_MOESM1_ESM.pdf (771 kb)
ESM 1 (PDF 770 kb)

References

  1. 1.
    Zhang L, Song P, Long H, Meng M, Yin Y, Xi R. Magnetism based electrochemical immunosensor for chiral separation of amlodipine. Sensors Actuators B. 2017;248:682–9.CrossRefGoogle Scholar
  2. 2.
    Monica B, Gabriel H, Aura R, Melania C, Daniela L. Chirality of modern antidepressants: an overview. Adv Pharm Bull. 2017;7:495–500.CrossRefGoogle Scholar
  3. 3.
    Takeshi Y, Reiko Y, Satoshi N, Satoshi M, Ryoji F, Syun-ichi K. Synthesis of (S)-ketamine via [1,3]-chirality transfer of a stereocenter created by enantioselective aldol reaction. Bull Chem Soc Jpn. 2009;82:1528–32.CrossRefGoogle Scholar
  4. 4.
    Li L, Li X, Luo Q, You T. A comprehensive study of the enantioseparation of chiral drugs by cyclodextrin using capillary electrophoresis combined with theoretical approaches. Talanta. 2015;142:28–34.CrossRefGoogle Scholar
  5. 5.
    Maider G, Maria L, Maria C. Enantioseparation by capillary electrophoresis using ionic liquids as chiral selectors. Crit Rev Anal Chem. 2018;48:429–46.CrossRefGoogle Scholar
  6. 6.
    Li J, Du Y, Yu T, Liu Z, Feng Z, Yang X, et al. Synthesis and application of ionic liquid functionalized β-cyclodextrin, mono-6-deoxy-6-(4-amino-1,2,4-triazolium)-β-cyclodextrin chloride, as chiral selector in capillary electrophoresis. J Chromatogr A. 2018;1559:178–85.CrossRefGoogle Scholar
  7. 7.
    Tabani H, Mahyari M, Sahragard A, Fakhari AR, Shaabani A. Evaluation of sulfated maltodextrin as a novel anionic chiral selector for the enantioseparation of basic chiral drugs by capillary electrophoresis. Electrophoresis. 2015;36:305–11.CrossRefGoogle Scholar
  8. 8.
    Juan J, Yolanda M, Salvador S, Rosa M, Maria J. Fast enantiomeric separation of propranolol by affinity capillary electrophoresis using human serum albumin as chiral selector: application to quality control of pharmaceuticals. Anal Chim Acta. 2004;507:171–8.CrossRefGoogle Scholar
  9. 9.
    Lee T, Lee W, Hyun MH, Park JH. Enantioseparation of alpha-amino acids on an 18-crown-6-tetracarboxylic acid-bonded silica by capillary electrochromatography. J Chromatogr A. 2010;1217:1425–8.CrossRefGoogle Scholar
  10. 10.
    Tran CD, Mejac I. Chiral ionic liquids for enantioseparation of pharmaceutical products by capillary electrophoresis. J Chromatogr A. 2008;1204:204–9.CrossRefGoogle Scholar
  11. 11.
    Zhang Q, Qi X, Feng C, Tong S, Rui M. Three chiral ionic liquids as additives for enantioseparation in capillary electrophoresis and their comparison with conventional modifiers. J Chromatogr A. 2016;1462:146–52.CrossRefGoogle Scholar
  12. 12.
    Daniel W, Kimber L, Jing-ran C. Evaluation of the macrocyclic antibiotic vancomycin as a chiral selector for capillary electrophoresis. Chirality. 1994;6:496–509.CrossRefGoogle Scholar
  13. 13.
    Timothy J, Alton B. Chiral separations using the macrocyclic antibiotics: a review. J Chromatogr A. 2001;906:73–89.CrossRefGoogle Scholar
  14. 14.
    Shuchi D, Jung H. Penicillin G as a novel chiral selector in capillary electrophoresis. J Chromatogr A. 2014;1326:134–8.CrossRefGoogle Scholar
  15. 15.
    Dixit S, Park JH. Application of rifampicin as a chiral selector for enantioresolution of basic drugs using capillary electrophoresis. J Chromatogr A. 2016;1453:138–42.CrossRefGoogle Scholar
  16. 16.
    Prokhorova AF, Shapovalova EN, Shpak AV, Staroverov SM, Shpigun OA. Enantiorecognition of profens by capillary electrophoresis using a novel chiral selector eremomycin. J Chromatogr A. 2009;1216:3674–7.CrossRefGoogle Scholar
  17. 17.
    Margarita V, Aleksandra F, Elena N, Oleg A. Clarithromycin as a chiral selector for enantioseparation of basic compounds in nonaqueous capillary electrophoresis. Electrophoresis. 2014;35:2759–64.CrossRefGoogle Scholar
  18. 18.
    Pandey S. Analytical applications of room-temperature ionic liquids: a review of recent efforts. Anal Chim Acta. 2006;556:38–45.CrossRefGoogle Scholar
  19. 19.
    Martina M, Clarence C, Francesco D, Frederic L, Jean M, Evelina C. Poly(ethylene glycol)-based ionic liquids: properties and uses as alternative solvents in organic synthesis and catalysis. ChemPubSoc Europe. 2014;7:45–65.Google Scholar
  20. 20.
    Garcíaalvarezcoque MC, Ruizangel MJ, Berthod A, Carda-Broch S. On the use of ionic liquids as mobile phase additives in high-performance liquid chromatography. A review. Anal Chim Acta. 2015;883:1–21.CrossRefGoogle Scholar
  21. 21.
    González ML, González-Álvarez J, Fernández GC, Arias-Abrodo P, Altava B, Luis SV, et al. Gas chromatographic analysis of fatty acid methyl esters of milk fat by an ionic liquid derived from L-phenylalanine as the stationary phase. Talanta. 2015;143:212–8.CrossRefGoogle Scholar
  22. 22.
    Jin Y, Chen C, Meng L, Chen J, Li M, Zhu Z. Simultaneous and sensitive capillary electrophoretic enantioseparation of three β-blockers with the combination of achiral ionic liquid and dual CD derivatives. Talanta. 2012;89:149–54.CrossRefGoogle Scholar
  23. 23.
    Wu D, Yin Q, Cai P, Zhao X, Pan Y. Enhancement of visual chiral sensing via an anion-binding approach: novel ionic liquids as the chiral selectors. Anal Chim Acta. 2017;962:97–103.CrossRefGoogle Scholar
  24. 24.
    Li L, Wu C, Ma Y, Zhou S, Li Z, Sun T. Effectively enhancing the enantioseparation ability of β-cyclodextrin derivatives by de novo design and molecular modeling. Analyst. 2017;142:3699–706.CrossRefGoogle Scholar
  25. 25.
    Minji K, Jung H. Enantioseparation of chiral acids and bases on a clindamycin phosphate-modified zirconia monolith by capillary electrochromatography. J Chromatogr A. 2012;1251:244–8.CrossRefGoogle Scholar
  26. 26.
    Xu G, Du Y, Du F, Chen J, Yu T, Zhang Q, et al. Establishment and evaluation of the novel tetramethylammonium-L-hydroxyproline chiral ionic liquid synergistic system based on clindamycin phosphate for enantioseparation by capillary electrophoresis. Chirality. 2015;27:598–604.CrossRefGoogle Scholar
  27. 27.
    Sun X, Liu K, Du Y, Liu J, Ma X. Investigation of the enantioselectivity of tetramethylammonium-lactobionate chiral ionic liquid based dual selector systems toward basic drugs in capillary electrophoresis. Electrophoresis. 2019.  https://doi.org/10.1002/elps.201800422.
  28. 28.
    Morris GM, Ruth H, Lindstrom W, Sanner MF, Belew RK, Goodseli DS, et al. Software news and updates AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009;30:2785–91.CrossRefGoogle Scholar
  29. 29.
    Ravichandran S, Collins JR, Singh N, Wainer IW. A molecular model of the enantioselective liquid chromatographic separation of (R,S)-ifosfamide and its N-dechloroethylated metabolites on a teicoplanin aglycon chiral stationary phase. J Chromatogr A. 2012;1269:218–25.CrossRefGoogle Scholar
  30. 30.
    Yee P, Shah JK, Maginn EJ. State of hydrophobic and hydrophilic ionic liquids in aqueous solutions: are the ions fully dissociated? J Phys Chem B. 2013;117:12556–66.CrossRefGoogle Scholar
  31. 31.
    Wang H, Wang J, Zhang S, Pei Y, Zhuo K. Ionic association of the ionic liquids [C4mim][BF4], [C4mim][PF6], and [Cnmim]Br in molecular solvents. Chemphyschem. 2009;10:2516–23.CrossRefGoogle Scholar
  32. 32.
    Zhang J, Du Y, Zhang Q, Lei Y. Evaluation of vancomycin-based synergistic system with amino acid ester chiral ionic liquids as additives for enantioseparation of non-steroidal anti-inflammatory drugs by capillary electrophoresis. Talanta. 2014;119:193–201.CrossRefGoogle Scholar
  33. 33.
    Jiang J, Mu X, Qiao J, Su Y, Qi L. New chiral ligand exchange capillary electrophoresis system with chiral amino amide ionic liquids as ligands. Talanta. 2017;175:451–6.CrossRefGoogle Scholar
  34. 34.
    Bezhan C, Wolfgang L, Gerhard K. Enantiomer separations in capillary electrophoresis in the case of equal binding constants of the enantiomers with a chiral selector: commentary on the feasibility of the concept. Anal Chem. 2004;76:4256–60.CrossRefGoogle Scholar
  35. 35.
    Nascimento CS, Lopes JF, Guimarães L, Borges KB. Molecular modeling study of the recognition mechanism and enantioseparation of 4-hydroxypropranolol by capillary electrophoresis using carboxymethyl-β-cyclodextrin as the chiral selector. Analyst. 2014;139:3901–10.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education)China Pharmaceutical UniversityNanjingChina
  2. 2.State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjingChina

Personalised recommendations