Skip to main content
SpringerLink
Log in

Study of the enantioselectivity and recognition mechanism of chiral dual system based on chondroitin sulfate D in capillary electrophoresis

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Several chiral reagents including cyclodextrins (CDs) and derivatives, crown ethers, proteins, chiral surfactants, and polymers have been involved in dual-selector systems for enantioseparation of a series of compounds by capillary electrophoresis (CE). In this paper, chondroitin sulfate D-based dual-selector system (CSD/CM-β-CD) was firstly established and investigated for the enantioseparation of six basic racemic drugs in capillary electrophoresis. Compared to the single-selector systems, synergistic effect and significantly improved separations for all tested analytes were observed in CSD/CM-β-CD system. The effect of several parameters, such as buffer pH, chiral selector concentration, and applied voltage, was systematically optimized. Meanwhile, to investigate the possible chiral recognition mechanisms in CSD/CM-β-CD synergistic system, we tried to apply the molecular docking method to simulate the host-guest binding procedures of the polysaccharide-based dual system for the first time. The difference in binding free energy was found to correspond to the chiral selectivity factor. The existence of CSD-CM-β-CD complex may give rise to a higher discriminatory ability against the enantiomers, indicating the synergistic effect in CSD/CM-β-CD system.

ᅟ

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Horvâth C, Nikelly JG. Capillary electrophoresis and chromatography[J]. Anal Chem. 1990;62(20).

  2. Wang Z, Ouyang J, Baeyens WRG. Recent developments of enantioseparation techniques for adrenergic drugs using liquid chromatography and capillary electrophoresis: a review [J]. J Chromatogr B Anal Technol Biomed Life Sci. 2008;862(1):1–14.

    Article  CAS  Google Scholar 

  3. Du YX, Honda S, Taga A, et al. A novel polybrene/chondroitin sulfate C double coated capillary and its application in capillary electrophoresis [J]. Chin J Chem. 2002;20(12):1557–65.

    Article  CAS  Google Scholar 

  4. Chen B, Du Y. Evaluation of the enantioseparation capability of the novel chiral selector clindamycin phosphate towards basic drugs by micellar electrokinetic chromatography [J]. J Chromatogr A. 2010;1217(11):1806–12.

    Article  CAS  PubMed  Google Scholar 

  5. Cucinotta V, Contino A, Giuffrida A, et al. Application of charged single isomer derivatives of cyclodextrins in capillary electrophoresis for chiral analysis [J]. J Chromatogr A. 2010;1217(7):953–67.

    Article  CAS  PubMed  Google Scholar 

  6. Escuder-Gilabert L, Martín-Biosca Y, Medina-Hernández MJ, et al. Cyclodextrins in capillary electrophoresis: recent developments and new trends [J]. J Chromatogr A. 2014;1357:2–23.

    Article  CAS  PubMed  Google Scholar 

  7. Saz JM, Marina ML. Recent advances on the use of cyclodextrins in the chiral analysis of drugs by capillary electrophoresis [J]. J Chromatogr A. 2016;1467:79–94.

    Article  CAS  PubMed  Google Scholar 

  8. Zhu F, Du Y, Chen J, et al. Enantioselective separation of basic drugs by CE with polygalacturonic acid as a novel chiral selector [J]. Chromatographia. 2009;69(11–12):1315–20.

    Article  CAS  Google Scholar 

  9. Yang F, Du Y, Chen B, et al. Enantiomeric separation of nefopam hydrochloride by affinity electrokinetic chromatography using chondroitin sulfate A as chiral selector and its chiral recognition mechanism [J]. Chromatographia. 2010;72(5–6):489–93.

    Article  CAS  Google Scholar 

  10. Tabani H, Fakhari AR, Nojavan S. Maltodextrins as chiral selectors in CE: molecular structure effect of basic chiral compounds on the enantioseparation [J]. Chirality. 2014;26(10):620–8.

    Article  CAS  PubMed  Google Scholar 

  11. Jang J, Cho SI, Chung DS. Comparative studies of various run buffers for chiral capillary electrophoresis using chiral crown ether as a chiral selector [J]. Electrophoresis. 2001;22(20):4362–7.

    Article  CAS  PubMed  Google Scholar 

  12. Kakhki RM, Assadi H. Capillary electrophoresis analysis based on crown ethers [J]. J Incl Phenom Macrocycl Chem. 2015;81(1–2):1–12.

    Article  CAS  Google Scholar 

  13. Yu T, Du Y, Chen B. Evaluation of clarithromycin lactobionate as a novel chiral selector for enantiomeric separation of basic drugs in capillary electrophoresis [J]. Electrophoresis. 2011;32(14):1898–905.

    Article  CAS  PubMed  Google Scholar 

  14. Greño M, Castro-Puyana M, Ángeles García M, et al. Analysis of antibiotics by CE and CEC and their use as chiral selectors: an update [J]. Electrophoresis. 2017.

  15. Chen J, Du Y, Zhu F, et al. Evaluation of the enantioselectivity of glycogen-based dual chiral selector systems towards basic drugs in capillary electrophoresis [J]. J Chromatogr A. 2010;1217(45):7158–63.

    Article  CAS  PubMed  Google Scholar 

  16. Müllerová L, Dubský P, Gaš B. Twenty years of development of dual and multi-selector models in capillary electrophoresis: a review [J]. Electrophoresis. 2014;35(19):2688–700.

    Article  CAS  PubMed  Google Scholar 

  17. Chen J, Du Y, Zhu F, et al. Study of the enantioseparation capability of chiral dual system based on chondroitin sulfate C in CE [J]. Electrophoresis. 2015;36(4):607–14.

    Article  CAS  PubMed  Google Scholar 

  18. Su Y, Mu X, Qi L. Development of a capillary electrophoresis system with Mn (II) complexes and β-cyclodextrin as the dual chiral selectors for enantioseparation of dansyl amino acids and its application in screening enzyme inhibitors [J]. RSC Adv. 2015;5(36):28762–8.

    Article  CAS  Google Scholar 

  19. Zhang Y, Du S, Feng Z, et al. Evaluation of synergistic enantioseparation systems with chiral spirocyclic ionic liquids as additives by capillary electrophoresis [J]. Anal Bioanal Chem. 2016;408(10):2543–55.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Q, Du Y, Chen J, et al. Investigation of chondroitin sulfate D and chondroitin sulfate E as novel chiral selectors in capillary electrophoresis [J]. Anal Bioanal Chem. 2014;406(5):1557–66.

    Article  CAS  PubMed  Google Scholar 

  21. Park KL, Kim KH, Jung SH, et al. Enantioselective stabilization of inclusion complexes of metoprolol in carboxymethylated β-cyclodextrin [J]. J Pharm Biomed Anal. 2002;27(3):569–76.

    Article  CAS  PubMed  Google Scholar 

  22. Faucci MT, Melani F, Mura P. Computer-aided molecular modeling techniques for predicting the stability of drug–cyclodextrin inclusion complexes in aqueous solutions [J]. Chem Phys Lett. 2002;358(5):383–90.

    Article  CAS  Google Scholar 

  23. Bikádi Z, Fodor G, Hazai I, et al. Molecular modeling of enantioseparation of phenylazetidin derivatives by cyclodextrins [J]. Chromatographia. 2010;71(1):21–8.

    Article  CAS  Google Scholar 

  24. Shi J, Ding Z, Hu Y. Theoretical study on chiral recognition mechanism of methyl mandelate enantiomers on permethylated β-cyclodextrin [J]. J Mol Model. 2012;18(2):803–13.

    Article  CAS  PubMed  Google Scholar 

  25. Lavecchia A, Cosconati S, Novellino E, et al. Exploring the molecular basis of the enantioselective binding of penicillin G acylase towards a series of 2-aryloxyalkanoic acids: a docking and molecular dynamics study [J]. J Mol Graph Model. 2007;25(6):773–83.

    Article  CAS  PubMed  Google Scholar 

  26. Bednarek E, Bocian W, Michalska K. NMR and molecular modeling study, as complementary techniques to capillary electrophoresis method to elucidate the separation mechanism of linezolid enantiomers [J]. J Chromatogr A. 2008;1193(1):164–71.

    Article  CAS  PubMed  Google Scholar 

  27. Elbashir AA, Suliman FEO. Computational modeling of capillary electrophoretic behavior of primary amines using dual system of 18-crown-6 and β-cyclodextrin [J]. J Chromatogr A. 2011;1218(31):5344–51.

    Article  CAS  PubMed  Google Scholar 

  28. Suliman FEO, Elbashir AA. Enantiodifferentiation of chiral baclofen by β-cyclodextrin using capillary electrophoresis: a molecular modeling approach [J]. J Mol Struct. 2012;1019:43–9.

    Article  CAS  Google Scholar 

  29. Li W, Liu C, Tan G, et al. Molecular modeling study of chiral separation and recognition mechanism of β-adrenergic antagonists by capillary electrophoresis [J]. Int J Mol Sci. 2012;13(1):710–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Issaraseriruk N, Shitangkoon A, Aree T. Molecular docking study for the prediction of enantiodifferentiation of chiral styrene oxides by octakis (2, 3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-γ-cyclodextrin [J]. J Mol Graph Model. 2010;28(6):506–12.

    Article  CAS  PubMed  Google Scholar 

  31. Melani F, Pasquini B, Caprini C, et al. Combination of capillary electrophoresis, molecular modeling and NMR to study the enantioselective complexation of sulpiride with double cyclodextrin systems [J]. J Pharm Biomed Anal. 2015;114:265–71.

    Article  CAS  PubMed  Google Scholar 

  32. Armstrong DW. Separation of enantiomers by capillary electrophoresis using pentosan polysulfate [J]. Electrophoresis. 1999;20:162–70.

    Article  PubMed  Google Scholar 

  33. Feng L, Fawaz R, Hovde S, et al. Crystal structures of Escherichia coli branching enzyme in complex with cyclodextrins [J]. Acta Crystallogr D. 2016;72(5):641–7.

    Article  CAS  Google Scholar 

  34. Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility [J]. J Comput Chem. 2009;30(16):2785–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. M.F. Sanner, R. Huey, S. Dallakyan, S. Karnati, W. Lindstrom, G.M. Morris, B. Norledge, A. Omelchenko, D. Stoffler, G. Vareille. AutoDockTools, Version 1.4.5, The Scripps Research Institute, La Jolla, CA, USA, 2007.

  36. Ravichandran S, Collins JR, Singh N, et al. 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]. J Chromatogr A. 2012;1269:218–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang X, Wang J, Hong C, et al. Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents [J]. Acta Pharmacol Sin. 2015;5(1):67–73.

    Article  Google Scholar 

  38. Németh K, Tárkányi G, Varga E, et al. Enantiomeric separation of antimalarial drugs by capillary electrophoresis using neutral and negatively charged cyclodextrins [J]. J Pharm Biomed Anal. 2011;54(3):475–81.

    Article  CAS  PubMed  Google Scholar 

  39. Fang L, Du Y, Hu X, et al. Carboxymethyl β-cyclodextrin as chiral selector in capillary electrophoresis: enantioseparation of 16 basic chiral drugs and its chiral recognition mechanism associated with drugs' structural features [J]. Biomed Chromatogr. 2017;31

Download references

Funding

This work was supported by the Project of National Natural Science Foundation of China (No.: 81072610), the Natural Science Foundation of Jiangsu Province (Program No.: BK20150697), and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Author information

Authors and Affiliations

  1. Department of Analytical Chemistry, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, 210009, Jiangsu, China

    Xuan Yang, Zhi Yan, Tao Yu, Yingxiang Du, Jiaquan Chen, Zongran Liu & Ying Xi

  2. Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, 210009, Jiangsu, China

    Yingxiang Du

  3. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China

    Yingxiang Du

Authors
  1. Xuan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yingxiang Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiaquan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zongran Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ying Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yingxiang Du.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, X., Yan, Z., Yu, T. et al. Study of the enantioselectivity and recognition mechanism of chiral dual system based on chondroitin sulfate D in capillary electrophoresis. Anal Bioanal Chem 410, 5889–5898 (2018). https://doi.org/10.1007/s00216-018-1208-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-018-1208-2

Keywords

Search

Navigation