Skip to main content
SpringerLink
Log in

β-Cyclodextrin functionalized ionic liquid as chiral stationary phase of high performance liquid chromatography for enantioseparation of β-blockers

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Two covalently bonded β-Cyclodextrin (β-CD) based CSPs were prepared by immobilizing the native β-CD and mono-6-deoxy-6-(3-benzylimidazolium tosylate)-β-CD (β-CD-BIMOTs) onto modified silica gel. β-CD-BIMOTs is a β-CD based CSP with ionic liquid (3-benzylimidazolium tosylate) substituent. The enantioseparation capability of the synthesized CSPs was examined using 4 racemic mixtures of β-blockers (propranolol, metoprolol, pindolol and atenolol). The results indicated that β-CD-BIMOTs based CSP afforded more favorable enantioseparations than native β-CD based CSP. In order to study the mechanism of enantioseparation, inclusion complexes β-CD-BIMOTs and β-blockers were prepared and these inclusion complexes were characterized by using 1H NMR and NOESY. In addition, the separation conditions such as pH and composition of mobile phase were varied to study the role of β-CD and ionic liquid in enantioseparation. In general, it can be concluded that the complete enantioseparation of propranolol and metoprolol is achieved through the formation of inclusion complex with β-CD-BIMOTs and the formation π-π interaction with the ionic liquid moiety of β-CD-BIMOTs. The result also showed the poor enantioseparation of pindolol and atenolol on the β-CD-BIMOTs based CSP due to the strong interaction at the exterior torus of β-CD-BIMOTs.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Mehvar, R., Brocks, D.R.: Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans. J. Pharm. Pharm. Sci. 4, 185–200 (2001)

    CAS  Google Scholar 

  2. Wilson, A.G., Brooke, O.G., Lloyd, H.J., Robinson, B.F.: Mechanism of action of β-adrenergic receptor blocking agents in angina pectoris: comparison of action of propranolol with dexpropranolol and practolol. Br. Med. J. 4, 399–401 (1969)

    Article  CAS  Google Scholar 

  3. Borchard, U.: Pharmacological properties of beta-adrenoceptor blocking drugs. J. Clin. Bas. Cardiol. 1, 5–9 (1998)

    CAS  Google Scholar 

  4. Hoffman, B.B.: Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists, The pharmacological basis of therapeutics (1996)

  5. Armstrong, D.W.: Direct enantiomeric separations in liquid chromatography and gas chromatography. In: Issaq, H.J. (ed.) A Century of Separation Science, pp. 555–578. Marcel Dekker, New York (2002)

    Google Scholar 

  6. Stoschitzky, K., Lindner, W., Zernig, G.: Racemic beta-blockers-fixed combinations of different drugs. J. Clin. Bas. Cardiol. 1, 15–19 (1998)

    Google Scholar 

  7. Hedeland, M., Isaksson, R., Pettersson, C.: Cellobiohydrolase I as a chiral additive in capillary electrophoresis and liquid chromatography. J. Chromatogr. A 807, 297–305 (1998)

    Article  CAS  Google Scholar 

  8. Aboul-Enein, H.Y., Abou-Basha, L.I.: HPLC separation of nadolol and enantiomers on chiralcel OD column. J. Liq. Chrom. Rel. Techno. 19, 383–392 (1996)

    Article  Google Scholar 

  9. Armstrong, D.W., DeMond, W.: Cyclodextrin bonded phases for the liquid chromatographic separation of optical, geometrical, and structural isomers. J. Chromatogr. Sci. 22, 411–415 (1984)

    Article  CAS  Google Scholar 

  10. Armstrong, D.W., Ward, T.J., Armstrong, R.D., Beesley, T.E.: Separation of drug stereoisomers by the formation of beta-cyclodextrin inclusion complexes. Science 232, 1132–1135 (1986)

    Article  CAS  Google Scholar 

  11. Stalcup, A.M., Chang, S.C., Armstrong, D.W., Pitha, J.: (S)-2-Hydroxyprophyl-β-cyclodextrin, a new chiral stationary phase for reversed-phase liquid chromatography. J. Chromatogr. A 513, 181–194 (1990)

    Article  CAS  Google Scholar 

  12. Armstrong, D.W., Stalcup, A.M., Hilton, M.L., Duncan, J.D., Faulkner Jr., J.R., Chang, S.C.: Separation of metallocene enantiomers by liquid chromatography: chiral recognition via cyclodextrin bonded phases. Anal. Chem. 57, 481–484 (1985)

    Article  CAS  Google Scholar 

  13. Scriba, G.K., Altria, K.: Using cyclodextrins to achieve chiral and non-chiral separations in capillary electrophoresis. LC GC EUROPE. 22, 420 (2009)

    CAS  Google Scholar 

  14. Hinze, W.L., Riehl, T.E., Armstrong, D.W., Demond, W., Alak, A., Ward, T.: Liquid chromatography separation of enantiomers using a chiral β-cyclodextrin bonded stationary phase and conventional aqueous-organic mobile phase. Anal. Chem. 57, 237–242 (1985)

    Article  CAS  Google Scholar 

  15. Daffe, V., Fastrez, J.: Cyclodextrin-catalysed hydrolysis of oxazol-5(4H)-ones. Enantioselectivity of the acid-base and ring-opening reactions. J. Chem. Soc. Perkin Trans. 2, 789–796 (1983)

    Article  Google Scholar 

  16. Juvancz, Z., Szejtli, J.: The role of cyclodextrins in chiral selective chromatography. Trends Anal. Chem. 21, 379–388 (2002)

    Article  CAS  Google Scholar 

  17. Szejtli, J.: Medicinal applications of cyclodextrins. Med. Res. Rev. 14, 353–386 (1994)

    Article  CAS  Google Scholar 

  18. Wang, Y., Young, D.J., Tan, T.T.Y., Ng, S.C.: “Click” immobilized perphenylcarbamated and permethylated cyclodextrin stationary phases for chiral high-performance liquid chromatography application. J. Chromatogr. A 1217, 5103–5108 (2010)

    Article  CAS  Google Scholar 

  19. Poon, Y.F., Muderawan, I.W., Ng, S.C.: Synthesis and application of mono-2 A-azido-2 A-deoxyperphenylcarbamoylated β-cyclodextrin and mono-2 A-azido-2 A-deoxyperacetylated β-cyclodextrin as chiral stationary phases for high-performance liquid chromatography. J. Chromatogr. A 1101, 185–197 (2006)

    Article  CAS  Google Scholar 

  20. Ahuja, S.: Chiral Separations by Chromatography. American Chemical Society, Oxford University Press, Oxford (2000)

    Google Scholar 

  21. Zhou, Z., Li, X., Chen, X.: Synthesis of ionic liquids functionalized β-cyclodextrin-bonded chiral stationary phases and their applications in high-performance liquid chromatography. Anal. Chim. Acta 678, 208–214 (2010)

    Article  CAS  Google Scholar 

  22. Wang, R.Q., Ong, T.T., Ng, S.C.: Chemically bonded cationic β-cyclodextrin derivatives as chiral stationary phases for enantioseparation applications. Tetrahedron Lett. 53, 2312–2315 (2012)

    Article  CAS  Google Scholar 

  23. Wang, R.Q., Ong, T.T., Tang, W., Ng, S.C.: Cationic cyclodextrins chemically-bonded chiral stationary phases for high-performance liquid chromatography. Anal. Chim. Acta 718, 121–129 (2012)

    Article  CAS  Google Scholar 

  24. Zhang, J., Shen, X., Chen, Q.: Separation processes in the presence of cyclodextrins using molecular imprinting technology and ionic liquid cooperating approach. Curr. Org. Chem. 15, 74–85 (2011)

    Article  CAS  Google Scholar 

  25. Zhou, Z., Li, X., Chen, X., Hao, X.: Synthesis of ionic liquids functionalized β-cyclodextrin-bonded chiral stationary phases and their applications in high-performance liquid chromatography. Anal. Chim. Acta 678, 208–214 (2010)

    Article  CAS  Google Scholar 

  26. Wasserscheid, P., Keim, W.: Ionic liquids-new “solutions” for transition metal catalysis. Angew. Chem. 39, 3772–3789 (2000)

    Article  CAS  Google Scholar 

  27. Pandey, S.: Analytical applications of room-temperature ionic liquids: a review of recent efforts. Anal. Chim. Acta 556, 38–45 (2006)

    Article  CAS  Google Scholar 

  28. Canongia Lopes, J.N., Pádua, A.A.: Nanostructural organization in ionic liquids. J. Phy. Chem. B 110, 3330–3335 (2006)

    Article  CAS  Google Scholar 

  29. Anderson, J.L., Armstrong, D.W.: High-stability ionic liquids. A new class of stationary phases for gas chromatography. Anal. Chem. 75, 4851–4858 (2003)

    Article  CAS  Google Scholar 

  30. Li, X., Zhou, Z.: Enantioseparation performance of novel benzimido-β-cyclodextrins derivatized by ionic liquids as chiral stationary phases. Anal. Chim. Acta 819, 122–129 (2014)

    Article  CAS  Google Scholar 

  31. Li, X., Zhou, Z., Dai, W.L., Li, Z.: Preparation of a novel cyclodextrin derivative of benzimido-β-cyclodextrin and its enantioseparation performance in HPLC. Analyst 136, 5017–5024 (2011)

    Article  CAS  Google Scholar 

  32. Zhong, N., Byun, H.S., Bittman, R.: An improved synthesis of 6-O-monotosyl-6-deoxy-β-cyclodextrin. Tetrahedron Lett. 39, 2919–2920 (1998)

    Article  Google Scholar 

  33. Ong, T.T., Tang, W., Muderawan, W., Ng, S.C., Chan, H.S.O.: Synthesis and application of single-isomer 6-mono (alkylimidazolium)-β-cyclodextrins as chiral selectors in chiral capillary electrophoresis. Electrophoresis 26, 3839–3848 (2005)

    Article  CAS  Google Scholar 

  34. Yatabe, J., Kageyama, T.: Preparation of hydrophobic silica with isocyanate. J. Ceram. Soc. Jpn. 102, 595–598 (1994)

    Article  Google Scholar 

  35. Cwiertnia, B., Hladon, T., Stobiecki, M.: Stability of diclofenac sodium in the inclusion complex with β-cyclodextrin in the solid state. J. Pharm. Pharmacol. 51, 1213–1218 (1999)

    Article  CAS  Google Scholar 

  36. Daruházi, Á.E., Szente, L., Balogh, B., Mátyus, P., Béni, S., Takács, M., Lemberkovics, E.: Utility of cyclodextrins in the formulation of genistein: Part 1. Preparation and physicochemical properties of genistein complexes with native cyclodextrins. J. Pharm. Biomed. Anal. 48, 636–640 (2008)

    Article  Google Scholar 

  37. Arnold, R.G., Nelson, J.A., Verbanc, J.J.: Recent advances in isocyanate chemistry. Chem. Rev. 57, 47–76 (1957)

    Article  CAS  Google Scholar 

  38. Simons, D.M., Arnold, R.G.: Relative reactivity of the isocyanate groups in toluene 2,4-diisocyanate. J. Am. Chem. Soc. 78, 1658–1659 (1956)

    Article  CAS  Google Scholar 

  39. Lumley, B., Khong, T.M., Perrett, D.: The characterization of chemically bonded chromatographic stationary phases by thermogravimetry. Chromatographia 60, 59–62 (2004)

    Article  CAS  Google Scholar 

  40. Pino, V., Afonso, A.M.: Surface-bonded ionic liquid stationary phases in high-performance liquid chromatography-a review. Anal. Chim. Acta 714, 20–37 (2012)

    Article  CAS  Google Scholar 

  41. Li, S., Purdy, W.C.: Direct separation of enantiomers using multiple-interaction chiral stationary phases based on the modified β-cyclodextrin-bonded stationary phase. J. Chromatogr. A 625, 109–120 (1992)

    Article  CAS  Google Scholar 

  42. Zhang, D.D., Zhao, P.Y., Huang, N.J., Wu, Y.L., Zhai, Y.M.: Study of α-cyclodextrin or dimethylcyclodextrin/toluene in CF COOD/DO. In: The 5th International Symposium on Cyclodextrins. Editions de Sante´, pp. 146–149 (1990)

  43. Guo, Z., Jin, Y., Liang, T., Liu, Y., Xu, Q., Liang, X., Lei, A.: Synthesis, chromatographic evaluation and hydrophilic interaction/reversed-phase mixed-mode behavior of a “Click β-cyclodextrin” stationary phase. J. Chromatogr. A 1216, 257–263 (2009)

    Article  CAS  Google Scholar 

  44. Buszewski, B., Noga, S.: Hydrophilic interaction liquid chromatography (HILIC)-a powerful separation technique. Anal. Bioanal. Chem. 402, 231–247 (2012)

    Article  CAS  Google Scholar 

  45. Raoov, M., Mohamad, S., Abas, M.R.: Removal of 2, 4-dichlorophenol using cyclodextrin-ionic liquid polymer as a macroporous material: characterization, adsorption isotherm, kinetic study, thermodynamics. J. Hazard. Mater. 263, 501–516 (2013)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Authors would like to seize this opportunity to express their gratitude to the University Malaya for the IPPP grant PG027/2013A and UMRG grant (RP006A-13SUS and RP011B-14SUS). The authors also acknowledge Ministry of Higher Education (MOHE) for providing fellowship to one of the authors-cum-researchers, Ms. NurulYani Rahim.

Author information

Authors and Affiliations

  1. Chemistry Department, Faculty Science, University Malaya, 50603, Kuala Lumpur, Malaysia

    Nurul Yani Rahim, Kheng Soo Tay & Sharifah Mohamad

  2. University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, 50603, Kuala Lumpur, Malaysia

    Sharifah Mohamad

Authors
  1. Nurul Yani Rahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kheng Soo Tay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharifah Mohamad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharifah Mohamad.

Ethics declarations

Conflict if interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 119 kb)

Supplementary material 2 (DOCX 224 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rahim, N.Y., Tay, K.S. & Mohamad, S. β-Cyclodextrin functionalized ionic liquid as chiral stationary phase of high performance liquid chromatography for enantioseparation of β-blockers. J Incl Phenom Macrocycl Chem 85, 303–315 (2016). https://doi.org/10.1007/s10847-016-0629-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-016-0629-9

Keywords

Search

Navigation