Skip to main content
SpringerLink
Log in

Spectroscopic investigation of β-cyclodextrin -metoprolol tartrate inclusion complexes

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

Abstract

Aqueous-solution complexes of β-cyclodextrin (β-CD) with metoprolol tartrate (MET) have been analysed with 1H NMR and UV–vis spectroscopy. With 1H NMR a [1:1] stoichiometry could be established for the β-CD-MET complex while its stability constant was determined with UV–vis spectroscopy. Powder diffraction data of a polycrystalline sample of the β-CD-MET complex show that a novel product has been formed, likely to be a β-CD-MET [1:1] inclusion complex. Also Hyperchem MM+ molecular-dynamics results suggest an inclusion complex and from 1H NMR data it is inferred that probably the MET is docked in the CD with the formers methoxyethyl-benzene moiety in front.

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

Similar content being viewed by others

References

  1. Moloney, G., Craik, D.J., Irkouder, M.N., Nero, T.L.: Synthesis, NMR studies and conformational analysis of oxazilidine derivatives of the beta-adrenoreceptor antagonists metoprolol, atenolol and timolol. J.C.S. Perkin Trans. 2, 199–206 (1998).

    Article  Google Scholar 

  2. Szjejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1753 (1998).

    Article  Google Scholar 

  3. Ficarra, R., Ficarra, P., Di Bella, M.R., Raneri, D., Tommasini, S., Calabrò, M.L., Gamberini, M.C., Rustichelli, C.: Study of beta-blockers/beta-cyclodextrins inclusion complex by NMR, DSC, X-ray and SEM investigation. J. Pharm. Biomed. Anal. 23, 33–40 (2000).

    Article  CAS  Google Scholar 

  4. Park, K.L., Kim, K.H., Jung, S.-H., Lim, H.M., Hong, Ch.H., Kang, J.S.: Enantioselective stabilization of inclusion complexes of metoprolol in carboxymethylated β-cyclodextrin. J. Pharm. Biomed. Anal 27, 569–576 (2002).

    Article  CAS  Google Scholar 

  5. Radulovic, D.M., Karljikovic-Rajic, K.D., Lucic, B.M., Vujic, Z.B.: A preliminary study of beta-cyclodextrin/metoprolol tartrate inclusion complex for potential enantiomeric separation. J. Pharm Biomed. Anal. 24, 871–876 (2001).

    Article  CAS  Google Scholar 

  6. Bratu, I., Gavira-Vallejo, J.M., Hernanz, A.: 1H-NMR study of the inclusion processes for α- and γ-cyclodextrin with fenbufen. Biopolymers 77, 361–367 (2005).

    Article  CAS  Google Scholar 

  7. Ikeda, Y., Hirayama, F., Arima, H., Uekama, K., Yoshitake, Y., Harano, K.: NMR spectroscopic characterization of metoprolol/cyclodextrin complexes in aqueous solution: cavity size dependency. J. Pharm. Sci. 93, 1659–1671 (2004).

    Article  CAS  Google Scholar 

  8. Job, P.: Formation and stabitity of inorganic complexes in solution. Ann. Chem. 9, 113–203 (1928).

    CAS  Google Scholar 

  9. Bogdan, M., Farcas, S.I., Bojita, M.: Nuclear magnetic resonance study of naproxen and ibuprofen interaction with beta-CD in solution. Studia Univ. Babes-Bolyai, Ser. Phys. Special issue 115–120 (2000).

  10. Bratu, I., Gavira-Vallejo, J.M., Hernanz, A., Bogdan, M., Bora, Gh.: Inclusion complex of fenbufen with β-cyclodextrin. Biopolymers-Biospectroscopy 73, 451–456 (2004).

    Article  CAS  Google Scholar 

  11. Saenger, W.: Cyclodextrin inclusion compounds in research and industry. Angew. Chem. Int. Ed. Engl. 92, 343–361 (1980).

    Article  CAS  Google Scholar 

  12. Li, S., Purdy, W.C.: Cyclodextrins and their applications in analytical chemistry. Chem. Rev. 92, 1457–1470 (1992).

    Article  CAS  Google Scholar 

  13. Junquera, E., Aicart, A.: Potentiometric study of the encapsulation of ketoprophen by hydroxypropyl-β- cyclodextrin. Temperature, solvent, and salt effects. J. Phys. Chem. B 101, 7163–7171 (1997).

    Article  CAS  Google Scholar 

  14. Tran, Ch.D., De Paoli Lacerda, S.H.: Determination of binding constants of cyclodextrins in room-temperature ionic liquids by near-infrared spectrometry. Anal. Chem. 74, 5337–5341 (2002).

    Article  CAS  Google Scholar 

  15. Scott, R.L.: Some comments on the Benesi-Hildebrand equation. Rec. Trav. Chim. 75, 787–789 (1956).

    Article  CAS  Google Scholar 

  16. Liu, L., Guo, Q.-X.: The driving forces in the inclusion complexation of cyclodextrins. J. Inclus. Phenom. Macro. Chem. 42, 1–14 (2002).

    Article  CAS  Google Scholar 

  17. HyperChemTM Release 4, Hypercube, Inc. (1994), Waterloo, Ontario N2l 3X2, Canada.

  18. “Computational Chemistry”, Hypercube, Inc. Waterloo, Ontario N2l 3X2, Canada (1994).

  19. Origin® 7.0, OriginLab Corporation, Northhampton, MA 01060, USA.

  20. Zubiaur, M., Jaime, C.: Complexation between tert-butyl ketones and β-cyclodextrin. Structural study by NMR and MD simulations. J. Org. Chem. 65(24), 8139–8145 (2000).

    Article  CAS  Google Scholar 

  21. Gavira, J.M., Hernanz, A., Bratu, I.: Dehydration of β-cyclodextrin: An IR ν (OH) band profile analysis. Vib. Spectrosc. 32(2), 137–146 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the ESRF (Grenoble, France) for the opportunity to perform the synchrotron diffraction experiments and Dr. H. Emerich for his help at beamline BM01B (Swiss-Norwegian CRG). They also thank Dr. M.M. Pop, Dr. V. Brodski and Dr. D.J.A. De Ridder for their assistance in collecting the data. One of the authors (Borodi) is indebted to the Netherlands Foundation for Scientific research (NWO) for financial support (NB 71-135) to carry out part of the research in Amsterdam. The spectroscopic investigations and molecular modelling were supported by the CEEX no7/2005 VIASAN project. Thanks are due also to Dr. L. Copolovici from the Faculty of Chemistry, “Babes-Bolyai” University for his assistance in the determination of the association constant from the optical spectra.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, University of Oradea, 1 Armatei Romane st, Oradea, Romania

    Felicia Dragan

  2. National R&D Institute of Isotopic and Molecular Technologies, P.O. Box 700, 400293, Cluj-Napoca 5, Romania

    I. Bratu & Gh. Borodi

  3. Dep. CCTT Físicoquimicas, UNED Madrid, Senda del Rey 9, 28040, Madrid, Spain

    Mihaela Toma & A. Hernanz

  4. Faculty of Physics, ’Babes-Bolyai’ University, 1 Kogalniceanu st, Cluj-Napoca, Romania

    S. Simon & Gh. Cristea

  5. Laboratory for Crystallography, Universiteit van Amsterdam, Van ‘t Hoff Institute for Molecular Sciences, Valckenierstraat 65, 1018XE, Amsterdam, The Netherlands

    R. Peschar

Authors
  1. Felicia Dragan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Bratu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gh. Borodi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mihaela Toma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Hernanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gh. Cristea
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. Peschar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Bratu.

Additional information

Mihaela Toma is Socrates/Erasmus student at UNED Madrid

About this article

Cite this article

Dragan, F., Bratu, I., Borodi, G. et al. Spectroscopic investigation of β-cyclodextrin -metoprolol tartrate inclusion complexes. J Incl Phenom Macrocycl Chem 59, 125–130 (2007). https://doi.org/10.1007/s10847-007-9304-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-007-9304-5

Keywords

Search

Navigation