Download PDF

ESI-mass spectrometry analysis of unsubstituted and disubstituted β-cyclodextrins: fragmentation mode and identification of the AB, AC, AD regioisomers

  • Stefano Sforza
  • Gianni Galaverna
  • Roberto Corradini
  • Arnaldo Dossena
  • Rosangela Marchelli
Articles
Received:
Revised:
Accepted:

Abstract

The study of unsubstituted and disubstituted β-cyclodextrins (β-CDs) by ESI-mass spectrometry is reported, applying a cone-induced fragmentation in the presence of a twofold excess of sodium chloride, in order to gain information about the fragmentation of the different regioisomers. On the basis of the fragmentation pattern observed for the unsusbstituted β-CD, a statistical model shows that the fragments generated by every regioisomer of a disubstituted CD (AB, AC, and AD) are expected to differ in their relative intensity and, therefore, they can be used for correctly identifying the three different regioisomers. The model was tested on the three regioisomeric (AB, AC, and AD) diamino-β-CDs and ditosyl-β-CD and on the AC and AD regioisomers of dimesitylenesulphonyl-β-CD, allowing in every case through statistical analysis of the fragmentation pattern the correct assignment of every regioisomer on the basis of an ESI mass spectrum (single quadrupole analyzer, high cone voltage) of the pure compounds. The absolute intensities of the fragmentation peaks were voltage-dependent but their ratios was voltage-independent, indicating that no mass bias in peak ratios is introduced by the analyzer. Given the fast time of analysis and its general applicability, independently from the substituents, we propose our method as an easy way to identify the regioisomers of disubstituted β-CDs.

Keywords

Cyclodextrin Monomeric Unit Glucose Unit Diamino Glucose Moiety 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Download to read the full article text

References

  1. 1.
    Atwood, J. L.; Davies, J. E.; MacNicol, D.; Vogtle, F.; Lehn, J. M. Comprehensive Supramolecular Chemistry; Elsevier Science Ltd.: Oxford, 1996, Vol. IIIGoogle Scholar
  2. 2.
    Li, S.; Purdy, W. C. Circular Dichroism, Ultraviolet, and Proton Nuclear Magnetic Resonance Spectroscopic Studies of the Chiral Recognition Mechanism of β-Cyclodextrin. Anal. Chem. 1992, 64, 1405–1412.CrossRefGoogle Scholar
  3. 3.
    Szejtli, J. Cyclodextrin Technology. Kluwer Academic: Dordrecht, 1988.Google Scholar
  4. 4.
    Lehn, J.-M. Supramolecular Chemistry. VCH: Weinheim, 1995, 109, 44–45.Google Scholar
  5. 5.
    Szejtli, J. Introduction and General Overview on Cyclodextrin Chemistry. Chem. Rev. 1998, 98, 1743–1753.CrossRefGoogle Scholar
  6. 6.
    Wenz, G. Cyclodextrins as Building Blocks for Supramolecular Structures and Functional Units. Angew. Chem. Int. Ed. Engl. 1994, 33, 803–822.CrossRefGoogle Scholar
  7. 7.
    Khan, A. R.; Forgo, P.; Stine, K. J. D.’; Souza, V. T. Methods for Selective Modifications of Cyclodextrins. Chem. Rev. 1998, 98, 1977–1996.CrossRefGoogle Scholar
  8. 8.
    Fujita, K.; Matsunaga, A.; Imoto, T. 6A6B, 6A6C, and 6A6D-ditosylates of β-Cyclodextrin. Tetrahedron Lett 1984, 25, 5533–5536.CrossRefGoogle Scholar
  9. 9.
    Fujita, K.; Yamamura, H.; Imoto, T. Unsymmetrically Disubstituted β-Cyclodextrins. 6A,6X-Dideoxy-6A-azido-6X-[(mesitylsulfonyl)oxy] Derivatives. J. Org. Chem. 1985, 50, 4393–4395.CrossRefGoogle Scholar
  10. 10.
    Tabushi, I.; Yamamura, K.; Nabeshima, T. Characterization of Regiospecific A,C- and A,D-Disulfonate Capping of β-Cyclodextrin. Capping as an Efficient Production Technique. J. Am. Chem. Soc. 1984, 106, 5267–5270.CrossRefGoogle Scholar
  11. 11.
    Tabushi, I.; Nabeshima, T.; Fujita, K.; Matsunaga, A.; Imoto, T. Regiospecific A,B Capping onto β-Cyclodextrin. Characteristic Remote Substituent Effect on 13C NMR Chemical Shift and Specific Taka-Amylase Hydrolysis. J. Org. Chem. 1985, 50, 2638–2643.CrossRefGoogle Scholar
  12. 12.
    Breslow, R.; Canary, J. W.; Varney, M.; Waddell, S. T.; Yang, D. Artifical Transaminases Linking Pyridoxamine to Binding Cavities: Controlling the Geometry. J. Am. Chem. Soc. 1990, 112, 5212–5219.CrossRefGoogle Scholar
  13. 13.
    Galaverna, G.; Paganuzzi, M. C.; Corradini, R.; Dossena, A.; Marchelli, R. Enantiomeric Separation of Hydroxy Acids and Carboxylic Acids by Diamino-β-Cyclodextrins (AB, AC, AD) in Capillary Electrophoresis. Electrophoresis 2001, 22, 3171–3177.CrossRefGoogle Scholar
  14. 14.
    Tabushi, I.; Nabeshima, T.; Yamamura, K.; Fujita, K. 400 MHz Two-Dimensional NMR Studies of Cyclodextrin Derivatives for 1H and 13C Chemical Shift Determination. Bull. Chem. Soc. Japan. 1987, 60, 3705–3712.CrossRefGoogle Scholar
  15. 15.
    Yamamura, H.; Nagaoka, H.; Saito, K.; Kawai, M.; Butsugan, Y.; Nakajima, T.; Fujita, K. Determination of the Structure of Tris(6-O-mesitylenesulfonyl)-α-Cyclodextrin Regioiomers by 1H NMR Analyses of the Corresponding 3,6-Anhydrocyclodextrin Derivatives. J. Org. Chem. 1993, 58, 2936–2937.CrossRefGoogle Scholar
  16. 16.
    Yuan, D. Q.; Koga, K.; Yamagushi, M.; Fujita, K. Synthesis and Unique NMR Behavior of a Novel Capped α-Cyclodextrin. J. Chem. Soc. Chem. Commun. 1996, 16, 1943–1944.Google Scholar
  17. 17.
    Cucinotta, V. D.’; Alessandro, F.; Impellizzeri, G.; Pappalardo, G.; Rizzarelli, E.; Vecchio, G. Cyclopeptide Functionalized β-Cyclodextrin. A New Class of Potentially Enzyme Mimicking Compounds with Two Recognition Sites. J. Chem. Soc. Chem. Commun. 1991, 5, 293–294.CrossRefGoogle Scholar
  18. 18.
    Bonomo, P. R.; Impellizzeri, G.; Pappalardo, G.; Rizzarelli, E.; Vecchio, G. Cyclo-L-Histidyl-L-Histidyl Capped β-Cyclodextrin. A New Potentially Enzyme-Mimicking Compound or Artificial Receptor with Two Recognition Sites. Gaz. Chim. Ital. 1993, 123, 593–595.Google Scholar
  19. 19.
    Tabushi, I.; Nabeshima, T. Regiospecific A,B Capping onto β-Cyclodextrin. Characteristic Remote Substituent Effect on 13C NMR Chemical Shift and Specific Taka-Amylase Hydrolysis. J. Org. Chem. 1985, 50, 2638–2643.CrossRefGoogle Scholar
  20. 20.
    Tabushi, I.; Kuroda, Y.; Yokota, K.; Yuan, L. C. Regiospecific A,C- and A,D-Disulfonate Capping of β-Cyclodextrin. J. Am. Chem. Soc. 1981, 103, 711–712.CrossRefGoogle Scholar
  21. 21.
    Fujita, K.; Yamamura, H.; Matsunaga, A.; Imoto, T.; Mihashi, K.; Fujioka, T. 6-Polysubstituted α-Cyclodextrins. Application of Koerner’s Absolute Method of Isomer Determination. J. Am. Chem. Soc. 1986, 108, 4509–4513.CrossRefGoogle Scholar
  22. 22.
    Atsumi, M.; Izumida, M.; Yuan, D.-Q.; Fujita, K. Selective Synthesis and Structure Determination of 6A,6C,6E-Tri(O-sulfonyl)-β-Cyclodextrins. Tetrahedron Lett 2000, 41, 8117–8120.CrossRefGoogle Scholar
  23. 23.
    Yamamura, H.; Iida, D.; Araki, S.; Kobayashi, K.; Katakai, R.; Kano, K.; Kawai, M. Polysulfonylated Cyclodextrins. Part II. Preparation and Structural Validation of Three Isomeric Pentakis(6-O-mesitylsulfonyl)cyclomaltoheptaoses. J. Chem. Soc. Perkin Trans. 1 1999, 21, 3111–3115.CrossRefGoogle Scholar
  24. 24.
    Pearce, A. J.; Sinay, P. Diisobutylaluminum-Promoted Regioselective De-O-benzylation of Perbenzylated Cyclodextrins: A Powerful New Strategy for the Preparation of Selectively Modified Cyclodextrins. Angew. Chem. Int. Ed. Engl. 2000, 39, 3610–3612.Google Scholar
  25. 25.
    Hanessian, S.; Benalil, A.; Laferriere, C. The Synthesis of Functionalized Cyclodextrins as Scaffolds and Templates for Molecular Diversity, Catalysis, and Inclusion Phenomena. J. Org. Chem. 1995, 60, 4786–4797.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2003

Authors and Affiliations

  • Stefano Sforza
    • 1
  • Gianni Galaverna
    • 1
  • Roberto Corradini
    • 1
  • Arnaldo Dossena
    • 1
  • Rosangela Marchelli
    • 1
  1. 1.Departments of Organic and Industrial ChemistryUniversità di ParmaParmaItaly

Personalised recommendations