Hydrolysis of glutaric anhydride to glutaric acid in the presence of β-cyclodextrin. Crystallographic and NMR study

  • Anastasia Paulidou
  • Konstantina Yannakopoulou
  • Irene M. Mavridis
Original Article


Crystallization of glutaric anhydride in the presence of β-cyclodextrin (βCD) from aqueous solution resulted in crystals of the glutaric acid/βCD inclusion complex. The result was verified by NMR spectroscopic experiments, which moreover showed that βCD does not protect glutaric anhydride from hydrolysis. The structure determination by X-ray crystallography revealed a host:guest ratio of 1:1 and crystal packing identical to that of natural βCD, i.e., herring bone packing, as is common for guest molecules of small size. Glutaric acid has partial occupancy in the complex and it is disordered in three positions and conformations inside the cavity. All three conformations are stabilised by: (a) Interactions among its carboxyl groups and the host’s primary side hydroxyls pointing towards the cavity, thus justifying the conformations of the latter and (b) by two water molecules located on either side of the cavity, as well as hydroxyl groups of neighbouring hosts. In all conformations the guest is not extended, oxygen atoms between the two carboxyl groups being within H-bond distance.


Cyclomaltoheptaose Glutaric acid Glutaric anhydride Hydrolysis Dicarboxylic acid Crystal structure 



This work was supported by NCSR “Demokritos” (post-doctoral scholarships to A.P.). The support of the NoE program Nano2Life (NMP-4-CT-2003-500057) is acknowledged.


  1. 1.
    Szejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1753 (1998)CrossRefGoogle Scholar
  2. 2.
    Uekama, K., Hirayama, F., Irie, T.: Cyclodextrin drug carrier systems. Chem. Rev. 98, 2045–2076 (1998)CrossRefGoogle Scholar
  3. 3.
    Davis, M.E., Brewster, M.E.: Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. 3, 1023–1035 (2004)Google Scholar
  4. 4.
    Dodziuk, H. (ed.): Cyclodextrins and their complexes. Chemistry, analytical methods, applications. Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim (2006)Google Scholar
  5. 5.
    Harata, K.: Structural aspects of stereodifferentiation in the solid state. Chem. Rev. 98, 1803–1827 (1998)CrossRefGoogle Scholar
  6. 6.
    Zabel, V., Saenger, W., Mason, S.A.: Neutron diffraction study of the hydrogen bondingin β-cyclodextrin undecahydrate at 120 K: from dynamic flip-flop to static homodromic chains. J. Am. Chem. Soc. 108, 3664–3673 (1986)CrossRefGoogle Scholar
  7. 7.
    Jogun, K.H., Stezowski, J.J.: Metastable crystals of beta-cyclodextrin complexes and the membrane-diffusion model. Nature 278, 667–668 (1979)CrossRefGoogle Scholar
  8. 8.
    Lindner, K., Saenger, W.: Crystal and molecular structures of cyclomaltoheptaose inclusion complexes with HI and methanol. Carbohydr. Res. 107, 7–16 (1982)CrossRefGoogle Scholar
  9. 9.
    Gessler, K., Steiner, T., Koellner, G., Saenger, W.: Crystal structure of cyclomaltoheptaose (beta cyclodextrin) complexed with ethylene glycol·8.0H2O and glycerol·7.2H2O. Carbohydr. Res. 249, 327–344 (1993)CrossRefGoogle Scholar
  10. 10.
    Steiner, T., Koellner, G., Saenger, W.: A vibrating flexible chain in a molecular cage: crystal structure of the complex cyclomaltoheptaose(beta cyclodexytin)-1,4-butanediol·6.25H2O. Carbohydr. Res. 228, 321–332 (1992)CrossRefGoogle Scholar
  11. 11.
    Aree, T., Chaichit, N.: Crystal form III of β-cyclodextrin-ethanol inclusion complex: layer type structure with dimeric motif. Carbohydr. Res. 343, 2285–2291 (2008)CrossRefGoogle Scholar
  12. 12.
    Lisnyak, Y.V., Martynov, A.V., Baumer, V.N., Shishkin, O.V., Gubskaya, A.V.: Crystal and molecular structure of β-cyclodextrin inclusion complex with succinic acid. J. Incl. Phenom. Macrocycl. Chem. 58, 367–375 (2007)CrossRefGoogle Scholar
  13. 13.
    Makedonopoulou, S., Mavridis, I.M., Yannakopoulou, K., Papaioannou, J.: Organization of long aliphatic monocarboxylic acids in β-cyclodextrin channels. Crystal structures of the inclusion complexes of tridecanoic acid and (Z)-tetradecenoic acid in β-cyclodextrin. Chem. Commun. 2133–2134 (1998)Google Scholar
  14. 14.
    Makedonopoulou, S., Tulinsky, A., Mavridis, I.M.: The dimeric complex of β-cyclodextrin with 1,13-tridecanedioic acid. Supramol. Chem. 11, 73–81 (1999)CrossRefGoogle Scholar
  15. 15.
    Makedonopoulou, S., Mavridis, I.M.: Structure of the inclusion complex of β-cyclodextrin with 1,12-dodecanedioic acid using synchrotron radiation data; a detailed dimeric β-cyclodextrin structure. Acta Crystallogr. 56, 322–331 (2000)CrossRefGoogle Scholar
  16. 16.
    Makedonopoulou, S., Mavridis, I.M.: The dimeric complex of β-cyclodextrin with 1,14-tetradecanedioic acid. Comparison with related complexes. Carbohydr. Res. 335, 213–220 (2001)CrossRefGoogle Scholar
  17. 17.
    Rontoyanni, A., Mavridis, I.M.: β-Cyclodextrin nonanoic acid 1:1 complex. Acta Crystallogr. C52, 2277–2281 (1996)Google Scholar
  18. 18.
    Johnson, C.K.: ORTEPII, ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA (1976)Google Scholar
  19. 19.
    Sheldrick, G.M.: SHELXL-97, Release 97–2. University of Göttingen, Germany (1997)Google Scholar
  20. 20.
    DeLano, W.L.: The PyMOL Molecular Graphics System. DeLano Scientific LLC, San Carlos, CA, USA. http://www.pymol.org (2002)
  21. 21.
    Mavridis, I.M., Hadjoudis, E.: The crystal structure of the inclusion complex of cyclomaltoheptaose (β-cyclodextrin) with 4-tert-butyltoluene. Carbohydr. Res. 229, 1–15 (1992)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Anastasia Paulidou
    • 1
  • Konstantina Yannakopoulou
    • 1
  • Irene M. Mavridis
    • 1
  1. 1.Institute of Physical ChemistryNational Center for Scientific Research “Demokritos”AthensGreece

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