Stable complexes of tertiary ammonia derivative of phenothiazine with tertramethylsulfonated resorcin[4]arenes obtained under substoichiometric conditions

  • Ella Kh. Kazakova
  • Victor V. Syakaev
  • Julia E. Morozova
  • Nelly A. Makarova
  • Liya A. Muslinkina
  • Gennady A. Evtugyn
  • Alexander I. Konovalov
Original Article


Eight water insoluble complexes of tetramethylsulfonated calix[4]resorcinarenes 1 and 2 (–CH3 and –C5H11) with phenothiazine derivative, 3, were obtained under substoichiometric conditions by mixing aqueous solutions of the initial reagents. It was found that complexation of cationic 3 by macrocycles was provided by both Coulomb interaction with the negative sulfonato-groups on the upper rim and by cation-π interactions with the aromatic cavity. The complexes precipitated and, therefore, were studied in organic solvents—DMSO, CD3OD, and CDCl3 using IR-, UV-, and NMR- spectroscopy. Formation of the complexes accompanied by gradual dehydratation of the host—estimated quantity of water in the complexes decreased with increase of the initial concentration of 3. Driving forces of precipitation and complexation, the role of water coordinated by the hosts, and distribution of phenothiazine derivative between two kinds of binding sites are discussed.


Host-guest systems Association Multiple interactions Self-diffusion Phenothiazine Resorcinarene 



We thank Collaboration linkage grant of NATO (PCT.CLG.979178) and Russian Foundation of Basic Research for financial support of this work (RFBR 06-03-32189a and 05-03-32558-a)). We are also grateful to Prof. Wolf D. Habicher and Mrs. Margaret Grüner from TU Dresden for active support of the experimental part of the present research.


  1. 1.
    Dobler, M.: Crystal structure of nonactin. Helv. Chim. Acta 55, 1371–1384 (1972).CrossRefGoogle Scholar
  2. 2.
    Arena, G., Bonomo, R.P., Cali, R., Gulino, F.G., Lombardo, G.G., Sciotto, D., Ungaro, R., Casnati, A.: Water-soluble calixarenes as synthetic receptors. Remarkable influence of stereochemistry on the coordination properties of two new conformational isomers of a calix[4]arene tetracarboxylate. Supramol. Chem. 4, 287–295 (1995); Zhang, Y., Pham, T.H., Pena, M.S., Agbaria, R.A., Warner, I.M.: Spectroscopic studies of brilliant cresyl blue/water-soluble sulfonated calyx[4]arene complex. App. Spectrosc. 52(7), 952–957 (1998), and references therein.Google Scholar
  3. 3.
    Kazakova, E.Kh., Makarova, N.A., Ziganshina, A.Yu., Muslinkina, L.A., Muslinkin, A.A., Habicher, W.D.: Novel water-soluble tetrasulfonatomethylcalix[4]rsorcinarenes. Tetrahedron Lett., 41, 10111–10115(2000).CrossRefGoogle Scholar
  4. 4.
    Mustafina, A.R., Fedorenko, S.V., Makarova, N.A., Kazakova, E.Kh., Bazhanova, Z.G., Kataev, V.E., Konovalov, A.I.: The inclusion properties of a new watersoluble sulfonated calix[4]resorcinarene towards alkylammonium and N-methylpyridinium cations. J. Inclusion Phenom. Macrocyclic Chem., 40(1/2), 73–76 (2001); Kazakova, E. Kh., Ziganshina, A.U., Muslinkina, L.A., Morozova, J.E., Makarova, N.A., Mustafina, A.R., Habicher, W.D.: The complexation properties of the water-soluble tetrasulfonatomethylcalix[4]resorcinarene toward α-aminoacids. J. Inclusion Phenom. Macrocyclic Chem., 43(1/2), 65–69 (2002).Google Scholar
  5. 5.
    Phenothiazines are competitive inhibitors of cholinesterase and are used as neuroleptics.Google Scholar
  6. 6.
    Evtugyn, G.A., Ionina, V.V., Makarova, N.A., Kazakova, E. Kh., Budnikov, H.C.: Determination of neuroleptics with amperometric enzyme sensors modified with tetrasulfonated calix[4]resorcinolarene. Paper presented at the 17th international symposium on bioelectrochemistry and bioenergetics, Florence, Italy, 19–24 June 2003.Google Scholar
  7. 7.
    Koblenz, T.S., Dekker, H.L., de Koster, Ch.G., van Leeuwen, N P.W.M., Reek, J.N.H.: Bisphosphine based hetero-capsules for the encapsulation of transition metals. Chem. Commun. 1700 –1702 (2006); Nishida, M., Ishii, D., Shinkai, S.: Molecular association of water-soluble calixarenes with several stilbene dyes and its application to the facile determination of cationic surfactant concentrations. Bull. Chem. Soc. Jpn. 70(9), 2131–2140 (1997).Google Scholar
  8. 8.
    Rose, K.N., Barbour, L.J., Orr, G.W., Atwood, J.L.: Self-assembly of carcerand-like dimers of calix[4]resorcinarene facilitated by hydrogen bonded solvent bridges. Chem. Commun. 407–408 (1998); Mansikkamki, H., Nissinen, M., Rissanen K.: Noncovalent π-π-stacked exo-functional nanotubes: subtle control of resorcinarene self-assembly. Angew. Chem. 116, 1263–1263 (2004); Angew. Chem., Int. Ed. 43, 1243–1243 (2004); Mansikkamaki, H., Nissinen, M., Schalley, C.A., Rissanen, K.: Self-assembling resorcinarene capsules: solid and gas phase studies on encapsulation of small alkyl ammonium cations. New J. Chem. 27, 88–97 (2003); MacGillivray, L.R., Atwood, J.L.: A chiral spherical molecular assembly held together by 60 hydrogen bonds. Nature 389, 469–472 (1997); Shivanyuk, A., Rebek, Ju.: Assembly of resorcinarene capsules in wet solvents. J.Am. Chem. Soc. 125 (12), 3432–3433 (2003); Yamanaka, M., Shivanyuk, A., Rebek, Ju. Jr.: Kinetics and thermodynamics of hexameric capsule formation. J.Am. Chem. Soc. 126 (9), 2939–2943 (2004).Google Scholar
  9. 9.
    Cohen, Y., Avram, L., Frish, L.: Diffusion NMR spectroscopy in supramolecular and combinatorial chemistry: an old parameter - new insights. Angew. Chem. 117, 524–560 (2005); Angew. Chem. Int. Ed. 44, 520–554 (2005).Google Scholar
  10. 10.
    Lindon, J.C., Ferrige, A.G.: Digitisation and data processing in Fourier transform NMR. Prog. NMR Spectrosc. 14, 27–66 (1980).CrossRefGoogle Scholar
  11. 11.
    Brand, T., Cabrita, E.J., Berger, S.: Intermolecular interaction as investigated by NOE and diffusion studies. Prog. NMR Spectrosc. 46, 159–196 (2005).CrossRefGoogle Scholar
  12. 12.
    Pregosin, P.S., Kumar, P.G.A., Ferna´ndez, I.: Pulsed gradient spin-echo (PGSE) diffusion and 1H,19F heteronuclear overhauser spectroscopy (HOESY) NMR methods in inorganic and organometallic chemistry: something old and something new. Chem. Rev. 105, 2977–2998 (2005).CrossRefGoogle Scholar
  13. 13.
    Schneider, Y.-J., Yatsimirsky, A.K.: Principles and Methods in Supramolecular Chemistry. John Wiley & Sons, New York (2000).Google Scholar
  14. 14.
    Position of \( \nu _{{{\text{SO}}_{{\text{3}}} ^{{\text{ - }}} }} \) bands changes from 1219, 1150, and 1044 cm−1 in spectrum of 1 to 1227, 1142, and 1035 cm−1 in complexes 1&3. The absorbance of \( \nu _{{{\text{(CH}}_{{\text{3}}} {\text{)}}_{{\text{2}}} {\text{NH}}^{{\text{ + }}} }} \) observed in the spectrum of 3 as a wide band well structured in the high frequency part and the maximum at 2409 cm−1 is converted into the complex absorbance outline at 2730–2500 cm−1. The intensity of \( \nu _{{{\text{OH}}}} \) band at 3300 cm−1 attributed to atmospheric water absorbed by macrocycle 1 is somewhat decreased for complexes 1&3.Google Scholar
  15. 15.
    Intensity and position of the characteristic band of resorcinarene, 287 nm, remains unaffected by complexation, while absorbance band of phenotiazine at 303 nm in complexes 1&3 and 2&3 undergoes batochromic shift of 10 nm.Google Scholar
  16. 16.
    Morozova, J.E., Kazakova, E.Kh., Gubanov, E.Ph., Makarova, N.A., Archipov, V.P., Timoshina, T.V., Idijatullin, Z.Sh., Habicher, W.D., Konovalov, A.I.: Aggregation and adsorption properties of tetramethylsulfonatoresorcinarenes and their associates with nonionogenic guest molecules in aqueous solutions. J. Inclusion Phenom. Macrocyclic Chem. 55, 173–183 (2006).CrossRefGoogle Scholar
  17. 17.
    de laTorre, J.G., Huertas, M.L., Carrasco, B.: HYDRONMR: prediction of NMR relaxation of globular proteins from atomic-level structures and hydrodynamic calculations. J. Magn. Reson. 147(1), 138–146 (2000).CrossRefGoogle Scholar
  18. 18.
    Biros, Sh.M., Ullrich, E.C., Hof, F., Trembleau, L. Jr Rebek, Ju.: Kinetically stable complexes in water: the role of hydration and hydrophobicity. J. Am. Chem. Soc. 126(9), 2870–2876 (2004).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Ella Kh. Kazakova
    • 1
  • Victor V. Syakaev
    • 1
  • Julia E. Morozova
    • 1
  • Nelly A. Makarova
    • 1
  • Liya A. Muslinkina
    • 3
  • Gennady A. Evtugyn
    • 2
  • Alexander I. Konovalov
    • 1
  1. 1.A.E. Arbuzov Institute of Organic & Physical ChemistryRussian Academy of SciencesKazanRussia
  2. 2.A.M. Butlerov Chemical InstituteKazan State UniversityKazanRussia
  3. 3.INOQuebecCanada

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