Molecular recognition: minimizing the acid–base interaction of a tunable host–guest system changes the selectivity of binding

  • Michael Pittelkow
  • Christian B. Nielsen
  • Anders Kadziola
  • Jørn B. Christensen
Original Article

Abstract

Two new receptors incorporating a 4-n-butyl aniline moiety has been designed, synthesized and evaluated for their binding properties towards a series of ureido-glycine derivatives. The host design is based on an urea adamantyl host motif known from large generations of poly(propylene imine) dendrimers functionalized with urea adamantyl moieties on the periphery. The design of the host molecules was directed towards a study of the effects of basicity of an amine function versus the effect of molecular recognition on the binding strength as seen from comparing the results obtained in the present work with previously guest–host studies. The guest–host interaction features an electrostatic interaction and multiple hydrogen binding interactions, where the main difference between the hosts described here and previously described is a substitution from an amine to aniline. Anilines are weaker bases than aliphatic amines and they generally give lower binding constants when treated with acidic guest molecules. The association constants have been measured using NMR titrations and the nature of the guest–host system is discussed based on these results. A general decrease in binding affinities is observed upon changing from the trialkyl amine hosts to the dialkyl aniline based hosts. One exception was observed where the weaker base host had stronger affinity to one of the guests. Thus, when the basicity of the host is decreased other factors influence the binding such as a better geometric fit. A crystal structure of one of the receptors has been solved and it shows no intramolecular hydrogen bonding.

Keywords

Anilines Hydrogen bonding NMR Supramolecular chemistry X-ray crystallography 

Supplementary material

10847_2008_9515_MOESM1_ESM.doc (327 kb)
MOESM1 (DOC 327 kb)

References

  1. 1.
    Lehn, J.M.: Supramolecular Chemistry. VCH, Weinheim (1995)CrossRefGoogle Scholar
  2. 2.
    Atwood, J.L., Davies, J.E.D., Macnicol, D.D., Vögtle, F.: Comprehensive Supramolecular Chemistry. Elsevier Science Ltd, Oxford (1997)Google Scholar
  3. 3.
    Schneider, H.J., Yatsimirsky, A.K.: Principles and Methods in Supramolecular Chemistry. Wiley, New York (2000)Google Scholar
  4. 4.
    Chang, S., Hamilton, A.D.: Molecular recognition of biologically interesting substrates: synthesis of an artificial receptor for barbiturates employing six hydrogen bonds. J. Am. Chem. Soc. 110, 1318 (1988). doi:10.1021/ja00212a065 CrossRefGoogle Scholar
  5. 5.
    Baars, M.W.P.L., Karlsson, A.J., Sorokin, V., de Waal, B.F.M., Meijer, E.W.: New dendrimer-peptide host–guest complexes: towards dendrimers as peptide carriers. Angew. Chem. 112, 4432 (2000). doi:10.1002/1521-3773(20001201)39:23<4262::AID-ANIE4262>3.0.CO;2-YCrossRefGoogle Scholar
  6. 6.
    Baars, M.W.P.L., Karlsson, A.J., Sorokin, V., de Waal, B.F.M., Meijer, E.W.: Non-covalent synthesis of supramolecular dendritic architectures in water. Angew. Chem. Int. Ed. 39, 4262 (2000). doi:10.1002/1521-3773(20001201)39:23<4262::AID-ANIE4262>3.0.CO;2-YCrossRefGoogle Scholar
  7. 7.
    Pittelkow, M., Christensen, J.B., Meijer, E.W.: Guest–host chemistry with dendrimers: stable polymer assemblies by rational design. J. Pol. Sci. A 42, 3792 (2004). doi: 10.1002/pola.20276 CrossRefGoogle Scholar
  8. 8.
    Banerjee, D., Broeren, M.A.C., van Genderen, M.H.P., Meijer, E.W., Rinaldi, P.L.: An NMR study of supramolecular chemistry of modified poly(propyleneimine) dendrimers. Macromolecules 37, 8313 (2004). doi:10.1021/ma049146z CrossRefGoogle Scholar
  9. 9.
    Pittelkow, M., Nielsen, C.B., Broeren, M.A.C., van Dongen, J.L.J., van Genderen, M.H.P., Meijer, E.W., Christensen, J.B.: Molecular recognition: comparative study of a tunable host–guest system by using a fluorescent model system and collision-induced dissociation mass spectrometry on dendrimers. Chem. Eur. J. 11, 5126 (2005). doi:10.1002/chem.200401230 CrossRefGoogle Scholar
  10. 10.
    Hermans, T.M., Broeren, M.A.C., Gomopoulos, N., Smeijers, A.F., Mezari, B., van Leeuwen, E.N.M., Vos, M.R.J., Magusin, P.C.M.M., Hilbers, P.A.J., van Genderen, M.H.P., Sommerdijk, N.A.J.M., Fytas, G., Meijer, E.W.: Stepwise non-covalent synthesis leading to dendrimer-based assemblies in water. J. Am. Chem. Soc. 129, 15631–15638 (2007). doi:10.1021/ja074991t CrossRefGoogle Scholar
  11. 11.
    Chang, T., Pieterse, K., Broeren, M.A.C., Kooijman, H., Spek, A.L., Hilbers, P.A.J., Meijer, E.W.: Structural elucidation of dendritic host-guest complexes by X-ray crystallography and molecular dynamics simulations. Chem. Eur. J. 13, 7883–7889 (2007). doi:10.1002/chem.200700572 CrossRefGoogle Scholar
  12. 12.
    Broeren, M.A.C., van Dongen, J.L.J., Pittelkow, M., Christensen, J.B., van Genderen, M.H.P., Meijer, E.W.: Molecular recognition: comparative study of a tunable host-guest system by using a fluorescent model system and collision-induced dissociation mass spectrometry on dendrimers. Angew. Chem. 116, 3579 (2004). doi:10.1002/anie.200453707 CrossRefGoogle Scholar
  13. 13.
    Broeren, M.A.C., van Dongen, J.L.J., Pittelkow, M., Christensen, J.B., van Genderen, M.H.P., Meijer, E.W.: Multivalency in the gas phase: the study of dendritic aggregates by Mass Spectrometry. Angew. Chem. Int. Ed. 3, 3557 (2004). doi:10.1002/anie.200453707 CrossRefGoogle Scholar
  14. 14.
    Gillies, E.R., Frechet, J.M.J.: Dendrimers and dendritic polymers in drug delivery. J. Org. Chem. 69(1), 46 (2004). doi:10.1021/jo035329s CrossRefGoogle Scholar
  15. 15.
    Smith, P.A.S., Yu, T.: Some syntheses of compounds related to julolidine. J. Am. Chem. Soc. 74, 1096 (1952). doi:10.1021/ja01124a524 CrossRefGoogle Scholar
  16. 16.
    Dimroth, K., Aurich, H. G.: Cyanomethylation of weakly basic amines. Chem. Ber. 98, 3902 (1965). doi:10.1002/cber.19650981217 Google Scholar
  17. 17.
    Liu, R.C.W., Fung, P., Xue, F., Mak, T.C.W., Ng, D.K.P.: Synthesis of mixed aza, oxa and thia crown ethers. J. Chem. Res. Miniprint 8, 1744 (1998)Google Scholar
  18. 18.
    Duisenberg, A.J.M., Kroon-Batenburg, L.M.J., Schreurs, A.M. M.: Preparation and properties of some substituted Julolidines. J. Appl. Cryst. 36, 220 (2003). doi:10.1107/S0021889802022628 Google Scholar
  19. 19.
    Sheldrick, G.M.: An intensity evaluation method. Acta. Crysallogr. A 46, 467 (1990). doi:10.1107/S0108767390000277
  20. 20.
    Sheldrick, G.M.: SHELXL97 Program for the Refinement of Crystal Structures. University of Göttingen, Germany, 1997Google Scholar
  21. 21.
    Mackey, S., Gilmore, C.J., Edwards, C., Stewart, N., Shankland, K.: MaXus Computer Program for the Solution and Refinement of Crystal Structures. Bruker Nonius. Macscience, Japan & The University of Glasgow, The Netherlands 1999Google Scholar
  22. 22.
    Boas, U., Karlsson, A.J., de Waal, B.F.M., Meijer, E.W.: Synthesis and properties of new thiourea-functionalized poly(propylene imine) dendrimers and their role as hosts for urea functionalized guests. J. Org. Chem. 66, 2136 (2001). doi:10.1021/jo001573x CrossRefGoogle Scholar
  23. 23.
    Boas, U., Söntjens, S.H.M., Jensen, K.J., Christensen, J.B., Meijer, E.W.: New dendrimer-peptide host–guest Complexes: towards dendrimers as peptide carriers. ChemBioChem 3, 433 (2002). doi:10.1002/1439-7633(20020503)3:5<433::AID-CBIC433>3.0.CO;2-0CrossRefGoogle Scholar
  24. 24.
    Mosher, H.S., Cornell J. Jr., Stafford, O.L., Roe T.J. Jr.: Synthesis of piperazines by reductive cyclization. Am. Chem. Soc. 75, 4949 (1953). doi:10.1021/ja01116a020 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Michael Pittelkow
    • 1
  • Christian B. Nielsen
    • 1
  • Anders Kadziola
    • 1
  • Jørn B. Christensen
    • 1
  1. 1.Department of ChemistryUniversity of CopenhagenCopenhagen ØDenmark

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