Molecular recognition: minimizing the acid–base interaction of a tunable host–guest system changes the selectivity of binding
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.
KeywordsAnilines Hydrogen bonding NMR Supramolecular chemistry X-ray crystallography
We gratefully acknowledge Flemming Hansen for collecting the crystal structure data and the Center for Crystallographic Studies at the University of Copenhagen for the use of their equipment.
- 2.Atwood, J.L., Davies, J.E.D., Macnicol, D.D., Vögtle, F.: Comprehensive Supramolecular Chemistry. Elsevier Science Ltd, Oxford (1997)Google Scholar
- 3.Schneider, H.J., Yatsimirsky, A.K.: Principles and Methods in Supramolecular Chemistry. Wiley, New York (2000)Google Scholar
- 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.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.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.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
- 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
- 19.Sheldrick, G.M.: An intensity evaluation method. Acta. Crysallogr. A 46, 467 (1990). doi: 10.1107/S0108767390000277
- 20.Sheldrick, G.M.: SHELXL97 Program for the Refinement of Crystal Structures. University of Göttingen, Germany, 1997Google Scholar
- 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