Selective Binding of cis-1,3,5-Cyclohexane Tricarboxylic Acid vs Its Epimeric trans Isomer by a Tripodal Amidopyridine Receptor; Crystal Structures of the 1:1 Complexes Pablo Ballester,* ,† Magdalena Capo ´, † Antoni Costa, † Pere M. Deya `, † Rosa Gomila, † Andreas Decken, ‡ and Ghislain Deslongchamps ‡ Departament de Quı ´mica, UniVersitat de les Illes Balears, 07071 Palma de Mallorca, Spain, and Departament of Chemistry, UniVersity of New Brunswick, Fredericton, NB E3B 6E2, Canada pablo.ballester@uib.es Received November 22, 2000 ABSTRACT A tripodal tris-amidopyridine receptor forms a 1:1 complex with trans-1,3,5-cyclohexane tricarboxylic acid that is 1 order of magnitude less stable than the one formed with the corresponding cis-triacid epimer. The X-ray crystal structures of the complexes have been determined, confirming the binding geometry derived from NMR data in solution and force-field calculations, and its geometrical features are used to explain the observed selectivity. The design of molecular receptors capable of selective recognition of carboxylic acids and their anions is a matter of current interest in bioorganic chemistry. 1 Recently, we have been interested in the three-dimensional recognition of tricarboxylic acids using tripodal abiotic receptors. 2 The design of our tripodal receptors is based on the spatially ordered positioning of three amidopyridine groups, which we use as complementary hydrogen-bonding partners for the carboxylic acid function. 3 If a carboxylic acid group is properly oriented with respect to an amidopyridine binding unit, up to two hydrogen bonds can be formed, one to the acidic proton and one to the syn lone pair of the carboxylic acid. 4 Using a 1,3,5-triarylbenzene as molecular scaffold, we † Universistat de les Illes Balears. ‡ University of New Brunswick. (1) (a) Sebo, L.; Diederich, F.; Gramlich, V. HelV. Chim. Acta 2000, 83, 93. (b) Sebo, L.; Schweizer, B.; Diederich, F. HelV. Chim. Acta 2000, 83, 80. (c) Lavigne, J. J.; Anslyn, E. V. Angew. Chem., Int. Ed. 1999, 38, 3666. (d) Metzger, A.; Anslyn, E. V. Angew. Chem., Int. Ed. 1998, 37, 649. (2) (a) Ballester, P.; Costa, A.; Deya `, P. M.; Vega, M.; Morey, J.; Deslongchamps, G. Tetrahedron Lett. 1999, 40, 171. (b) Ballester, P.; Costa, A.; Deslongchamps, G.; Mink D.; Decken A.; Prohens R.; Toma `s S.; Vega M. J. Chem. Soc., Chem. Commun. 1997, 357.(c) Ballester, P.; Costa, A.; Deya `, P. M.; Gonza ´lez, J. F.; Rotger, M. C. Tetrahedron Lett. 1994, 35, 3813. (3) Garcı ´a-Tellado, F.; Goswami, S.; Chang, S.-K.; Geb, S. J.; Hamilton, A. D. J. Am. Chem. Soc. 1990, 112, 7393. (4) Hamilton, A. D. In Bioorganic Chemistry Frontiers; Dugas, H., Ed.; Springer-Verlag: Berlin, Heidelberg, 1991; Vol. 2, p 127. ORGANIC LETTERS 2001 Vol. 3, No. 2 267-270 10.1021/ol0069148 CCC: $20.00 © 2001 American Chemical Society Published on Web 12/28/2000