Anion Receptors: A New Class of Amide/Quaternized Amine Macrocycles and the Chelate Effect Md. Alamgir Hossain, Sung Ok Kang, Douglas Powell, and Kristin Bowman-James* Department of Chemistry, UniVersity of Kansas, Lawrence, Kansas 66045 Received December 31, 2002 A new class of tetraamide macrocyclic receptors for anions with two quaternized amine functionalities exhibited higher affinities for anions compared with the corresponding neutral amides. In two crystal structures of halide complexes of the prototypes with phenyl and pyridine spacers, the anions are held by hydrogen bonding with the amide hydrogens. The pyridine analogues display higher affinities in general than the phenyl systems, a phenomenon which is attributed to the anion version of the chelate effect. Synthetic nitrogen-based receptors designed for the selec- tive binding of anions usually consist of either positively charged ammonium salts, i.e., protonated polyamines and/ or quaternized amines, or neutral species such as amides, sulfonamides, pyrroles, ureas, and thioureas. 1-3 The fact that nature chose the robust amides for its anion receptors has led to considerable focus on these systems by us 4-6 and others 7-12 for selective targeting of a variety of anions. Our dual amide/amine macrocyclic prototype receptor, 1a, based on the isophthalamide receptors of Crabtree, 7,8 was found to be selective for both monohydrogen sulfate and dihydrogen phosphate over other oxo anions and halides. 13 Moreover, the structural features are reminiscent of the sulfate and phosphate binding proteins. 14,15 By adding quaternized ammonium functionalities to neutral amide receptors, we have obtained a new class of macro- cyclic anion receptors, 2, with significantly higher anion affinities. These anionophores retain the benefits of the amide hydrogen bonds but have an added component of electrostatic complementarity. Only a few mixed amide/quaternary amine systems have been reported, 16,17 and to our knowledge, these have not been explored as anion receptors. Additionally, significant differences in binding affinities between the phenyl (X ) CH) and pyridine (X ) N) analogues were observed for most of the anions. This observation is consistent for both the neutral precursor macrocycles and the new quaternized systems. Crystal- lographic results indicate that it is traceable to the anion version of the chelate effect, well-documented for transition metal complexes. We now report preliminary binding and crystallographic studies for this new class of mixed amide/ quaternized amine receptors 2a and 2b, as well as some new insight to the chelate effect as it pertains to anion coordina- tion chemistry. The quaternized salts were obtained from the neutral cyclic amides, 1, by methylation followed by conversion to the BPh 4 - salts. The neutral cyclic amides 1 13 (0.22 mmol) were * To whom correspondence should be addressed. E-mail: kbowman- james@ku.edu. (1) Supramolecular Chemistry of Anions; Bianchi, A., Bowman-James, K., Garcı ´a-Espan ˜a, E., Eds; Wiley-VCH: New York, 1997. (2) Schneider, H.-J.; Yatsimirsky, A. Principles and Methods in Su- pramolecular Chemistry; John Wiley and Sons: New York, 2000. (3) Beer, P. D.; Smith, D. K. Prog. Inorg. Chem. 1997, 46,1-96. (4) Danby, A.; Seib, L.; Alcock, N. W.; Bowman-James, K. Chem. Commun. 2000, 973-974. (5) Kavallieratos, K.; Danby, A.; Van Berkel, G. J.; Kelly, M. A.; Sachleben, R. A.; Moyer, B. A.; Bowman-James, K. Anal. Chem. 2000, 72, 5258-5264. (6) Qian, Q.; Wilson, G. S.; Bowman-James, K.; Girault, H. H. Anal. Chem. 2001, 73, 497-503. (7) Kavallieratos, K.; de Gala, S. R.; Austin, D. J.; Crabtree, R. H. J. Am. Chem. Soc. 1997, 119, 2325-2326. (8) Kavallieratos, K.; Bertao, C. M.; Crabtree, R. H. J. Org. Chem. 1999, 64, 1675-1683. (9) Valiyaveettil, S.; Engbersen, J. F. J.; Verboom, W.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1993, 32, 900-901. (10) Beer, P. D.; Drew, M. G. B.; Gradwell, K. J. Chem. Soc., Perkin Trans. 2, 2000, 511-519. (11) Kubik, S.; Goddard, R. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5127- 5132. (12) Choi, K.; Hamilton, A. D. J. Am. Chem. Soc. 2001, 123, 2456-2457. (13) Hossain, M. A.; Llinares, J. M.; Powell, D.; Bowman-James, K. Inorg. Chem. 2001, 40, 2936-2937. (14) Luecke, H.; Quiocho, F. A. Nature 1990, 347, 402-406. (15) He, J. J.; Quiocho, F. A. Science 1991, 251, 1479-1481. (16) Wisner, J. A.; Beer, P. D.; Drew, M. G. B. Angew. Chem., Int. Ed. 2001, 40, 3606-3609. (17) Kral, V.; Rusin, O.; Schmidtchen, F. P. Org. Lett. 2001, 3, 873-876. Inorg. Chem. 2003, 42, 1397-1399 10.1021/ic0263140 CCC: $25.00 © 2003 American Chemical Society Inorganic Chemistry, Vol. 42, No. 5, 2003 1397 Published on Web 02/13/2003