Selection between Pinching-Type and Supramolecular Polymer-Type Complexes by r-Cyclodextrin--Cyclodextrin Hetero-Dimer and Hetero-Cinnamamide Guest Dimers Hirokazu Takahashi, Yoshinori Takashima, Hiroyasu Yamaguchi, and Akira Harada* Department of Macromolecular Science, Graduate School of Science, Osaka UniVersity, Toyonaka, Osaka 560-0043, Japan harada@chem.sci.osaka-u.ac.jp ReceiVed March 4, 2006 Novel supramolecular complexes have been prepared from an R-cyclodextrin--cyclodextrin hetero- dimer (R-CD--CD hetero-dimer) and hetero-cinnamamide guest dimers, G-t-Boc and G-NH 2 , having adamantyl groups in aqueous solutions. On addition of the competitive guest, the supramolecular structure formed by a mixture of the R-CD--CD hetero-dimer and G-t-Boc was found to be different from that of a mixture of the R-CD--CD hetero-dimer and G-NH 2 by the 1 H NMR spectroscopy, the ROESY NMR spectroscopy, and the circular dichroism spectroscopy. The size of the supramolecular complex from the mixture of the R-CD--CD hetero-dimer and G-NH 2 is larger than that from the mixture of the R-CD--CD hetero-dimer and G-t-Boc, which was proved by the pulse field gradient spin-echo NMR and the atomic force microscopy. These results suggest that the mixture of the R-CD--CD hetero- dimer and G-t-Boc formed a pinching-type complex, and the mixture of the R-CD--CD hetero-dimer and G-NH 2 formed a supramolecular polymer-type complex. Introduction Biological systems offer several excellent examples of supramolecular polymers including double- and triple-helical DNA, as well as protein -sheet and tobacco mosaic virus. 1 Microtubles are supramolecular polymers consisting of hetero- dimers of R-tubulin and -tubulin with alternating structures. 2 Chemists have challenged the formation of supramolecules based on host-dimers as supramolecular architectures of artificial assemblies. 3 Cyclodextrins (CDs) have been used frequently as a component of supramolecular complexes. CD dimers, used for molecular recognition and drug delivery, possess the structural characteristics to completely encapsulate a guest molecule. CD dimers were prepared by some researchers to increase the association constants with CDs, because association constants for complexations of appropriate guests with CDs show 10 4 M -1 , whereas the corresponding values for complex- ations of substrates with antibody are more than 100 times larger. 4,5 Many researchers are actively working on producing enzyme models based on CD dimers that strongly bind appropriate substrates to both CD cavities such as a pinching- type structure. 6,7 Although there are some papers on the cooperative binding of guests by CD hetero-dimers, 8,9 there are * Corresponding author. Tel.: +81-6-6850-5445. Fax: +81-6-6850-5445. (1) Aggeli, A.; Bell, M.; Boden, N.; Keen, J. N.; Knowles, P. F.; McLeish, T. C. B.; Pitkeathly, M.; Radford, S. E. Nature 1997, 386, 259-262. (2) (a) Amos, L. A.; Baker, T. S. Nature 1979, 279, 607-612. (b) Luduena, R. F. Mol. Biol. Cell 1993, 4, 445-457. (c) Stullivan, K. F. Annu. ReV. Cell Biol. 1988, 4, 687-716. (d) Wade, R. H.; Chre ¨tien, D. J. Struct. Biol. 1993, 110,1-27. (3) (a) Yamaguchi, N.; Gibson, H. W. Angew. Chem., Int. Ed. 1999, 38, 143. (b) Yamaguchi, N.; Nagvekar, D. S.; Gibson, H. W. Angew. Chem., Int. Ed. 1998, 37, 2361. (c) Gibson, H. W.; Yamaguchi, N.; Jones, J. W. J. Am. Chem. Soc. 2003, 125, 3522. (4) (a) Pease, A. R.; Jeppeson, J. O.; Stoddart, J. F.; Lop, Y. I.; Collier, C. P.; Heath, J. R. Acc. Chem. Res. 2001, 34, 433. (b) Harada, A. Acc. Chem. Res. 2001, 34, 456. (c) Harada, A.; Kawaguchi, Y.; Hoshino, T. J. Inclusion Phenom. Macrocyclic Chem. 2001, 41, 115. (d) Miyauchi, M.; Takashima, Y.; Yamaguchi, H.; Harada, A. J. Am. Chem. Soc. 2005, 127, 2984-2989. (5) Mulder, A.; Reinhoudt, D. N. Chem. Commun. 2002, 22, 2734- 2735. (6) (a) Bender, M. L.; Komiyama, M. Cyclodextrin Chemistry; Springer: Berlin, 1978. (b) Bender, M. L.; Bergeron, R. J.; Komiyama, M. The Bioorganic Chemistry of Enzymatic Catalysis; Wiley: New York, 1984. (7) (a) Breslow, R. Acc. Chem. Res. 1991, 24, 317. (b) Zhang, B.; Breslow, R. J. Am. Chem. Soc. 1997, 119, 1676-1681. (c) Breslow, R.; Zhang, X.; Huang, Y. J. Am. Chem. Soc. 1997, 119, 4535-4536. 4878 J. Org. Chem. 2006, 71, 4878-4883 10.1021/jo0604686 CCC: $33.50 © 2006 American Chemical Society Published on Web 06/02/2006