C O M M U N I C A T I O N S
gave association constants (Ka) of 1.3((0.1) × 105 M-1 for 5,
1.2((0.1) × 106 M-1 for 6, and >107 M-1 for 7. Here, the asso-
ciation constants of 6 and 7 were too high to determine accurately
in CH3CN, and therefore, the magnitudes were compared in a more
competitive medium, 10% (v/v) H2O/CH3CN. Under these condi-
tions, the association constants were determined to be 2.1((0.1)
× 102 M-1 for 6 and 2.3((0.2) × 104 M-1 for 7. The latter value
is unexpectedly high in a polar aqueous solution, considering that
hydrogen bonds are a main driving force for the association. As
anticipated, the association constants increase greatly with increasing
number of the hydrogen-bond donors, indole NHs. In addition, Job’s
plots demonstrated that the oligoindoles formed 1:1 complexes with
chloride (see Supporting Information). Again, these results are all
consistent with the helical folding of the oligoindoles.10
In conclusion, a series of oligoindoles described here fold into
a helical conformation by entrapping chloride inside the tubular
cavity through hydrogen-bonding interactions. Modification of the
oligomer length and the side chain may produce an oligoindole-
based foldamer that gives a more stable helical conformation with
a longer cavity, thus serving as an artificial chloride channel.11
Acknowledgment. This work was financially supported by the
Korea Science and Engineering Foundation through the Center for
Bioactive Molecular Hybrids (CBMH).
Figure 1. 1H NMR (500 MHz, CD3CN) spectral changes of oligoindoles
(2-5 × 10-4 M) upon addition of chloride (1 equiv) at 25 °C: (a) 5, (b)
5 + Cl-, (c) 6, (d) 6 + Cl-, (e) 7, and (f) 7 + Cl-. Herein, magnitudes of
chloride-induced changes (∆δ) in the NH chemical shifts are 2.5 and
1.8 ppm for 5, 2.4, 1.1, and 0.3 ppm for 6, and 1.9, 1.5, 0.3, and 0.1 ppm
for 7.
Supporting Information Available: Synthesis, modeling structures,
2D NMR spectra, and UV/visible binding studies. This material is
References
(1) For reviews, see: (a) Gellman, S. H. Acc. Chem. Res. 1998, 31, 173. (b)
Stigers, K. D.; Soth, M. J.; Nowick, J. S. Curr. Opin. Chem. Biol. 1999,
3, 714. (c) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore,
J. S. Chem. ReV. 2001, 101, 3893. (d) Gong, B. Chem.sEur. J. 2001, 7,
4337. (e) Schmuck, C. Angew. Chem., Int. Ed. 2003, 42, 2448. (f) Huc,
I. Eur. J. Org. Chem. 2004, 17.
(2) For selected recent examples, see: (a) Jiang, H.; Dolain, C.; Le´ger, J.-
M.; Gornitzka, H.; Huc, I. J. Am. Chem. Soc. 2004, 126, 1034. (b)
Heemstra, J. M.; Moore, J. S. J. Am. Chem. Soc. 2004, 126, 1648. (c)
Sugiura, H.; Nigorikawa, Y.; Saiki, Y.; Nakamura, K.; Yamaguchi, M. J.
Am. Chem. Soc. 2004, 126, 14858. (d) Yang, X.; Yuan, L.; Yamato, K.;
Brown, A. L.; Feng, W.; Furukawa, M.; Zeng, X. C.; Gong, B. J. Am.
Chem. Soc. 2004, 126, 3148. (e) Yuan, L.; Zeng, H.; Yamato, K.; Sanford,
A. R.; Feng, W.; Atreya, H. S.; Sukumaran, D. K.; Szyperski, T.; Gong,
B. J. Am. Chem. Soc. 2004, 126, 16528.
(3) (a) Prince, R. B.; Barnes, S. A.; Moore, J. S. J. Am. Chem. Soc. 2000,
122, 2758. (b) Tanatani, A.; Hughes, T.; Moore, J. S. Angew. Chem., Int.
Ed. 2002, 41, 325. (c) Stone, M. T.; Moore, J. S. Org. Lett. 2004, 6, 469.
(d) Inouye, M.; Waki, M.; Abe, H. J. Am. Chem. Soc. 2004, 126, 2022.
(e) Hou, J.-L.; Shao, X.-B.; Chen, G.-J.; Zhou, Y.-X.; Jiang, X.-K.; Li,
Z.-T. J. Am. Chem. Soc. 2004, 126, 12386. (f) Garric, J.; Le´ger, J.-M.;
Huc, I. Angew. Chem., Int. Ed. 2005, 44, 1954.
(4) (a) Prince, R. B.; Okada, T.; Moore, J. S. Angew. Chem., Int. Ed. 1999,
38, 233. (b) Petitjean, A.; Cuccia, L. A.; Lehn, J.-M.; Nierengarten, H.;
Schmutz, M. Angew. Chem., Int. Ed. 2002, 41, 1195. (c) Barboiu, M.;
Lehn, J.-M. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5201. (d) Petitjean,
A.; Nierengarten, H.; van Dorsselaer, A.; Lehn, J.-M. Angew. Chem., Int.
Ed. 2004, 43, 3695. (e) Stone, M. T.; Moore, J. S. J. Am. Chem. Soc.
2005, 127, 5928.
(5) (a) Sa´nchez-Quesada, J.; Seel, C.; Prados, P.; de Mendoza, J. J. Am. Chem.
Soc. 1996, 118, 277. (b) For a foldamer which binds a piperazium
dichloride salt, see: Goto K.; Moore, J. S. Org. Lett. 2005, 7, 1683.
1
Figure 2. (a) H-1H ROESY spectrum of 6 + Cl- (1 equiv) and (b) the
energy-minimized structure (MacroModel 7.1, Amber* force field), where
side chains were replaced by hydrogens. The structure is arbitrarily drawn
in a M-helix.
(6) For a review, see: Vilar, R. Angew. Chem., Int. Ed. 2003, 42, 1460.
(7) Sonogashira, K. In Metal-Catalyzed Cross-Coupling Reactions; Diederich,
exist in the presence of chloride (1 equiv), diagnostic of stacking
between two indoles. In the absence of chloride, however, these
NOE correlations could not be seen under the same experimental
conditions. This is definitive evidence for a helically stacked
conformation of 6 upon complexation with chloride.
The binding studies of the oligoindoles with chloride provided
additional evidence for the helical conformation of oligoindoles.
The UV/visible absorption spectra of 5, 6, and 7 (1.0 × 10-5 M in
CH3CN) were gradually changed as a solution of chloride was added
while keeping the oligoindole concentration constant at 22 ( 1
°C. Nonlinear least-squares fitting analyses9 of the titration curves
F., Stang, P. J., Eds; Wiley-VCH: Weinheim, Germany, 1998; p 203.
(8) The modeling studies were conducted using Amber* force field imple-
mented in MacroModel 7.1 program. For details, see Supporting Informa-
tion.
(9) (a) Long, J. R.; Drago, R. S. J. Chem. Educ. 1982, 59, 1037. (b) Connors,
K. A. Binding Constants; John Wiley & Sons: New York, 1987.
(10) In various organic solvents (CHCl3, CH2Cl2, CH3CN, THF, acetone,
DMSO, etc.), solvophobically driven folding of free 6 and 7 could not be
noticed in the UV/visible and florescence spectroscopy.
(11) (a) For a natural chloride channel, see: Dutzler, R.; Campbell, E. B.;
Cadene, M.; Chait, B. T.; MacKinnon, R. Nature 2002, 415, 287. (b) For
a review of artificial chloride transporters, see: Smith, B. D.; Lambert,
T. N. Chem. Commun. 2003, 2261.
JA0547984
9
J. AM. CHEM. SOC. VOL. 127, NO. 35, 2005 12215