C O M M U N I C A T I O N S
Figure 3. FRET from pyrene salt 9 inside the hexamer to the perylene
resorcinarene 8 (A) in the hexamer. λexc ) 350 nm.
Figure 2. Development of FRET with time upon mixing 4 (D) and 8 (A)
hexamer solutions at 250 nM, (times shown from 0 to 4 h). λexc ) 350 nm.
The inset shows the first-order kinetic treatment of the data.
In summary, resorcinarenes labeled with donor and acceptor
fluorophores probe the dynamic behavior of hexameric capsules
in solution through FRET observation. Additionally, FRET occurs
from a fluorescent guest to a labeled resorcinarene host. While
several examples exist of FRET in mechanically linked rotaxanes,11
to our knowledge, this represents the first observation of FRET
across a capsular boundary.
Table 1. Relative Rates of Exchange of Resorcinarenes in the
Hexamer
b
solventa
added guest
half-lifeb (min)
krel
CHCl3
C6H6
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
46
3
10
14
14
16
21
292
100
70
70
59
Hex4N+Br-
Bu4N+Br-
Bu4SbBr
Acknowledgment. We are grateful to the Skaggs Institute for
Chemical Biology and the NIH (Grant GM 50174) for financial
support. E.S.B and T.J.D. are Skaggs postdoctoral and predoctoral
fellows, respectively.
a In all cases water-saturated solvents were used. b Half-life for the system
to reach equilibrium; uncertainties in krel and half-lives are (10%.
Supporting Information Available: Key experimental and char-
acterization of new compounds, absorption and emission spectra, details
of kinetic experiments and methanol titrations. This material is available
were monitored in different wet solvents and in the presence of
known guest molecules (Table 1). The capsules were slowest to
exchange resorcinarene monomers in chloroform compared to
dichloromethane or benzene; apparently, a more stable hexameric
capsule is formed in chloroform. Known guests for the hexamer
showed a longer half-life for monomer exchange: as expected a
guest has a stabilizing effect on the assembly and a more robust
capsule exists when a guest other than solvent molecules is inside.
The exchange of resorcinarene monomers was relatively fast at
these low concentrations, in contrast to a diffusion NMR study of
Cohen et al. where more than 24 h was required for a mixture of
two hexamers to reach heteromeric equilibrium.2e We attribute this
disparity to the vastly different concentration of the experiments.
At the nanomolar concentrations of the fluorescence studies there
are more monomeric resorcinarenes in solution relative to the
hexamers and the rate of exchange of the assembly is increased. A
similarly fast exchange of monomers was observed in a recent mass
spectrometric study.9
References
(1) MacGillivray, L. R.; Atwood, J. L. Nature 1997, 389, 469-472.
(2) (a) Shivanyuk, A.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 2001, 98,
7662-7665. (b) Avram, L.; Cohen, Y. J. Am. Chem. Soc. 2002, 124,
15148-15149. (c) Shivanyuk, A.; Rebek, J., Jr. J. Am. Chem. Soc. 2003,
125, 3432-3433. (d) Yamanaka, M.; Shivanyuk, A.; Rebek, J., Jr. J. Am.
Chem. Soc. 2004, 126, 2939-2943. (e) Avram, L.; Cohen, Y. J. Am. Chem.
Soc. 2004, 126, 11556-11563. (f) Evan-Salem, T.; Baruch, I.; Avram,
L.; Cohen, Y.; Palmer, L. C.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A.
2006, 103, 12296-12300. (g) Ugono, O.; Holman, K. T. Chem. Commun.
2006, 2144-2146.
(3) Fluorophores have been crystallized in related pyrogallolarene hexamers.
Dalgarno, S. J.; Tucker, S. A.; Bassil, D. B.; Atwood, J. L. Science 2005,
309, 2037-2039. Dalgarno, S. J.; Bassil, D. B.; Tucker, S. A.; Atwood,
J. L. Angew. Chem., Int. Ed. 2006, 45, 7019-7022.
(4) (a) Stryer, L. Annu. ReV. Biochem. 1978, 47, 819-846. (b) Wu, P.; Brand,
L. Anal. Biochem. 1994, 218, 1-13. (c) Jameson, D. M.; Croney, J. C.;
Moens, P. D. J. Methods Enzymol. 2003, 360, 1-43.
(5) (a) Castellano, R. K.; Craig, S. L.; Nuckolls, C.; Rebek, J., Jr. J. Am.
Chem. Soc. 2000, 122, 7876-7882. (b) Azov, V. A.; Schlegel, A.;
Diederich, F. Angew. Chem., Int. Ed. 2005, 44, 4635-4638.
(6) (a) Hauke, F.; Myles, A. J.; Rebek, J., Jr. Chem. Commun. 2005, 4164-
4166. (b) Saito, S.; Rudkevich, D. M.; Rebek, J., Jr. Org. Lett. 1999, 1,
1241-1244.
(7) Skorobogatyi, M. V.; Pchelintseva, A. A.; Petrunina, A. L.; Stepanova, I.
A.; Andronova, V. L.; Galegov, G. A.; Malakhov, A. D.; Korshun, V. A.
Tetrahedron 2006, 62, 1279-1287.
(8) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2002, 41, 2596-2599. (b) Chan, T. R.; Hilgraf, R.;
Sharpless, K. B.; Fokin, V. V. Org. Lett. 2004, 6, 2853-2855.
(9) Beyeh, N. K.; Kogej, M.; Aahman, A.; Rissanen, K.; Schalley, C. A.
Angew. Chem., Int. Ed. 2006, 45, 5214-5218.
(10) Dale, T. J.; Rebek, J., Jr. J. Am. Chem. Soc. 2006, 128, 4500-4501.
(11) (a) Perez, E. M.; Dryden, D. T. F.; Leigh, D. A.; Teobaldi, G.; Zerbetto,
F. J. Am. Chem. Soc. 2004, 126, 12210-12211. (b) Onagi, H.; Rebek, J.,
Jr. Chem. Commun. 2005, 4604-4606.
To further probe the assembly, a fluorescent guest inside the
capsule made it possible to observe FRET across the mechanical
boundary of the hexamer. A number of pyrene derivatives were
1
examined as potential guests by H NMR analysis and the pyrene
salt 910 was encapsulated. A solution of 5:1 unlabeled resorcinarene
to perylene resorcinarene 8 (A) was prepared and pyrene salt 9
was added. Comparison of the emission spectra of the individual
components to that of the mixture of 8 (A) and 9 revealed FRET
from the guest inside the capsule to the perylene resorcinarene
appended to the capsule (Figure 3). Upon addition of methanol,
the FRET disappeared as the capsule was reduced to its constituent
monomers and the guest was released.
JA0700956
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