affords full exploitation of the hydrophobic effect—not possi-
ble in organic or organic : water mixes.
The development of supramolecular switches is significant:
1
pH responsive rotaxanes, multi-station catenanes, as well
2
13
1
4
as light sensitive cavitands have relevance towards mole-
1
cular devices. Multi-component assemblies that exhibit
5
1
‘pH-controlled guest swapping’’ exist as well. Our report
6
‘
is unique in that one guest can orient itself in two different
ways in one host. To our knowledge this is a first example of
such behavior in small molecule host–guest systems. Several
questions remain: do these changes occur simply due to a
buildup of negative charge, or does the cavitand geometry
alter as well? The exact location of the cavitand in the micelle
is also unknown at neutral or high pH. Presumably it is
exposed to the solvent exterior and not completely buried in
the hydrophobic interior of the micelle as guest exchange
1
Fig. 5 Binding of 3 with 2 in aqueous HPC micelles (300 MHz
NMR, 298 K, 550 mL D O, 10 mg HPC, 1.6 mg 2, 4.8 mg guest
A), then 5 mL 4% NaOD (B), and 10 mL total 4% NaOD (C)).
H
2
4
happens. We propose that the aqueous micelle environment
(
used to demonstrate switching serves as a basis for future work
1
7
component host–guest system where pH alters the direction-
ality of binding, in essence giving rise to pH switchable
isomers.
towards functional devices in lipid bilayers. In these more
well characterized environments we aim to find answers to
these questions.
These discoveries are explained through the buildup of
4
negative charge in the seam of the benzimidazole locus. We
We are grateful for financial support from the College of
Natural Science and Mathematics. We thank Prof. Richard
Hooley for providing us with Cavitand 2 and helpful discussions.
We thank Prof. Krzysztof Slowinski for helpful comments.
note that the control 4-tert-butyl aniline molecule was not
observed in 2 upon treatment with the base, thus its affinity for
the cavitand is related to the charge. When the cationic
trimethylammonium group is present as in 3, it now becomes
the guest of choice. This negative charge is significant enough
to eject the tert-butyl group and to entice the cationic portion
of 3 resulting in a switch of orientation.
Notes and references
1
S. M. Biros, E. C. Ullrich, F. Hof, L. Trembleau and J. Rebek,
J. Am. Chem. Soc., 2004, 126, 2870–2876.
2 D. M. Rudkevich, G. Hilmersson and J. Rebek, J. Am. Chem. Soc.,
998, 120, 12216–12225.
1
H. J. Choi, Y. S. Park, J. Song, S. J. Youn, H. S. Kim, S. H. Kim,
We next repeated the same experiment using the imidazole
cavitand 1 that lacks the water soluble carboxylate groups.
At neutral pH, 3 bound with the tert-butyl group buried
3
K. Koh and K. Paek, J. Org. Chem., 2005, 70, 5974–5981.
4 M. P. Schramm, R. J. Hooley and J. Rebek, J. Am. Chem. Soc.,
007, 129, 9773–9779.
2
(
À3.10 ppm, Dd = 4.41) consistent with the results for 2.
5
6
R. J. Hooley, S. M. Biros and J. Rebek, Chem. Commun., 2006, 509.
L. Trembleau and J. Rebek, Science, 2003, 301, 1219–1220.
Addition of 5.34 equivalents of base resulted in complete switching:
the trimethylammonium group is now deep in the cavitand
7 Dd calculated between the guest in D O and the guest when bound
2
(
À1.44 ppm, Dd = 5.08) (see ESIw). Neither cavitand 1 nor 2 is
to the host in micelles. Neither the base nor HPC alone resulted in
measurable changes in the chemical shift of several guests tested.
S. M. Biros and J. Rebek, Chem. Soc. Rev., 2007, 36, 93–104.
F. Hof, L. Trembleau, E. C. Ullrich and J. Rebek, Angew. Chem.,
Int. Ed., 2003, 42, 3150–3153.
so deep as to be able to encase both groups at the same time.
Previously pH titration experiments with 1 show that the
addition of 8 equivalents of base resulted in maximum change
in the chemical shift of several key protons of the cavitand.
Modified Job’s plot gave a 2.33 : 1 ratio of the base to the
cavitand. While these titrations were not performed on 2, the
results for 1 and 2 are almost identical—guest 3 switches its
orientation with addition of the base. We repeated the experi-
8
9
1
1
1
0 M. P. Schramm and J. Rebek, Chem.–Eur. J., 2006, 12, 5924–5933.
1 On a mole base per mole cavitand basis.
2 M. V. Martı
Chem., Int. Ed. Engl., 1997, 36, 1904–1907.
13 D. A. Leigh, J. K. Y. Wong, F. Dehez and F. Zerbetto, Nature,
003, 424, 174–179.
4 O. B. Berryman, A. C. Sather and J. Rebek Jr, Chem. Commun.,
011, 47, 656–658.
nez-Dıaz, N. Spencer and J. F. Stoddart, Angew.
´ ´
2
1
6 2
ment with 3 and 1 in 50 : 50 DMSO-d /D O with no micelles
2
and failed to observe binding at neutral pH. Addition of the
base gave rise to a new peak consistent with trimethyl-
ammonium binding. The micellar environment plays a signifi-
cant role. The stability of the C2v conformation of both 1 and 2 is
enhanced in micelles. Additionally, the micelle environment
15 V. Balzani, M. Gomez-Lopez and J. F. Stoddart, Acc. Chem. Res.,
1998, 31, 405–414.
1
6 S. Chakrabarti, P. Mukhopadhyay, S. Lin and L. Isaacs, Org.
Lett., 2007, 9, 2349–2352.
17 Y. Liu, P. Liao, Q. Cheng and R. J. Hooley, J. Am. Chem. Soc.,
2010, 132, 10383–10390.
9
638 Chem. Commun., 2011, 47, 9636–9638
This journal is c The Royal Society of Chemistry 2011