A light controlled cavitand wall regulates guest binding

Article abstract of DOI:10.1039/c0cc03865b

Here we report a cavitand with a photochemical switch as one of the container walls. The azo-arene switch undergoes photoisomerization when subjected to UV light producing a self-fulfilled cavitand. This process is thermally and photochemically reversible

Full text of DOI:10.1039/c0cc03865b

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A light controlled cavitand wall regulates guest bindingw
Orion B. Berryman, Aaron C. Sather and Julius Rebek Jr.*
Received 14th September 2010, Accepted 10th November 2010
DOI: 10.1039/c0cc03865b
Here we report a cavitand with a photochemical switch as one of
the container walls. The azo-arene switch undergoes photo-
isomerization when subjected to UV light producing a self-
fulfilled cavitand. This process is thermally and photochemically
reversible. The reported cavitand binds small molecules and
these guests can be ejected from the cavitand through this
photochemical process.
Molecular devices on the nanoscale continue to attract
attention,1 and a variety of stimuli to drive the machinery
are available. Changes in redox,2 pH,3 metal ion presence,4
and other chemical inputs5 have been used to cycle between
well-defined molecular states, but perhaps the oldest—and one
of the most frequently used stimuli—is light. In supramolecular
devices the trans/cis photoisomerism of the azo benzene
module provided the first switching mechanism applied to
the binding behavior of cyclodextrins6 and crown ethers.7 Its
ease of introduction, reliable shape and distance changes and
broad applicability, even to foldamers8 and biological
molecules such as proteins comprising ion channels,9 have
insured the popularity of the photoisomerization process.
Surprisingly, the azobenzene module has not appeared in deep
cavitands and we correct that omission here.10
Scheme 1 Synthesis of azo cavitands 1 and 2.
cavitand void where it can enjoy stabilizing CH–p interactions.
In contrast, the unsubstituted azo cavitand cis-2 can neither
reach the same CH–p distances nor adequately fill the space.
The switching capabilities of 1 and 2 were investigated in
d12-mesitylene. Both cavitands present only trans configura-
1
tion by H NMR after heating to reflux and cooling to room
temperature in the dark. Under ambient conditions a small
percentage of cis cavitand is observed, 8% for 1 and 5%
for 2.13
Computational and crystallographic studies reveal that
cis-azobenzene derivatives adopt a non-planar conformation
with a CCNN dihedral angle of B531.14 Photoisomerization
converts both cavitands to their respective cis configurations
but with different consequences. Irradiating cavitand 2 with
365 nm light for 15 minutes converts it to cis-2 where it can
adopt numerous cis conformations. In contrast, the photo-
isomerization of cavitand 1 places the tert-butyl substituent
inside the cavitand in a contorted conformational preference.
This isomerization can be monitored by 1H NMR. Exposing
trans-1 (Fig. 1, bottom) to 365 nm light for 15 minutes
converts it to the self-contained cis-1 (Fig. 1, top); the shielded
magnetic environment of the cavitand’s interior causes the
characteristic upfield shift of the tert-butyl group to À2.2 ppm
(see ESIw for NOE analysis). Cis-1 and cis-2 revert to their
trans configurations by heating to 164 1C for 5 minutes or
irradiating with 450+ nm light for 20 minutes. This switching
cycle can be repeated 5 times without detectable degradation
of the system.
In contrast to most photo-switchable devices—where the
photo-responsive unit is appended on the structure’s periphery
to impart function—we integrated it into the cavitand’s
structure. We devised two light-responsive cavitands that
exhibit very different guest binding behavior when exposed
to light. Control of guest uptake and release is achieved
through an unusual conformational preference, but only when
a tert-butyl group is present on the azo-arene substituent. The
switching is dictated by weak attractive forces and not through
typical covalent bonds or steric constraints.
We prepared azo cavitands 1 and 2 in one step from the
known mono-amine cavitand 311 (Scheme 1). Mixing
nitrosoarenes12 at room temperature in glacial acetic acid with
cavitand 3 resulted in the precipitation of pure azo-arene
cavitands as orange solids (see ESIw for 1H, 13C NMR and
mass spectrometry characterization data).
In the resting configuration azo-arene cavitands trans-1
and trans-2 present deep cavities for guest binding. Upon
irradiation with UV light, the azo substituent undergoes
photoisomerization to produce cis-1 and cis-2. The tert-butyl
substituent of 1 was expected to fold into and occupy the
Cavitands 1 and 2 feature a cavity defined by 8 aromatic
panels. This concave surface is suited to complement neutral
or cationic small molecules of appropriate shape and size.
Adamantane derivatives, for example, are taken up by trans-1
in d12-mesitylene with binding constants ranging from 5 to
>600 MÀ1 (Table 1). The exchange rates of these guests in and
out of the cavity are slow on the NMR time scale and separate
(upfield) signals are seen for the bound adamantane guests.
The largest association constants are observed for adaman-
tanes 7 and 8 which are stabilized by hydrogen bonding and
The Skaggs Institute for Chemical Biology, The Scripps Research
Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
E-mail: jrebek@scripps.edu; Fax: +1 858 784-2876;
Tel: +1 858 784-2876
w Electronic supplementary information (ESI) available: Character-
ization details, equilibrium studies, computations and kinetics of
photoisomerization. See DOI: 10.1039/c0cc03865b
c
656 Chem. Commun., 2011, 47, 656–658
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Fig. 2 1H NMR spectra in d12-mesitylene showing cavitand 2 binding
2-adamantanone (8, 9.3 eq.) both in the trans configuration (top) and
cis configuration (bottom). The guest remains bound when cavitand 2
is in either configuration and the bound guest signals are marked with
red squares.
Fig. 1 1H NMR spectra in d12-mesitylene showing trans-1 (bottom)
and self-contained cis-1 (top). The inverted tert-butyl signal is marked
by a blue circle.
Table 1 Association constants of 1 and 2 with adamantane guests
4–8a,b
Guests
1
2 Ka/MÀ1
1-Adamantanemethanol (4)
1-Chloroadamantane (5)
1-Adamantaneamine (6)
1-Adamantanecarbonitrile (7)
2-Adamantanone (8)
5
37
166
311
653
6
45
145
226
703
a
The Ka (MÀ1) values are the average of 3–6 experiments with errors
b
estimated at 20% (see ESIw). All experiments were performed in
d
12-mesitylene at 300 K, with initial [1] or [2] = 2.3 to 5.8 mM.
polar interactions with the upper rim of the cavitand.
Cavitand 2 binds the same adamantane guests with similar
trends in affinity and magnitude as those observed for 1 with
association constants ranging from 6 to >700 MÀ1
.
The effect of UV radiation on guest binding was different
for the two types of cavitands. When cavitand 2 adamantane
complexes were subjected to UV light, there was no change in
the concentrations of bound guest.15 Only the magnetic
environment of the guest was altered. Fig. 2 shows the relevant
spectra of cavitand 2 containing 2-adamantanone (8) in both
the trans (top) and cis (bottom) configuration. The broadened
1H NMR spectrum observed for cis-2 is due to the multiple cis
conformations that cavitand 2 adopts when a guest molecule is
present. The rate of the switching process in the presence of
guest molecules is slightly retarded and can be achieved by
heating or application of light (ESIw). However, bound
adamantane signals are present in either cavitand configura-
tion confirming that light cannot be used to control guest
uptake and release in 2.
Fig. 3 Select regions of the 1H NMR spectra in d12-mesitylene
illustrate how UV light affects guest binding in 1. Complex with 8
(7.8 eq.) before UV irradiation (bottom), after UV irradiation (middle)
and after heating to 164 1C for 5 minutes (top). Signals for bound
2-adamantanone (8) are marked by red squares; the introverted
tert-butyl is marked by a circle.
UV irradiation, these signals disappear as 2-adamantanone is
released into solution (Fig. 3 middle). The process is reversed
by heating the system to 164 1C for 5 minutes (Fig. 3, top) or
by application of visible light for 20 minutes where it reaches a
photostationary state of 71% trans-1. The process was cycled
5 times without noticeable degradation. Light can be used to
completely control the uptake and release of all adamantane
guests (4–8) in cavitand 1.
In contrast, light does control the uptake and release of
adamantane guests in cavitand 1. Exposing its host/guest
complexes to UV light for 15 minutes forces out the resident
guests and replaces them with the inwardly-directed tert-butyl
group. For instance, the bound guest 2-adamantanone (8)
exhibits 5 upfield signals (Fig. 3, red squares, bottom); after
The well-defined molecular environments of cavitands have
afforded numerous applications.16 Although the conformations
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of these molecules can be manipulated by temperature,17 pH18
or metal ions,19 there are few methods that reversibly control
guest binding. Diederich and co-workers used acid/base
chemistry to control the uptake and release of cycloalkanes,20
and we have used metal ions to manipulate a self-included
‘‘ouroborand’’ cavitand.21 These systems function well, but
less invasive switching processes are also desirable.22 The two
new cavitands presented here respond to light and heat by
changing their conformations, but only the tert-butyl substi-
tuted 1 forces guests out upon irradiation. The process is
reversible and can be cycled numerous times. The control of
guest binding underscores the subtle influence of appropriate
filling of space in recognition processes.23
R. H. Kramer, E. Y. Isacoff and D. Trauner, Nat. Chem. Biol.,
2006, 2, 47–52.
10 Two examples of azo-arenes attached to resorcin[4]arenes have
been reported. However, these molecules are not deep cavitands
and their guest binding function was not investigated, see:
(a) L. Husaru, M. Gruner, T. Wolff, W. D. Habicher and
R. Salzer, Tetrahedron Lett., 2005, 46, 3377–3379; (b) V. K. Jain
and P. H. Kanaiya, J. Inclusion Phenom. Macrocyclic Chem., 2008,
62, 111–115.
11 A. Lledo and J. Rebek Jr., Chem. Commun., 2010, 46, 1637–1639.
For other uniquely functionalized cavitands see: M. S. Brody,
C. A. Schalley, D. M. Rudkevich and J. Rebek, Jr., Angew. Chem.,
Int. Ed., 1999, 38, 1640–1644.
12 The synthesis of 3-tert-butyl nitrosobenzene is adapted from the
literature procedure: A. Defoin, Synthesis, 2004, 706–710. Experi-
mental details can be found in the ESIw.
13 The photostationary state is dependent on the conditions
employed. For instance, after heating in the dark, nearly all of 1
persists in the trans conformation for extended periods of time
(Fig. 1, bottom). Under ambient conditions a small amount of cis-1
is present. The quartz metal halide light employed in later experi-
ments produces even more cis-1 at that photostationary state.
14 For computational analysis see: (a) C. R. Crecca and A. E.
Roitberg, J. Phys. Chem. A, 2000, 110, 8188–8203; (b) P. C.
Chen and Y. C. Chieh, J. Mol. Struct. (Theochem), 2003, 624,
191–200. For a structural study see: A. Mostad and C. Romming,
Acta Crystallogr., Sect. C, 1983, 39, 1121.
We are grateful to the Skaggs Institute and the NIGMS
(GM 27953) for financial support. A postdoctoral fellowship
for O.B.B. was provided by NIH (F32GM087068). A.C.S. is a
Skaggs Pre-doctoral Fellow.
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