Photochemical control of reversible encapsulation

Article abstract of DOI:10.1002/anie.201000876

(Figure Presented) Remote control: Molecules can be transferred in a chemical system between capsules and bulk solution by using light and heat. The principle is based on the isomerization of azobenzene, the trans isomer of which is encapsulated, but the cis isomer is not (see picture; C gray and brown, Br mauve; O red, N blue, H white). The photochemical control can also be used to switch between different capsular assemblies.

Full text of DOI:10.1002/anie.201000876

Communications
DOI: 10.1002/anie.201000876
Host–Guest Chemistry
Photochemical Control of Reversible Encapsulation**
Henry Dube, Dariush Ajami, and Julius Rebek, Jr.*
The cis–trans photoisomerization of azobenzenes is a well-
known phenomenon that is the basis of many molecular
devices;[1,2] it is also probably one of the earliest switching
mechanisms in supramolecular chemistry, with applications in
crown ethers[3–5] and cyclodextrins.[6,7] The changes in molec-
ular shape on isomerization are large and predictable, a
feature that has also made them useful in biological applica-
tions.[8,9] We show herein that the photoisomerization can be
indirectly used as a method to control encapsulation phe-
nomena. This remote control is a consequence of the snug fit
of trans-4,4’-dimethylazobenzene (trans-1) in the capsule
2·2.[10] Photoisomerization causes trans-1 to “break out” of
the capsule, thus allowing the entry of other guest species.
Occupancy of the extended assembly 2·34·2 can be controlled
using the longer trans-4-methyl-4’-hexylazobenzene[11] (trans-
4), and it is possible to switch between assemblies 2·2 and
2·54·2 by using photoisomerization.
The cylindrical capsule 2·2 recognizes guests that are
congruent in shape and complementary in chemical sur-
face.[12] The host may be filled with several small guests, or a
suitable single guest, including benzanilides,[13] n-alkanes,[14]
and stilbenes.[15] The latter guest showed unexpected photo-
physical properties when complexed: unlike the enhanced
fluorescence seen when complexed with snugly-fitting anti-
bodies,[16] the stilbene fluorescence is quenched when encap-
sulated by 2·2, a result that is attributed to the gently twisted
(nonplanar) conformation that it assumes in the capsule.[17]
Given the parallels in behavior of stilbenes and azobenzenes,
particularly with respect to cis–trans isomerism in a photo-
stationary state, we undertook the examination of encapsu-
lated azobenzene under the effects of irradiation.
Figure 1. a) Light-induced guest exchange of trans-1 by n-tridecane in
2·2. b) Indicative regions of the 1H NMR spectra ([D12]mesitylene,
208C) are shown before irradiation (trans-1 is the only guest) and after
irradiation at 365 nm wavelength for 50 min at 208C (n-tridecane is the
only guest). After heating the sample to 1608C for 2 min, the initial
state was completely restored.
azobenzene out of the capsule. This effect apparently occurs
by photoexcitation of trans-1 to its cis-conformation, which no
longer fits within 2·2. Simultaneously, signals of cis-1 in
solution appeared at d = 6.59 ppm and 6.67 ppm in the
1H NMR spectrum. On heating the sample to 1608C for
2 minutes, cis-1 reverted to its trans conformation and rapidly
replaced n-tridecane in the capsule. This cycle was repeated
many times without deteriorating the integrity of the system
(four cycles are shown in Figure S4 in the Supporting
Information).
In principle, the encapsulation of any other suitable guest
could be initiated by light. For example, 4,4’-dimethylbenzil is
a comparable guest for 2·2. When ten equivalents of trans-1
were also present in solution, only the azo compound was
encapsulated by 2·2. After irradiation, the 1H NMR spectrum
showed that benzil was the only encapsulated species. After
heating the sample to 1608C for 2 minutes, the guests
completely exchanged their locations and the system reverted
to its original state.
The photochemical manipulation extends to other encap-
sulation arrangements. Typically, a single guest is able to
replace two occupants in an entropy-driven process[18] that
increases the number of free molecules. For example, hydro-
gen-bonded homodimers of benzoic acid or benzamide are
suitable guests for capsule 2·2. Three equivalents of trans-1
were sufficient to suppress binding of the acid or amide, but,
after irradiation, the azo compound was replaced by the
respective homodimers. After heating, the initial state was
The arrangement is shown in Figure 1a; trans-1 in capsule
2·2 was treated with an equimolar amount of n-tridecane in
[D12]mesitylene. The azobenzene is much more strongly
bound and no n-tridecane was observed inside the capsule
by 1H NMR spectroscopy (Figure 1b). The solution was then
irradiated with 365 nm light and the encapsulated 1 was
completely replaced by the encapsulated alkane within
50 minutes (Figure 1b), that is, the irradiation forces the
[*] Dr. H. Dube, Prof. D. Ajami, Prof. J. Rebek, Jr.
The Skaggs Institute for Chemical Biology and
Department of Chemistry, The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Fax: (+1)858-784-2876
E-mail: jrebek@scripps.edu
[**] We are grateful to the Skaggs Institute for Research for financial
support and the Alexander von Humboldt Stiftung for a Feodor
Lynen Fellowship for H.D, who is also a Skaggs Postdoctoral Fellow
and was supported by the Swiss National Science Foundation
(SNF).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201000876.
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restored and the cycle can be repeated many times (see
Figure S5 in the Supporting Information for 1H NMR spectra
recorded for substitution of trans-1 by 4,4’-dimethylbenzil,
benzoic acid, and benzamide).
The two possible mechanisms for light-induced guest
switching are illustrated in Figure 2. In the first mechanism,
Rates were measured to resolve the mechanistic choices
(Figure 2c). Firstly, the light-induced isomerization of trans-1
was investigated. After 8 minutes, 97% of trans-1 isomerized
into the cis-form in solution. When trans-1 was encapsulated
in the absence of a competitive guest, the end point of
isomerization was reached after 40 minutes of irradiation and
only 84% of free cis-1 was obtained (the remaining trans-1
stayed inside the capsule). Light-induced isomerization of
encapsulated trans-1 did not proceed faster in the presence of
30 equivalents of n-tridecane as an additional guest: again the
end point was reached after 40 minutes, however 95% of cis-1
was obtained in solution outside the capsule. The percentage
of n-tridecane inside the capsule at each measurement
matches the percentage of cis-1 outside the capsule.
The rate of exchange of encapsulated trans-1 with n-
tridecane as an incoming guest was determined under
conditions where no irradiation was applied: 30 equivalents
of n-tridecane were required in order to partially displace
encapsulated trans-1, although only 19% of trans-1 was
ultimately replaced at equilibrium. Thus, 19% exchange
corresponds to 95% (within the experimental error) of
conversion in this system. In Figure 2c, the 19% exchange
is normalized to 95% to facilitate visualization. The end point
was reached after about 1600 min; that is, the displacement of
azobenzene by another guest is very slow. This finding was
confirmed by ROESY NMR spectroscopy, which showed no
exchange peaks between trans-1 inside and outside of the
capsule at 300 K or 335 K (Figures S6 and S7 in the Support-
ing Information). The exchange rates of similar shaped guests
and capsule halves determined by fluorescence methods at
much lower concentrations are also fully consistent with these
findings.[19]
These experiments rule out the possibility that cis–trans
isomerization of 1 takes place outside the capsule; instead, the
light-induced guest switching proceeds by a “breakout”
mechanism. The folding of the excited azobenzene forces
the walls outward and facilitates guest exchange. Such wall
motions are involved in vase-to-kite conformational changes
of cavitands;[20] Diederich and co-workers have shown that
the mobility of only two such walls is enough to enable guest
exchange in related cases.[21]
Figure 2. Two possible mechanisms for light-induced guest exchange:
a) Fast exchange of the more strongly bound trans-1 by n-tridecane is
required for light-induced cis–trans isomerization outside the capsule.
b) cis–trans isomerization takes place inside the capsule, thus leading
to steric clashes with the walls that promote the “breakout” of 1 and
occupancy by n-tridecane. c) Kinetic data for light-induced cis–trans
isomerization of 1 (1.2 mm in [D12]mesitylene) and correlated guest
exchange. All data points were obtained by integration of appropriate
1H NMR signals after the irradiation time corresponding to the x-axis
values or after the corresponding waiting time in case the sample was
&
not irradiated. : conversion of trans-1 to cis-1 in [D12]mesitylene.
The slow isomerization of encapsulated trans-1 compared
to that of free guest in solution is also consistent with this
interpretation. The encapsulated excited state may transfer
energy to the capsule walls either electronically or mechan-
ically by forcing the walls outward and breaking some of the
hydrogen bonds. In either case, the partitioning of the excited
state is affected, thus leading to a decrease in the rate of
isomerization.
*
: conversion of encapsulated trans-1 to free cis-1. ꢀ: conversion of
encapsulated trans-1 to free cis-1 on irradiation in the presence of
30 equivalents of n-tridecane; : percentage of encapsulated n-tride-
cane under these conditions. : percentage of encapsulated n-tride-
cane without irradiation of encapsulated trans-1 in the presence of
30 equivalents of n-tridecane (two different time scales are used).
^
~
in–out exchange of trans-1 is faster than the light-induced
conformational change and isomerization to the cis-form
takes place outside 2·2. Since cis-1 is not encapsulated, any
potential guest can then rush into the evacuated (solvent or
solvent-impurity-filled) capsule. In the second mechanism,
in–out exchange of trans-1 is slow and the isomerization takes
place inside of the capsule. The cis-geometry of the guest
clashes with the capsule walls and forces them outward, thus
breaking hydrogen bonds and facilitating exchange, that is, a
“breakout” mechanism.
Parallel experiments were applied to guest occupation of
the extended capsule 2·34·2. Four molecules of a glycoluril
such as dibutylaniline derivative 3 are incorporated into the
capsule in order to form an extended assembly when suitable
guests are present.[22] For example, when the longer trans-4 is
deployed as light-responsive guest, the mono-extended
1
assembly 2·34·2 is formed, as revealed by H NMR spectros-
copy (Figure S8 in the Supporting Information). Because 4
bears different substituents at the 4 and 4’ positions, and is too
long to tumble inside, the assembly is desymmetrized: the two
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Communications
cavitand ends show separate sets of 1H NMR signals as do the
was obtained. The resulting solution is slightly turbid, which
indicates that 5 precipitates from solution once it is freed from
the assembly. On heating the solution at 1608C for 2 minutes,
the original extended assembly 2·54·2 was restored, with trans-
4 as the only encapsulated guest (Figure 4, see also Figure S11
hydrogen atoms on the two edges of the glycoluril units.
Binding of the homodimer of 4-ethylbenzamide into 2·34·2 is
suppressed in a solution containing 10 equivalents of trans-4
and 2 equivalents of 4-ethylbenzamide. However, after irra-
diation with 365 nm light, the encapsulated homodimer of 4-
ethylbenzamide is the only “social isomer”[23] present. This
hydrogen-bonded dimer is symmetric and its 1H NMR
spectrum is simplified accordingly. Heating the sample to
1608C for 2 min restored the initial state and the cycle could
be repeated many times (Figure 3 and Figure S9 in the
Figure 4. a) Light-induced guest exchange with concomitant change of
assembly. b) 1H NMR spectrum ([D12]mesitylene, 208C) is shown
before irradiation (trans-4 is the guest in the extended assembly 2·54·2)
and after irradiation at 365 nm for 50 min at 208C (4,4’-dibromobenzil
is the guest in the capsule 2·2). After heating the sample to 1608C for
2 min, the original state was completely restored.
in the Supporting Information). Accordingly, an external
signal can reversibly switch not only encapsulated guests, but
the very nature of the capsules that they occupy.
It should be possible to bring this system to the next level
of complexity where photoisomerization can be used to affect
chemical reactions that are not known to be photosensitive;
we are currently working toward this goal.
Figure 3. a) Light-induced guest exchange of trans-4 by 4-ethylbenza-
mide in the extended assembly 2·34·2. b) Indicative regions of the
1H NMR spectra ([D12]mesitylene, 208C) are shown before irradiation
(trans-4 is the only guest) and after irradiation at 365 nm for 50 min at
208C (the homodimer of 4-ethylbenzamide is the only guest). After
heating the sample to 1608C for 2 min, the initial state was completely
restored. This cycle was repeated three times (see Figure S9 in the
Supporting Information).
Received: February 11, 2010
Published online: March 22, 2010
Supporting Information). Similarly, encapsulation of two
molecules of p-cymene can be controlled in this way
(Figure S10 in the Supporting Information); 4 equivalents of
trans-4 and 16 equivalents of p-cymene were optimal for this
series of reversible changes in occupancy. There are three
social isomers of p-cymene possible in 2·34·2, but only two
were observed, as previously described.[22]
Keywords: azobenzenes · encapsulation · host–guest chemistry ·
photoisomerization · supramolecular chemistry
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