A transparent photo-responsive organogel based on a glycoluril supergelator

Article abstract of DOI:10.1039/c1cc11354b

The synthesis of an azo-benzene glycoluril supergelator is reported. The control over the gel/sol state can be accomplished by irradiation and heat, but also (in a unidirectional sense) by incorporation of the glycoluril into a more stable supramolecular

Full text of DOI:10.1039/c1cc11354b

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A transparent photo-responsive organogel based on a glycoluril
supergelatorwz
Konrad Tiefenbacher, Henry Dube, Dariush Ajami and Julius Rebek, Jr.*
Received 8th March 2011, Accepted 17th May 2011
DOI: 10.1039/c1cc11354b
The synthesis of an azo-benzene glycoluril supergelator is
reported. The control over the gel/sol state can be accomplished
by irradiation and heat, but also (in a unidirectional sense) by
incorporation of the glycoluril into a more stable supramolecular
assembly.
the hydrazinecarboxylates 13, 14 and 15 in 17–27% yield.
Another palladium catalyzed coupling to 4,40-dibromobenzil
gave compounds 16, 17 and 18 in 50–77% yield. After oxidation
to the corresponding azobenzenes using NBS,22 the glycoluril
heterocyles were installed by refluxing the benzils in the
presence of urea and TFA in a Dean–Stark-apparatus to yield
2, 3 and 4 in 32–48% yields over the two steps.
Gels are intensely studied materials with diverse applications
ranging from drug delivery, sensing, surface engineering and
hardening liquid waste.1,2 Organogels are formed by the
assembly of low molecular weight organic molecules into
entangled three-dimensional networks that entrap solvent
molecules. There is considerable interest in the development
of gels responsive to external stimuli with a special focus
on photo-responsive organogels.3–15 Easy and reversible
manipulation of the sol–gel state is especially desirable for
the creation of gel-based smart materials.16 We report here the
synthesis and characterization of glycolurils 2–4 bearing
azobenzene substituents. Glycoluril 2 was found to act as a
photoresponsive supergelator that can be switched reversibly
from the gel to the sol state by irradiation.
Glycolurils 2, 3, and 4 were tested for their gelation properties
in a variety of different solvents, and the results are given in
Table 1. The glycolurils were added to the solvent, the
mixtures were heated to nearly the boiling point then allowed
to cool to 20 1C. While compounds 3 and 4 did not form gels
at the initial test concentrations of 30 mg mLꢀ1, compound 2
gelated DMSO, CCl4, anisole, p-xylene, mesitylene and toluene
(Table 1). Subsequently the minimum gelation concentrations
of 2 were determined for these solvents. The best gelation
ability of 2 was observed in toluene, where a transparent gel
was formed at concentrations as low as 0.06% (w/v) at 20 1C.
Therefore 2 can be regarded as a supergelator—a group of
exceptional low molecular weight gelators, which are effective
at concentrations below 0.1% (w/w).1
Glycolurils are versatile building blocks for a variety of
host-structures in supramolecular chemistry.17–19 Nevertheless,
we know of only one report of a glycoluril forming a supra-
molecular gel: compound 1 gels at 20 mg mLꢀ1 in benzyl
alcohol, a relative high concentration.17,20 Accordingly, we
prepared new glycolurils 2–4 with azobenzenes on their
peripheries to explore the possibility of influencing their
aggregation properties by light (Fig. 1).
We investigated the microscopic structure of the toluene-
organogel by transmission electron microscopy (TEM, Fig. 2).
The TEM image of the xerogel of glycoluril 2 indicates that
molecules of 2 are self-assembled into an entangled network
of thin fibers with lengths up to tens of micrometers.
The synthetic routes are outlined in Scheme 1. Buchwald–
Hartwig-type reaction of bromoarenes 8, 9 and 10 (commercially
available or prepared from 1,3,5-tribromobenzene 7 and 5 or 6
in two steps) with t-butyl-carbazate (11) was unsuccessful,21
but the use of 2-di-t-butylphosphino-20,40,60-triisopropyl-
biphenyl (12) as ligand yielded the desired regio-isomers of
The Skaggs Institute for Chemical Biology and Department of
Chemistry, The Scripps Research Institute, 10550 North Torrey Pines
Road, La Jolla, California 92037, USA. E-mail: jrebek@scripps.edu
w This article is part of a ChemComm ‘Supramolecular Chemistry’
web-based themed issue marking the International Year of Chemistry
2011
z Electronic supplementary information (ESI) available: Experimental
details, synthetic procedures and characterization data for compounds
2–18, 1H-NMR spectrum of assembly 20. See DOI: 10.1039/
c1cc11354b
Fig. 1 Structures of benzil 1 and azo-benzils 2–4.
Chem. Commun., 2011, 47, 7341–7343 7341
c
This journal is The Royal Society of Chemistry 2011

Scheme 1 Syntheses of azo-glucolurils 2–4.
Table 1 Results of the gelation experiments with compound 2
(at 30 mg mLꢀ1) at 20 1C
organogels1 and are likely contributors to the gelation properties
of 2. Since compounds 2–4 contain the same glycoluril
H-bonding features, it is likely that the larger p-surface in 2 is
responsible for the gelation ability of these compounds.
Solvent
Statea
Toluene
Mesitylene
p-Xylene
Anisole
CCl4
DMSO
G (0.06%; 0.6 mg mLꢀ1
G (0.08%; 0.8 mg mLꢀ1
G (0.09%; 0.9 mg mLꢀ1
G (0.15%; 1.5 mg mLꢀ1
)
)
)
)
The influence of light on the sol/gel state was next investigated.
Typically, azobenzenes can be isomerized between trans- and
cis-conformations by irradiation with light at 365 nm. Irradiation
of gel-samples led to a phase transition to the sol-state (Fig. 3,
top). To quantify the trans-/cis- ratio in the gel state, sol state
G (1.0%; 10 mg mLꢀ1
G (3.0%; 30 mg mLꢀ1
S
)
)
CHCl3, THF, Et2O, Ethyl acetate,
Pyridine,
1
and photo-stationary state H-NMR studies were performed
Benzene, Benzyl alcohol, DMF
n-Hexane, Cylohexane, Acetone,
Water, MeCN, MeOH, EtOH
P
I
(for discussion see SIw): We found that the featureless spectra
recorded in D12-mesitylene (0.1% m/v of 2) were turned into
well-resolved ones by addition of 40% (v/v) of D8-THF
followed by agitation, just before NMR-acquisition. The
cis/trans ratios could now be determined by integration of
the well-separated proton signals of these species. In the gel-
state only the trans/trans isomer was observable, whereas after
the phase transition to the sol-state 11% cis/cis-, 37% trans/
cis- and 52% trans/trans-glycoluril 2 were detected. Accordingly,
switching 30% of the azobenzene moieties of glycoluril 2 from
their trans- into the corresponding cis-conformation disrupts
the entangled gel structure severely enough to revert the
system back to the sol state. At the photo-stationary state
19% cis/cis-, 30% trans/cis- and 51% trans/trans-glycoluril 2
were detected. Interestingly, attempts to convert samples af
ter the phase transition (11% cis/cis-, 37% trans/cis- and
52% trans/trans-glycoluril 2) back to the trans/trans- isomeric
gel by the use of irradiation with 450 nm—even after extended
irradiation—failed: 11% cis/cis- and 89% trans/trans-
a
G = gel; S = solution; P = precipitate at 20 1C; I = insoluble. For
gels the minimum gelation concentration at 20 1C are given.
Fig. 2 TEM images of the xerogel obtained from organogel (0.1%
(w/v) 2 in toluene) after evaporation of the solvent under vacuum.
Magnification of 25 000, scale bar: 500 nm.
glycoluril
2 were detected. Although the cis/cis-isomer
resisted isomerisation by irradiation (450 nm), heating any
sample (160 1C, 1 min) and then allowing it to cool to
20 1C in the dark, readily regenerated the (all trans/trans)
gel-state.
The diameter of the fibers is approx. 26 nm (see SIw). What
structural features are responsible for the gelation abilities of 2?
H-bonding motifs and p-surfaces are found in a variety of
c
7342 Chem. Commun., 2011, 47, 7341–7343
This journal is The Royal Society of Chemistry 2011

It is known that fluoride ions also efficiently compete with
urea-H-bonds and this interaction has been used to exert
control over the gel-sol state.24,25 A similar effect of fluoride
can be observed with gelator 2: After addition of 0.5 eq of
TBAF to a mesitylene gel sample (0.4% m/v, see SIw), the
sample lost the ability to support its own weight.
In conclusion, we have shown that azobenzene-appended
glycoluril 2 is a supergelator, which forms transparent gels
with a variety of solvents. The control over the gel/sol state of
2 can be accomplished by irradiation and heat, or (in a
unidirectional sense) by its incorporation in a more stable
supramolecular assembly.
We thank the Skaggs Institute for Research for financial
support. The Austrian Science Fund provided an Erwin-
Schroedinger Scholarship for K.T. and the Alexander von
Humboldt Stiftung provided a Feodor Lynen Fellowship for
H. D. K. T. and H. D. are also Skaggs Postdoctoral Fellows. The
authors are grateful to Malcolm R. Wood for the TEM-analysis.
Notes and references
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Fig. 3 Influencing the gel/sol sate of glycoluril 1 by light or by the
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alkyl groups and most glycoluril substituents have been removed.
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Transformation of the gel into a sol-state through assembly
of a different supramolecular structure was also established
(Fig. 3). Addition of cavitand 19 (0.5 eq.) and a suitable guest
(n-tetradecane, 0.25 eq.) to a gel sample of 2 in D12-mesitylene,
followed by heating (to allow a homogenous distribution of all
components) resulted (after allowing the sample to cool to
20 1C) in a solution of an extended capsular assembly,23 which
was characterized as 20 by 1H NMR (see SIw). In each of these
capsular assemblies four glycolurils 2 are efficiently bound
between two cavitands in a chiral belt by a network of
hydrogen bonds (green dotted lines in Fig. 3) and therefore
are excluded from assembling into the gel fiber-structure
(Fig. 2). The minimum required concentration of added
capsule components has been determined for a mesitylene-gel
sample of 2 at 0.4% (m/v): The sample lost its ability to
support its weight at a concentration of 1.2 mM in cavitand
19. At this concentration of 19, the remaining concentration of
‘free’ gelator 2 (not bound in assembly 20) was reduced to
0.8 mM or 0.1% (w/v)-slightly above the minimum gelation
concentration of 0.08% (w/v) in the original sample (Table 1).
Thus, the main contribution of the capsular assembly to
disruption of the gel structure can be regarded as a dilution
effect.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 7341–7343 7343