A four-component organogel based on orthogonal chemical interactions

Article abstract of DOI:10.1039/c4cc03398a

A thermoresponsive organogel was obtained by orthogonal assembly of four compounds using dynamic covalent boronate ester and imine bonds, as well as dative boron-nitrogen bonds. It is shown that the gel state can be disrupted or reinforced by chemicals which undergo exchange reactions with the gel components. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc03398a

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A four-component organogel based on
orthogonal chemical interactions†
Nicolas Luisier,a Kurt Schenkb and Kay Severin*a
Cite this: Chem. Commun., 2014,
50, 10233
Received 6th May 2014,
Accepted 12th July 2014
DOI: 10.1039/c4cc03398a
www.rsc.org/chemcomm
A thermoresponsive organogel was obtained by orthogonal assembly These first reports are evidence that dative B–N bonds can be
of four compounds using dynamic covalent boronate ester and imine used for the generation of supramolecular organogels. Several
bonds, as well as dative boron–nitrogen bonds. It is shown that the studies have shown that boronate ester linkages can be formed
gel state can be disrupted or reinforced by chemicals which simultaneously with imine bonds.8,11 These results prompted
undergo exchange reactions with the gel components.
us to investigate whether it is possible to obtain organogels by
simultaneous utilization of boronate esters, imines, and dative
The syntheses and the properties of gels based on mixtures of two B–N bonds. To examine this question, we have performed a
or more low molecular weight components have been investigated small screening using four different types of compounds: aryl-
extensively over the last years.1 As pointed out in a review article by boronic acids containing a formyl group (A1, A2), arylboronic
Hirst and Smith, these multicomponent gels provide ‘‘exquisite acids with a primary amine group (B1, B2), catechols (C1–C3),
tunability and controllability’’.1b The gel properties can be altered and ditopic N-donor ligands (D1–D4) (Table 1). Upon condensa-
by structural modifications of the individual building blocks or tion, the catechols were expected to react with the boronic
by variation of the building block ratio. Furthermore, multi- acid functions, and the amine groups with the aldehydes. This
component gels are typically based on reversible chemical inter- polycondensation reaction should give a diboronate ester, which
actions between the gel components. Consequently, they qualify as could aggregate via dative B–N bonds (Scheme 1). The resulting
supramolecular gels,2 and they are able to respond to changes in assembly might induce gelation.
temperature or to chemicals which alter the interaction between
The screening was performed as follows: the four different
the gel components.3,4 While there are numerous reports about compounds were mixed in the ratio A : B : C : D = 1 : 1 : 2 : 1 in
two-component gels,1 there are relatively few studies about gels toluene ([A] = 20 mM). The mixture was heated for 4 h under
based on three or more distinct building blocks (solvent not reflux using a Dean–Stark trap and then it was allowed to cool.
included).5 Below, we describe a thermoresponsive gel which is Out of the ten different combinations that we have tested, most
formed by orthogonal assembly6 of four compounds using two reactions resulted in the formation of a precipitate (Table 1,
different dynamic covalent bonds and dative boron–nitrogen entries 1–7). This result was not unexpected because previous
bonds. It is shown that gel formation can be reversed by selective studies had shown that the aggregation of polyboronate esters with
disruption of one of the three interactions.
polytopic N-donor ligands tends to give insoluble (sometimes crystal-
Dative bonds between Lewis acidic boronate esters and line) materials.7d,8a The use of highly soluble catechol C3 afforded a
N-donor ligands are increasingly being used for the construction viscous liquid (Table 1, entry 8). For two of the combinations,
of molecular nanostructures and polymeric materials.7,8 In 2011, however, we observed the formation of a gel as evidenced by
we have reported the formation of an organogel by reaction of a the tube-inversion test (Table 1, entries 9 and 10). Preliminary
triboronate ester with 4,40-bipyridine in toluene.9 More recently, the test revealed that gel formation for GEL1 could be reversed and
group of Iwasawa has demonstrated the formation of a gel by cross- re-induced by heating–cooling cycles, whereas GEL2 was less
linking of oligomeric boronic esters with 1,3-diaminopropane.10 well behaved (precipitates were observed). Therefore, we focused
on GEL1 for more detailed investigations.
To study the molecular basis for gel formation, we performed
a
´
´
´ ´
Institut des Sciences et Ingenierie Chimiques, Ecole Polytechnique Federale de
Lausanne (EPFL), 1015 Lausanne, Switzerland. E-mail: kay.severin@epfl.ch
b Laboratoire de Cristallographie, EPFL, 1015 Lausanne, Switzerland
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc03398a
a control experiment using only three compounds: A2, B2, and
C1. Heating of the three compounds in the ratio 1 : 1 : 2 in
toluene resulted in the formation of the boronate ester 1, which
could be isolated in 82% yield (Scheme 2). Addition of the
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Table 1 The different starting materials used for the 4-component reaction
Scheme 2 Synthesis of GEL1 by a direct 4-component reaction or by a
two-step process involving the intermediate 1.
Entry
Combination in toluene
Sample state
1
2
3
4
5
6
7
8
9
10
A1 + B2 + 2C1 + D2
A2 + B1 + 2C1 + D1
A2 + B1 + 2C1 + D3
A2 + B2 + 2C2 + D2
A2 + B2 + 2C1 + D4
A1 + B2 + 2C2 + D2
A2 + B2 + 2C2 + D1
A2 + B2 + 2C3 + D2
A2 + B2 + 2C1 + D2
A2 + B1 + 2C1 + D2
Precipitate
Precipitate
Precipitate
Precipitate
Precipitate
Precipitate
Precipitate
Viscous liquid
GEL1
calorimetry (ITC) experiments in chloroform with 1 and the
model compound N-methylimidazole. The data could be fitted to
a 1 : 2 binding model assuming two identical and independent
binding sites (see ESI†). The resulting association constants are
Ka1 = 4.4(ꢀ0.7) ꢁ 103 Mꢂ1 and Ka2 = 1.1(ꢀ0.2) ꢁ 103 Mꢂ1. NMR
titration experiments in CDCl3 showed that the complexation of
N-methylimidazole is fast on the NMR time scale. Plotting the
changes in chemical shifts vs. concentration resulted in binding
isotherms, which could be nicely fitted using the association
constants obtained by ITC (see ESI†).‡ Taken together, these
results are good evidence that the chemistry outlined in Scheme 2
is indeed responsible for gel formation.
GEL2
We then explored the gelation properties of the 1–D2 mixture
in different solvents (Table 2). We chose non-protic, medium-to-
low polarity solvents because highly polar solvents were expected
Table 2 Gelation tests with a mixture of 1 and D2 in different solvents
a
CGC
CGC
Tsol–gel
Solvent
Gelation
[wt%]
[mM]
[1C]
Tetrahydrofuran
Toluene
No
Yes
No
Yes
No
No
Yes
Yes
No
—
0.065
—
0.25
—
—
0.1
0.2
—
—
0.9
—
4.6
—
—
2.4
5.2
—
—
75
—
60
—
—
55
77b
—
—
90
45
65
Scheme 1 Synthesis of a supramolecular gel based on dynamic covalent
bonds and dative B–N bonds using a 4-component reaction.
Nitrobenzene
Chlorobenzene
1,2-Dichlorobenzene
1,3-Dichlorobenzene
1,2,4-Trichlorobenzene
Carbon tetrachloride
Chloroform
Mesitylene
o-Xylene
m-Xylene
p-Xylene
N-donor D2 to a suspension of 1 in toluene, followed by a
heating–cooling cycle, gave a gel which behaved very similarly
to the one obtained by a one-step reaction.
The fact that gelation can be induced upon addition of the
bisimidazole D2 to 1 suggests that dative B–N bonds are
responsible for network formation. The ability of 1 to bind
imidazole-type N-donors was confirmed by isothermal titration
No
—
—
Yes
Yes
Yes
0.1
1.0
0.25
1.4
14.2
3.6
a
b
Tsol–gel for 1.0 wt% of GEL1. The gel was only broken in boiling CCl4.
10234 | Chem. Commun., 2014, 50, 10233--10236
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to interfere with the dative B–N bonds, and protic solvents might
disrupt the ester linkage. Apolar solvents such as hexane
were likewise omitted because the starting materials are not
sufficiently soluble. Toluene and CCl4 gave gels with low critical
gel concentrations (CGC) – as low as to 0.065 percent in weight
for toluene.§ Xylenes were tested as well and showed that the
relative position of both methyl groups have strong influence
on the gel properties, with o-xylene giving a more robust gel
compared to m-xylene. No gelation was observed with THF,
presumably because it is already too polar to allow efficient
B–N bond formation. Interestingly, both chlorobenzene and
1,2,4-trichlorobenzene gave gels, but neither 1,2- nor 1,3-dichloro-
benzene resulted in gelation. These results show that the system
is very sensitive to the nature of the solvent.
With 1.0 wt% of the gel components, the sol–gel tempera-
ture was estimated with the tube inversion test. The corre-
sponding values are listed in Table 2. In m-xylene, solubilization
was already observed at 45 1C. In the less polar CCl4, on the other
hand, gel disruption was only observed when reaching the
boiling point of the solvent.
Scheme 3 The gel state of GEL1 can be disrupted of reinforced by
addition of chemicals.
Scanning electron microscopy images of the xerogels obtained N-methylimidazole (a substitute for D2) and aniline. The addition
by air-drying samples of GEL1 in all gelating solvents were taken to of methanol or dichlorocatechol to a solution of 1 in CDCl3
investigate the gel morphology. The results revealed the coexistence resulted in partial liberation of catechol. In the gel state, the
of spherical aggregates along with a variable amount of fibrous transesterification with C2 leads to the formation of an insoluble
structures in all cases (ESI,† Fig. S10–S16).
precipitate (similar to what was observed in 4-component
Wide-angle X-ray scattering (WAXS) measurements of the GEL1 reactions involving C2; see Table 1).
xerogel from toluene revealed a mainly amorphous material,
Addition of 4-t-butylcatechol (C3) to GEL1 in toluene followed
while the xerogel sample from p-xylene showed a slightly higher by a heating–cooling cycle resulted in a modified gel GEL1–C3,
degree of crystallinity (ESI,† Fig. S17). The scattering peaks which exhibited an increased mechanical resistance compared
appear at the same angles for both samples, indicating that the to its precursor GEL1. This was evidenced by putting a metallic
molecular packing of the crystalline part of the xerogel is sphere on freshly prepared samples of GEL1 and GEL1–C3. After
similar. Due to the low crystallinity of the samples, we have 2 minutes, the sphere had sunken into GEL1, while it was still on
not attempted to derive more detailed structural information top of GEL1–C3 (ESI,† Fig. S18). This result was unexpected,
from the WAXS patterns.
since a boronate ester with the more electron-rich catechol
Finally, we tried to prepare a gel by omitting one out of the C3 (obtained by catechol exchange) should form slightly weaker
four compounds A2, B2, C1, or D2. None of these reactions gave B–N bonds.12 When GEL1 was treated with normal catechol C1
a gel, indicating that all four compounds are required.
instead of C3, an increased mechanical resistance of the resulting gel
An attractive feature of a supramolecular gel based on was not observed. These results are further evidence that minor
orthogonal interactions is the possibility to selectively disrupt structural modifications can have a large impact on the gel proper-
these interactions by chemical or physical means. As outlined ties. Importantly, the results show that one can use exchange
above, heating of GEL1 in toluene above 75 1C results in its reactions via dynamic covalent chemistry to reinforce the mechanical
solubilization. It is likely that temperature affects the weakest properties of a multicomponent gel such as GEL1.
links of the assembly, that is the dative B–N bonds. We have also
To summarize: we have reported a thermoresponsive organogel
studied the disassembly of GEL1 by chemical stimuli.3 In these which is based on four different low molecular weight compounds.
experiments, we have placed an excess of the corresponding In solution, three of the compounds undergo a polycondensation
chemical in pure form on top of a 1.0 wt% gel in toluene. The reaction to give an imine-linked diboronate ester (1). The latter
following compounds were found to disrupt the gel state: methanol, aggregates with the fourth component (D2) via dative B–N bonds,
N-methylimidazole, dichlorocatechol (C2), and aniline. Importantly, thereby inducing gel formation. A unique feature of the system is
these chemicals appear to be selective stimuli, since they disturb the presence of three types of dynamic interactions between the gel
mainly one of the three reversible interactions of the assembly components: dynamic covalent imine and boronate ester bonds, as
(Scheme 3). The selectivity was substantiated by a series of control well as dative B–N bonds. These interactions are largely orthogonal
experiments (see ESI†). The addition of aniline, for example, to each other.¶ It is thus possible to selectively address them
results in a transimination reaction as shown by a model with physical or chemical stimuli, resulting in rupture or
reaction of 1 with aniline. The dative B–N bond, on the other reinforcement of the gel state.
hand, is less disturbed by aniline as evidenced by competition
experiments using a simple boronate ester in combination with Foundation and by the Ecole Polytechnique Federale de
The work was supported by the Swiss National Science
´ ´
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‡ A direct fit of the NMR titration data did not provide reliable results
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§ Despite the low CGC values, the gels are rather soft. Rheology
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¶ They are not perfectly independent: imines and boronate esters are
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