Exploiting molecular self-assembly: From urea-based organocatalysts to multifunctional supramolecular gels

Article abstract of DOI:10.1002/chem.201402436

We describe the self-assembly properties of chiral N,N′-disubstituted urea-based organocatalyst 1 that leads to the formation of hierarchical supramolecular gels in organic solvents at low concentrations. The major driving forces for the gelation are hydr

Full text of DOI:10.1002/chem.201402436

DOI: 10.1002/chem.201402436
Full Paper
&
Multifunctional Materials
Exploiting Molecular Self-Assembly: From Urea-Based
Organocatalysts to Multifunctional Supramolecular Gels
[a]
[b]
[b]
[c]
Eva-Maria Schçn, Eugenia Marquꢀs-Lꢁpez, Raquel P. Herrera,* Carlos Alemꢂn, and
[a, d]
David Dꢃaz Dꢃaz*
Abstract: We describe the self-assembly properties of chiral
N,N’-disubstituted urea-based organocatalyst 1 that leads to
the formation of hierarchical supramolecular gels in organic
solvents at low concentrations. The major driving forces for
the gelation are hydrogen bonding and p–p interactions ac-
tence of a unique set of molecular interactions and an opti-
mal hydrophilic/hydrophobic balance in 1 that drive the for-
mation of stable gels. Responses to thermal, mechanical, op-
tical, and chemical stimuli, as well as multifunctionality were
demonstrated in some model gel materials. Specifically,
1 could be used for the phase-selective gelation of organic
solvent/water mixtures. The gel prepared in glycerol was
found to be thixotropic and provided a sensitive colorimetric
1
cording to FTIR and H NMR spectroscopy, as well as quan-
tum-mechanical studies. The gelation scope could be inter-
preted based on Kamlet–Taft solvatochromic parameters.
TEM, SEM, and AFM imaging revealed that a variety of mor-
phologies including helical, laths, porous, and lamellar nano-
structures could be obtained by varying the solvent. Experi-
mental gelation tests and computational structural analysis
of various structurally related compounds proved the exis-
I
method for the detection of Ag ions at millimolar concentra-
tions in aqueous solution. Moreover, the gel matrix obtained
in toluene served as a nanoreactor for the Friedel–Crafts al-
kylation of 1H-indole with trans-b-nitrostyrene.
Introduction
of materials with different functions due to critical technologi-
cal barriers.
[2]
Multifunctional stimuli-responsive structures have drawn great
attention in the last decade due to their potential use in ad-
vanced devices and help to expand fundamental scientific un-
In the above context, self-assembled gels constitute prom-
ising candidates to achieve multifunctional materials for differ-
[
3]
[4]
ent applications. In contrast to chemical gels, which are
[
1]
[5]
derstanding. Such systems possess properties that allow
them to perform more than one function in a device or materi-
al in which interfacial properties are coupled. Inspired by abun-
dant examples in nature for which multifunctionality is a norm
based on covalent bonds, physical or supramolecular gels are
made of either low-molecular-weight (LMW) compounds or
polymers through noncovalent interactions (e.g., hydrogen
bonding, p–p stacking) that usually provide a reversible re-
sponse to external stimuli (e.g., gel-to-sol thermal transition).
In general, the solidlike appearance of gels is derived from
a very efficient entrapment of the solvent molecules, usually
(e.g., multifunctional extracellular matrices), the main need for
the development of multifunctional materials is that specific
problems cannot always be solved by the mere combination
[6]
by capillary forces, into the interstices of a solid matrix with
high surface area formed upon the entanglement of 1D supra-
molecular fibrilar assemblies. There is an extensive collection of
functional moieties that can induce the formation of such as-
[
a] Dr. E.-M. Schçn, Prof. D. D. Dꢀaz
Institut fꢁr Organische Chemie, Universitꢂt Regensburg
Universitꢂtsstr. 31, 93053 Regensburg (Germany)
E-mail: David.Diaz@chemie.uni-regensburg.de
[2c,3c,5]
semblies in solution.
Among those, the ureide group is
[
b] Dr. E. Marquꢃs-Lꢄpez, Dr. R. P. Herrera
Departamento de Quꢀmica Orgꢅnica.
Instituto de Sꢀntesis Quꢀmica y Catꢅlisis Homogꢃnea (ISQCH)
CSIC-Universidad de Zaragoza
one of the best-known hydrogen-bonding functional groups,
which has been widely used to fabricate valuable supramolec-
[7]
ular architectures, including gel networks based on mono- or
Pedro Cerbuna 12, 50009 Zaragoza (Spain)
E-mail: raquelph@unizar.es
[8]
polyurea gelators, by a directional assembly process.
Herein, we report and rationalize the self-assembly proper-
ties of a known urea-based organocatalyst that leads to the
formation of multifunctional and multiresponsive supramolec-
ular gels in organic solvents.
[
c] Prof. C. Alemꢅn
Departament d’Enginyeria Quꢀmica
-
ETSEIB and Center for Research in Nano-Engineering
Universitat Politꢆcnica de Catalunya, Av. Diagonal 647
8028 Barcelona (Spain)
0
[d] Prof. D. D. Dꢀaz
IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona (Spain)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402436.
Chem. Eur. J. 2014, 20, 10720 – 10731
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fluoromethyl groups (compound 7) since they are also known
to lower the basicity and/or confer distinctive solvation proper-
ties of organic compounds, which play a key role on the gela-
Results and Discussion
Design and synthesis of compounds
[2–6]
tion phenomena.
All synthesized compounds were satisfactorily characterized
During our research programs focused on both the develop-
ment of new organocatalysts and the use of unconventional
reaction media (e.g., softgel materials, ionic liquids), we paid
close attention to the tendency of the known N,N’-disubstitut-
[10]
after purification by silica gel column chromatography.
[
9]
Gelation ability and gel stability
ed urea-based organocatalyst (+)-1 (Scheme 1) to increase
the viscosity of some common organic solvents leading to the
in situ formation of jelly-like lumps during its synthesis. We de-
cided to investigate in detail the gelation ability of 1 after
taking into consideration the facile and scalable synthesis of
this type of compound, its intrinsic potential as a multifunction-
al molecule, and the previous studies reported so far on urea-
The gelation ability of urea 1 was first evaluated for 33 differ-
ent solvents by using the classical heating-cooling process
within a broad concentration range. The state of the resulting
mixture was initially examined by the “stable-to-inversion of
a test tube” method. After the visual inspection, the viscoelas-
tic gel nature of those samples showing no gravitational flow
upon turning the vial upside-down was further confirmed by
oscillatory rheological measurements in model solvents (vide
infra).
[
8]
based organogelators. Compound 1 is easily accessible by an
equimolar reaction of commercial (1S,2R)-1-amino-2,3-dihydro-
1
H-inden-2-ol and 3,5-bis(trifluoromethyl)phenyl isocyanate in
methylene chloride at room temperature (Scheme 1).
We were delighted to observe that compound 1 induced
gelation of 14 solvents at a critical gelation concentration
ꢀ
1
(
CGC) between 3 and 50 gL (Table 1) (the procedure to de-
termine the CGC is described in the Experimental Section).
2
3
These values imply the immobilization of 10 –10 (order of
Table 1. Gelation scope of 1, optical appearance (OA) of the gels, critical
Scheme 1. Synthesis of the N,N’-disubstituted urea (+)-1.
gelation concentrations (CGC), gelation times, and gel-to-sol transition
[
a]
temperatures (Tgel).
[
d]
To correlate the structural features of 1 with the gelation
properties, we designed and synthesized a library of analogous
compounds 2–7 (Figure 1) following a similar synthetic proce-
dure. The structural complexity of 1 was greatly reduced by re-
placing both aromatic residues by 3,5-bis(trifluoromethyl)phen-
yl groups (compound 3) or phenyl groups (compound 4). To
study the influence of the stereochemical configuration of the
stereogenic centers we also carried out the synthesis of the
diastereomer 5. The evident intramolecular hydrogen bonding
between the carbonyl group and the hydroxyl group at the
Entry Solvent
Phase OA CGC
Gelatin time Tgel
ꢀ
1
[gL
]
[8C]
1
2
3
4
5
6
7
8
9
1
toluene
benzene
chlorobenzene
1,2-dichlorobenzene
1,3-dichlorobenzene
mesitylene
o-xylene
m-xylene
nitrobenzene
glycerol
G
G
G
G
G
G
G
G
G
G
G
G
G
G
T
T
T
T
T
T
T
T
O
T
T
T
T
T
3
3
30ꢁ5 min
30ꢁ5 min
7ꢁ2 min
7ꢁ2 min
7ꢁ2 min
5ꢁ1 h
55
41
54
62
64
nd
nd
nd
41
74
46
nd
84
nd
3.6
3.6
3.6
3.5
3.5
3.5
50
3
4
7
5
25
8ꢁ2 h
5ꢁ1 h
30ꢁ5 min
40ꢁ10 min
20ꢁ5 min
45ꢁ10 min
10ꢁ5 min
24 h
[b]
[c]
0
2,3-dihydro-1H-indene residue inspired us to prepare com-
11
12
methylene chloride
chloroform
pound 6 lacking the hydroxy group and thiourea derivative 2.
Additionally, we considered the removal of only the bulky tri-
1
1
3
4
carbon tetrachloride
nitromethane
[
c]
[
a] Gels obtained after heating–cooling cycle. Volume=1 mL. Abbrevia-
tions: G=gel; T=transparent gel; O=opaque gel; nd=not determined
due to gel weakness. [b] Commercial sample contained 10 wt.% water.
[
c] A minor fraction of insoluble material remained. [d] Values calculated
at the CGC by the inverse flow method. Estimated error ꢁ28C.
magnitude) solvent molecules per gelator molecule. In most
cases, complete gelation was achieved within 5 min and 1 h. A
clear preference for gelation of aromatic (entries 1–9) and
chlorinated solvents (entries 11–13) was observed. All organo-
gels obtained at the CGC were transparent except in nitroben-
zene, which was completely yellowish opaque, which indicated
the formation of aggregates smaller than the visible wave-
length range (l=400–700 nm) (Figure 2). Such optical differen-
ces highlight the importance of the interactions between sol-
Figure 1. Library of additional compounds 2–7 used in this work.
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It is worth mentioning that all our attempts to obtain iso-
tropic solutions of potential gelators in the model solvents and
subsequent formation of stable gels using either 1) sonication
instead of the heating–cooling cycle or 2) predissolving the
compound in the minimum amount of a nonprotic polar sol-
vent, such as DMSO followed by addition of the testing solvent
(
e.g., maintaining the CGC value as given in Table 1) at room
temperature were fruitless.
Thermal and temporal stability
The organogels were found to be thermoreversible and stable
to multiple heating–cooling cycles without any detriment on
the gelation ability and gel properties. The gel-to-sol transition
temperatures (T ) of all organogels were determined by the
gel
[12]
inverse flow method. As this method depends on the cool-
ing rate and thermal history, among other factors, the values
were correlated for model examples with the first endothermic
transition observed by differential scanning calorimetry (DSC)
Figure 2. Representative digital photographs of upside-down vials contain-
ing organogels made of 1 in different solvents at the CGC as shown in
Table 1.
(
see Figure S5 in the Supporting Information). Consistently
with the formation of more entwined networks, Tgel increased
considerably until reaching a plateau with increasing the con-
centration of the urea gelator 1 (e.g., DTgel (toluene) ~388C
upon increasing 2.3-fold the concentration defined by the
CGC, Figure 3). Interestingly, we found that the amount of
vent and gelator molecules for the growth and stabilization of
the supramolecular network.
Compound 1 was found to be insoluble in both water and
n-heptane upon heating and/or extensive sonication (2 h),
ꢀ
1
whereas stable clear solutions were obtained at 50 gL upon
heating–cooling in acetonitrile, ethyl acetate, ethanol, metha-
nol, DMSO, DMF, dimethylacetamide, THF, diethyl ether, 1,2-di-
methoxyethane, acetone, cyclohexanone, 3-methyl-butan-2-
one, methyl tert-butyl ether, 1,4-dioxane, benzonitrile, and ra-
peseed oil. Exceptionally, gels in nitromethane (Table 1,
entry 14) and 90 wt.% glycerol (entry 10) could also be ob-
tained. The case of glycerol is particularly interesting since 1) it
was the only alcoholic solvent in which gelation was successful
and 2) it is a nontoxic, nonhazardous, nonvolatile, and biode-
gradable solvent widely used in manifold industries including,
among others, food, antifreeze, pharmaceutical, and personal
[
11]
care applications.
Based on the solvent parameters (vide infra) and to optimize
the number of experiments, we chose three representative
model solvents (i.e., CH Cl , toluene, and glycerol), among
2
2
Figure 3. Phase diagram and evolution of Tgel as a function of the concentra-
tion of gelator 1 in toluene.
those gelled by 1, to conduct comparative gelation experi-
ments with the structurally related compounds 2–7. Very inter-
estingly, the analogues 2–6 did not show any gelation ability
in the model solvents. Only compound 7, lacking the trifluoro-
methyl groups, was able to form a transient weak gel in tolu-
water present in commercial 90 wt.% glycerol was necessary
to prepare the isotropic solution of the gelator and subse-
quent gels. Attempts to dissolve 1 in 99 wt.% glycerol upon
heating were unsuccessful. The Tgel values increased considera-
bly from 60 to 90 wt.% glycerol (e.g., 648C at 70 wt.% and
748C at 90 wt.%. The gels prepared with 60 wt.% glycerol
were too fragile to resist inversion of the vial).
ꢀ
1
ene at a concentration of 3 gL , and a stable gel in glycerol at
ꢀ
1
5
gL . Compound 7 required not only a five-fold higher con-
centration than 1 to form a steady homogeneous gel in glycer-
ol, but also an approximately five-fold longer gelation time.
These results clearly suggested the existence of unique inter-
and/or intramolecular interactions as well as an optimum bal-
ance between hydrophobic and hydrophilic domains that
largely favor the spontaneous self-assembly of 1 in solution
leading to supramolecular aggregates with a lifetime long
enough to allow their anisotropic growth and consequent
stable gel formation.
Organogels made of 1 at the CGC remained stable for at
least one month when stored undisturbed at room tempera-
ture. After this period, optical microscopic imaging of some
materials revealed a very slow crystal growth (Figure 4), which
clearly underlines the thermodynamic equilibrium between gel
[13]
and crystalline phases. Nevertheless, the robustness of the
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showed this ability with a broad scope of organic sol-
vents. Typically, a 1:1 v/v mixture containing water
and any water-immiscible organic solvent from
Table 1 was heated and vigorously shaken in the
presence of 1 at the corresponding CGC. After cool-
ing down the homogeneous dispersion to room tem-
perature, the organic phase was entirely gelled,
whereas the water phase remained liquid. Depending
on the density of the organic phase, the gel material
was located either above or below the water layer.
For the latter case, the gel was stiff enough to hold
the upper water phase upon inversion of the vial
Figure 4. Optical microscope picture showing crystal formation in the gel matrix made of
ꢀ1
1
at CGC (left) and at 15 gL (right) after five weeks.
(
Figure 6A). Both phases could be further separated
gel network permitted its coexistence with the crystal nuclea-
tion for several months while remaining stable to the inversion
of the vial. As expected, the crystallization kinetics also in-
creased with gelator concentration.
by simple decantation or filtration. The thermal stability of the
gel phase remained very similar to the gel obtained from the
pure organic solvent (i.e., DTgel ca. ꢁ58C).
Influence of enantiomeric purity
[
14]
As chirality plays a key role in the formation of gels, we in-
vestigated the gelation ability of 1 prepared at different enan-
tiomeric excesses by mixing appropriate amounts of the pure
enantiomers (+)-1 and (ꢀ)-1. Stable gels upon inversion of the
vials were only obtained when the enantiomerically pure urea
gelator was used (Figure 5 and Figure S14 in the Supporting
Figure 5. Influence of enantiomeric purity on the gelation ability of 1. Per-
cent values indicate the enantiomeric excess of 1 used in each case.
Information). As expected, (+)-1 and (ꢀ)-1 showed identical
gelation properties. Precipitation or small pieces of jelly-like ag-
gregates were observed when the urea compound was used
with enantiomeric excesses below 80%. The material made
from the urea with 80% ee consisted of a mixture of precipi-
tate and gel (gelation time in this case was double than when
using pure 1) and could support the inversion of the vial. How-
ever, after 48 h, the material collapsed and only the sample
made with 100% ee remained homogeneous, transparent, and
stable to the inversion of the vial.
Figure 6. A) Representative digital photographs of phase-selective gelation
of organic solvent/water mixtures (total volume=2 mL). The organic solvent
is marked with an asterisk. B) High-scale phase-selective gelation of 1:1 v/v
ꢀ1
toluene/water mixture (total volume=0.1 L ). Water-soluble T-1824 dye
(Evans Blue) was used to differentiate better both phases. The aqueous
phase remained completely liquid after gelation of the upper organic phase
as evidenced by usual spinning of the magnetic stir bar. Inset in the
bottom-right picture) Photograph of a water drop on a thin film of the gel
made in toluene.
Moreover, the phase-selective gelation could be scaled up
Phase-selective gelation ability
5
0-fold without any difficulty (Figure 6B). When the aqueous
Selective organogelation from organic solvent/water mixtures
phase was stained with Evans Blue, the organic phase re-
mained clear upon gelation, which indicated no diffusion of
water through the interface. This is also understandable if we
consider the intrinsic hydrophobicity of polyfluorinated 1 (e.g.,
water contact angle (WCA) ~1108), which is even enhanced
[
15]
is an important task in environmental remediation. This abili-
ty has been reported for some efficient LMW organogela-
[
15,16]
tors,
albeit it is still an uncommon feature in the area of
supramolecular gels. Interestingly, water-insoluble urea 1 also
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upon the formation of the nanostructured gel network as
a result of combining the low surface energy with a superior
roughness (e.g., WCA of the xerogel obtained from the gel
ones for a Hansen model, although a model based on the
Kamlet–Taft parameters is comparatively more adequate for
developing a gelation model in our case. No significant ten-
[
17]
made in toluene ~1408). Moreover, we observed that the
dencies were observed for the gel properties (i.e., CGC, T ) in
gel
model gels remained stable in the presence of water, NaOH
function of the individual solvent parameters.
(
0.1m), or even HCl (0.1m) aqueous solutions (the experiments
were carried out by placing 1 mL of the test solution on top of
mL of gel material).
Driving force study and computer modeling
1
FTIR measurements
In agreement with other urea-based gelators, comparison of
the FTIR spectra of model xerogels prepared from the corre-
sponding organogels by freeze-drying with those in solution
phase and 1 in the solid state supported the involvement of
hydrogen bonding in the gelation phenomenon (see Figure S4
in the Supporting Information). In general, the gel-based mate-
Correlation between gelation ability and solvent parameters
To rationalize the organogel formation we built and compared
3D plots according to the Kamlet–Taft solvatochromic parame-
ters (i.e., hydrogen-bond donor ability (a), hydrogen-bond ac-
[
18]
ceptor (b), and polarizability (p*)) and the Hansen solubility
parameters (i.e., dispersive interactions (d ), dipolar interactions
rials displayed ꢀNH stretch vibration bands at approximately
d
ꢀ1
3
311–3257 cm , whereas amide I (C=O) and amide II vibra-
(
d ), and hydrogen bonding (d ) interactions) (see Table S1 in
p h
tions appeared at approximately 1641–1637 and 1562–
[
19]
the Supporting Information). The Kamlet–Taft solvent param-
eters have been associated with the ability of forming hydro-
gen-bonded gels (a value), thermal stability of the networks (b
value) and stabilization of charges and dipoles during the gela-
ꢀ
1
1
546 cm , which typically correspond to molecules aggregat-
ed by hydrogen bonding (non-hydrogen-bonded amides dis-
play the above vibrations at approximately 3430, 1660, and
ꢀ
1
1
515 cm , respectively). No vibrational bands were observed
[
20]
tion process (p* value). With glycerol being the only excep-
tion, these parameters clearly delimited a gelation cuboid
space (ca. 0.045 cubic units) defined by the following approxi-
mate dimensions: 0<b<0.3,0<a<0.2 and 0.25<p*<
ꢀ
1
in the region of 3700–3500 cm (ꢀOH stretching, free), which
suggests that the hydroxyl group is also hydrogen bonded,
likely to the carbonyl group in an intramolecular manner. Inter-
estingly, the solid and freshly prepared 1 showed the selected
absorption bands at the same positions within the experimen-
1
(Figure 7). These limits indicate that p* has the lower influ-
ence in the formation of gels, whereas having relatively low
and balanced hydrogen-bond donor and acceptor abilities is
critical. On the other hand, Hansen solubility parameters also
provided an acceptable gelation space albeit only approxi-
mately 70% of the gelled solvents were found inside the
cuboid space defined approximately by 0<d <9,17.5<d <
ꢀ
1
tal uncertainty (ꢁ2 cm ), which indicates that urea 1 is also
aggregated by hydrogen bonding in the solid state and hence
the existence of some similarity between the solid and the gel
structures. In agreement, although compound 1 has a very low
degree of crystallinity as deduced from its PXRD pattern, the
xerogel obtained by freeze-drying the corresponding organo-
gel in toluene still preserved part of this crystallinity (i.e., major
broad peak centered at 208, 2(q)) (Figures S16–17).
p
d
2
0 and 0.5<d <6 (see Figure S3 in the Supporting Informa-
h
tion). Thus, dipolar interactions seem to be the most critical
1
Temperature-dependent H NMR spectroscopic experiments
[21]
As we have observed with peptide-based physical gels, the
protons involved in the stabilization of the supramolecular net-
work could be experimentally tracked by NMR spectroscopic
experiments at different temperatures. Thus, we recorded
1
H NMR spectra of the model organogel made of 1 in
[
D ]toluene within a temperature range for which both gel and
8
solution phases could be gradually interconverted. An upfield
ꢀ5
ꢀ1
shift (i.e., Dd/DTꢂ5.3ꢅ10 ppmK ) of the ꢀNH urea protons
was first observed in the range of 27–358C, followed by a clear
ꢀ
4
ꢀ1
downfield shift (i.e., Dd/DTꢂ1.5ꢅ10 ppmK ) in the range
of 35–558C (gel phase). A further increase of the temperature
until 708C (solution phase) was accompanied by another up-
ꢀ
3
ꢀ1
field shift (i.e., Dd/DTꢂ6.3ꢅ10 ppmK ) (Figure 8).
The unusual and diffident upfield shift observed at the be-
ginning of the experiment is presumably associated with a ho-
mogenization process of the sample. The marked maximum
point observed at 558C (~328 K; breaking of hydrogen bond-
ing) matched with the Tgel of the material. The ꢀOH proton dis-
played a very similar chemical shift pattern. All other protons
Figure 7. 3D scattering plot showing the results of the gelation tests and
the Kamlet–Taft parameters of each solvent. * =gelated solvents; * =non-
gelated solvents.
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Figure 8. Representative temperature-induced chemical shifts of the ꢀNH
urea proton of 1 in [D ]toluene.
8
not involved in hydrogen bonding showed the opposite pat-
tern (i.e., upfield shift until 558C and subsequent downfield
shift until 708C) (see Figure S6 in the Supporting Information).
Overall, these results are in good agreement with the marked
influence of hydrogen bonding and p–p stacking interactions
in the gelation process, involving a different type of disassem-
[
22]
bly process during the initial heating period.
1
It should be noted that the H NMR spectroscopic signals of
gelator molecules that form the gel network are unlikely to be
[
23]
observed due to long correlation times. The observed sig-
nals are then attributed to small amounts of gelator molecules,
either aggregated or disaggregated, dissolved in the immobi-
lized solvent. Thus, the improvement of the signals resolution
and increment of their intensity upon heating (see Figure S6 in
the Supporting Information) is associated with the enhance-
ment of molecular mobility and segregation of the network.
gp
sol
ꢀ1
Figure 9. Range of variation of A) DEi and B) DEi (both in kcalmol ) for
the calculated dimers of compounds 1–7.
gp
sol
ꢀ1
DEi and DEi (ꢀ46.4 and ꢀ27.6 kcalmol , respectively) re-
veals the coexistence of one parallel p–p stacking interaction,
three hydrogen-bond interactions (two NꢀH···O and one Oꢀ
H···O), and one CꢀH···p stabilizing interaction. In addition, dis-
Quantum-mechanical calculations
To evaluate the strength of the intermolecular interactions in
1
–7, quantum-mechanical calculations at the M06L/6-31+
G(d,p) level were performed on model complexes formed by
two interacting molecules (dimers). More specifically, seven dif-
ferent complexes were constructed for the dimer of 1 by con-
sidering stabilizing p–p stacking, dispersion, hydrogen bond-
ing, and dipole–dipole intermolecular interactions. After this,
the seven dimers of 1 were used to construct equivalent
dimers for 2–7 (i.e. introducing the required changes in the
chemical structure without altering the relative orientation be-
tween the cores of the two molecules). All these structures
were used as starting points for complete geometry optimiza-
tions in dichloromethane solution.
Figure 9, which represents the interaction energies calculat-
gp
i
ed in absence of external forces (DE ) and in CH Cl solution
2
2
sol
(
DE ), indicates that the association is significantly more fa-
i
vored for 1 than for the compounds 2–7, which is fully consis-
tent with the gelation abilities discussed above. Although the
interaction energy increases with the polarity of the environ-
ment, the functionality and molecular architecture of 1 is the
most appropriate for the formation of intermolecular interac-
tions. Figure 10A, which depicts the dimer of 1 with lowest
Figure 10. Representation of the most stable complex calculated for dimers
of a) 1, b) 7, and c) 5. Intermolecular hydrogen bonds (a), p–p stacking
(
(
$) and CꢀH···p interactions (!) are displayed. Labels refer to the distances
in ꢆ) found for each stabilizing interaction: H···O distance in hydrogen
bonds; center of masses to center of masses in p–p stacking; and H···center
of masses in CꢀH···p. See the Supporting Information for a color version of
this figure.
Chem. Eur. J. 2014, 20, 10720 – 10731
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tances displayed in Figure 10A are typically associated with
strong secondary interactions. Interestingly, the dimer of 7
gp
sol
ꢀ1
with lowest DEi and DEi (ꢀ34.6 and ꢀ20.0 kcalmol , re-
spectively), which is depicted in Figure 10B, shows the same
number and type of interactions. As the only difference be-
tween 1 and 7 refers to the ꢀCF groups, which have been
3
eliminated in the latter, the reduction in the interaction ener-
gies that amounts to approximately 25% should be attributed
to the fluorine-induced electrostatic and dispersive interac-
[
24]
tions.
Both the number and, especially, the strength of intermolec-
ular interactions are lower for dimers of compounds 2–4, as is
gp
sol
evidenced in the complex of lowest DEi and DEi displayed
for each compound in Figure S21 (Supporting Information).
This reduction is essentially due to the thiourea in 2, which
forms weaker hydrogen bonds than the replaced urea, and to
the removal of the hydroxyl group in 3 and 4, which affects
not only intermolecular interactions but also to the interaction
of the dimers with the solvent. Thus, the dimerization of 2 re-
sults in the formation of two weak NꢀH···S hydrogen bonds
and two parallel p–p stacking interactions (Figure S21A, Sup-
porting Information), whereas the most stable dimer of 3 and
Figure 11. Representative TEM and AFM images of xerogels obtained from
the corresponding organogels prepared at the CGC as shown in Table 1. The
high aspect ratio of the images suggests a highly anisotropic supramolecular
assembly. TEM: A,B) toluene, C) methylene chloride. AFM: D) Benzene.
SEM imaging of the xerogels revealed a remarkable influ-
ence of the solvent nature on the morphology of the supra-
molecular aggregates (Figure 12 and Figure S10 in the Sup-
porting Information). For instance, accurate laths of 100–
400 nm widths were obtained with mesitylene (1,3,5-trimethyl-
benzene), whereas dense ribbonlike fibrilar structures (Ø~10–
40 nm) were observed in toluene, benzene, and xylenes. In
sharp contrast, chlorinated solvents provided fibrilar and
highly interconnected macroporous structures (Ø~100–
500 nm). Other solvents, such as nitromethane featured unique
lamellar layer microstructures that were not observed with
other solvents. The exact mechanism for which each solvent
induced a specific morphology remains elusive.
4
shows two NꢀH···O hydrogen bonds and two p–p stacking
interactions, one with the aromatic rings arranged in parallel
and the other with a T-shaped disposition (Figure S21B and
S21C, Supporting Information). Compound 5 deserves special
attention since its chemical composition is identical to that of
1
, the only difference between the two species involving the
stereochemistry of the urea group with respect to the five-
membered ring. As it can be seen in Figure 10C, which displays
gp
sol
the dimer of 5 with lowest DE and DEi (ꢀ22.4 and
i
ꢀ
1
ꢀ
20.1 kcalmol , respectively), the hydroxyl groups only inter-
act with the solvent, the stereochemistry precluding their par-
ticipation in stabilizing intermolecular hydrogen bonds. Conse-
gp
sol
quently, the interval of variation of DEi and DEi is significant-
ly lower for 5 than for 1. Indeed, comparison of the energies
computed for the dimers of the stereoisomers displayed in Fig-
ure 10A and 10C indicates that 5 is less stable than 1 by 8.3
and 11.8 in dichloromethane solution and in the gas-phase, re-
spectively. The most stable dimers of compound 6 in terms of
Moreover, the anisotropic and thermoreversible nature of
the organogels enabled us to turn on/off their birefringence
under polarized light (Figure 13 and Figure S12 in the Support-
ing Information), an important property widely searched for in
[25]
optical devices.
gp
sol
DEi and DEi are different (Figures S21D and S21E, Support-
ing Information, respectively), even though the characteristics
of the secondary interactions found for these complexes are
very similar to those described above for 2–5.
Oscillatory rheological measurements
Dynamic rheological measurements of some model materials
confirmed their viscoelastic properties. Typically, the storage
modulus G’ and loss modulus G’’ were first measured at room
temperature as a function of the frequency (dynamic frequen-
cy sweep experiment, DFS) and shear strain (dynamic strain
sweep experiment, DSS) to establish the linear viscoelastic
regime (Figure 14 and Figures S7–S9 in the Supporting Infor-
mation). A relatively constant tan d (G’’/G’) value during the
DFS measurement was indicative of a good tolerance of the
gel against external forces. Within the linearity limits of defor-
mation (e.g., 1 Hz frequency and 0.1% strain), G’ was found
always one order of magnitude higher than G’’ (e.g., G’ꢂ2.3
Morphological characterization of organogels
The fibrilar nature of the gel networks was evidenced by TEM
imaging of the corresponding xerogels. Typically, entangled
supramolecular fibers with average diameters in the range of
10–30 nm and a few micrometer lengths were observed for
different solvents (Figure 11). Complementary images of dense
fibrilar bundles with average heights between 15 and 30 nm
were also obtained by AFM. Interestingly, a close look to the
photographs revealed that the fibers corresponding to the gel
in some solvents like toluene displayed a helical morphology
4
3
ꢅ10 Pa, G’’ꢂ6.8 ꢅ10 Pa, for the gel made of 1 in toluene at
5 gL ). The stability of the material over time at room temper-
ꢀ
1
(Figure 11 and Figure S11 in the Supporting Information).
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Figure 12. Representative SEM images of xerogels obtained by freeze-drying the corresponding organogels prepared in different solvents at the CGC as
shown in Table 1. A) benzene, B) toluene, C) chlorobenzene, D) 1,3-dichlorobenzene, E) 1,2-dichlorobenzene, F) nitrobenzene, G) mesitylene, H) m-xylene, I) o-
xylene, J) methylene chloride, K) carbon tetrachloride, L) nitromethane.
strain as defined by DTS experiments (G’>G’’-gel-), further in-
crease of the strain until the gel fractures (G’<G’’-sol-) and
final return at the same rate to the initial strain value (G’>G’’-
gel-). Figure 15 shows up to 50% recovery of the original gel
strength within 1 min after the second step and full recovery
after 3 h. The thixotropic behavior was also macroscopically
observed in a glass vial upon a vigorous shaking/resting cycle.
This property is highly pursued for the use of gel-based materi-
Figure 13. Polarized light microscope images of A) organogel made of 1 in
methylene chloride at CGC and B) the corresponding solution obtained
als in many real-life applications.
upon the thermal gel-to-sol transition. The polarizing filter is oriented 908 to
the plane of the polarized light.
Responsiveness to silver ions
Responsiveness tests of model gels in the presence of various
ature was finally confirmed by dynamic time sweep (DTS)
measurements at 0.1% strain and 1 Hz frequency.
ions revealed that they maintained their integrity after incuba-
tion with CuSO , NaI, KOAc, or KNO aqueous solutions (0.1m).
4
3
[
26]
Interestingly, a thixotropic response to the large external
strain of the gel made in glycerol was confirmed by a three-
However, glycerol gel showed an evident color change from
colorless to orange/brownish after 30 min in the presence of
[
27]
+
step loop test consisting of the initial application of a shear
solutions containing Ag ions (e.g., AgNO , AgOAc, AgOTf)
3
(
Figure 16A). The color change
was still visible to the naked eye
after 24 h for concentrations of
I
Ag ions as low as 0.01 mm. A
series of control experiments
demonstrated that the counter-
ion was not involved in the al-
teration of the color. In addition,
the presence of the urea was
necessary for the optical
change, albeit it was neither lim-
ited to compound 1 nor to the
Figure 14. Representative oscillatory rheological experiments (DSS, DFS, DTS) of model gels prepared in toluene
and glycerol (90 wt.%) at 5 gL . *: G’ (Tol); ~: G’’ (Tol); *: G’ (Gly); ~: G’’ (Gly).
ꢀ
1
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Scheme 2. Alkylation of 1H-indole with trans-b-nitrostyrene in solution and
the gel phase.
[30]
reaction vessels with enhanced selectivity.
Within our re-
search program devoted to investigate reactivities in organized
and confined media, we also decided to examine the ability of
the self-assembled gel network made from 1 to serve as
a nanoreactor for the metal-free Friedel–Crafts alkylation of 1H-
indole with trans-b-nitrostyrene (Scheme 2). We have previous-
ly studied both urea 1 and thiourea 2 as organocatalysts for
this reaction in solution. The results obtained there clearly
demonstrated a higher catalytic efficiency for the thiourea,
which was attributed to its greater hydrogen-bond donor abili-
ty and less tendency to self-assembly in comparison to 1. Re-
markably, when the above reaction was carried out in the gel
phase provided by 1 in toluene, the product yield of 8 in-
creased approximately 1.4-fold compared with that in solution
Figure 15. Loop test of the gel made from 1 at CGC in glycerol (90 wt.%).
Steps: 1) 1 Hz, 0.1% strain, 20 min (tan d=0.1017ꢁ0.002); 2) 1 Hz, 10000%
strain, 30 min; 3) 1 Hz, 0.1% strain (tan d=0.108ꢁ0.002).
[9]
(
Figure S18, Supporting Information).
This result is especially relevant if we consider that kinetics
of diffusion-controlled processes can be 10–20 times faster in
[31]
stirred solutions than in nonstirred gel media. In addition,
the average level of enantioselectivity observed in the gel
phase was slightly superior than in solution, which may sug-
gest among different possibilities that the fibrilar network
could somehow provide an additional shielding effect respon-
sible for facial discrimination. In addition, the supramolecular
porous network could also contribute to some level of catalyst
spatial isolation, which has been elegantly achieved by means
of porous MOF environments for which the reaction occurs pri-
Figure 16. A) Color change of the glycerol-gel phase upon addition of
I
a 0.1m AgNO
3
solution on top. B) Detection of Ag ions in aqueous solution
by using a piece of glycerol gel made of 1 at CGC. Zoom-in: Removal of the
piece of gel after coloring.
existence of the gel phase. Thus, the color change was also ob-
served either with compound 1 at a concentration below the
CGC or in the presence of other urea analogues in solution,
which is in agreement with the considerable tendency of urea
[32]
marily within the pores.
I
[28]
compounds to coordinate Ag salts. Furthermore, the colori-
metric test was also compatible with other solvents (e.g. pink-
ish and yellowish colors were observed in CH CN and THF, re-
3
Conclusion
spectively), albeit glycerol provided the best results in terms of
color intensity.
The results of this study confirm the potential of some urea-
based organocatalysts, such as 1, as building blocks for the
preparation of physical organogels at concentrations ranging
In contrast to a solution of urea 1, the use of the glycerol
gel was more convenient as a colorimetric assay. For instance,
a piece of gel could be added to the aqueous solution to be
ꢀ
1
from 3 to 50 gL . According to FTIR, NMR, and quantum-me-
chanical studies, the major driving forces for the gelation of or-
ganic solvents by 1 are hydrogen-bonding and p–p interac-
tions. In comparison to the Hansen solubility parameters, the
Kamlet–Taft solvatochromic parameters offer here a more con-
venient scenario to rationalize the gelation ability. Moreover,
a variety of morphologies including helical, laths, macroporous,
or lamellar nanostructures could be obtained depending on
the solvent nature. Variations of the most important structural
segments (compounds 2–7) that could influence the self-as-
sembly of 1 and computer modeling proved the existence of
unique molecular interactions in this molecule that drive the
formation of stable hierarchical supramolecular aggregates.
I
tested for the presence of Ag ions. Afterwards, the gel frag-
ment could be easily separated from the solution by decanta-
tion (Figure 16B). UV/Vis spectroscopy of the colored gel
showed a broad absorbance peak in the range 400–500 nm
(Figure S19A), which has been previously associated with the
formation of stable silver nanoparticles by simple glycerol oxi-
[
29]
dation in the absence of any stabilizer.
Catalytic alkylation reaction in gel media
During the last decade, a number of publications have shown
the potentiality of functional gels as recyclable catalysts and/or
Chem. Eur. J. 2014, 20, 10720 – 10731
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Multistimuli responsive behaviors (e.g., thermal, mechanical,
optical, and chemical responses) and a multifunctional nature
were demonstrated in some of the gel materials. In this re-
spect, 1 could be used for the phase selective gelation of oil/
water mixtures, the gel in glycerol was found to be thixotropic
(m, 4H), 6.89 (d, J=8.3 Hz, 1H), 5.33 (d, J=5.5 Hz, 1H), 4.95 (dd,
J=6.7, 8.1 Hz, 1H), 4.29–4.22 (m, 1H), 3.14 (dd, J=7.1, 15.6 Hz,
13
1
H), 2.72 ppm (dd, J=7.27, 15.6 Hz, 1H); C NMR (100 MHz,
[
D ]DMSO): d=154.9, 142.4 141.8, 139.6, 130.5 (q, J=32.5 Hz,
6
CCF ), 127.6, 126.6, 124.6, 123.8, 123.3 (q, J=272.8 Hz, CF ), 117.5–
3
3
1
17.2 (m, 1C), 113.6–113.4 (m, 1C), 77.9, 61.6, 38.5 ppm; IR (KBr
I
and provided a sensing ability for Ag ions at millimolar con-
ꢀ1
film): n˜ =3395, 3326, 2923, 2853, 1634, 1278, 1129, 1073, 749 cm
;
centrations in aqueous solutions. In addition, the gel matrix
obtained in toluene behaved as a nanoreactor for the Friedel–
Crafts alkylation of 1H-indole with trans-b-nitrostyrene cata-
lyzed by 1. Efforts towards the development of other multi-
functional materials are currently underway in our laboratories.
MS (ESI): m/z: calcd for C H F N NaO : 427.1; found: 427.1
18
14
6
2
2
[M+Na].
R)-1-[3,5-Bis(trifluoromethyl)phenyl]-3-(2,3-dihydro-1H-inden-1-
yl)urea (6): By following the general procedure, compound 6 was
(
2
2
obtained as a white solid in 75% yield. M.p. 215–2178C; [a] =
D
1
ꢀ
48.7 (c=0.77 in DMSO); H NMR (400 MHz, CD COCD ): d=8.58
3 3
(
brs, 1H), 8.20 (s, 2H), 7.55 (s, 1H), 7.36–7.34 (m, 1H), 7.26–7.17 (m,
H), 6.34 (brd, J=7.3 Hz, 1H), 5.35 (q, J=7.7 Hz, 1H), 2.96 (ddd,
J=3.6, 8.7, 15.9 Hz, 1H), 2.89–2.81 (m, 1H), 2.59–2.51 (m, 1H),
3
Experimental Section
13
1
1
1
.91–1.82 ppm (m, 1H); C NMR (100 MHz, [D ]DMSO): d=154.6,
43.9, 142.7, 142.4, 130.5 (q, J=32.5 Hz, CCF ), 127.4, 126.3, 124.5,
23.7, 123.3 (q, J=272.8 Hz, CF ), 117.4–117.3 (m, 1C), 113.6–113.4
6
Synthesis and characterization of compounds
3
Materials: All commercially available solvents and reagents for syn-
thesis and analysis were used as received without further purifica-
tion. Compound 4 was available from commercial sources.
3
(
1
m, 1C), 54.5, 33.3, 29.5 ppm; IR (KBr film): n˜ =2923, 2853, 1639,
457, 1276, 1130 cm ; MS (ESI): m/z: calcd for C H F N NaO:
18 14 6 2
ꢀ1
4
11.1; found: 411.1 [M+Na].
-[(1S,2R)-2-Hydroxy-2,3-dihydro-1H-inden-1-yl]-3-phenylurea
7): Following the general procedure, compound 7 was obtained
Characterization methods: Purification of reaction products was
carried out by flash chromatography using silica gel (0.063–
1
(
0
.200 mm) or medium-pressure liquid chromatography by using
21
as white solid in 94% yield. M.p. 224–2268C; [a] = +53.9 (c=
0
prepacked silica columns. Analytical TLC analysis was performed
on 0.25 mm silica gel 60-F plates. The products were visualized by
exposure to UV light (254 nm) and phosphomolybdic acid as
a stain. MS were obtained by using ESI ionization on a Bruker Dal-
tonics Esquire 3000 plus (MicroTof-Q) spectrometer. Unless other-
wise indicated, NMR spectra were recorded at room temperature
D
1
.64 in DMSO); H NMR (400 MHz, [D ]DMSO): d=8.85 (s, 1H), 7.45
6
(
(
d, J=8.5 Hz, 1H), 7.26–7.18 (m, 6H), 6.91 (t, J=7.3 Hz, 1H), 6.44
d, J=8.7 Hz, 1H), 5.24 (d, J=4.2 Hz, 1H), 5.10 (dd, J=5.0, 8.5 Hz,
1
2
H), 4.45 (dd, J=4.1, 8.9 Hz, 1H), 3.07 (dd, J=4.8, 16.2 Hz, 1H),
13
.80 ppm (d, J=16.2 Hz, 1H); C NMR (100 MHz, [D ]DMSO): d=
6
1
155.2, 143.1, 140.5, 140.3, 128.6, 127.0, 126.2, 124.8, 123.8, 120.9,
on a Bruker AVANCE-II instrument. H NMR spectra were recorded
1
3
117.4, 72.0, 57.1, 39.6 ppm; IR (KBr film): n˜ =3469, 3365, 3292,
at 400 MHz and C NMR spectra were recorded at 100 MHz, by
using [D ]DMSO and D CCOCD as the deuterated solvents. Chemi-
ꢀ1
2
923, 2854, 1623, 1568, 1458, 1246, 1050, 766, 748, 735 cm ; MS
6
3
3
(
ESI): m/z: calcd for C H N NaO : 291.1; found: 291.1 [M+Na].
cal shifts were reported in the d scale relative to residual DMSO
16 16
2
2
1
13
(
d=2.50 ppm for H NMR spectra and d=39.43 ppm for C NMR
1
spectra) and acetone (d=2.05 ppm for H NMR spectra). Coupling
constants (J) were expressed in Hertz. Melting points were deter-
mined on a Gallenkamp variable heating apparatus. Optical rota-
tions were measured in a JASCO DIP-370 polarimeter. IR spectra
were recorded on a Nicolet Avatar 360 FTIR spectrophotometer.
HPLC was carried out by using a Waters 2695 Alliance detector.
Preparation and characterization of gel materials
Characterization methods: Oscillatory rheological measurements
were performed at 258C with an AR 2000 Advanced Rheometer
from TA Instruments equipped with a cooling system (Julabo C). A
2
0 mm plain plate geometry (stainless steel) was used. Dynamic
strain sweep (DSS) measurements were first carried out between
.01% and 100% strain at 1 Hz frequency to estimate the strain
General procedure for the synthesis of compounds 1–3 and 5–7:
The corresponding commercially available amine (1.0mmol) (i.e.,
0
(
7
1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol for compounds 1, 2, and
; (1R,2R)-1-amino-2,3-dihydro-1H-inden-2-ol for compound 5; 3,5-
value at which reasonable torque values were given (i.e., about 10
times of the transducer resolution limit). Dynamic frequency sweep
bis(trifluoromethyl)aniline for compound 3; (R)-2,3-dihydro-1H-
inden-1-amine for compound 6) was added in one portion to
(
DFS) measurements (i.e., from 0.1 to 10 Hz at 0.1% strain) and
time sweep measurements (DTS) within the viscoelastic regime
i.e., 0.1% strain, 1 Hz frequency) were subsequently performed.
a
stirred solution of 3,5-bis(trifluoromethyl)phenyl isocyanate
(
(
1.1mmol; for the synthesis of compounds 1, 3, 5, and 6), 3,5-bis(-
Additionally, the thixotropic behavior of the gels was investigated
by a 3-step loop experiment: 1) Application of a low shear strain as
established by previous DTS experiments (the material is in the gel
state, G’>G’’), 2) increase of the shear strain until the gel fractures
trifluoromethyl)phenyl isothiocyanate (1.1mmol; for the synthesis
of compound 2), or phenyl isocyanate (1.1mmol; for the synthesis
of compound 7) in CH Cl (5mL). After stirring the resulting solu-
2
2
tion at room temperature overnight, the solvent was evaporated
under reduced pressure and the product was purified by flash
(the material turns into a viscous solution, G’<G’’), and 3) return at
the same rate to the initial strain% value (the gel phase has been
recovered, G’>G’’). FTIR spectra were recorded by using a Diamond
ATH (attenuated total reflection) accessory (Golden Gate) in
chromatography or medium-pressure liquid chromatography (SiO ,
2
1
13
hexane/EtOAc 7:3).
(
H
and C NMR spectra for compounds
+)-1, (ꢀ)-1, 2, and 3 were consistent with values previ-
[33]
[34]
[9]
[35]
TM
a VARIAN 1000 FTIR Scimitar Series) spectrophotometer. Morpho-
ously reported in the literature.
logical characterization of the samples was carried out by TEM,
field-emission SEM (FESEM) and atomic force microscopy (AFM).
a) TEM: Images were recorded using a JEOL-2000 FXII TEM (resolu-
tion=0.28 nm) equipped with a CCD Gatan 694 digital camera and
operating at 10 kV (accelerating voltage). Sample preparation:
10 mL of the gel suspension was allowed to adsorb for 30 s onto
1
-[3,5-Bis(trifluoromethyl)phenyl]-3-[(1R,2R)-2-hydroxy-2,3-dihy-
dro-1H-inden-1-yl]urea (5): Following the general procedure, com-
pound 5 was obtained as a white solid in 92% yield. M.p. 232–
2
D
0
1
2
[
348C; [a] = ꢀ88.1 (c=0.74 in DMSO); H NMR (400 MHz,
D ]DMSO): d=9.21 (brs, 1H), 8.14 (s, 2H), 7.57 (s, 1H), 7.22–7.19
6
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carbon-coated grids (300 mesh, from TED PELLA, Inc.). After the ad-
sorption, the excess solvent was removed by touching the edges
with a small piece of filter paper. The specimens were then dried
overnight in a desiccator at low pressure and RT. b) FESEM: Images
were obtained with a Carl Zeiss Merlin field emission SEM (FESEM,
resolution=0.8 mm resolution) equipped with a digital camera
and operating at 10 kV (accelerating voltage) and 10 mA (emission
current). Sample preparation: Specimens were prepared by the
solvent were placed into a screw-capped glass vial (4.5 cm lengthꢅ
1.2 cm diameter). The closed vial was gently heated with a heat
gun until the solid material was completely dissolved. The resulting
isotropic solution was then spontaneously cooled down to room
temperature. The material was preliminary classified as a gel if it
did not exhibit gravitational flow upon turning the vial upside-
down at room temperature. The gel state was further confirmed
by rheological measurements.
[
36]
freeze-drying method. Prior to imaging, a 5 nm sized Pt film was
sputtered (40 mA, 30 seconds) on the samples placed on carbon
tape. c) AFM: Imaging was performed on a Ntegra Aura (NT-MDT)
instrument in tapping mode at 1 Hz scanning rate using directly
polycrystalline sapphire (24ꢅ19.3ꢅ0.5 mm) as substrate and
a single-crystal silicon tip coated with TiN (NSG01/TiN, 0.01–
Phase-selective gelation tests: The specified amount of the gela-
tor (+)-1 according to its CGC, the desired organic solvent
(1.0 mL), and distilled water (1.0 mL) were added to a screw-
capped glass vial (4.5 cm lengthꢅ1.2 cm diameter). The vial was
closed and gently heated with a heat gun until the gelator was dis-
solved. The state of the material was evaluated after cooling down
the mixture to room temperature by turning the vial upside-down.
0
.025 Wcm, Antimony doped) at 200–400 kHz drive frequency.
Drive amplitude ranged from 60 to 100 mV. Sample preparation:
–10 mL of a gel suspension (ca. 10-fold dilution in the correspond-
Responsiveness experiments: Gel material 1.0 mL was prepared
at the corresponding CGC as described above. The gel was allowed
to equilibrate for at least 1 h before 1.0 mL of test solution (e.g.,
5
ing solvent) was placed on the substrate and homogeneously dis-
persed with a spatula to form a thin layer that was allowed to dry
in air for at least 30–60 min before measurement. The growth of
crystals in gel phases was monitored using a Wild Makroskop
M420 optical microscope equipped with a Canon Power shot A640
digital camera for digital imaging. An additional polarization filter
was used to observe the gel material under polarized light. Differ-
ential scanning calorimetry (DSC) spectra were measured on
1
.0 mL with 0.1m AgNO ) was placed on top of the gel. The effect
3
of the test solution on the gel (e.g., induction to gel-to-sol transi-
tion, color change) was monitored over time at room temperature.
Friedel–Crafts alkylation in gel media: Dry toluene (0.1 mL) was
added to a screw-capped vial containing a mixture of trans-b-nitro-
styrene (0.1 mmol), 1H-indole (0.15 mmol), and 20 mol% of the
urea gelator (+)-1. The mixture was gently heated until an isotrop-
ic solution was formed. Complete gelation occurred within 20 min
and the reaction was allowed to proceed for 118 h at room tem-
perature. After this time, the solvent was removed under reduced
pressure. The crude product was analyzed by NMR spectroscopy
using DMA (0.1 mol) as the internal standard. For HPLC analysis,
the product was purified by column chromatography using n-hex-
anes/ethyl acetate 8:2 as the eluent.
ꢀ1
a DSC7 (PerkinElmer) instrument at a scan rate of 108C min
under a nitrogen atmosphere. For the measurements, an appropri-
ate amount of gel was placed into a pre-weighted Al pan, which
was sealed and weight on a six-decimal plate balance. The pans
were weighted again after each measurement to check for possible
1
leakage. Temperature-dependent H NMR spectroscopic studies
were carried out on
a 400 MHz Bruker Avance instrument
equipped with a BVT 2000 heating system (Bruker BioSpin GmbH).
Specific surface area, pore volume, pore-size and gas adsorption/
desorption isotherms were measured by a Micromeritics ASAP
Quantum-mechanical calculations: Quantum-mechanical calcula-
[37]
tions were performed by using the Gaussian 09 computer pro-
gram, applying default therholds and algorithms. The meta-gener-
alized gradient approximation (GGA) functional M06L of Truhlar
2
8
020 analyzer at 77 K after vacuum degassing of the sample at
08C for 24 h. Powder X-ray diffraction (PXRD) patterns were col-
[38]
[39]
and Zhao was combined with the 6–31+G(d,p) basis set for
calculations on dimers of 1–7. The M06L function is known to pro-
vide geometry and interaction energy of dimers stabilized by non-
covalent interactions, including p-stacking, with accuracy close to
that of coupled cluster with both single and double substitutions
lected on a Rigaku D/max-2500 rotating-anode powder diffractom-
eter with CuKa radiation operated at 40 kV and 80 mA. Conditions:
0
.038, time 5 s/step, 2 theta range 5–608. Distilled water contact
angles and surface energies were measured with a PG goniometer
ASTM D5946) with the droplet size (4 mL) controlled by a pump-
(
[40]
(CCSD). Environmental effects (here dichloromethane) have been
dosing unit. Absorption spectra were recorded on a Varian Cary
BIO 50 UV/Vis scanning spectrophotometer by using 1 cm quartz
cuvettes (Suprasil ꢇ, Hellma). Critical gelation concentrations, CGC,
were estimated by adding solvent in several portions (0.1 mL each)
into the vial where no gelation was achieved at the previous con-
centration and some material remained insoluble. The initial con-
accounted for using the well-known Polarizable Continuum Model
[41]
(PCM) model.
Complete geometry optimizations of all dimer
were performed by using the PCM approach. Intermolecular inter-
action energies in the gas phase (i.e., in absence of environmental
forces) were estimated as the difference between the energy in
the gas-phase of the dimer optimized in dichloromethane solution
and the energies of the isolated subsystems in the gas-phase with
the geometries obtained from the optimization in solution of the
dimer. The basis set superposition error of the energies of the sub-
ꢀ1
centration for gelation tests was 5 gL . The state of the mixture
was determined after the heating-cooling cycle as described
above. New tests were carried out at lower concentration if stable
ꢀ
1
clear solutions were obtained at 5 gL . Gel-to-sol transition tem-
peratures, Tgel, were typically determined by the inverse flow
method. The average values of at least two random experiments
were given. The seal vial containing the organogel was hung hori-
[42]
systems were corrected using the counterpoise (CP) method.
Similarly, intermolecular interaction energies in dichloromethane
were calculated as the difference between the energies in solution
of the dimer and the subsystems.
ꢀ1
zontally into an oil bath, which was heated up at 28C min
.
Herein, the temperature at which the gel started to break was de-
fined as Tgel. These values were correlated with the first DSC endo-
thermic transition of selected examples.
Acknowledgements
General procedure for the preparation of organogels: Solvents
used for gelation tests were purchased from commercial suppliers
and were at least of p.a. quality. Typically, a weighted amount of
the corresponding compound (1–7) and 1 mL of the appropriate
Financial support from the Universitꢈt Regensburg (Fçrderlinie
C des Finanziellen Anreizsystems fꢉr Drittmitteleinwerbung),
Spanish Ministry of Economꢃa y Competitividad (MINECO,
Chem. Eur. J. 2014, 20, 10720 – 10731
www.chemeurj.org
10730
ꢄ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Madrid, Spain, Projects CTQ2010–19606 and MAT2012–34498),
and the Governments of Aragꢁn (Zaragoza, Spain, Research
Group E-10) and Catalunya (research group 2009 SGR 925,
XRQTC and “ICREA Academia” Award for excellence in research
to C.A.) is gratefully acknowledged. We thank Prof. A. Gçpfer-
ich (Universitꢈt Regensburg) for granting us access to the AR
7698; b) S. Bhattacharya, Y. Krishnan-Ghosh, Chem. Commun. 2001,
185–186.
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responsiveness · organogels · self-assembly · ureas
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Received: March 1, 2014
Published online on June 25, 2014
Chem. Eur. J. 2014, 20, 10720 – 10731
www.chemeurj.org
10731
ꢄ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim