Study of the effect of polymorphism on the self-assembly and catalytic performance of an l-proline based molecular hydrogelator

Article abstract of DOI:10.1039/c5nj00072f

An exhaustive study of the polymorphism found for aggregates and hydrogels of an l-proline based hydrogelator under different preparation conditions is undertaken. The effect of heating temperature, aging time, ultrasound and pH switching on the self-assembly in water has been studied. WAXD analysis of the freeze-dried materials revealed the presence of four polymorphs, three of which could be isolated under specific conditions. Polymorphic differences have been studied by DSC, FTIR, circular dichroism and electron microscopy. Furthermore, the catalytic activity of each polymorph has been tested for the direct aldol reaction between cyclohexanone and 4-nitrobenzaldehyde revealing differences in the reaction rates that could be attributed to differences in molecular packing and aggregate morphology among them. The current study highlights the role that polymorphism plays in the application of functional supramolecular soft materials.

Full text of DOI:10.1039/c5nj00072f

NJC
View Article Online
View Journal | View Issue
PAPER
Study of the effect of polymorphism on the
self-assembly and catalytic performance of an
Cite this: New J. Chem., 2015,
L-proline based molecular hydrogelator†
3
9, 3785
Santiago Dıaz-Oltra, Cristina Berdugo, Juan F. Miravet* and Beatriu Escuder*
´
An exhaustive study of the polymorphism found for aggregates and hydrogels of an L-proline based
hydrogelator under different preparation conditions is undertaken. The effect of heating temperature,
aging time, ultrasound and pH switching on the self-assembly in water has been studied. WAXD analysis
of the freeze-dried materials revealed the presence of four polymorphs, three of which could be isolated
under specific conditions. Polymorphic differences have been studied by DSC, FTIR, circular dichroism and
electron microscopy. Furthermore, the catalytic activity of each polymorph has been tested for the direct
aldol reaction between cyclohexanone and 4-nitrobenzaldehyde revealing differences in the reaction rates
that could be attributed to differences in molecular packing and aggregate morphology among them. The
current study highlights the role that polymorphism plays in the application of functional supramolecular
soft materials.
Received (in Montpellier, France)
th January 2015,
Accepted 17th February 2015
9
DOI: 10.1039/c5nj00072f
www.rsc.org/njc
8
aqueous media (hydrogels). In particular, hydrogelator 1 has been
recently reported as an efficient catalyst for the reaction of
Introduction
Supramolecular hydrogels formed by low molecular weight cyclohexanone and 4-nitrobenzaldehyde and an extension of the
compounds (molecular hydrogels) have attracted much atten- work towards the substrate selectivity of aliphatic ketones has been
9
,10
tion in the last few years because of their potential application achieved (Fig. 1).
as valuable materials for regenerative medicine, drug delivery have been proposed to act as enzyme mimics in which active sites
or as optoelectronic materials among others.
Indeed, hydrogels formed by compound 1
1
–5
These gels, for binding and catalysis are created in a process mainly driven by
formed by the self-assembly of small molecules by weak non- the hydrophobic effect. In all these studies the wide potential of
covalent interactions, offer the possibility to create materials self-assembled low molecular weight hydrogels in the field of
with appealing features by simply including a functionality in catalysis has been revealed not only as passive phase separated
the molecular structure and leave it to be spontaneously supports but specially because of their superior catalytic properties
expressed at the supramolecular level. In this way hydrogels related to the emergence of new properties such as cooperation of
have been prepared possessing functional groups able to respond functional groups, multivalent binding of substrates or changes in
to the presence of physical or chemical stimuli (i.e. light, ultra- the reactivity of some groups (i.e. pK shifts...).
sounds, pH, enzymes,...) that can be applied, for instance, as
sensing devices or in controlled drug release. Moreover, catalytic gels in catalysis has been only barely studied
Despite this potential, the application of molecular hydro-
6,7
11,12
and a deep
materials can be obtained by the conjugation of known catalytic understanding of the factors that could affect the process has
fragments with the structure of a hydrogelator. In this field, our
group has reported several examples in which L-proline is included
as an organocatalytic fragment in the molecular structure of the
gelator. These gels have been studied as heterogeneous catalysts
for C–C bond forming reactions such as direct aldol reaction and
Michael addition in organic solvents (organogels) as well as in
Departament de Qu ´ı mica Inorg a` nica i Org a` nica, Universitat Jaume I,
1
2071 Castell o´ , Spain. E-mail: miravet@uji.es, escuder@uji.es;
Fax: +34 964728214
Electronic supplementary information (ESI) available: WAXD graphs, the
†
macroscopic aspect of the aggregates, the pH-titration procedure and additional
electron microscopy figures. See DOI: 10.1039/c5nj00072f
Fig. 1 Structure of gelator 1 and direct aldol reaction catalysed by self-
assembled 1.
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015
New J. Chem., 2015, 39, 3785--3791 | 3785

View Article Online
Paper
NJC
not been performed yet. Due to the fact that these supramole- as benchmark reaction the catalytic activity of these hydrogels
cular systems are under the control of weak non-covalent was studied after 16 to 24 h and at 25 and 5 1C leading to high
interactions very subtle changes in the environment or in the yields and moderate to high stereoselectivities of the aldol
9
methodology of preparation can have a remarkable influence product. During this study we noticed that randomly, under
on the outcome of the material. For instance, Adams et al. have apparently similar conditions some samples failed to form
recently reported on the relevance of the gelation process hydrogels leading to weak gels, dispersions or precipitates.
(
heating–cooling, pH switch, enzymatic control, etc.. . .) on the However, the addition of reagents to these non-jellified samples
1
3
mechanical properties of low molecular weight hydrogels.
led again to high yields of aldol after 24 h. These intriguing
These different methodologies may give rise to differences in results prompted us to develop a careful study of the influence
the nano/microstructure of the gel. Indeed, some examples of different preparation conditions on the self-assembly of
have been reported revealing the influence of the preparation compound 1 and thereafter on its catalytic performance.
procedures not only on the morphologies of the aggregates but
1
4,15
also on the polymorphism of molecular packing.
The Self-assembly studies
heating–cooling rate, aging time or sample concentration have
been shown to play a crucial role in this sense. All those factors
could have an enormous effect on the performance of catalytic
hydrogels (activity, selectivity).
Here we undertake an exhaustive study of the polymorphism
found for aggregates and hydrogels of compound 1 under
different preparation conditions: heating temperature, aging
time, ultrasounds and pH switching. Furthermore, as we iden-
tify several polymorphs, we isolate some of them and analyse
their individual catalytic efficiency.
A summary of the experiments is shown in Table 1 including
changes in heating temperature, aging temperature, aging time
and use of ultrasounds. Additionally, as the proline moiety
presents a basic centre, samples were also prepared by dissolu-
tion of compound 1 in acidic solution and further dilution with
solutions at pH 7 and 8. After observation of their macroscopic
aspects, samples were frozen in liquid nitrogen and lyophilised
to obtain a xerogel that was studied by wide-angle X-ray
diffraction (WAXD).
In a first set of tests, samples were prepared at a concen-
tration of 2 mM in pure water and heated at 100 1C (Table 1,
entries 1–7). Heating was maintained either for 2 h or 16 h and
then they were lyophilised immediately or after being aged at
Results and discussion
Hydrogel formation
25 1C for 10 minutes (entries 1–4). The macroscopic aspect of
As mentioned above, hydrogels formed by compound 1 have the samples was that of a translucent dispersion. In some cases
been described recently in our group as organocatalysts for the an additional time of ultrasound was applied and a jelly suspen-
direct aldol reaction between ketones and 4-nitrobenzaldehyde sion was observed (entries 5–7). The xerogels were studied by
(Fig. 1). Catalytic hydrogels were formed by dissolution of WAXD and, as can be seen in Table 1, two different polymorphs
compound 1 (2 mM) in water applying strong heating and were observed, A and B (Fig. 2). Polymorph B was favoured by long
sudden cooling at 25 1C accompanied by 1 min of sonication. heating time and polymorph A appeared as a major component
Taking the coupling of cyclohexanone and 4-nitrobenzaldehyde after 10 minutes of ultrasound. Experimental conditions could
a
Table 1 Summary of the aggregation behaviour of compound 1
Concentration
(mM)
Heating
temperature (1C)
Ultrasounds
time
Macroscopic
aspect
Figure
WAXD ESI
b,c
Entry
Heating time
Aging time
Polymorph
1
2
3
4
5
6
7
8
9
2
2
2
2
2
2
2
2
2
2
2
2
100
100
100
100
100
100
100
80
80
80
80
—
—
Melt (A)
—
—
—
—
100
2 h
2 h
16 h
16 h
2 h
2 h
2 h
2 h
15 min
2 h
10 min
—
10 min
—
—
—
2 h
10 min
—
—
—
—
—
—
—
10 min
2 h
1 min
—
—
—
B + a
B
B
B
A + b
Disp
Disp
Disp
Disp
Disp
Disp
WG
S
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
A
A + B
A + C + b
A + b
B + a
A + c
A
A + b
A + B
D
D
A
A + d
B
S
S
S
10
11
12
13
14
15
16
17
18
19
15 min
—
—
10 min
2 h
—
—
—
Disp
Solid
Solid
S
S
G
—
—
2 (pH 7)
2 (pH 8)
4 (pH 8)
5 (pH 8)
2
—
—
—
—
2 h
10 min
10 min
18 h
10 min
2 h (80 1C)
—
—
—
—
—
G
S
a
b
Major component polymorphs: A, B, C and D; minor component polymorphs: a, b, c and d. See ESI for WAXD graphs. Macroscopic aspect:
c
G: gel; WG: weak gel; Disp: dispersion; S: suspension. Dispersions are converted into weak gels after long time (16–18 h).
3
786 | New J. Chem., 2015, 39, 3785--3791
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015

View Article Online
NJC
Paper
Fig. 2 Wide-angle X-ray diffraction (WAXD) patterns for polymorphs A–D.
be set up to obtain samples with pure A (entry 6) and B growth of new aggregates. In the current case, ultrasounds not
(entries 2–4 and 19).
only could help to spread seeds of polymorph A but could also
Secondly, heating temperature was reduced to 80 1C provide the energy to overcome the kinetic barrier for the
entries 8–11) and under some conditions a new polymorph conversion between polymorphs B and A.
(
appeared (polymorph C, Fig. 2C). Again, long heating times
On the other hand, hydrogels could be prepared by
without aging at 25 1C favoured polymorph B (entry 10) whereas pH-switching. Compound 1 was dissolved by addition of
aging and ultrasounds favoured polymorph A (entries 8, 9 and 11). 1 equiv. of HCl and slight heating and diluted with buffered
All samples remained as jelly suspensions. In the view of these solutions of pH 7 and 8, (entries 15–18). Polymorph A was
results it seems reasonable to propose that A is stable at low predominant at pH 8 although higher concentrations (44 mM)
temperatures and it is favoured under thermodynamic control were required for gelation (entries 17 and 18). At low concen-
(
long aging time) whereas B is accessible only at high temperature tration (2 mM) a suspension was formed and a new diffraction
long heating time) and it is kinetically trapped by fast cooling pattern was observed, polymorph D. This last pattern was also
either at 25 1C (entry 3) or under nitrogen freezing conditions predominant at pH 7.
entry 4). The pure starting solid 1 was also analysed by WAXD
directly from the synthesis batch (entry 13) and after a melting–
(
(
Characterization of the polymorphs
cooling cycle (entry 14). As can be seen, the solid was formed Thermal polymorphic transitions involving polymorphs A, B
mainly by polymorph A with a small amount of B, and after and C were studied by DSC. As can be seen in Fig. 3, starting
melting on a glass slide and spontaneous cooling at r.t., the from polymorph A the heating curve shows an endothermic
amount of B increased considerably.
transition at 71 1C and a melting peak at 101 1C. After cooling,
The effect of ultrasound deserves a particular discussion. only a shifted exothermic peak can be seen due to hysteresis.
Sonochemical effects have been widely described in self- This transition is related to the enantiotropic transformation
1
6–18
19,20
assembled systems.
It is believed that cavitation produced between polymorphs A and B.
These two polymorphs are in
by ultrasound produces a local increase of temperature and equilibrium and their relative population depends on tempera-
pressure that may lead to unexpected changes in packing/ ture, B being formed at high temperature and A obtained after
crystallization resulting in different crystalline polymorphs or slow cooling or equilibration at room temperature. On the
in nanoobjects with variable shapes and sizes. As has been other hand, the DSC diagram of pure polymorph B kinetically
pointed before, ultrasound can induce the process of crystallo- captured at high temperature (see Table 1, entry 3) shows an
graphic nucleation and growth, breaking the existing aggre- exothermic transition at ca. 68 1C. This transition corresponds
gates into ‘‘infecting’’ seeds that would act as templates for the to the conversion of polymorph B back to polymorph A after
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015
New J. Chem., 2015, 39, 3785--3791 | 3787

View Article Online
Paper
NJC
Fig. 4 Circular dichroism (CD) of KBr pellets of polymorphs A, B and D.
in both polymorphs. A similar conclusion can be drawn from
the IR absorption band in the amide (CQO) region where both
À1
polymorphs present similar bands at 1640 cm (see Fig. 5
bottom). However, IR spectroscopy reveals some slight differ-
ences between A and B in the CH stretching vibration bands
2
(
see Fig. 5 top) that would be in agreement with a difference in
2
1
the packing of the alkyl tails in both polymorphs. Polymorph
D shows an alkyl packing similar to polymorph B but exhibits
differences in the position of the amide CQO stretching band
Fig. 3 Differential scanning calorimetry (DSC) analysis of polymorphs A
and B.
À1
shifted 5 cm to higher wavelengths and a stronger CD effect
than the other polymorphs, suggesting higher rigidity in the
dipeptide region of these aggregates.
overcoming the kinetic barrier between B and A. Polymorph C
remain difficult to capture under pure conditions and could not
be fully characterized.
The structural differences between polymorphs are also
revealed at the microscopic level by TEM and FESEM. As can
be seen in Fig. 6 polymorph A and polymorph B present slightly
different fibrillar structures. Polymorph A (Fig. 6A and B) is
formed by fibrils longer and wider than in the case of polymorph
B (Fig. 6C and D). Polymorph B forms a meshed network made
of very thin fibrils of ca. 10 nm of width whereas polymorph A
On the other hand, polymorph D is obtained at pH values
close to the pK
potentiometric titration to be 6.4 at [1] = 1 mM and 6.0 at [1] =
mM (see Fig. S20, ESI† for details). These values are quite
shifted from the pK value determined for a propylamide pro-
a a
of the molecule. The pK was determined by
5
a
line analogue in solution (8.8, data not shown here) and are the
result of the aggregation process that disfavors the presence of
vicinal charged species in the aggregates. Consequently, it can
be estimated that at pH 7 there is about 20% of compound 1 in
a protonated state. We have previously reported that 1ÁHClÁ
1
0
2
2H O crystallizes in aqueous acidic solution. Besides, the
main low angle diffraction peak of polymorph D (Fig. 2) is
coincident with the 001 diffraction plane distance found for the
simulation of the powder diffraction pattern obtained from the
X-ray single crystal (see Fig. S21, ESI†). It seems reasonable to
propose that few of those crystals could be formed and act as
seeds for the aggregation of 1 into a similar polymorph, but
highly oriented in the direction of the 001 diffraction plane.
A similar effect is observed at pH 8 at 2 mM (entry 17) but
polymorph D tends to disappear for higher concentrations
(entries 18 and 19) where the seeding effect will be less effective
and other factors drive the aggregation towards polymorph A
that leads to the formation of a hydrogel.
Spectroscopic techniques – circular dichroism and IR – have
been also used to find differences in the structure of the
polymorphs. As can be seen in Fig. 4, there is no difference
between polymorphs A and B in their CD spectra meaning that
the amide chromophores are placed in a similar environment Fig. 5 FTIR of KBr pellets of polymorphs A, B and D.
3
788 | New J. Chem., 2015, 39, 3785--3791
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015

View Article Online
NJC
Paper
Fig. 6 TEM (top) and FESEM (bottom) of polymorphic aggregates A (A,B), B (C,D) and D (E,F).
forms fibrils of ca. 30 nm of width. These subtle microscopic
differences have an influence on the ability of each polymorph to
form hydrogels: polymorph A forms gels immediately after
sonication whereas polymorph B needs additional aging time
to give a self-sustainable gel.
Finally, TEM images of polymorph D show the presence of
long and flat aggregates of tens of micrometres of length that
are formed by the alignment of thinner tapes of up to 10 nm of
width following a preferred direction (Fig. 6E and F).
Catalytic studies
The catalytic performance of polymorphs A, B and D was
studied for the direct aldol coupling (Fig. 1). Aggregated samples
Fig. 7 Catalytic performance of polymorphs A, B and D.
were prepared following the conditions of entries 6, 3 and
5 respectively and the mixture of 4-nitrobenzaldehyde and
1
cyclohexanone was added on top. All the reactions were initially
conducted at 25 1C for 24 h. After this period of time, the three
polymorphs gave a quantitative yield of the aldol product with
slight differences in diastereo and enantioselectivity (Table 2).
However, a significant difference was observed in the rate of
reaction (Fig. 7). Polymorph A showed quantitative conversion
after 2 h of reaction whereas yields of polymorphs B and D after
this time were only 70% and 35% respectively. The sample of
polymorph B gave full conversion after 4 h and in the case of
polymorph D the yield increased to 85% after 15 h. In order to
explain these results two options could be foreseen. First, it
could be proposed that these polymorphs presented differences
in their solubility in water leading to different concentrations of
free catalysts in solution. This fact would imply that catalysis
takes place in solution. This possibility has been previously
ruled out by studying soluble analogues which have been
shown to be catalytically inactive or by the fact that these
systems are not reacting at all with polar substrates that remain
a
Table 2 Summary of the catalytic results at 25 1C after 24 h
b
b
c
Polymorph
Yield (%)
d.r. (anti : syn)
e.r.
9
,10
A
B
D
495
495
495
86 : 14
85 : 15
80 : 20
85 : 15 in solution.
Secondly, if we consider that the reaction takes
79 : 21
place on the fibre surface it makes sense to propose that there
could be differences in the accessibility of the catalytic sites
among the three polymorphs since they present different
molecular packing. Moreover, electron microscopy studies
revealed that polymorphs A and B (fibres) present a higher
78 : 22
a
Hydrogel: 0.008 mmol of 1 (0.2 eq.) in water (4 mL); reagents:
-nitrobenzaldehyde (1 eq.), ketone (10 eq.). Determined by NMR.
Determined by chiral-phase HPLC of the anti product (major enantiomer:
b
4
c
S,R-anti).
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015
New J. Chem., 2015, 39, 3785--3791 | 3789

View Article Online
Paper
NJC
aspect ratio than polymorph D (tapes) also supporting a higher action using a filter paper. The grids were immediately stained
accessibility for A and B than for D.
with one drop of phosphotungstic acid 1% for 1 min. Excess of
stain was removed by capillarity. TEM images were recorded
using a JEOL 2100 Transmission Electron Microscope.
Conclusions
FTIR and circular dichroism
In summary, we have reported an example of the relevance of
polymorphism in the performance of a functional supramole- Sample discs were prepared by mixing the freeze-dried solids
cular system. We have shown that a simple low-molecular with 200–300 mg of KBr in an agate mortar and pressing the
weight gelator upon very slight modification of the environ- mixture at 10 ton for ca. 10 min. Transparent discs of less than
mental parameters (temperature, aging time, ultrasounds,. . .) 0.5 mm were obtained. FT-IR spectra were collected using a
can exhibit different packing arrangements which are reflected JASCO FTIR-6200 spectrometer. CD spectra were recorded
in the functional role of the aggregates. There are many using a JASCO J-810 spectrometer. Spectra were randomly taken
examples in the literature where water dispersions of the in at least six different positions of the disc and averaged.
hydrophobic catalyst are used for organic transformations –
the so-called ‘on-water’ reactions – and quite often no specific Catalysis
details are given on the nano/microscopic characterization of
6
4
.04 mg (0.04 mmol) of 4-nitrobenzaldehyde were dissolved in
1 mL (0.4 mmol) of cyclohexanone, added on top of the
2
2–24
the catalytic phase.
current study is that upon working with such complex systems
even though they could seem simple a priori – one should
Our ‘lesson to take home’ from the
hydrogel (0.008 mmol) and left to diffuse and react at 25 1C.
The reaction was quenched by addition of 2 mL of 0.1 M HCl,
diluted with 10 mL of water and extracted twice with 5 mL of
dichloromethane. The combined organic extracts were dried
with anhydrous sodium sulfate and the solvent was evaporated
–
have a detailed picture of the polymorphism landscape in order
to avoid unexpected and/or unreproducible results. Moreover,
the current work exemplifies that the role of polymorphism is a
transversal issue with relevance not only in crystal engineering
and pharmaceutical science where it has been studied for
decades but also in soft matter and in catalysis.
under vacuum. The resulting yellow solid was analyzed by
1
H-NMR in CDCl in order to determine the yield and diastereo-
3
10
selectivity, and by chiral HPLC to determine the enantioselectivity.
Experimental section
Preparation of samples
Acknowledgements
This work was supported by the Ministry of Economy and Compe-
titiveness of Spain (Grant CTQ2012-37735 and an FPI fellowship
for C.B.), Universitat Jaume I (Grant P1-1B2013-57) and COST
Action CM1005 ‘‘Supramolecular Chemistry in Water’’.
Hydrogels and dispersions were prepared by placing compound
1
(3 mg, 8 mmol) and solvent (4 mL) in 8 mL screw-capped
vials under the experimental conditions described in Table 1.
Samples for pH-controlled aggregation were prepared by addi-
tion of the required volumes of phosphate buffer solution over
1
ÁHCl 10 mM. Xerogels were obtained after lyophilisation of the
Notes and references
samples by immersion into liquid nitrogen and connected to a
Telstar Lyoquest freeze-drying system operating at À85 1C and
1
Molecular Gels: Materials with Self-assembled Fibrillar
Networks, ed. P. Terech and R. G. Weiss, Springer,
Dordrecht, 2006.
0
.005 mbar. All the samples were freeze-dried for at least 72 h.
Wide-angle X-ray diffraction
2
3
F. Fages, Top. Curr. Chem., 2005, 256, 1.
Data collection was performed at room temperature with a Bruker
D4 Endeavor X-ray powder diffractometer by using Cu-a radiation.
A sample of the respective freeze-dried powder was placed on a
sample holder and data were collected for 2y values between 21
and 401 with a step size of 0.031 and a time step of 10 s.
D. K. Smith, in Molecular Gels – Nanostructured Soft Materials,
in Organic Nanostructures, ed. J. L. Atwood and J. W. Steed,
Wiley-VCH, Weinheim, 2008.
Functional Molecular Gels, ed. B. Escuder and J. F. Miravet,
RSC, Cambridge, 2014.
4
5
L. E. Buerkle and S. J. Rowan, Chem. Soc. Rev., 2012,
Field-Emission Scanning Electron Microscopy (FESEM)
41, 6089.
Field-emission scanning electron micrographs were taken on a
JEOL 7001F microscope equipped with a digital camera. The
corresponding freeze-dried gels were placed on the top of an
aluminium specimen mount stub and sputtered with Pt.
6 X. Yang, G. Zhang and D. Zhang, J. Mater. Chem., 2012,
22, 38.
7 M. D. Segarra-Maset, V. J. Nebot, J. F. Miravet and
B. Escuder, Chem. Soc. Rev., 2013, 42, 7086.
8
B. Escuder, F. Rodr ´ı guez-Llansola and J. F. Miravet, New
J. Chem., 2010, 34, 1044.
Transmission Electron Microscopy (TEM)
Samples were applied directly onto a 200 mesh carbon coated
copper grids. Excess solvent was carefully removed by capillary
9 F. Rodr ´ı guez-Llansola, J. F. Miravet and B. Escuder, Chem.
Commun., 2009, 7303.
3790 | New J. Chem., 2015, 39, 3785--3791
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015

View Article Online
NJC
Paper
10 C. Berdugo, J. F. Miravet and B. Escuder, Chem. Commun., 16 J. M. J. Paulusse and R. P. Sijbesma, Angew. Chem., Int. Ed.,
2013, 49, 10608. 2006, 45, 2334.
1
1
1 M. O. Guler and S. I. Stupp, J. Am. Chem. Soc., 2007, 129, 12082. 17 G. Cravotto and P. Cintas, Chem. Soc. Rev., 2009, 38, 2684.
2 Z. Huang, S. Guan, Y. Wang, G. Shi, L. Cao, Y. Gao, Z. Dong, 18 D. Bardelang, Soft Matter, 2009, 5, 1969.
J. Xu, Q. Luo and J. Liu, J. Mater. Chem. B, 2013, 1, 2297.
3 J. Raeburn, A. Z. Cardoso and D. J. Adams, Chem. Soc. Rev., 20 J.-O. Henck and M. Kuhnert-Brandstatter, J. Pharm. Sci.,
013, 42, 5143. 1999, 88, 103.
4 V. Nebot, S. D ´ı az-Oltra, J. Smets, S. Fern ´a ndez Prieto, 21 M. Masuda, V. Vill and T. Shimizu, J. Am. Chem. Soc., 2000,
J. F. Miravet and B. Escuder, Chem. – Eur. J., 2014, 20, 5762. 122, 12327 and references therein.
5 J. A. Foster, R. M. Edkins, G. J. Cameron, N. Colgin, 22 J. Mlynarski and J. Paradowska, Chem. Soc. Rev., 2008,
K. Fucke, S. Ridgeway, A. G. Crawford, T. B. Marder, 37, 1502.
A. Beeby, S. L. Cobb and J. W. Steed, Chem. – Eur. J., 2014, 23 M. Raj and V. K. Singh, Chem. Commun., 2009, 6687.
0, 279. 24 R. N. Butler and A. G. Coyne, Chem. Rev., 2010, 110, 6302.
19 A. Burger and R. Ramberger, Mikrochim. Acta, 1979, II, 259.
1
1
1
2
2
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015
New J. Chem., 2015, 39, 3785--3791 | 3791