PH-tunable hydrogelators for water purification: Structural optimisation and evaluation

Article abstract of DOI:10.1002/chem.201102137

A focused library of potential hydrogelators each containing two substituted aromatic residues separated by a urea or thiourea linkage have been synthesised and characterized. Six of these novel compounds are highly efficient hydrogelators, forming gels i

Full text of DOI:10.1002/chem.201102137

DOI: 10.1002/chem.201102137
pH-Tunable Hydrogelators for Water Purification:
Structural Optimisation and Evaluation
Daniel M. Wood,[a] Barnaby W. Greenland,[a] Aaron L. Acton,[a]
Francisco Rodrꢀguez-Llansola,[b] Claire A. Murray,[a] Christine J. Cardin,[a]
Juan F. Miravet,[b] Beatriu Escuder,[b] Ian W. Hamley,[a] and Wayne Hayes*[a]
Abstract: A focused library of poten-
tial hydrogelators each containing two
substituted aromatic residues separated
by a urea or thiourea linkage have
been synthesised and characterized. Six
of these novel compounds are highly
efficient hydrogelators, forming gels in
aqueous solution at low concentrations
(0.03–0.60 wt%). Gels were formed
through a pH switching methodology,
by acidification of a basic solution
(pH 14 to ꢀ4) either by addition of
HCl or via the slow hydrolysis of gluco-
no-d-lactone. Frequently, gelation was
accompanied by a dramatic switch in
the absorption spectra of the gelators,
resulting in a significant change in
colour, typically from a vibrant orange
to pale yellow. Each of the gels was ca-
pable of sequestering significant quan-
tities of the aromatic cationic dye,
methylene blue, from aqueous solution
(up to 1.02 g of dye per gram of dry ge-
lator). Cryo-transmission electron mi-
croscopy of two of the gels revealed an
extensive network of high aspect ratio
fibers. The structure of the fibers al-
tered dramatically upon addition of
20 wt% of the dye, resulting in aggre-
gation and significant shortening of the
fibrils. This study demonstrates the fea-
sibility for these novel gels finding ap-
plication as inexpensive and effective
water purification platforms.
Keywords: electron microscopy
·
gels · self-assembly · supramolec-
ular chemistry · X-ray diffraction
Introduction
ular structures during gelation. Thus, there have been a
series of elegant structural optimisation studies based on a
varied range of skeletal motifs as detailed in an excellent
recent review on this topic.[5] Interest in these intriguing
molecules is maintained as a consequence of the increasing
number of practical applications for which they may be
suited, spanning areas as diverse as catalysis,[6] or electro-
nic[1b] and photonic materials.[7] Within this expanding re-
search field is the design and synthesis of molecules that gel
in aqueous conditions, so-called hydrogelators.[8] The ability
to form gels from aqueous rather than organic solvents (i.e.,
organogels) opens exciting new opportunities, moving the
field into new areas including biomaterials,[9] drug deliv-
ery[10] and water purification.[11] In a recent communica-
tion,[12] we reported the synthesis of a structurally simple
urea based hydrogelator that is accessed through a one-pot
synthesis from commercially available materials.[13] The gela-
tor was readily soluble at room temperature in water under
basic conditions (pH 12, NaOH), but formed gels rapidly as
the aqueous solution was acidified. As the pH was reduced
the system underwent a dramatic change in colour from a
vivid orange solution to a pale yellow gel. In addition, the
gel was found to extract large quantities of the aromatic cat-
ionic dye methylene blue from solution, demonstrating clear
potential for water purification. In this paper, we report the
synthesis of a family of structurally related potential gelators
and evaluate their ability to form hydrogels through a pH
switching protocol. Dye extraction studies, combined with
rheological analysis and inspection of the solid-state struc-
tures of three of these new gelators provide new insights to
The design and synthesis of low molecular weight gelators
(LMWG) has been a rapidly expanding field of research
over the previous 15 years.[1] A typical LMWG is a molecu-
lar species that self-assembles into extended fibrillar struc-
tures from solution. Under ideal conditions, the supramolec-
ular[2] fibrils increase in size to almost macroscopic length
scales, eventually producing an interpenetrating network
that percolates throughout the liquid phase, immobilizing
the solvent through capillary action. Thus, small quantities
of the LMWG (<1% w/v) can inhibit the flow of a large
volume of solvent.[3] The design of LMWGs presents a great
challenge with the success (or not) of a new gelator depen-
dent on the subtle interplay between the relative solubility[4]
of the potential gelator under different conditions (i.e., tem-
perature or pH), coupled with the position and directionali-
ty the key residues that drive the formation the supramolec-
[a] D. M. Wood, Dr. B. W. Greenland, A. L. Acton, C. A. Murray,
Prof. C. J. Cardin, Prof. I. W. Hamley, Dr. W. Hayes
Department of Chemistry, University of Reading
Whiteknights, Reading, RG6 6AD (United Kingdom)
Fax : (+44)118-378-6331
E-mail: w.c.hayes@reading.ac.uk
[b] Dr. F. Rodrꢀguez-Llansola, Prof. J. F. Miravet, Prof. B. Escuder
Departament de Quꢀmica Inorgꢁnica i Orgꢁnica
Universitat Jaume I, Avda.Sos Baynat s/n
12071 Castellꢂ (Spain)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201102137.
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Chem. Eur. J. 2012, 18, 2692 – 2699

FULL PAPER
help guide the de novo production of these fascinating mol-
ecules.
Results and Discussion
Inspection of the structure of our recently reported gelator
1 reveals three distinct structural motifs with an aromatic
nitro group (ring A) and an ar-
Figure 1. Structure of urea 1 highlighting the three distinct potential rec-
ognition motifs contained within the low molecular weight hydrogelator.
Table 1. Synthesis of potential low molecular weight hydrogelators.[a]
omatic diacid (ring B) separat-
ed by urea residue (C,
a
Figure 1). To gain a better un-
derstanding of how each struc-
tural feature influences the ge-
lation and dye extraction prop-
erties of the hydrogelator, a li-
brary of closely related com-
pounds, differing in the number
and positioning of key function-
al groups on the aromatic rings
A and B (Figure 1) were syn-
thesised. Production of the li-
brary was facilitated by the
modular nature of the synthesis,
which typically involved the ad-
dition of a commercially avail-
able aromatic amine to an iso-
cyanate (Table 1), allowing
rapid access to a series of close-
ly related structures for further
analysis. Thus, nine novel po-
tential gelator compounds were
synthesised (1–9). For the ma-
jority of cases (1–5), synthesis
was achieved in a high yield (>
84%) via addition of either 5-
amino isophthalic acid (10) or
4-aminobenzoic acid (11) to an
aromatic isocyanate (12–15).
The five novel urea compounds
produced via this route differed
by the inclusion and relative
positions of the nitro group on
ring A of the molecule (1, 3, 4
and 5) and the number and po-
sition of carboxylic acid groups
on the B ring of the molecules
(1 and 3). Attempts to access
thiourea 7 and nitrile 8 through
the one-pot route resulted in
the formation of multiple prod-
Isocyanate
Aromatic amine
Conditions/Overall yield [%]
a/95
Product
a/84
a/85
10
10
10
a/92
a/93
b/28
13
13
16
16
c/86
d/62
ucts
(as
determined
by
10
a/26
1H NMR spectroscopic analy-
sis), from which the desired
product could not be isolated in
a pure form. It was found, how-
[a] Reaction conditions: a) THF, RT, 24 h; b) 1) THF, RT, 24 h; 2) EtOH/EtOAc, H2, Pd/C, RT, 1 h; THF/
H2O, KOH, RT, 24 h; c) 1) THF, RT, 24 h; 2) THF/H2O, KOH, RT, 24 h; d) 1) THF, RT, 24 h; 2) THF/H2O,
ever, that the formation of side- LiOH, RT, 24 h.
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W. Hayes et al.
products could be suppressed by addition of the known[14]
aromatic amino-diethyl ester, 16 to either the aromatic iso-
cyanate 13 or isothiocyanate 17, followed by saponification
to deliver the targeted diacids 7 and 8. To expand the library
of potential gelators further, a palladium-catalysed reduction
of thenitro group on 1 afforded aniline 6. It was thought
that the interchange of the hydrogen-bond accepting nitro
group for a hydrogen bond donor such as the amine group
would provide further insight into the nature of the self-as-
sembled supramolecular gels formed by this class of material.
to 50 mm). These results demonstrate the critical importance
of a group that has hydrogen bond accepting ability in pro-
moting gelation. Through the employment of the glucono-d-
lactone pH switching methodology, the critical gelation con-
centration (cgc) was established between 0.9 and 20 mm for
the six gelating molecules. As a consequence of the ex-
tremely low molecular weight of these compounds (each
under 400 Da) all six molecules are “super gelators”,[3] form-
ing stable gels below 1% w/v under these experimental con-
ditions. The cgc for hydrogelator 1 (0.03% w/v) is amongst
the lowest reported to date. Comparison of the mono acid
gelator 3 and diacid gelator 1 reveals that the cgc values
differ by over twenty times (20 and 0.9 mm, respectively),
demonstrating the importance of both of the two acids of 1
in maintaining the supramolecular gel structure. The cgc
values for the isomeric series 4, 5 and 1 where the nitro
group is positioned at the ortho, meta or para position of the
“A” aromatic ring decreases the cgc by over an order of
magnitude (17 to 0.9 mm, respectively). These results clearly
show that successful gel formation was equally dependent
on the relative directionality of the hydrogen-bond motifs
on both the aromatic rings and the total number of hydro-
gen-bond donors and acceptors. Exchange of the ortho nitro
group for a nitrile residue (compare 1 and 8), or replace-
ment of the urea with a thiourea (compare 1 and 7) also re-
sulted in a small increase in the cgc value in both examples.
It is interesting to note that whilst the hydrogels formed
from 1, 3, 7 and 8 were stable over long time periods (degra-
dation was not observed over several weeks), the gels
formed from 4 and 5 (ortho and meta nitro species, respec-
tively) formed crystal-like structures a few hours after the
initial gelation, resulting in a breakdown in the integrity of
the gel (Figure 2). Intriguingly, gel metastability[16] was only
observed when gelation was induced slowly through the hy-
drolysis of glucono-d-lactone rather than if the gel was
formed quickly through direct addition of HCl (where gels
remained indefinitely stable). This observation suggests that
the kinetics of gel formation may play a key role in deter-
mining the longevity of the resulting hydrogel, although
clearly many other factors including salt type and concentra-
tion will vary between the gels formed through the two pH
switching methods. To investigate the stability of all the hy-
drogels in detail, thermal response studies of the gels were
performed (Table 3 20 mm, glucono-d-lactone pH switching
method). Vials containing the gels were immersed in an oil
bath and the temperature was increased to 1008C over
about 1 h whilst the gel stability assessed by the tube inver-
sion test at 58C intervals. Comparison of the stability results
Gelation studies by pH switching: The relative gel-forming
potential of each of the novel compounds was assessed ini-
tially by the operationally simple tube inversion test. In
many gel studies, this is achieved through heating a known
quantity of the potential gelator in a solvent to form a ho-
mogeneous solution. Subsequent cooling of the solution
allows the formation of the gel-state product. This method
was not found to be appropriate in order to assess the per-
formance of these potential hydrogelators (1–9) as a conse-
quence of the poor solubility that they exhibit in pure water
even at elevated temperature. It was found, however, that
all nine potential gelators were readily soluble in basic solu-
tions (NaOH 0.2m, pH 13). Subsequent acidification of the
homogeneous solutions either by the addition of HCl or by
using the robust glucono-d-lactone protocol introduced by
Adamsꢄ group[15] resulted in rapid (i.e., less than 1 h) homo-
geneous gel formation for solutions of six of the potential
gelator molecules (1, 3–5, 7 and 8, Table 3). The compounds
without an electron-withdrawing group on the A ring of the
urea (that is 2, 6 and 9) did not to produce a stable gel
under these conditions (gelation studies were carried out up
Table 2. Results of gelation studies via the tube inversion test for the
novel ureas 1–9.
Compound
Observation
cgc [mm]
wt% gel
2
3
4
5
1
6
7
8
9
precipitate
gel
gel
gel
gel
precipitate
gel
gel
precipitate
20
17
4.5
0.9
0.60
0.16
0.56
0.03
2.7
4.6
0.10
0.15
Table 3. Thermal stability study of the hydrogels assessed by the tube in-
version test for gels. All gels were formed via the glucono-d-lactone pH
switching method (20 mm).
Gelator
T [8C] failed inversion test
T [8C] precipitate formed
1
3
4
5
7
8
>100[a]
70
40
60
65
>100
70
42
61
70
40
43
[a] At 858C 1 visibly released water forming a layer above the gel, how-
ever the gel remained stable upon inversion up to 1008C.
Figure 2. Tube inversion tests for gels formed from 4 and 5 at A) t=1 h
and B) t=6 h. For a colour image see the Supporting Information.
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pH Tunable Hydrogelators
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Table 4. lmax at pH 14 and pH 7 for solutions containing gelators 1, 3–5,
7, 8 (water with 10% DMSO v/v, 0.3 mm).
for the isomeric series of gels 1, 4 and 5 reveals a close cor-
relation with the cgc values exhibited by the gels. The para-
nitro gelator 1 remained stable when held at the boiling
point of water,[17] whereas the ortho- (4) and meta-nitro (5)
gels failed the tube inversion test at 40 and 608C, respective-
ly. Intriguingly, failure of gels 4 and 5 was accompanied by
subsequent precipitation from solution. This trend for gel
dispersion and precipitation was observed for each of the re-
maining hydrogels which were all stable at elevated temper-
atures ranging from 40 and 708C. Despite solvent con-
straints preventing the precipitation of hydrogel 1 from
being observed, these results indicate that metastability[16]
may be a general feature of all these structurally related
gels.
Gelator
lmax [nm] at pH 14
lmax [nm] at pH 7
Shift in lmax [nm]
3
4
5
1
7
8
418
440
350
419
386
314
345
414
350
343
371
285
ꢁ75
ꢁ26
0
ꢁ76
ꢁ15
ꢁ29
regimes as all appreciable absorbance bands fall outside the
visible spectrum. This behaviour is reasonable considering
the different electronic properties of nitrile and nitro sub-
stituents. For example, the maximum absorbance of nitro-
benzene is considerably red-shifted when compared to that
of benzonitrile (lmax values for the K band are 251 and
224 nm, respectively).[18]
Gelation through pH switching and UV/Vis absorption stud-
ies: Whilst conducting the gelation experiments it became
apparent that several of the compounds underwent a dra-
matic colour change as the pH was lowered to produce the
gel state, typically changing from a vibrant orange to a pale
yellow (see Figure 3, inset, and Supporting Information).
Gel rheology studies: Mechanical studies of the six new gels
at constant concentration (20 mm) were performed using a
cone and plate rheometer with a shear frequency sweep at
1.0% strain to determine how structural variations impacted
on their macroscopic rheological characteristics. All of gels
exhibited similar rheological profiles and behave as typical
Bingham fluids (exemplified for nitrile gel 8 in Figure 4 and
in Table 5). Each gel was observed to have a storage modu-
lus (G’) that was essentially independent of the shear rate
above a certain threshold. In addition, all of the gels except
5, exhibited a value of G’ that was between one and two
orders of magnitude greater than G’’. Comparison of the
measured values for G’ and G’’ (Table 5) with the cgc pa-
rameters for these gels (Table 2) reveals little correlation be-
tween these two properties within this series of gelators.
Figure 3. UV/Vis spectra (water with 10% DMSO v/v), for a solution of
gelator
3 at pH 14 and pH 7 (concentration for both solutions=
1 mgmLꢁ1). Photo inset: Vial A, solution of 3 at pH 14, vial B, hydrogel
3 at pH 1. For a colour image see the Supporting Information.
Absorbance bands for the gelators in basic solutions (pH 14,
NaOH in water) may be determined readily by UV/Vis
spectroscopy, whereas similar absorbance measurements
under acidic conditions were hindered by scattering caused
by the gel, which spontaneously forms at low pH. To over-
come this problem, neutral solutions (pH 7) of gelator were
prepared by gentle heating of 1 mg of gelator in 10 mL of
water and 10% DMSO (v/v). Under these conditions, the
gelators remained soluble allowing for accurate determina-
tion of the absorbance bands (exemplified for 3 in Figure 3,
see Supporting Information for spectra for other com-
pounds). UV/Vis data under basic and neutral conditions
for all six hydrogelators are summarised in Table 4. From
Table 4 it can be seen that five of the six gelators exhibit sig-
nificant differences in lmax in solution at pH 14 when com-
pared to that at neutral pH. It should be noted, however,
that the nitrile gelator 8 appears colourless under both pH
Figure 4. Rheological data for nitrile gel 8 (20 mm) in water, G’: ꢅ, G’’: &.
Table 5. Maximum storage and loss moduli for the hydrogels.
Gelator
Maximum G’ [kPa]
Maximum G’’ [kPa]
3
4
5
1
7
8
84.2
166
359
294
34.4
123
1.4
7.1
23.6
31.9
4.6
13.4
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W. Hayes et al.
This can be exemplified by comparison of G’ for the nitro-
substituted gelators 1 and 5, the para-substituted gelator 1
possesses the lower cgc value, yet the meta nitro substituted
gelator 5 formed the physically more robust gel.
Methylene blue absorption studies: To facilitate the study of
contaminant extraction from aqueous media, initial experi-
ments were conducted by measuring the dye uptake of the
novel gelator compounds from aqueous solutions.[11,12,19] The
advantage of using a dye with a high absorption coefficient
for these experiments is that the relative efficiencies of the
gelators can be quantified easily by UV/Vis absorption stud-
ies, or even by visual inspection. For these specific gelators,
this process is facilitated by fact that the maxima in the ad-
sorption bands for the gelators occur between 285 and
414 nm (see Table 4), far removed that of methylene blue
which exhibits a lmax =667 nm, allowing simple determina-
tion of the relative dye uptake of the gelators. This process
is exemplified in Figure 5 which shows photographs of meth-
ylene blue removal for the three isomeric nitro-diacid deriv-
atives 1, 4, and 5 after 48 h. In contrast to previously report-
ed results, experiments were conducted by addition the pre-
formed gel (1 mL, 20 mm) to a solution of methylene blue
that was stirred gently (for a time lapse video of a typical
experiment see Supporting Information). Comparison with
the control sample, where the gelator was not added clearly
shows that all three gels were capable of extracting dye
from aqueous solutions. Dye uptake was quantified by anal-
ysis of the absorbance band at 667 nm in the UV/Vis ab-
sorption spectra of the four solutions which confirms that
the relative absorbance efficien-
Figure 5. Top: Photograph of a solution of methylene blue (8 mgmLꢁ1
)
and flasks containing the same initial concentration 48 h after addition of
the pre formed gels (1 mL, 20 mm) of 4, 5 or 1 (left to right, respectively).
Bottom: UV/Vis spectra of a filtered sample of the solution from each of
the flasks. For a colour image see the Supporting Information.
formation) and 9 (both prior to and post gel formation) re-
vealed dye uptake values of 28, 28 and 49%, respectively
(see Figure S13 in the Supporting Information). Comparison
of the dye extraction rates for the isomeric gelators 1, 4 and
5 revealed that whereas the ortho and meta-nitro substituted
gels reached saturation within the timescale of the experi-
ment, exhibiting a maximum dye uptake of 34 and 50% for
cies were 70% (4), 87% (5)
and >99% (1), respectively. To
measure the kinetics of dye ex-
traction by the gelators, a time
dependent dye uptake experi-
ment was conducted. For each
compound, 1 mL of the hydro-
gel (20 mm, pH 1, ~7 mg) was
added to a stirred solution of
aqueous methylene blue solu-
tion (100 mL, 8 mgLꢁ1) and the
concentration of dye remaining
in solution was measured peri-
odically over 280 min by UV/
Vis spectroscopy (exemplified
for a typical experiment using
para-nitro urea gelator 1, Fig-
ure 6A). A plot of the lmax
(667 nm) as a function of time
for all six gelators (Figure 6B:
1, 4 and 5 and C: 3, 7 and 8) re-
veals a significant difference in
both the maximum dye uptake
for the gelators and the relative
rates of dye extraction. Analo-
Figure 6. Plot A: UV/Vis absorption spectra a stirred solution of aqueous methylene blue (100 mL, 8 mgLꢁ1
up to 280 min after addition of 1 mL of the hydrogel 1 (20 mm, ~7 mg). Plots B and C: lmax (667 nm) for the
)
gous studies for 1 (prior to gel methylene blue absorption in solution (100 mL, 8 mgLꢁ1) up to 280 min after addition of gels.
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pH Tunable Hydrogelators
FULL PAPER
4 and 5, respectively, the para-nitro gel 1 extracted essential-
ly all of the dye from solution (98%). Under the same con-
ditions mono acid gelator 3 was the least effective at dye ex-
traction (28%), whilst the gelators with the nitrile (8) and
thiourea gelators (7) extracted 98 and 79% of the dye, re-
spectively. Although the maximum dye absorption for gels 1
and 8 was similar (>98%), the nitrile gelator (8) reached
this level of dye extraction after a period of only 20 min,
when compared to 280 min for the nitro-substituted gelator
1. Table 6 shows the quantity of dye sequestered by the pre-
lengths extending over 10 mm in length. Cryo-TEM analysis
of a sample of gel 8 containing 20 wt% dye revealed a dra-
matic change in the appearance of the fibrils (Figure 7C, see
Figure 7D for a photograph of the dye containing gel). In-
clusion of the dye caused a significant decrease in the length
of the fibers to approximately 600 nm. In addition there is
clear evidence for aggregation of the fibers, with the result-
ing bundles exhibiting a width of up to 50 nm. It is apparent,
however, that gelator 8 is sufficiently robust in order to
maintain its extended network during preparation for cryo-
TEM in the absence of the dye (see Figure 7B), thus inclu-
sion of methylene blue within the fibrils must at least have
an impact on the strength of the fibrils.
Table 6. Maximum absorption of methylene blue dye from water by pre-
formed hydrogels.
Gelator
Weight dye uptake
[mggꢁ1
Dye uptake per molecule
of gelator [molmolꢁ1
]
Solid-state analysis: In order to gain an insight into the mo-
lecular ordering within the gel networks, differential scan-
ning calorimetry (DSC) of the xerogel forms of the hydro-
gels was conducted. In all cases, the first heating ramp of
the DSC exhibited multiple thermal events, which were not
apparent in the second heating ramp (see Figure S9A to F
for thermograms). Analysis of the complex DSC traces was
hindered by the composition of the residual mass which con-
tained the gelator, glucono-d-lactone and NaOH (see Fig-
ure S9G for the thermogram)—the latter two components
were required to effect hydrogel formation via the pH
switching methodology. The dye uptake characteristics of
the hydrogel materials could potentially be related to the
corresponding solid-state structures. Previous solid state
structural analysis of para-nitro hydrogelator 1[12] revealed a
highly ordered and regular array with ribbons of strictly
planar molecules connected via nitro to urea hydrogen
bonds[23] which were incorporated into extended two dimen-
sional layers through dimerisation of the carboxylic acid
groups. Solid-state analysis of the mono-acid gelator 3 did
not reveal such a regular extended array (Figure 8). In the
solid state 3 is evident as discrete dimers maintained via car-
boxylic acid hydrogen bonds (O-H···O, 1808, 2.62 ꢆ,
Figure 8). Each dimer was incorporated into a higher or-
dered solvated array through hydrogen bonding to protic
solvent. The methanol molecules permit indirect nitro to
urea links (OH···ON 169ꢂ88, 2.95ꢂ0.09 ꢆ, N-H··· O-N,
1598 ꢂ3, 2.93ꢂ0.04 ꢆ, because Z’=2,[24] the range includes
the values for the two distinct molecules in each asymmetric
unit). The solid state structure of the meta-nitro gelator 5
also contains two molecules in the asymmetric unit (Z’=2,
Figure 9). Each molecule adopts a highly twisted conforma-
tion, with the two aromatic rings offset by 47 and 638
(Figure 9). Tapes were evident that consisted of alternating
bifurcated urea hydrogen bonding and N-Hurea···O-N interac-
tions. These tapes are, in turn, connected via carboxylic acid
dimers (4 distinct hydrogen bonds all within the range O-
H···O, 174ꢂ38, 2.62ꢂ0.03 ꢆ). Thus, in contrast to 1, both
mono acid 3 and meta nitro-compound 5 do not possess
such a dramatic extended layered aromatic surface in the
solid state that is suitable for efficient dye uptake.
G
]
3
4
5
1
7
8
37
39
58
1020
88
0.03
0.04
0.05
1.1
0.08
1.1
1020
formed hydrogels after addition to stirred solutions of an
excess of methylene blue. The maximum absorbed by the
gels varied widely from approximately 4 wt% dye uptake
(4) to over 100 wt% (1000 mggꢁ1) dye uptake (1 and 8).
These values may be compared to those for previously re-
ported hydrogelators such as the tripeptide produced by
Banerjee and co-workers, which exhibited a maximum
uptake of 10.6 mggꢁ1 of the dye rhodamine red from
water.[11]
Hydrogel analysis by cryo-transmission electron microscopy
(TEM): Cryo-TEM has become an increasing important
analysis technique for the study
of gels. The vitrification of the
solvated gel prior to analysis re-
tains the nanoscale structure in
its native hydrated-state, pro-
viding valuable insights into the
self-assembled structures of the
unperturbed hydrogel.[20] The
technique has been used exten-
sively to study peptidic gela-
tors,[21] but less frequently to
image non-biologically inspired
Figure 7. Cryo-TEM images of
hydrogels: A) 1, 20 mm; B) 8, hydrogelators.[22] Figure 7A and
20 mm, C) 8 (20 mm) contain-
B show cryo-TEM images for
ing 20 wt% methylene blue.
the para-nitro (1) and nitrile (8)
D) Tube inversion test of the
gels that exhibited the maxi-
gel
8
(20 mm) containing
mum dye uptake values within
these studies. Both gels exhibit
an extended network consisting
of high aspect ratio fibers each
of which measured approxi-
mately 8 nm wide and fiber
20 wt% methylene blue. All
gels formed through the gluco-
no-d-lactone pH switching
methodology, scale bars on
TEM images all 200 nm. For a
colour image see the Support-
ing Information.
Chem. Eur. J. 2012, 18, 2692 – 2699
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2697

W. Hayes et al.
change of a nitro group with a nitrile functionality, both ex-
hibited high aspect ratio single fibres by cryo-TEM analysis,
but analysis of fibres of 8 that had absorbed 20 wt% of
methylene blue showed a significant decrease in fibre length
and evidence of aggregation. Hydrogels 1 and 8 were able
to sequester over 1 gram of dye per gram of gelator from
aqueous solution, with 8 achieving high levels of dye absorp-
tion more rapidly than 1. These structure property relation-
ship studies will enable the realization of inexpensive and
highly effective purification systems for contaminated water.
Experimental Section
Chemical characterisation: NMR spectra were recorded on either a
Bruker Nano400 (9.39 T) or a Bruker DPX 400 (9.39 T) instrument, with
1
both operating at 400 MHz or 100 MHz for H and 13C nuclei, respective-
ly. IR spectra were recorded on a PerkinElmer Spectrum 100 FT-IR in
transmission mode. All samples were analyzed as solid powders using a
diamond ATR sampling accessory. Mass spectrometry was conducted
using a ThermoFischer Scientific Orbitrap XL LCMS. The sample was in-
troduced via liquid chromatography. Ionisation was achieved by electro-
spray ionisation (ESI). Melting points were acquired on a Stuart SMP10
melting point apparatus using a temperature ramp of 28Cminꢁ1. UV
spectra were recorded using a Varian Cary 300 Bio or a PerkinElmer
Lambda 25 UV/Vis Spectrometer. Samples were analysed in quartz cur-
ettes with a 5.0 mm path length and were baseline corrected with respect
to a blank cell with the appropriate solvent.
Figure 8. Top: Solid-state structure of hydrogelator 3 revealing a discrete
hydrogen bonded dimer and the role of the methanol within the crystal
lattice.
Conclusion
Shear rheology: Experiments were carried out using a TA Instruments
AR2000 rheometer. Samples were tested in the cone-and-plate geometry
using a 20 mm diameter cone. The material was analysed via frequency
sweeps at low strain (1.0%).
A library of structurally related
and synthetically accessible hy-
drogelators has been synthes-
ised and characterized. Gela-
tion was induced by acidifica-
tion of a basic solution of the
small molecule gelator either
by addition of HCl or by the
slow hydrolysis of glucono-d-
lactone. The most efficient gela-
tor produced hydrogels at an
extremely low cgc values (ca.
0.03 wt%). Frequently, gelation
Single-crystal X-ray diffraction: Data were collected with CuKa radiation
on an Oxford Diffraction Gemini S Ultra CCD diffractometer equipped
with an Oxford Cryosystems low-temperature device operating at 150 K.
Both structures were solved by direct methods (SIR92[25]) and refined by
2
full-matrix least squares against jFj using all data (CRYSTALS[26]).
Though all H atoms could be distinguished in the difference Fourier map,
the H-atoms were included at geometrically idealized positions and re-
fined in riding-model approximation. All full-weight non-H atoms were
modelled with anisotropic displacement parameters.
Cryo-TEM: Sample preparation was carried out using a CryoPlunge 3
unit (Gatan Instruments) employing a double blot technique. A small
quantity of sample was pipetted onto a plasma etched (15 s) 400 mesh
holey carbon grid (Agar Scientific) held in the plunge chamber at approx
90% humidity. The samples were blotted, from both sides for around 6 s
dependant on sample viscosity. The samples were then plunged into
liquid ethane at a temperature of ꢁ1708C. The grids were blotted to
remove excess ethane then transferred, under liquid nitrogen to the cryo
TEM specimen holder (Gatan 626 cryo holder) at ꢁ1708C. Samples were
examined using a Jeol 2100 TEM operated at 200 KV and imaged using a
Gatan Ultrascan 4000 camera and images captured using DigitalMicro-
graph software (Gatan).
occurred with
a concomitant
colour change from deep
orange to pale yellow which
was measured by UV/Vis spec-
trometry and could be observed
visually. Hydrogelators 4 and 5
were found to be metastable
when formed slowly under glu-
cono-d-lactone hydrolysis con-
ditions, but generated a highly
stable hydrogel with lifetimes
of several weeks when formed
rapidly by addition of HCl to
the basic solution. All of the
hydrogels were able to seques-
ter the planar cationic dye,
Figure 9. Solid-state structure
of hydrogelator 5 showing the
Synthesis and characterisation
three
dominant
hydrogen
General: All reagents were purchased from Sigma Aldrich and used as
received without further purification. Solvents were used as supplied with
the exception of THF that was distilled under argon from sodium and
benzophenone prior to use. Gelator synthesis is exemplified for mono-
acid hydrogelator 3, full synthetic procedures, characterisation and NMR
spectra for all new compounds are reported in the Supporting Informa-
tion.
bonding interactions of urea–
urea, nitro-urea and carboxylic
acid dimerisation (in both
cases the non-hydrogen bond-
ing hydrogen atoms removed
for clarity).
4-(3-(4-Nitrophenyl)ureido)benzoic acid (3): 4-Nitrophenylisocyanate
(0.31 g, 1.90 mmol) and 4-aminobenzoic acid (0.26 g, 1.90 mmol) were
dissolved in dry THF (30 mL) and stirred in an inert atmosphere for
24 h. On completion the resultant white solution was reduced in vacuo,
methylene blue, from solution. The structurally related hy-
drogels 1 and 8, which are differentiated only by the ex-
2698
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ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 2692 – 2699

pH Tunable Hydrogelators
FULL PAPER
added dropwise to hexane (150 mL) and
a
pale yellow precipitate
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as a pale yellow powder (0.48 g, 84%). M.p. 2418C (decomp); 1H NMR
(400 MHz, [D6]DMSO): d = 9.56 (s, 1H), 9.31 (s, 1H), 8.21 (d, 2H, J=
9.2 Hz), 7.90 (d, 2H, J=10.8 Hz), 7.71 (d, 2H, J=9.6 Hz), 7.58 ppm (d,
2H, J=5.6 Hz); 13C NMR (100 MHz, [D6]DMSO): d=166.9, 151.7, 146.0,
143.2, 141.2, 130.5, 124.3, 124.0, 117.7 ppm; IR (ATR): n = 3273, 3094,
2580, 1660, 1498, 1301, 1175, 858, 749 cmꢁ1; MS (ESI): m/z: calcd for
C14H12N3O5: 302.0777, found 302.0722.
Crystal structure information: Crystal structure data for 3 and 5 have
been deposited at the Cambridge Crystallographic Data Centre and allo-
cated the deposition numbers: CCDC-832322, and -832323 contain the
supplementary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
Work in the UK was supported by EPSRC EP/G026203/1 for BWG and
EPSRC for a studentship for A.L.A., a UROP studentship from the Uni-
versity of Reading for D.M.W. and grants from both the Diamond Light
Source Ltd and the University of Reading for C.A.M. Work at Castellꢂ
was supported by MCI, grant CTQ2009-13961 and Universitat Jaume I,
grants P1-1B2009-42 and P1-1B2007-11. F.R.L. thanks Generalitat Va-
lenciana for a FPI fellowship. We acknowledge Steve Furzeland and
Derek Atkins (Unilever, Colworth) for their expertise in performing the
cryo-TEM experiments.
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Received: July 12, 2011
Revised: October 21, 2011
Published online: January 26, 2012
Chem. Eur. J. 2012, 18, 2692 – 2699
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2699