Ultra-Low Molecular Weight Photoswitchable Hydrogelators

Article abstract of DOI:10.1002/anie.202015703

Two photoswitchable arylazopyrozoles form hydrogels at a concentration of 1.2 % (w/v). With a molecular weight of 258.28 g mol^?1, these are the lowest known molecular weight hydrogelators that respond reversibly to light. Photoswitching of the E- to the Z-form by exposure to 365 nm light results in a macroscopic gel→sol transition; nearly an order of magnitude reduction in the measured elastic and loss moduli. In the case of the meta-arylazopyrozole, cryogenic transmission electron microscopy suggests that the 29±7 nm wide sheets in the E-gel state narrow to 13±2 nm upon photoswitching to the predominantly Z-solution state. Photoswitching for meta-arylazopyrozole is reversible through cycles of 365 nm and 520 nm excitation with little fatigue. The release of a rhodamine B dye encapsulated in gels formed by the arylazopyrozoles is accelerated more than 20-fold upon photoswitching with 365 nm light, demonstrating these materials are suitable for light-controlled cargo release.

Full text of DOI:10.1002/anie.202015703

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Ultra-low molecular weight photoswitchable hydrogelators
Authors: Fayaz Ali Larik, Lucy L. Fillbrook, Sandra S. Nurttila, Adam
D. Martin, Rhiannon P. Kuchel, Karrar Al Taief, Mohan
Bhadbhade, Jonathon E. Beves, and Pall Thordarson
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RESEARCH ARTICLE
Ultra-low molecular weight photoswitchable hydrogelators
Fayaz Ali Larik,[a,b] Lucy L. Fillbrook, Sandra S. Nurttila,
[a]
[a,b]
Adam D. Martin, Rhiannon P. Kuchel,
[c]
[d]
Karrar Al Taief,[a,b] Mohan Bhadbhade, Jonathon E. Beves* and Pall Thordarson*
[e]
[a]
[a,b]
[
a]
F. A. Larik, L. L. Fillbrook, Dr. S. S. Nurttila, K. Al Taief, Dr. J. E. Beves, Prof. Pall Thordarson
School of Chemistry
The University of New South Wales
Sydney, NSW 2052, Australia
E-mail: j.beves@unsw.edu.au and p.thordarson@unsw.edu.au
F. A. Larik, Dr. S. S. Nurttila, K. Al Taief, Prof. Pall Thordarson
The Australian Centre for Nanomedicine and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
The University of New South Wales
Sydney, NSW 2052, Australia
Dr A. D. Martin
Dementia Research Centre, Department of Biomedical Science, Faculty of Medicine and Health Sciences
Macquarie University
Sydney, NSW 2109, Australia
[
[
[
[
b]
c]
d]
e]
Dr. R. P. Kuchel
Electron Microscopy Unit, Mark Wainwright Analytical Centre
The University of New South Wales
Sydney, NSW 2052, Australia
Dr. M. Bhadbhade
Solid State & Elemental Analysis Unit, Mark Wainwright Analytical Centre
The University of New South Wales
Sydney, NSW 2052, Australia
Supporting information for this article is given via a link at the end of the document
Abstract: Two photoswitchable arylazopyrozoles form hydrogels at
a concentration of 1.2% (w/v). With a molecular weight of 258.28
g/mol, these are the lowest known molecular weight hydrogelators
that respond reversibly to light. Photoswitching of the E- to the Z-
form by 365 nm light results in a macrocopic gel→sol transition;
nearly an order of magnitude reduction in the measured elastic and
loss moduli. In the case of the meta-arylazopyrozole, cryogenic
transmission electron microscopy suggests that the 29±7 nm wide
sheets in the E-gel state narrow to 13±2 nm upon photoswitching to
the predominantly Z-solution state. Photoswitching for meta-
arylazopyrozole is reversible through cycles of 365 nm and 520 nm
excitation with little fatigue. The release of a Rhodamine B dye
encapsulated in gels formed by the arylazopyrozoles is accelerated
more than 20-fold upon photoswitching with 365 nm light,
demonstrating these materials are suitable for light-controlled cargo
release.
has a clear advantage due to its ability to operate in a highly
precise manner without contaminating samples.[
10]
Hydrogels
have been made light responsive by the inclusion of a light
responsive photoswitchable unit in the gelator molecule.[
All previous examples have relied on the inclusion of peptides or
other additional groups to enable hydrogel formation (Figure
1a,b). Peptide-[11,10c,10d] or polymer-based[12] hydrogels have
been rendered photoresponsive by introducing molecular
10c,10d]
[
13]
spiropyran,[11,14a,10d,14b]
photoswitches such as diarylethene,
azobenzene,[
15a-l,10e,15m,15n]
stilbene,[16]
ortho-
fluoroazobenzenes,[17] and arylazopyrazoles.[18,12c]
Arylazopyrazoles (AAP) are a recently introduced class of
azohetereoarene photoswitches.[19] Azoheteroarenes[19c] are
related to azobenzenes but differ as one of the phenyl rings of
conventional azobenzene is replaced with heteroarene ring. The
Fuchter group has extensively studied these compounds
showing almost complete photoisomerization in both directions
with the thermal half-life of the metastable Z-isomer being
tunable from hours to 10 days.[19] Ravoo and co-workers[20] have
used arylazopyrazoles to form light responsive gels where a
central linker is connected to three photoswitching groups
Introduction
[
1]
The formation of cytoskeletal filaments and flagellar filaments
of bacteria[ rely on the self-assembly of smaller components.
Synthetic small molecules have also been shown to self-
assemble in water to form structures ranging from the
(Figure 1b, MW=1195.27 g/mol). Tetrapeptides gelators (Fmoc-
2]
RGDS) were combined with an arylazopyrazole photoswitching
[20]
unit attached via a linker chain (Fmoc-RGDS-AAP).
Most gelators reported in literature, including all
photoswitchable gelators, have a MW > 300 g/mol. The bulk of
light-responsive gelators contain long alkyl chains, peptides, or
polymers and hence the photoswitchable unit plays a secondary
role in the self-assembly of these systems. Herein we introduce
the first gelators with a molecular weight below 300 (MW=
[
3]
[4]
nanometer scale to micrometer scale, with hydrogelators
being one example. Controlling the self-assembly of hydrogels
using external stimuli has been challenging[5] but can be
achieved by introducing the appropriate responsive units within
the molecular components of these systems.
Hydrogel research[4] has evolved from static materials to
dynamic smart materials. Controlling the mechanical, physical
and chemical properties of hydrogels with external stimuli is
important for both medical and industrial uses such as controlled
2
58.28 g/mol – making it one of smallest hydrogelator
[21]
reported ) that form stable hydrogels at physiological pH and
respond to light in a bidirectional way (Figure 1c,d).
drug delivery,[ sensing, robotics and 3D cell cultures. Light
6]
[7]
[8]
[9]
1
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Figure 1. a) The three smallest photoswitchable single-component hydrogelators reported to date. b) The smallest single-component arylazopyrazole
photoswitchable gelator previously reported. c) The low molecular weight photoswitching arylazopyrazole compounds 1–4 (in their E-form) reported in this work.
Compounds 2–3 (MW 258.28 g/mol) form gel in water at 1.0% (w/v), while 1 and control compound 4 do not form gels reported here. d) The design and switching
mechanism of low molecular weight photoswitchable gelators 1–3.
Arylazopyrazole photoswitches 1–3 (Figure 1c) are isomers
that differ only in the substitution of the carboxylic acid group on
the aromatic ring. The carboxylic acid group can act as a
hydrogen bond donor and acceptor, and the pyrazole ring and
the diazo nitrogens can act as hydrogen bond acceptors to aid
the gelation process. The photoswitches 2 and 3 form hydrogels
as a result of intermolecular hydrogen bonding and hydrophobic
effects, and represent the minimal non-covalent interactions
usually required to trigger gelation. The arylazopyrazole
photoswitch 4 bears an ester group at the para position and is
used as a control compound not capable of intermolecular
hydrogen bonding and hence does not form a gel.
and then concentrated under reduced pressure to obtain 1–4 as
yellow solids in quantitative yields.
The photoswitching behavior of 1–4 was evaluated by UV-
vis absorption (SI-4) and NMR spectroscopy (SI-12).
Photoswitching using UV-vis absorption was recorded in a range
2 2
of solvents (DMSO, CH Cl , methanol, THF, ethyl acetate,
chloroform, toluene and acetonitrile) and the spectra in water are
shown in Figure 2a. No significant solvatochromism was
observed between the eight solvents that were studied (Table
S2-S5). The samples were irradiated with 365 nm and 520 nm
LED light sources for ~2 min to generate photostationary states
Z E
(PSS) enriched in the Z- or E-isomer, labelled PSS and PSS
respectively. The data is in agreement with that observed for
related arylazopyrazole compounds.[19b
1
The PSS compositions were quantified by H NMR spectroscopy.
Results and Discussion
1
The H NMR spectra in DMSO-d
6
of samples equilibrated in the
dark showed a single isomer in each case, the expected
thermodynamically stable E-isomer (see SI-12.9, SI-12.16, SI-
12.23 and SI-12.27). The samples were irradiated with 365 nm
Synthesis of photoswitches 1–4
Compounds 1–4 were synthesized using modified literature
procedures of related compounds.[19b] The ortho-, meta- or para-
aminobenzoic acid and ethylaminobenzoate were reacted with
hydrochloric acid and sodium nitrite to form the diazonium salt,
which was reacted with acetylacetone to obtain pentane-2,4-
diones (S1–S4) intermediates (see full characterization in SI-2,
SI-12, SI-13, analytical methods described in SI-3). The
intermediates (S1–S4) were refluxed for 3 h with N-methylamine
1
light for 60 min and H NMR spectra were recorded to obtain the
PSS distribution (PSS
SI-12.18, SI-12-25, SI-12.29). Each sample was then irradiated
with 520 nm light to produce a new photostationary state (PSS
92% Figure 2c). The PSS is thermally stable at 25 °C in water
over the time scale relevant to all the studies in this work with an
Z
≈ 90% Z for each of 1–4, see SI-12.11,
E
≈
Z
2
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apparent half-life measured by UV-vis absorption of 29–34 h for
compounds 1–4 (Figures S7, S12, S17, S22) All the compounds
showed excellent photoswitching behavior in water and DMSO-
6
d .
Figure 3. Single crystal X-ray structures of a-b) 2 and c-d) 3. The ortho
derivative 1 has an intramolecular hydrogen bond and does not form extended
chains (SI-6.5). Both the meta-2 and para-derivatives 3 form 1D hydrogen
bonded chains as shown. Centroid-to-plane distances are shown with black
dotted lines.
Table 1. Comparison of the key parameters of hydrogen bonding of isomers
1–3, obtained from the single crystal X-ray diffraction data.
Figure 2. Photoswitching of 2 monitored by a) UV-vis absorption spectra in
water of E-2 as prepared (black line) and at photostationary states upon
irradiation with 365 nm (blue line) and 520 nm (green line) light. b) Reversible
switching of absorption in water monitored at 334 nm upon alternating
irradiation with UV (365 nm, indicated with blue) and green (520 nm) light (red
error bars = ±1 std from n = 3 measurements). c) 1H NMR (400 MHz, DMSO-
1
2
3
Inter/Intra
O-H / Å
Intra-
Inter-
Inter-
0.840
1.822
0.98(4)
1.774
0.94(2)
1.793
H···N / Å
O···N / Å
O-H···N / o
d
6
) of i) as prepared E-2, ii) after irradiation with UV (365 nm) or iii) green (520
nm) light. d) NMR tube of E-2 in DMSO-d as prepared and PSS obtained
after irradiation with 365 nm light. See Figure SI-4, SI-12 for similar data on 1,
and 4.
6
Z
2.595(7)
152.3
2.712(4)
160(4)
2.689(2)
160(2)
3
Solid state interactions
(Figure S70) due to the intramolecular hydrogen bond between
the carboxylic acid and the diazo nitrogen.
Crystals suitable for single crystal X-ray diffraction were
grown of 1–4 from saturated solutions in DMF/diethyl ether,
DMSO and ethanol (SI-6 for details). The structure of 1 showed
an intramolecular hydrogen bond between the carboxylic acid
group and the adjacent diazo nitrogen (O···N = 2.595(7) Å).
Compound 2 is slightly twisted, with an angle of 20.1° between
the least-squares planes of the phenyl- and the pyrazole rings.
By comparison compound 3 is almost completely flat, with the
same angle between the two rings being just 5.39°. The
structures of both 2 and 3 show inter-molecular hydrogen bonds
between the carboxylic acid group and the free pyrazole
nitrogen of an adjacent molecule, with short and similar N···O
distances (2.712(4) and 2.689(2) Å, respectively. In each case
the hydrogen bonds result in 1D chains that are self-assembled
by - interactions (centroid-to-plane distances of 3.34 Å and
Hydrogel formation
Gelation was investigated using the pH switch method with
glucono--lactone (gL).[24] All the starting materials were in the
pure E-form and these experiments were carried out in the
absence of light. Compounds 2 and 3 were dissolved at pH 11,
followed by the addition of gL. After standing at room
temperature overnight, hydrogels were formed as determined by
the inverted vial test (see SI-9). The minimum gelation
concentration for both gelators was determined to be 1.0% (w/v),
however, to ensure better consistency in gel properties, all
subsequent studies were carried out at 1.2% (w/v) concentration
of 2 and 3. The kinetics of gelation of compounds 2 and 3 was
1
monitored by
H
NMR spectroscopy (see SI-11). The
1
3.30 Å for 2 and 3 respectively, see Figure 3b, d and Table 1).
disappearance of the H NMR signals of the monomeric gelator
over ~80 min for 2 or 3 was consistent with aggregation.
Compound 1, which does not form any intermolecular hydrogen
bonds in the solid state, does not form a gel in water (SI-8.1).
Compound 4, which also does not display any solid-state
intermolecular hydrogen bonding interactions (SI-6.8), does not
Details for the structures of 1 and 4 are given in SI-6.
Hirshfeld surface analysis[22] is a powerful tool for visualizing
short and long contacts within crystal structures. The so-called
“fingerprint” plots of 2–3 (SI-7) are superficially very similar,
highlighting the importance of the two intermolecular shorts
contacts show in Figures 3a and 3c. However, the Hirshfeld
fingerprint of 3 highlights a significant pairwise intermolecular
H···O interaction between the carbonyl oxygen and an aromatic
meta-hydrogen on a neighboring molecule. This suggests why
gelator 3 packs in an antiparallel fashion in the single crystal
structure, in contrast to gelator 2. Previous studies have shown
similar pair-wise interaction drive the formation of antiparallel
stacked aromatic molecules.[23] No significant intermolecular
short contacts were observed in the Hirshfeld fingerprint plot of 1
a
form a gel. The pK values of compound 1–3 are practically
indistinguishable (determined by pH titrations, see SI-10) with
pKa values of 6.4, 6.4 and 6.7 for 1, 2 and 3, respectively.
The viscoelastic properties of gels formed by 2 and 3 were
studied using a rheometer (Table 2, SI-3). In the dark, the gel
formed by 2 was stiffer (elastic modulus G’ ~10 kPa) than that of
3 (G’ ~1.2 kPa); both were prepared by the pH switch method
using gL (1.2% (w/v); dissolved in 0.1 M sodium hydroxide,
followed by the addition of gL, see SI-3). The frequency
sweeps (SI-8.4-8.5) showed that the storage modulus is
3
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independent of the applied frequencies up to ≈10 Hz with some
frequency hardening observed at higher frequencies. The strain
sweep (SI-8.2) for both 2 and 3 showed that both hydrogels
possess malleable-like characteristics, with the linear
viscoelastic region lasting until about 10% strain for both
gelators. Further increases in strain result in gel collapse at
about 60% and 80% strain for 2 and 3, respectively.
that argument is usually in the situation whereby the materials
appears to pass the inversion test while tan  > 1.[4b, 25] Here, the
opposite situation was observed, which is in line with recent
observation by Adams and co-workers who attribute this
phenomena to the formation of a structured liquid[26] (a liquid
with some remaining solid-like rheological properties), but further
work is required to explain why irradiation of 2 and 3 leads to an
apparent gel transition despite the fact that tan  < 1.
Table 2. Key physical properties of gels formed by 2 and 3 in the dark.
Gelator
mgc[a]
G’ b]
LVR [c]
10%
Fiber diameter[d]
12.2±0.5 nm
2
3
1% (w/v)
1% (w/v)
10 kPa
1.2 kPa
9.5%
13.4 ±0.6 nm
[
1
a] Minimum gelation concentration (mgc). [b] Elastic modulus (G’) at strain =
%, frequency = 1 Hz and 1.2% (w/v) concentration. [c] Elasticity (strain) or
linear viscoelastic region (LVR) at frequency = 1 Hz. [d] Histograms of the fiber
heights obtained from AFM microscopy and measured for 2 and 3 before
irradiation with light. The histograms represent 25 measurements in four
different areas for each sample (bin size = 100).
We postulate here that the approximately one order of
magnitude difference in the elastic modulus of gels formed by 2
and 3 in the dark can be explained with reference to the
observed parallel versus anti-parallel packing in the single
crystal structures of 2 and 3, respectively. Powder X-ray
diffraction of xerogels formed from 2 and 3 yielded patterns
similar to those predicted from the single crystal X-ray structures
Figure 4. Photoswitching of 2 by alternating irradiation with 365 nm and 520
nm light. Changes in a) rheology with in situ irradiation and b) Size of fibers
obtained from AFM microscopy before (blue) and after irradiation (orange)
after drop casting dilute (0.0006%, w/v) solution of 2 on to a mica surface.
Morphology of fibers obtained from cryo-TEM microscopy of gels formed from
(SI-6.11, SI-6.12). The single crystal X-ray structure data and
Hirshfeld surface analysis in turn indicate that pairwise
intermolecular H···O interactions drive the slightly less compact
packing of 3 in an antiparallel orientation.
2
in water (1.2% (w/v)) c) before light and d) after irradiation with 365 nm light,
scale bar is 200 nm. For the analogous data for compound 3, see SI-5.3.6 and
SI-8.4.
Gel→Sol Photoswitching
Immediately after the addition of gL, 1.2% (w/v) solutions of
2
and 3 were cast onto a rheometer fitted with a glass plate and
Microscopy studies of gel morphology
allowed to form hydrogel in dark over ~85 min. Dynamic in situ
time sweep rheological measurements were conducted on 2 and
3
illuminated area is significantly smaller than the diameter (25
mm) of the rheometer measurement plate, the ≈ 500 L gap was
only filled with ca 20% (110 L) of the gel solution. The absolute
elastic (G’) and loss (G’’) module obtained are therefore not
directly comparable to the rheological data obtained under
standard conditions in the dark discussed above (see SI-3.8 for
further information).
Atomic force microscopy (AFM) measurements were
conducted starting with 1.2% (w/v) solutions of 1–4 that were
then rapidly diluted (to 0.0006% w/v) and drop casted on a mica
substrate to investigate the size and topography of any self-
assembled fibers formed under such conditions (SI-5.1). We
have previously shown that AFM measurements on fibers
formed from dilute drop-cast solutions yield comparable
information to more experimentally challenging cryogenic
upon exposure to alternating 365 nm and 520 nm light. As the
transmission electron microscopy (cryo-TEM) and in situ small
angle neutron scattering (SANS) methods.
[27]
No fibers were
Upon the first irradiation with 365 nm UV light, G’ for 2
decreased from about 200 Pa to about 50 Pa over a period of 1
h (Figure 4). Subsequent irradiation of 2 with 520 nm green light
restored the initial elasticity of 2 (see Figure 4a). Both green and
UV light-irradiated states retained stable G’ values for at least
found for compounds 1 and 4, which is in line with the
observation that they did not self-assemble into gels. Compound
2
formed fibers with a diameter of 12.2±0.5 nm (in the dark) and
when irradiated with 365 nm light the diameter of the fibers
reduced to 7.2±0.4 nm, as measured by AFM (Figure 4b).
Similarly, compound 3 formed thin sheet-like fibers with a
diameter of 13.4±0.5 nm (in the dark) and 4.7±0.3 nm (after
irradiation with 365 nm). On all occasions, the fibers appear
longer than the maximum scan size used (5 x 5 m). Scanning
electron microscopy (SEM) was used to image the structures
formed from 1–4 when more concentrated 1.2% (w/v) solutions
15 min after the light was switched off. Multiple photoswitching
cycles were performed on 2 by alternating between UV and
green light irradiation and minimal fatigue was observed.
While a gel→sol transition appears to have occurred using a
conventional inversion test on 2 (Figure 4) and 3 (Figure S76),
the tan
 (the G’’/G’ ratio) remains well below 1—the
[
4b]
conventional rheological definition of a gel —during the entire
course of the light-switching experiments (Figure S75). Strong
arguments have been made in the literature that a tan  < 1 is a
more reliable indicator of gelation than the inversion test, albeit
(in the dark) were drop-cast onto silica (SI-5.2). The desiccated
gels from 2 and 3 showed fiber-like surfaces, while the
precipitates from compounds 1 and 4 were found to have
crystal-like surfaces (SI-5.2.1, SI-5.2.4). If the solutions were
4
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RESEARCH ARTICLE
irradiated with 365 nm light prior to being drop-cast, the
morphology observed for 2 and 3 changed from fibrous to
crystalline, consistent with disassembly (see SI-5.2.2, SI-5.2.3).
The combination of TEM and cryo-TEM techniques were
used to investigate the structural changes in the self-assembly
of 2 and 3 before and after illumination with 365 nm light (SI-5.3).
When comparing the cryo-TEM micrographs of the fibers from
gels formed by 2 at 1.2% (w/v) in water before (Figure 4c) and
after irradiation with 365 nm light (Figure 4d), a clear “thinning”
of the fibers is observed, as the 29±7 nm wide sheets narrow
down to 13±2 nm. These results are qualitatively consistent with
the AFM analysis above, given that the latter are presumably
dried out. This data is supported by conventional TEM analysis
on 1.2% (w/v) solutions of 2 (SI-5.3.2). Compounds 1 and 4 did
not show any fiber-like aggregates under these conditions. TEM
analysis of 3 was less conclusive; conventional TEM did not
show fibers but rather spherical, perhaps micellar-like objects
prior to illumination that disintegrated upon illumination with 365
nm light (SI-5.3.3). The cryo-TEM micrographs of 3 before
illumination showed very wide (≈ 400 nm) thin sheet like
structures that do also become thinner (≈ 200 nm) after
irradiation with 365 nm light (SI-5.3.6), which appear in some
cases less than 1 m long.
continuous irradiation with 365 nm light, the gels readily
released the dye, reaching approximately 80–90% dye release
over 4 h.
Figure 5. a) Release of Rhodamine B dye from hydrogels formed by a) 2 or b)
3
prepared by dissolving 1.2% (w/v) of 2 or 3 and 0.01% (w/v) of the dye in a
solution of sodium hydroxide (98 mmol/L), followed by the addition of 0.16%
w/v) gL. The samples were continually irradiated with UV light (365 nm) from
(
In an attempt to investigate the further the observed
above for the duration of the experiment. Release was monitored by
fluorescence emission spectroscopy (ex = 540 nm, em = 576 nm), relative to
complete release of the dye following by adding excess solvent to the top of
the gel sample. Solid lines: Fitted release according to a zero-order kinetic
“
thinning” and the mechanism of assembly/disassembly upon
1
photoswitching, H NMR studies were carried out on gels formed
from 2 and 3 (SI 11.1). In both cases, switching the initially
0
model based on the zero-order rate constant (k ) shown. Dotted lines indicate
prepared gels to PSS
Z
with a 365 nm light source resulted in
±1 standard deviations (std) of the fitted zero-order kinetics. Circles: Averages
of n = 3 repeat measurement of Rhodamine B releases. Shaded bands around
sharp peaks indicating that 2 and 3 are freely mobile in the “sol”
state, although in both cases, the signal intensity did not fully
recover and some precipitates were visible in the NMR tube. For
the “as prepared” gel from 2, some residual broad signals from 2
were observed in the gel state which were not present in the
the circles: ±1 std of the
n = 3 repeat measurements. c) Cartoon
representation of dye release from hydrogels upon irradiation with 365 nm light.
d) Injectability: a gel formed by 3 can be pushed through a syringe to form a
pattern.
PSS
PSS
E
gel state that was generated upon switching the sol Z-2
back to Z-2 PSS with the 520 nm light source. This
Z
E
The release of Rhodamine B from the hydrogel formed by 2
suggests that the gel initially formed by “as prepared” E-2 differs
significantly from the E-2 PSS gel state, most likely as the they
and 3 follow zero-order kinetics (k ), which is usually considered
0
desirable in second generation drug delivery systems.[ More
28]
E
are formed by two different kinetic pathways. In contrast, no
residual signals where observed in the “as prepared” gel from E-
importantly, the rate of Rhodamine B release from gels formed
by E-2 and E-3 increased more than 20-fold upon irradiation with
a 365 nm light source, or from k0 = 75±11 pM/s for E-2 to
3
but after switching to Z-3 PSS
Z
sol with a 365 nm light and
then back to a E-3 PSS state with a 520 nm light source
E
1990±110 pM/s for Z-2 and k = 67±8 pM/s for E-3 to 1770±80
0
resulted in a loss of the NMR signals and precipitation in the
NMR tube. This indicates the poor solubility of 3 in water and
that the initially observed gel formation for “as prepared” E-3 is
most likely a kinetic product, which up on rearrangement
pM/s for Z-3. This can be readily explained by the fact that the
365 nm excitation triggers a gel → sol transition for these
hydrogels over a period of ≈ 200 min (Figure 5). Hydrogels
formed by 2 and 3 also show good thixotropic properties at
37 °C (SI-8.3), indicating that they can be readily injected with
syringe (Figure 5d) – an advantageous property for application
of these gels in light-controlled release systems.
(
apparent thinning) will start to precipitate in the PSS
even more so in the PSS state. For 2, the aggregates in the sol
Z-2 PSS state are probably different in nature and they then go
on to form a gel again in the E-2 PSS state but further studies
Z
state and
E
Z
E
will be required to elucidate this mechanism in details.
Conclusion
Photocontrolled dye release from gels
Hydrogels formed with compounds 2 or 3 can be used for
controlled cargo release.[20] The fluorescent dye Rhodamine B
was encapsulated during the hydrogel formation. The hydrogels
were formed at the bottom of a quartz cuvette and allowed to gel
overnight (see SI-3.15 for details). Water was carefully layered
over the gels and the dye release was monitored by
fluorescence emission spectroscopy (Figure 5). In the dark, gels
of 2 and 3 released 15–25% of the dye load over 4 h (most of
this due to the initial burst release of Rhodamine B). Upon
Four photoswitchable arylazopyrazoles derivatives were
synthesized, of which two form hydrogels at 1.2% w/v. The
meta- and para-arylazopyrazoles 2 and 3, respectively, are the
lowest molecular weight photoswitchable hydrogelators reported
to date. This is significant as small hydrogelators can reveal
important details of gelation mechanisms by reducing degrees of
freedom. Using a 365 nm light source, photoswitching of gels
formed from the as synthesized E-2 and E-3, to the
corresponding photostationary state predominantly forms
5
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Angewandte Chemie International Edition
10.1002/anie.202015703
RESEARCH ARTICLE
(
>90%) Z-2 and Z-3. This results in nearly an order of magnitude
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reduction in the elastic (G’) and loss (G’’) modulus. Detailed
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fibers and in the case of 3, eventually irreversible precipitation or
crystallization. Noting that the initially formed gel from E-2 is
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mechanism of hydrogel assembly and disassembly is likely to
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This work was supported by the Australian Research Council
(FT170100094 to JEB and CE140100036 & DP190101892 to
PT) and UNSW Sydney through a PhD TFS award to FAL. We
acknowledge access and support from the facilities of the Mark
Wainwright Analytical Centre at UNSW Sydney. We like to thank
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Keywords: arylazopyrazole • gels • low molecular weight gelator
•
photoswitch • self-assembly
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