Small-peptide-based organogel kit: Towards the development of multicomponent self-sorting organogels

Article abstract of DOI:10.1002/chem.201303116

The results presented here highlight the extremely useful nature of ultra-short peptides as building blocks in the development of smart multicomponent supramolecular devices. A facile bottom-up strategy for the synthesis of a small library of stimuli-resp

Full text of DOI:10.1002/chem.201303116

DOI: 10.1002/chem.201303116
Small-Peptide-Based Organogel Kit: Towards the Development of
Multicomponent Self-Sorting Organogels
Rouzbeh Afrasiabi and Heinz-Bernhard Kraatz*[a]
15862
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FULL PAPER
Abstract: The results presented here
highlight the extremely useful nature
of ultra-short peptides as building
blocks in the development of smart
multicomponent supramolecular devi-
ces. A facile bottom-up strategy for the
synthesis of a small library of stimuli-
responsive smart organogelators has
been proposed based on the predictive
self-assembly of ultra-short peptides.
More importantly, the narcissistic self-
sorting of the gelators has been evalu-
ated as a simple method for the effi-
cient co-assembly of a donor–acceptor
dual-component gel, allowing the in-
vestigation of possible future applica-
tions of similar systems in the develop-
ment of a supramolecular photo-con-
version device. Interestingly, it was ob-
served that the self-organization of the
components can lead to highly ordered
systems in which discrimination be-
tween compatible and non-compatible
building blocks directs the effective or-
ganization of the chromophores and
gives rise to the formation of an excit-
ed-state complex with exciplex-like
emission. The current report may
prove important in the development of
Keywords: gels · nanomaterials ·
peptides · self-assembly · UV/Vis
spectroscopy
organogel-based
smart devices.
multicomponent
Introduction
predictive self-assembly of ultra-short peptides. Moreover,
the narcissistic self-sorting of the gelators has been exploited
for the efficient co-assembly of a donor–acceptor dual-com-
ponent gel as a simplified model for a supramolecular
photo-conversion device.[7] The effective organization of the
chromophores was found to give rise to the formation of an
excited-state complex with exciplex-like emission. Our strat-
egy was based upon the evidence that Boc-l-Phe-l-Lys(Z)-
OMe (Z = carboxybenzyl, 1; Scheme 1) can undergo a fold-
ing transition in aromatic solvents, which leads to hierarchi-
In the last two decades, low molecular weight gelators
(LMWGs) have been extensively investigated owing to their
advantages in the development of smart functional materi-
als.[1] Most often, one of the prerequisites for constructing
new functional devices is the presence of multiple compo-
nents in the same media.[2] In nature, self-sorting is
a common mechanism that allows the organization of multi-
ple components to create functional macromolecules.[3] The
photosynthetic system is one of the most interesting exam-
ples of self-assembly in which peptides direct the arrange-
ment of chromophores in a highly efficient manner.[4] The
remarkable properties of self-sorting biological architectures
has been the driving force behind the ever increasing inter-
est in artificial self-sorting systems.[5] In this respect, amino
acids and peptides can be useful building blocks for the de-
velopment of biomimetic materials with programmed self-
assembly.[6] Self-healing gels that exhibit reversible redox,
light- and sound-responsive switching can be attractive tools
for the generation of new gel-based molecular devices. De-
spite extensive research in the field of supramolecular orga-
nogels, no strategy is yet known that solely relies on the
self-assembly of ultra-short peptides to create various multi-
stimuli-responsive organogels with self-healing and self-sort-
ing properties. Moreover, transcription of such responsive
properties from one molecule to another, using simple
building blocks, is yet to be explored.
Herein, we report a facile method for the construction of
various stimuli-responsive organogels that is driven by the
[a] R. Afrasiabi, Prof. Dr. H.-B. Kraatz
Department of Physical and Environmental Sciences
University of Toronto, 1265 Military Trail
Toronto, M1C 1A4 (Canada)
Fax : (+1)416 287-7197
and
Department of Chemistry, University of Toronto
80 St George Street, Toronto, M5S 3H6 (Canada)
E-mail: bernie.kraatz@utoronto.ca
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201303116.
Scheme 1. Synthetic scheme outlining the different stimuli-responsive or-
ganogelators reported here.
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H.-B. Kraatz and R. Afrasiabi
cal self-assembly and gel formation.[8] Consequently, we had
envisioned that due to the inherent and predictable confor-
mational changes of 1, this molecule and its analogues can
serve as synthons to provide a straightforward method for
designing various stimuli-responsive smart organogels.
As an integral part of our strategy it was assumed that the
successful incorporation of synthons 3 and 4 into the corre-
sponding product conjugates (Scheme 1) will provide sys-
tems that exhibit a stimuli-responsiveness analogous to that
observed in the parent dipeptides, namely, spontaneous self-
assembly in aromatic solvents and a reversible responsive
change to sonication and mechanical stress (self-healing). To
examine the versatility of this strategy and extend the
number of external signals that the resulting molecules were
responsive to, the dipeptide synthons 3 and 4 were equipped
with three different classes of responsive moieties: 1) ferro-
cene as an example for a redox-triggered response moiety;
2) azobenzene as an example for a light-responsive mole-
cule, and 3) pyrene as a fluorescent moiety. The justification
for using the mentioned molecules lays in their ability to
function as molecular switches in a plethora of systems.[9]
Moreover, we were interested to study the intricate proper-
ties and behaviors associated with such systems, including
self-sorting and supramolecular logic-gate operations.
The target molecules were synthesized following conven-
tional solution-phase approaches for peptide synthesis and
the structures were confirmed by using a range of spectro-
1
scopic approaches, including H/13C NMR and IR spectros-
copies and ESI-MS (see the Supporting Information). Three
of the target molecules were obtained by coupling the C-ter-
minus of Boc-l-Lys(Z)-l-Phe-OH (Z = carboxybenzyl, 4 in
Scheme 1) to the e-amino group of lysine-functionalized fer-
rocene, azobenzene, and pyrene derivatives (compound 5 in
Scheme 1). To examine the effect of peptide sequence on
the properties of the gels, com-
pound 7a was also prepared by
using synthon 3, which has the
reverse amino acid sequence
compared with 4.
Considering our previous
knowledge of the helicogenic
effect of aromatic solvents on
peptide 1, unless otherwise
stated, toluene has been used as
the solvent in all the below-
mentioned studies. In tube-in-
version experiments, the gela-
tors displayed very strong gela-
tion behavior and had no ap-
preciable flow even at such low
concentrations as 0.2–0.25 wt%,
placing them in the class of
super-gelators for toluene at
ambient temperature. Impor-
tantly, sonication-triggered ge-
lation, thermo-reversible gel–
sol transition, and self-healing
behavior was present in all con-
jugates of 1 and 2 (see the Sup-
porting Information for condi-
tions used for preparing the
gels).
To ensure that the synthe-
sized molecules did in fact in-
herit the folding behavior ob-
served for the peptides 1 and 2,
compound 6a was examined as
a model to probe the transcrip-
tion of programmed self-assem-
bly. Figure 1 provides the re-
sults for NMR spectroscopic
Figure 1. A) 1H NMR spectra of 6a.in various ratios of chloroform/toluene (1:0, 2:1, 1:2, 0:1; total volume
0.6 mL). B) UV/Vis spectra of 6a in different solvents. C) UV/Vis spectra of 6a in various ratios of chloro-
form/toluene (1:0, 2:1, 1:2, 0:1). D) Thermal denaturation spectra for 6a; E) FTIR Spectra of 6a, solid state
(solid line), gel state (dotted line).
and UV/Vis data that support
the self-organization of 6a in
toluene. In solvent titration ex-
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Small-Peptide-Based Organogel Kit
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periments, performed by recording the 1H NMR spectro-
scopic signal as a function of solvent composition, com-
pound 6a demonstrated similar changes to those observed
for 1, including the downfield shift of amide proton resonan-
ces accompanied by the upfield shift of the proton signals in
the aromatic region (Figure 1A). These variations in
1HNMR spectra can be attributed to aggregation through
p–p stacking. The solvent dependence of self-assembly in
addition to the results from the solvent-denaturation experi-
ments conducted by using UV/Vis spectroscopy (Figure 1B
and C) were consistent with the folding of the structure in
toluene, whereas hypochromic and hypsochromic effects rel-
ative to the chloroform solution were detected. On the
other hand, temperature-dependent UV/Vis studies demon-
strated reversible spectral changes between 20 to 708C,
which complemented our previously mentioned results (Fig-
ure 1D). The FTIR spectra of the prepared compounds
showed no bands at 3400 cmÀ1 for the solid or gel state, indi-
cating that all the amide bonds were involved in intermolec-
ular hydrogen-bonding. In the solid form, compound 6a
demonstrated a strong band at 1682 cmÀ1. Interestingly,
a shift in the amide I band centered around 1640 cmÀ1 was
detected for 6a in the gel state, which may indicate the for-
mation of b-sheet conformation upon self-assembly (Fig-
ure 1E). In all the gel samples a band at around 1613 cmÀ1
was observed, which can be assigned to turn, helical, or ir-
regular loop-like structures (see the Supporting Information
for the complete FTIR spectra). Moreover, in temperature-
1
dependent H NMR experiments (Figure 2A for toluene gel
of 6a), a decrease in molecular motion was detected below
258C, which is evidenced by the absence of signals above
d=3 ppm. The peaks visible between d=0–3 ppm arise
from alkyl groups, which are expected to have more mobili-
ty even at lower temperatures.
The ferrocene moiety is speculated to be buried inside the
assembled structure due to the low intensity of related
proton signals below 808C (ꢀTgel) (Figure 2A). The folding
of the molecule to form a supramolecular polymer was also
supported by circular dichroism (CD) spectroscopy, which
shows the formation of a chiral supramolecular structure for
the toluene gel of 6a compared with the chloroform solution
of the gelator in which the monomeric form is present (Fig-
ure 2B). The spontaneous self-assembly of 6a in aromatic
solvents was further supported by using temperature-depen-
dent CD spectroscopy and scanning electron microscopy
(SEM) experiments (see below), indicating the formation of
stable and chiral assemblies in toluene. CD can be a potent
technique for distinguishing the chiral arrangement of mole-
cules in highly organized systems. The positive Cotton ef-
fects in the range 450–500 nm suggest a superhelical ar-
rangement of respective chromophores in the gel state, in-
duced by the molecular chirality of the synthon peptides
(Figure 2C). To affirm the formation of supramolecular chir-
ality, gels were subjected to thermal denaturation experi-
ments. Upon increasing the temperature (20–808C), a de-
crease in the CD signal was detected that eventually dimin-
ished to zero at temperatures higher than 808C (ꢁTgel) (Fig-
Figure 2. A) Temperature-dependent 1H NMR spectra of 6a gel in
[D8]toluene (at the minimum gel concentration (mgc)). B) Circular di-
chroism spectra of 6a in toluene and in chloroform. C) CD spectra of the
prepared gels. D)–G) Temperature-dependent CD spectra of toluene gels
of 6a, 6b, 6c, and 7a (a 0.5% gel sample has been investigated in all ex-
periments).
ure 2D–G). Interestingly, in the case of organogelator 6c,
a chiroptical switching phenomenon was observed at 1008C
(Figure 2F).
It must be pointed out that the presence of self-healing
ability is a key feature of the reported gels, which allows re-
constitution of the damaged structure following the applica-
tion of a destructive mechanical signal. To study the me-
chanical properties of the gels, rheological experiments were
carried out (Figure 3A–C show representative data for 6a,
also see the Supporting Information for complete rheologi-
cal experiments). The Winter–Chambon criterion for gela-
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H.-B. Kraatz and R. Afrasiabi
Figure 3C demonstrates one
cycle of breaking and recovery
for the gel of 6a based on
changes in viscosity.
Field-emission electron mi-
croscopy (FESEM) images of
the xerogels of 6a and 7a were
investigated as models to eluci-
date the nanoscale morphology
of the organogels (Figure 3D
and E). Surprisingly, a differ-
ence in morphology was ob-
served that may correlate di-
rectly to the difference in the
sequence of amino acids in the
parent synthons. Whereas nano-
fibers were found to constitute
the network of 6a, SEM images
of 7a showed the formation of
nanorods/nanotapes. We believe
this difference in nanostructure
is yet another merit of our
strategy that allows the transfer
of information from the molec-
ular level to the nanometer-
level morphology.
As outlined before, the smart
gels reported here were found
to be responsive to thermal,
mechanical, and sound signals.
Moreover, as we had expected,
this smart response to change
was inherited from the parent
synthons. However, to establish
that our strategy could be ex-
tended to other systems it was
necessary to investigate the re-
sponsive nature of the prepared
gels to their specific signals. To
be able to record the switching
Figure 3. A) Strain-sweep experiment for 6a at constant angular frequency of 1 Hz and strain ranging from 0–
1%. B) Frequency-sweep experiment for 6a at constant strain of 1% with angular frequency ranging from 1–
100 radsÀ1. C) Rheological experiment demonstrating changes in viscosity of toluene gel of 6a in response to
applied shear-rate stress. D) and E) FESEM micrographs of xerogels of 6a and 7a (scale bars indicate
100 nm).
tion points was used for determining the viscoelastic proper-
ties of the samples. Initially, strain-sweep experiments were
carried out at angular frequency of 1 Hz and the changes in
dynamic moduli were plotted with respect to an increasing
strain amplitude (Figure 3A for 6a). In all cases, the storage
modulus (G’) and loss modulus (G’’) exhibited a very weak
dependency on the strain amplitude and G’ values exceed
G’’ by at least one order of magnitude, an indication of
strong gel behavior. In frequency-sweep experiments, which
were performed at constant strain of 1% and between 0.1 to
100 radsÀ1 (Figure 3B for 6a), the gels showed a frequency-
independent storage modulus. Next, the successful transfer
of the self-healing property to the target molecules was eval-
uated (Figure 3C for 6a). The gels were subjected to me-
chanical loading and the recovery of the network was moni-
tored for each of the samples using different experiments.
behavior, spectroscopic changes were monitored for all the
gels as a function of applied external signal. Firstly, the
redox-responsive switching of the ferrocene gels was studied
by using an oxidizing agent ([Fe
rocene group (Fc) to ferrocenium (Fc+). A few drops of the
[Fe(ClO4)3] solution in acetone was added on top of the gel,
ACHTUNGTREN(NNUG ClO4)3]) to oxidize the fer-
AHCTUNGTRENNUNG
which induced concurrent oxidation of the ferrocene unit ac-
companied by a gel-to-solution transition after 3–5 h. Our
results demonstrate that due to the partial solubility of the
oxidized form of the gelator in toluene, the current system
suffers from the gradual precipitation of the gelator after
oxidation and hence limits the time the oxidized solution is
stable. Work is currently underway to eliminate this problem
by designing ferrocene–peptide conjugates capable of form-
ing gels in more polar solvent. Consequently, redox sol–gel
transitions were carried out on the gel of 6a or 7a in a mix-
ture of acetone and toluene. Oxidation of the gel leads to
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Small-Peptide-Based Organogel Kit
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a change in the color of the sample from light-orange to
dark-blue (characteristic for Fc+; Figure 4A and 4E, left).
The solution-to-gel transition was made possible through
the introduction of a reducing agent (ascorbic acid) followed
by heating/sonication to reduce Fc+ to Fc (Figure 4A and
4E, left). Despite the feasibility of carrying out chemical-
redox reactions, a decrease in gel strength was observed
after two cycles for both 6a and 7a (the chemically reconsti-
tuted gel is unstable and collapses after 2 min). Next, we
turned our attention to the azobenzene derivative of 4. The
viscous loose gel of 6b was irradiated with UV light
(365 nm) and the gradual changes in UV/Vis spectra were
recorded (Figure 4B). A 0.5% gel sample of 6b was found
to lose its mechanical properties and collapse after the ap-
plication of UV light for 30 min. Gel regeneration and re-
covery was possible by exposing the solution to visible light
for 60 min or sonication for 10 min (see Figure 4B and E).
Finally, fluorescence switching was examined for 6c under
thermal conditions and between sol and gel states. As men-
tioned before, variable-temperature CD experiments indi-
cated a change in chiroptical properties when 6c transi-
tioned from the gel-to-sol state. Consequently, in the case of
6c, an enhancement in fluorescence was observed upon gel
formation that is thought to arise from aggregation-induced
enhanced emission phenomenon (AIEE) (Figure 4C and
D). The above results demonstrate the generality of our
strategy as a straightforward method for constructing vari-
ous stimuli-responsive organogels.
Upon successful incorporation of the synthons and tailor-
ing of the desired properties into the target molecules, their
ability to logically and uniformly co-assemble in a hybrid
system was examined. As a simple model for a supramolec-
ular photo-conversion device, mixtures of the ferrocene and
pyrene gelators were selected for studying electron/energy
transfer in the dual-component organogels. The extent of
quenching of the excited state of pyrene by ferrocene was
deemed to provide a measure of the distance between the
supramolecular dyad and the effectiveness of the co-assem-
bly. In addition, it was assumed that the self-sorting behav-
ior of the gels can provide a method for understanding the
relative spatial orientation of the donor and acceptor chro-
mophores.
The possibility of a self-sorting mechanism was based on
the observation that various mixtures of 1 and 2 with differ-
ent ratios were incapable of gel formation in toluene and
the presence of both species in the same mixture, even at
very low concentrations, hindered organization under ther-
mal conditions. Interestingly, the same mixtures were also
incapable of gel formation in response to sonication unless
one of the components was available in very high concentra-
tions. Despite the attractive features of 6c for potential ap-
plications in constructing gels with logic-gate properties, the
thermal fluorescence switching of this derivative was
thought to complicate the understanding of the interactions
in the dual-component gels. To simplify the systems, we syn-
thesized two new gelators by conjugating a pyrene deriva-
tive to the N-terminus of 1 and 2 (compounds 8 and 9, re-
spectively, in Scheme 1). The new gelators exhibited very
little change in fluorescence intensity or position of the
peaks between the solution and the gel state (see the Sup-
porting Information). These fluorescent derivatives were
then used to investigate the co-assembly of the ferrocene
and pyrene gels under thermal (heating–cooling) and sonica-
tion (heating–sonication) conditions. Experiments were car-
ried out by mixing the components under conditions in
Figure 4. A) Reversible oxidation and reduction of the 6a/7a performed
in
a mixture of acetone/toluene. B) photo-induced switching of 6b.
C) Absorption and emission spectra for 6c demonstrating changes in
emission at different temperatures. D) Photographs of 6c in gel and solu-
tion state. E) Photographs of phase transitions in the prepared gels in re-
sponse to: redox (left), light (middle), heat (right); F) Schematic summa-
rization of the results for the mixtures under different conditions: sonica-
tion (S), thermal (T), gelation (G), precipitation (P), exciplex-like emis-
sion (*).
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H.-B. Kraatz and R. Afrasiabi
which the wt% of each component was less than half of
their individual minimum gel concentration (mgc) values to
maximize the consequences of constructive or destructive in-
teractions between the two components. Figure 4F summa-
rizes the results for the co-gels formed under thermal- and
sonication-induced conditions. Surprisingly, the two-compo-
nent organogels of ferrocene and pyrene (6a+8, 6a+9 and
7a+8, 7a+9) exhibited a similar behavior as that of mix-
tures of 1 and 2 under thermal conditions. A narcissistic
self-sorting response was observed, which was driven by the
amino acid sequence of the synthons. Mixtures of the ferro-
cene and pyrene gelators only exhibited co-gelation after
heating and cooling when the two components had the same
amino acid sequence (6a+8 and 7a+9). On the other
hand, selective and gradual aggregation/precipitation of the
components was noticed when co-assembly was not favored.
Interestingly, despite a delay in gelation time for 7a+8 and
6a+9, application of sonication resulted in gel formation in
these mixtures although they did not possess the same se-
quence of amino acids.
SEM images revealed a fibrous morphology for xerogels
of 8 and 9, which lack any vivid chiral features (Figure 5A
and B). Characterization of 6a+8 and 7a+9 showed subtle
changes in the morphology of the samples compared with
6a and 7a, which can be attributed to the self-recognition of
8 and 9 by their respective co-gelators. To investigate the
presence of a self-sorting phenomena, the nanoscale mor-
phology of 7a+8 was also investigated. This mixture of ge-
lators was selected due to the difference in morphology be-
tween 7a (nanotape) and 9 (nanofiber) compared with 6a+
9, in which both of the gelators have nanofiber morphology.
SEM images of the mixture of 7a and 8 with a molar ratio
of 0.25 and 1 for the gelators (Figure 5E) showed the for-
mation of a heterogeneous network that was dominated by
thin nanofibers of 8. In this heterogeneous network, the
nanotapes that were formed by 7a were also observed but
had a lower abundance. The predominance of nanofiber
morphology in comparison to nanotape structure is thought
to arise from the higher molar ratio of 8 compared with 7a.
Considering the fact that SEM investigations failed to prove
any change in the morphological features (in comparison to
the individual gelators) for the thermally formed 6a+8 and
sonication induced 6a+9 (Figure 5F), CD experiments
were carried out to evaluate the possibility of self-recogni-
tion in these mixtures. The CD spectra of the mentioned
mixtures were investigated in samples with varying molar
ratios of 6a relative to a fixed amount of 8 or 9 (Figure 5G).
Bisignate Cotton effects were observed in the CD spectra of
both 6a+8 and 6a+9 but the amplitude value was greater
for 6a+8 and this mixture exhibited a signal that could be
indicative of exciton coupling between two chromophores
(two pyrenes or pyrene and ferrocene).[10]
Figure 5. A)–F) FESEM micrographs of xerogels of: A) 8 (scale bar indi-
cates 1 mm); B) 9 (scale bar indicates 1 mm); C) 6a+8 (scale bar indicates
100 nm); D) 7a+9 (scale bar indicates 100 nm); E) 7a+8 (scale bar indi-
cates 1 mm); F) 6a+9 (scale bar indicates 100 nm). G) CD spectra of
mixtures of 6a with 8 and 9 with increasing molar ratio of 6a and con-
stant amount of 8 and 9 (all spectra are reported in the À10–+10 mdeg
range).
Interestingly, the CD spectra for 2:1 molar ratio mixtures
of 6a with 8 or 9 were found to be significantly different in
the 300–400 nm region (Figure 5G). At this molar ratio, the
CD spectrum for 6a+9 is mainly composed of the signals
from 6a in the 400–600 nm region and the peaks in 300–
400 nm were highly attenuated. This observation could indi-
cate that in the presence of 6a, the ability of 9 to undergo
self-assembly is highly suppressed and this component is ex-
cluded from the network of 6a. On the other hand, the
same results could be interpreted by the formation of two
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Small-Peptide-Based Organogel Kit
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types of fibers by 6a and 9, which have the opposite helical
handedness, resulting in a very weak CD signal upon appli-
cation of sonication, which allows the fibers to intertwine.
Both interpretations are in accordance with the predomi-
nance of the CD spectra by the signals from the component
with the higher molar ratio. On the contrary, a 2:1 mixture
of 6a and 8 appeared to have the signals related to the fer-
rocene and pyrene chromophores (Figure 5G). More impor-
tantly, the signals observed in the 300–400 nm region for
6a+8 mixture showed an opposite CD signal compared
with the signals from 8 alone. Considering the enhancement
of signals for the pyrene component compared with the mix-
ture 6a+9, we speculate that the observed changes for the
CD spectra of 6a+8 are the direct consequence of self-rec-
ognition between 6a and 8. Based on the above-mentioned
results, three mechanisms can be proposed for how the in-
teractions between 6a and 8 or 9 take place (Figure 6A–C).
To further investigate the interactions responsible for gel
1
formation in case of 6a+8, variable-temperature H NMR
experiments were performed on the toluene gel of this mix-
1
ture. It was assumed that H NMR experiments can provide
information regarding the interaction between the compo-
nents and clarify if 6a and 8 self-assemble independently
into fibers of a single component (Figure 6C) or form
a single fiber that consists of both of the components (Fig-
ure 6A and B). Comparison of the temperature-dependent
changes in the spectra of 6a and 6a+8 demonstrate slight
changes in the position of the amide-proton peaks and an
increase in hydrogen bonding, supported by the downfield
shift of amide-proton signals. Additionally, it was found that
the signals due to the ferrocene unit in the d=4.5–5 ppm
region exhibit an increase in the splitting between the two
peaks associated with the substituted-cyclopentadienyl ring
of ferrocene (Figure 6D). Since the observed changes for
6a+8 can be related to the presence of 6a and 8 molecules
in close proximity, we speculate that in a mixture of 6a+8
the organization mainly follows the schematic representa-
tion in Figure 6A or B, with a lower possibility through the
path shown in Figure 6B. However, the organization of the
components in 6a+9 is speculated to follow a similar pro-
cess as depicted in Figure 6C. To gain insight into the under-
lying interactions between the chromophoric moieties, vibra-
tional circular dichroism (VCD) experiments were per-
formed. VCD results demonstrate differences in the signals
observed for 6a+8 and 7a+9 (Figure 7A). Comparison be-
tween the VCD signals for the mixed gels that had formed
under thermal conditions, and had the same peptide se-
quence, with the sonication-induced gels, which lacked re-
semblance in the peptide sequence, demonstrated clear dif-
ferences in the intensity of the peaks in the region 1650–
1680 cmÀ1 (Figure 7A). The amplification of the VCD sig-
nals in this region for 6a+8 and 7a+9 is thought to arise
from the organization of the molecules in a highly ordered
manner, which results in the formation of well-ordered ar-
chitectures. The peaks observed in the 1650–1680 cmÀ1
region can be attributed to the formation of b-structures in
the case of 6a+8 and 7a+9, whereas the differences in the
Figure 6. A)–C) Speculated cartoon representation of organization of
molecules in a mixture of 6a with 8 or 9 (see the Supporting Information
for the color version of this figure). D) Temperature-dependent 1H NMR
spectra of 6a and 6a+8 that show differences in the position of the
peaks attributed to substituted-cyclopentadienyl ring of ferrocene (repre-
sented by + and V, whereas O is related to the unsubstituted-cyclopenta-
dienyl ring).
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15869

H.-B. Kraatz and R. Afrasiabi
The quenching was found to be most effective for the co-
gels prepared under thermal conditions and when the gels
contained the same peptide synthons (6a+8 and 7a+9).
Figure 7B demonstrates the decrease in fluorescence for 8
as the ratio of 6a is increased. To investigate the source of
quenching and confirm that the electron/energy transfer be-
tween the chromophores is responsible for the decrease in
fluorescence, toluene gels of 8 and 9 were investigated in ab-
sence of 6a and 7a (Figure 7C). Next, we investigated the
possibility of quenching in mixtures of 8 with 1 and 2. Fig-
ure 7D demonstrates the minor changes observed in the
fluorescence of 8 in co-gels of this gelator with 1 and 2.
These results indicate that the source of quenching is due to
interaction between the ferrocene and pyrene chromophores
and is not the result of self-quenching or quenching by the
peptide segment alone.
Interestingly, co-gels of the pyrene and ferrocene gelators
with the same parent dipeptide showed exciplex-like emis-
sion in equimolar mixtures under thermal and sonication-in-
duced conditions (Figure 7E for 6a+8). Very little differ-
ence was observed in the quenching of fluorescence for 6a+
8 and 7a+9 prepared under sonication or thermal condi-
tions (see the inset of Figure 7C for 6a+8). However, for
the co-gels 6a+9 and 7a+8 prepared under sonication, an
exciplex-like emission was first detected in 5:1 molar ratio
mixtures of the two components (Figure 7F).
We attribute the difference observed for the effectiveness
of quenching in the co-gels formed under thermal and soni-
cation-induced conditions to originate from the dissimilarity
of the organization of molecules in the two systems. Under
thermal conditions, unfavorable interactions avoid gel for-
mation for 6a+9 and 7a+8, and a narcissistic self-sorting
behavior is observed, which is due to the lack of interaction
between the fibers that impedes gel formation and results in
precipitation of one or both of the components. On the
other hand, when the same mixtures are sonicated (6a+9
and 7a+8), the fibers formed by each component is forced
to interact with the fibers from the second component and
this allows gel formation. The inefficiency of the quenching
for 6a+9 and 7a+8 under sonication and the requirement
for higher ratios of the quencher can then be related to the
difference between fiber–fiber quenching (Figure 6C) com-
pared with molecule–molecule quenching speculated for
6a+8 and 7a+9 co-gels (Figure 6A).
Figure 7. A) Vibrational circular dichroism spectra for the gels and mixed
gels prepared under thermal (T) and sonication (S) conditions: (I) 6a,
(II) 7a, (III) 9, (IV) 8, (V) 7a+9 (1:1), (VI) 7a+8 (1:1), (VII) 6a+8
(1:1), (VIII) 6a+9 (1:1). B) Photographs of the 6a+8 co-gel showing the
quenching of fluorescence as the ratio of the quencher (6a) is increased
(ratio of the quencher from left to right: 0:1, 0.5:1, 1:1). C) Absorption
and emission spectra for 8 and 9 (excitation at 400 nm). D) Emission
spectra for 8, 8+1 (S) and 8+2 (S) (excitation at 400 nm). E) Fluores-
cence spectra of 6a+8 mixture as a function of increasing ratio of 6a
(0:1 to 1:1). Inset shows the difference in fluorescence between thermally
and sonication induced 1:1 molar ratio co-gels of 6a+8. (excitation at
400 nm). F) Fluorescence spectra for a 5:1 co-gel of 6a+9 formed after
sonication for 15 min.
Conclusion
We have demonstrated here a facile bottom-up strategy for
the synthesis of various stimuli-responsive smart organogela-
tors based on the predictive self-assembly of analogous di-
peptides. Our results show that the successful incorporation
of the synthon peptides permits the transcription of informa-
tion and responsive behavior to the target molecules. The
prepared gels not only exhibit self-healing and a reversible
sol-to-gel transition towards sonication, but also have self-
sorting properties. As a proof of concept, these characteris-
sign and position of the peaks is compatible with a distinc-
tion in the modes of interaction and the supramolecular or-
ganization of the components.[11]
Next, fluorescence experiments were carried out to inves-
tigate the efficiency of the quenching for the mixed gels.
15870
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Chem. Eur. J. 2013, 19, 15862 – 15871

Small-Peptide-Based Organogel Kit
FULL PAPER
A. B. Holmes, N. W. Duffy, U. Bach, L. Spiccia, Nat. Chem. 2011, 3,
211–215; e) W. Edwards, D. K. Smith, J. Am. Chem. Soc. 2013;
f) F. G. Brunetti, C. Romero-Nieto, J. Lꢄpez-Andarias, C. Atienza,
J. L. Lꢄpez, D. M. Guldi, N. Martꢁn, Angew. Chem. 2013, 125, 2236–
2240; Angew. Chem. Int. Ed. 2013, 52, 2180–2184; g) R. Amemiya,
M. Mizutani, M. Yamaguchi, Angew. Chem. 2010, 122, 2039–2043;
Angew. Chem. Int. Ed. 2010, 49, 1995–1999.
tics were exploited in a simplified model for a light-harvest-
ing system. In donor–acceptor co-gels formed under thermal
conditions, narcissistic self-sorting resulted in effective
quenching and was accompanied by an exciplex-like emis-
sion from the mixed gels. The results presented here high-
light the extremely useful nature of ultra-short peptides in
developing smart functional materials. The reported strategy
may prove important in the development of responsive or-
ganogels and multicomponent smart devices.
[3] a) A. Wu, L. Isaacs, J. Am. Chem. Soc. 2003, 125, 4831–4835; b) P.
Mukhopadhyay, A. Wu, L. Isaacs, J. Org. Chem. 2004, 69, 6157–
6164; c) J. R. Moffat, D. K. Smith, Chem. Commun. 2009, 0, 316–
318; d) M. M. Safont-Sempere, G. Fernꢅndez, F. Wꢆrthner, Chem.
Rev. 2011, 111, 5784–5814; e) Y. Rudzevich, V. Rudzevich, F.
Klautzsch, C. A. Schalley, V. Bçhmer, Angew. Chem. 2009, 121,
3925–3929; Angew. Chem. Int. Ed. 2009, 48, 3867–3871; f) A. Wick-
lein, S. Ghosh, M. Sommer, F. Wꢆrthner, M. Thelakkat, ACS Nano
2009, 3, 1107–1114.
[4] a) J. H. Kim, M. Lee, J. S. Lee, C. B. Park, Angew. Chem. 2012, 124,
532–535; Angew. Chem. Int. Ed. 2012, 51, 517–520; b) P. D. Frisch-
mann, K. Mahata, F. Wꢆrthner, Chem. Soc. Rev. 2013, 42, 1847–
1870.
Acknowledgements
Financial support from NSERC and the University of Toronto is grateful-
ly acknowledged. We thank Tony Adamo for help with data collection
and acknowledge the Nanofabrication facility at Western University
Canada for FESEM imaging.
[5] a) A. Pal, S. Karthikeyan, R. P. Sijbesma, J. Am. Chem. Soc. 2010,
132, 7842–7843; b) L. E. Buerkle, S. J. Rowan, Chem. Soc. Rev.
2012, 41, 6089–6102.
[1] a) B.-K. An, D.-S. Lee, J.-S. Lee, Y.-S. Park, H.-S. Song, S. Y. Park, J.
Am. Chem. Soc. 2004, 126, 10232–10233; b) K. M. Anderson, G. M.
Day, M. J. Paterson, P. Byrne, N. Clarke, J. W. Steed, Angew. Chem.
2008, 120, 1074–1078; c) D. Bardelang, F. Camerel, J. C. Margeson,
D. M. Leek, M. Schmutz, M. B. Zaman, K. Yu, D. V. Soldatov, R.
Ziessel, C. I. Ratcliffe, J. A. Ripmeester, J. Am. Chem. Soc. 2008,
130, 3313–3315; d) Y. Gao, Y. Kuang, Z.-F. Guo, Z. Guo, I. J.
Krauss, B. Xu, J. Am. Chem. Soc. 2009, 131, 13576–13577; e) A.
Gopal, M. Hifsudheen, S. Furumi, M. Takeuchi, A. Ajayaghosh,
Angew. Chem. 2012, 124, 10657–10661; Angew. Chem. Int. Ed. 2012,
51, 10505–10509; f) A. R. Hirst, B. Escuder, J. F. Miravet, D. K.
Smith, Angew. Chem. 2008, 120, 8122–8139; Angew. Chem. Int. Ed.
2008, 47, 8002–8018; g) A. R. Hirst, S. Roy, M. Arora, A. K. Das, N.
Hodson, P. Murray, S. Marshall, N. Javid, J. Sefcik, J. Boekhoven,
J. H. van Esch, S. Santabarbara, N. T. Hunt, R. V. Ulijn, Nat. Chem.
2010, 2, 1089–1094; h) S. R. Jadhav, P. K. Vemula, R. Kumar, S. R.
Raghavan, G. John, Angew. Chem. 2010, 122, 7861–7864; Angew.
Chem. Int. Ed. 2010, 49, 7695–7698; i) K. T. Kim, C. Park, G. W. M.
Vandermeulen, D. A. Rider, C. Kim, M. A. Winnik, I. Manners,
Angew. Chem. 2005, 117, 8178–8182; Angew. Chem. Int. Ed. 2005,
44, 7964–7968; j) R. Klajn, P. J. Wesson, K. J. M. Bishop, B. A. Grzy-
bowski, Angew. Chem. 2009, 121, 7169–7173; Angew. Chem. Int.
Ed. 2009, 48, 7035–7039; k) J. Liu, P. He, J. Yan, X. Fang, J. Peng,
K. Liu, Y. Fang, Adv. Mater. 2008, 20, 2508–2511; l) P. Mukhopad-
hyay, Y. Iwashita, M. Shirakawa, S.-i. Kawano, N. Fujita, S. Shinkai,
Angew. Chem. 2006, 118, 1622–1625; Angew. Chem. Int. Ed. 2006,
45, 1592–1595; m) J. Puigmartꢁ-Luis, V. Laukhin, ꢂ. Pꢃrez del Pino,
J. Vidal-Gancedo, C. Rovira, E. Laukhina, D. B. Amabilino, Angew.
Chem. 2007, 119, 242–245; Angew. Chem. Int. Ed. 2007, 46, 238–
241; n) K. V. Rao, K. K. R. Datta, M. Eswaramoorthy, S. J. George,
Angew. Chem. 2011, 123, 1211–1216; Angew. Chem. Int. Ed. 2011,
50, 1179–1184; o) K. Sugiyasu, N. Fujita, S. Shinkai, Angew. Chem.
2004, 116, 1249–1253; Angew. Chem. Int. Ed. 2004, 43, 1229–1233;
p) J. Wu, T. Yi, T. Shu, M. Yu, Z. Zhou, M. Xu, Y. Zhou, H. Zhang,
J. Han, F. Li, C. Huang, Angew. Chem. 2008, 120, 1079–1083;
Angew. Chem. Int. Ed. 2008, 47, 1063–1067; q) S. Yagai, M. Ishii, T.
Karatsu, A. Kitamura, Angew. Chem. 2007, 119, 8151–8155; Angew.
Chem. Int. Ed. 2007, 46, 8005–8009; r) Y. Zhang, B. Zhang, Y.
Kuang, Y. Gao, J. Shi, X. X. Zhang, B. Xu, J. Am. Chem. Soc. 2013,
135, 5008–5011.
[6] a) M. Sarikaya, C. Tamerler, A. K. Y. Jen, K. Schulten, F. Baneyx,
Nat. Mater. 2003, 2, 577–585; b) T. Aida, E. W. Meijer, S. I. Stupp,
Science 2012, 335, 813–817; c) G. Angelici, G. Falini, H.-J. Hofmann,
D. Huster, M. Monari, C. Tomasini, Angew. Chem. 2008, 120, 8195–
8198; Angew. Chem. Int. Ed. 2008, 47, 8075–8078; d) D. M. Ryan,
T. M. Doran, B. L. Nilsson, Chem. Commun. 2011, 47, 475–477;
e) K. L. Morris, L. Chen, J. Raeburn, O. R. Sellick, P. Cotanda, A.
Paul, P. C. Griffiths, S. M. King, R. K. OꢇReilly, L. C. Serpell, D. J.
Adams, Nat Commun 2013, 4, 1480; f) Y. Liu, Y. Yang, C. Wang, X.
Zhao, Nanoscale 2013, 5, 6413–6421.
[7] S. S. Babu, S. Prasanthkumar, A. Ajayaghosh, Angew. Chem. 2012,
124, 1800–1810; Angew. Chem. Int. Ed. 2012, 51, 1766–1776.
[8] R. Afrasiabi, H.-B. Kraatz, Chem. Eur. J. 2013, 19, 1769–1777.
[9] a) S. Samanta, C. Qin, A. J. Lough, G. A. Woolley, Angew. Chem.
2012, 124, 6558–6561; Angew. Chem. Int. Ed. 2012, 51, 6452–6455;
b) M. Tropiano, N. L. Kilah, M. Morten, H. Rahman, J. J. Davis,
P. D. Beer, S. Faulkner, J. Am. Chem. Soc. 2011, 133, 11847–11849;
c) R. Zhang, Z. Wang, Y. Wu, H. Fu, J. Yao, Org. Lett. 2008, 10,
3065–3068; d) S.-n. Uno, C. Dohno, H. Bittermann, V. L. Malinov-
skii, R. Hꢈner, K. Nakatani, Angew. Chem. 2009, 121, 7498–7501;
e) D. Margulies, C. E. Felder, G. Melman, A. Shanzer, J. Am. Chem.
Soc. 2007, 129, 347–354; f) S. Amemori, K. Kokado, K. Sada,
Angew. Chem. 2013, 125, 4268–4272; Angew. Chem. Int. Ed. 2013,
52, 4174–4178; g) G. Haberhauer, C. Kallweit, C. Wçlper, D. Blꢈser,
Angew. Chem. 2013, 125, 8033–8036; Angew. Chem. Int. Ed. 2013,
52, 7879–7882; h) M. Nakahata, Y. Takashima, A. Hashidzume, A.
Harada, Angew. Chem. 2013, 125, 5843–5847; Angew. Chem. Int.
Ed. 2013, 52, 5731–5735; i) P. Fatꢅs, J. Bachl, S. Oehm, A. I. Jimꢃ-
nez, C. Cativiela, D. Dꢁaz Dꢁaz, Chem. Eur. J. 2013, 19, 8861–8874;
j) C.-S. Chen, X.-D. Xu, S.-Y. Li, R.-X. Zhuo, X.-Z. Zhang, Nano-
scale 2013, 5, 6270–6274.
[10] a) N. Berova, L. D. Bari, G. Pescitelli, Chem. Soc. Rev. 2007, 36,
914–931; b) P. Iavicoli, H. Xu, L. N. Feldborg, M. Linares, M. Para-
dinas, S. Stafstrçm, C. Ocal, B. Nieto-Ortega, J. Casado, J. T. Lꢄpez
Navarrete, R. Lazzaroni, S. D. Feyter, D. B. Amabilino, J. Am.
Chem. Soc. 2010, 132, 9350–9362; c) T. Ogoshi, M. Hashizume, T.-a.
Yamagishi, Y. Nakamoto, Langmuir 2010, 26, 3169–3173.
[11] a) G. Longhi, S. Abbate, F. Lebon, N. Castellucci, P. Sabatino, C.
ˇ
Tomasini, J. Org. Chem. 2012, 77, 6033–6042; b) V. Setnicka, J.
[2] a) Y. Ren, W. H. Kan, V. Thangadurai, T. Baumgartner, Angew.
Chem. 2012, 124, 4031–4035; Angew. Chem. Int. Ed. 2012, 51, 3964–
3968; b) M. Nakahata, Y. Takashima, H. Yamaguchi, A. Harada,
Nat. Commun. 2011, 2, 511; c) J. W. Chung, S.-J. Yoon, S.-J. Lim, B.-
K. An, S. Y. Park, Angew. Chem. 2009, 121, 7164–7168; Angew.
Chem. Int. Ed. 2009, 48, 7030–7034; d) T. Daeneke, T.-H. Kwon,
´
Novy, S. Bçhm, N. Sreenivasachary, M. Urbanovꢅ, K. Volka, Lang-
muir 2008, 24, 7520–7527; c) M. Urbanovꢅ, Chirality 2009, 21,
E215–E230.
Received: August 6, 2013
Published online: October 29, 2013
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15871