Embedding and Positioning of Two FeII4L4 Cages in Supramolecular Tripeptide Gels for Selective Chemical Segregation

Article abstract of DOI:10.1002/anie.201900429

An unreported d,l-tripeptide self-assembled into gels that embedded Fe^II₄L₄ metal–organic cages to form materials that were characterized by TEM, EDX, Raman spectroscopy, rheometry, UV/Vis and NMR spectroscopy, and circular dichroism. The cage type and concentration modulated gel viscoelasticity, and thus the diffusion rate of molecular guests through the nanostructured matrix, as gauged by ¹⁹F and ¹H NMR spectroscopy. When two different cages were added to spatially separated gel layers, the gel–cage composite material enabled the spatial segregation of a mixture of guests that diffused into the gel. Each cage selectively encapsulated its preferred guest during diffusion. We thus present a new strategy for using nested supramolecular interactions to enable the separation of small molecules.

Full text of DOI:10.1002/anie.201900429

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Embedding and positioning of two FeII4L4 cages in
supramolecular tripeptide gels for selective chemical segregation.
Authors: Marion Kieffer, Ana M. Garcia, Cally J. E. Haynes, Slavko
Kralj, Daniel Iglesias, Jonathan Nitschke, and Silvia
Marchesan
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201900429
Angew. Chem. 10.1002/ange.201900429
Link to VoR: http://dx.doi.org/10.1002/anie.201900429
http://dx.doi.org/10.1002/ange.201900429

10.1002/anie.201900429
Angewandte Chemie International Edition
COMMUNICATION
Embedding and positioning of two FeII L cages in
4 4
supramolecular tripeptide gels for selective chemical segregation.
Marion Kieffer,[a]ǂ Ana M. Garcia,[b]ǂ Cally J. E. Haynes,[a] Slavko Kralj,[b,c] Daniel Iglesias,[b] Jonathan R.
Nitschke[a]* and Silvia Marchesan[b]*
enzyme mimicry for catalysis,[21] thus are attractive components
for adaptive supramolecular materials. We envisaged a hybrid
Abstract: An unreported D,L-tripeptide self-assembled into gels that
embedded FeII L4 metal-organic cages, forming materials that were
4
characterized by TEM, EDX, Raman, rheometry, UV-Vis, NMR and
circular dichroism. The cage type and concentration modulated gel
viscoelasticity, and thus the diffusion rate of molecular guests
peptide gel could embed MOCs for functional guest binding via
hierarchical self-assembly. Such systems are capable of
separating and immobilizing different cages within distinct
regions of a gel, but within a single solvent phase without
requiring covalent linkages to be made between MOCs and
gelators. The high tunability of the process lies in the absence of
synthetic modification needed on either the MOCs or the peptide,
making it an extremely versatile strategy. The spatially-
separated cages may thus bind distinct guests, allowing these
guests to be segregated within defined parts of the gel, and thus
separated from a mixture by selective encapsulation.
1
through the nanostructured matrix, as gauged by 19F and H NMR.
When two different cages were added to spatially separated gel
layers, the gel-cage composite material enabled the spatial
segregation of a mixture of guests that diffused into the gel. Each
cage thus selectively encapsulated its preferred guest during
diffusion. This work thus presents a new strategy for using nested
supramolecular interactions to enable the separation of small
molecules.
Cyclic peptides that feature an alternation of D- and L-amino
acids have been shown to self-assemble into nanotubes and
hydrogels.[22] However, prediction of the gel formation behavior
for smaller, acyclic minimalistic peptides is difficult.[23]
Tripeptides of syndiotactic L-D-L stereochemistry have been
shown only recently to adopt an amphipathic conformation, with
side chains in an isotactic configuration that enables their long-
range self-organization into gel-forming fibers. An exception to
this design rule is L-Phe-D-Ala-L-Phe, which does not meet the
expected requirements of hydrophobicity and steric hindrance
and was thus not observed to form a gel.[24] We hypothesized
that the addition of a p-aminobenzoyl moiety at the N-terminus
could address both issues to yield a new gelator, potentially
useful in cases where the presence of a primary aliphatic amine
is undesirable. Indeed, a free N-terminus could result in
unwelcome substitution of MOC amine subcomponents and
reduce MOC stability, whereas an aniline substituted with an
electron-deficient amide group would not be expected to
substitute more electron-rich aniline residues incorporated into
the periphery of a cage.[25]
Gels share properties of solids and liquids, and exhibit
stimuli-responsiveness,[1] which enables applications that
include environmental remediation[2] and cargo delivery.[3] The
incorporation of metal complexes and hollow metal-organic
cages[4] (MOCs) into gels[5] can alter the responsiveness of the
material to stimuli,[6] thus endowing it with useful properties
comprising fluorescence[7] and self-healing.[8] Chemically
modified MOCs have been reported to act as nodes within gels[9]
and polymers,[10] with linkages between cages formed by
polymeric chains[11] or binders.[12] However, we envisaged that
covalent linkages between the hollow architectures and the gel
matrix[13] may be unnecessary for embedding MOCs in a
supramolecular gel matrix. In addition, we hypothesized that the
ability of MOCs to selectively encapsulate molecular cargoes[14]
could allow us to prepare cage-containing gels that can separate
molecules spatially,[15] by extracting guests from solution as they
diffuse through a gel.
This strategy requires the identification of a suitable gel
matrix that is compatible with MOCs. Minimalistic peptides[16] are
readily obtained, biocompatible materials[17] that form fibrillar
gels under a wide variety of conditions. Although the resulting
nanostructures often display size heterogenerity due to
hierarchical assembly,[18] the addition of a second component
into the supramolecular system can limit fibril bundling and allow
a more homogeneously defined nanomorphology.[19] Peptides
can also display recognition motifs for cell internalization,[20] and
The tripeptide (p-aminobenzoyl)-L-Phe-D-Ala-L-Phe-NH2
(Fig. 1) was thus synthesized and probed for gelation in various
solvents, among which CH3CN was chosen as the most suitable
choice for stable gels and cages (Table S2). Two MOCs (Fig. 1)
were prepared[25] to encapsulate different guests in CH3CN;
MOC 1 binds trifluoroacetate (TFA) moderately and perrhenate
−
1
(ReO4 ) strongly, as evidenced by H and 19F NMR (Figs. S13-
17), whereas MOC 2 encapsulates fluoroadamantane (FA, Fig.
S18-19).
[ǂ]
[a]
These authors contributed equally to this work.
M. Kieffer, Dr. C. J. E. Haynes, Prof. J. R. Nitschke
Department of Chemistry, University of Cambridge
Lensfield Road, Cambridge, CB2 1EW, UK
Email: jrn34@cam.ac.uk
The tripeptide formed gels (50 mM, 2.5 wt.) that incorporated
either of the cages at concentrations up to 5 mM (10:1
tripeptide:cage in this case). The gels were visibly colored, even
at a MOC concentration of 0.1 mM (Fig. 2a-b); for analyses
MOCs were employed at 1 or 5 mM and the peptide at 50 mM to
facilitate detection. Energy-dispersive X-ray (EDX) spectra
showed homogenous distribution of iron (Fig. 2c-d, Table S4,
Figs. S30-S34). The cages were inferred to remain intact and
evenly distributed within the gels, as confirmed by the other
techniques noted below. Rheology revealed that both cages
affected the gel viscoelastic properties, providing a means to
fine-tune gelation kinetics, stiffness and resistance to applied
Homepage: https://www.nitschkegroup-cambridge.com/
Dr. A. M. Garcia, Dr. S. Kralj, Dr. D. Iglesias, Prof. S. Marchesan
Department of Chemical & Pharmaceutical Sciences
University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy
E-mail: smarchesan@units.it
[b]
[c]
Homepage: https://www.marchesanlab.com/
Dr. S. Kralj
Materials Synthesis Department, Jožef Stefan Institute
Jamova 39, 1000 Ljubljana, Slovenia
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201900429
Angewandte Chemie International Edition
COMMUNICATION
stress (Figs. 2e-f and S21-23). Frequency sweeps indicated that
both the elastic (G’) and the viscous (G”) moduli were
independent of the applied frequency, and G’ > G” (Table S3),
confirming gelation. In particular, gelation kinetics revealed a
two-stage process with a lag-phase only in the presence of
either MOC, suggesting a longer nucleation phase relative to the
peptide alone.[26]
UV-vis (Fig. S24) and Raman (Fig. S35) spectroscopic
analyses confirmed MOC integrity in 1⊂Gel and 2⊂Gel. Raman
imaging of 1⊂Gel and 2⊂Gel revealed
a homogeneous
distribution of MOCs in the gels at the microscale (Figs. S35D-E).
Circular dichroism indicated that the peptide conformation was
not changed by either MOC (Fig. S20).
Transmission electron microscopy (TEM) was used to
investigate the morphology of the three different gels, i.e., the
peptide alone, and the hybrids 1⊂Gel and 2⊂Gel (Figs. 2c-d,
S25-S29). The peptide yielded a colorless, transparent gel
containing a matrix of homogeneous thin fibrils of average
diameter 9.8 ± 1.7 nm (n=100, Fig. S25). Either cage 1 or 2 at a
concentration below 1 mM did not significantly alter the fibril
diameter (8.9 ± 1.9 nm for 1⊂Gel and 9.0 ± 2.1 nm for 2⊂Gel,
respectively, Figs. S26-27). However, at the higher MOC
concentration of 5 mM, 1⊂Gel displayed thinner fibrils 6.5 ± 2.0
nm in diameter (Figs. S28), while 2⊂Gel showed instances of
amorphous aggregates along with 11.7 ± 1.9 nm-wide fibrils (Fig.
S29).
a)
c)
b)
d)
2
1
+
+
1⊂Gel
2⊂Gel
peptide
peptide
Fe-K
Fe-K
100 nm
100 nm
keV
keV
e)
f)
1000
1000
10
10
0.1
Gel
CH3CN
0.1
Elastic modulus (G')
Viscous modulus (G'')
Elastic modulus (G')
Viscous modulus (G'')
0.001
0.001
0
1000 2000 3000 4000
Time (s)
0
1000 2000 3000 4000
Time (s)
TFA−
−
ReO4
Figure 2. a-b) Peptide and either cage 1 or 2 yield 1⊂Gel and 2⊂Gel,
respectively. c-d) TEM micrographs show the fibrils of the gels and EDX
spectra (insets) show the presence of Fe from MOCs at 1 mM in 1⊂Gel (c)
and 2⊂Gel (d). Scale bar = 100 nm. e-f) Gelation kinetics depict G’ (dark blue
and dark purple) and G’’ (light blue and light pink) for 1⊂Gel (e) and 2⊂Gel (f).
>
CH3CN
CH3CN
−
ReO4 ⊂ 1
1
FA
The host–guest chemistry of 1⊂Gel and 2⊂Gel was studied
by 1H and 19F NMR over time (Fig. 3).
We infer the rate of guest uptake by cages in the gel thus to
depend upon both guest diffusion through the sample, purely
controlled by kinetics, and guest encapsulation, which is
influenced by both thermodynamic (binding affinity) and kinetic
factors (guest uptake rate). Indeed, the rate of guest uptake in
gels was substantially slower than in solution due to the kinetic
contributions (diffusion in gels for guest uptake) while the
binding affinity likely remained unchanged (Fig 3).
2
FA ⊂ 2
Figure 1. a) Self-assembly of (p-aminobenzoyl)-L-Phe-D-Ala-L-Phe-NH2 into
gel-forming fibrils. b-c) Synthesis of cages 1 and 2 by sub-component self-
assembly and encapsulation of ReO4− or TFA− in 1 and FA in 2.
−
We hypothesize that more ReO4 was encapsulated in
MOC stability in the gels was probed by 1H and 19F NMR. In
gels incorporating TFA-⊂1 or FA⊂2, MOC integrity was
evidenced by the absence of NMR resonances associated with
free cage subcomponents (e.g., the aldehyde peak at 10 ppm);
free guests were also not observed (SI Section 5.1). The gel
stabilized the MOCs at trifluoroacetate concentrations that
resulted in their decomposition, aggregation and precipitation
when free in solution (Fig. S36-39). Intact 1 and 2 were
observed by ESI-MS after dilution and filtration of 1⊂Gel and
2⊂Gel (Fig. S44-45). Minor substitution (below 6%) was
observed when 1 (5 mM) was combined with (p-aminobenzoyl)-
L-Phe-OMe (50 mM) after 1 week, with the extent of substitution
limited by the electron-deficient character of the aniline. We
hypothesized that, similarly, the peptide substituted only minor
amounts of the p-toluidine of MOC 1 in the gels (see SI, section
5.1.3).
1⊂Gel, relative to 1 in solution, because of binding of TFA−
anions by the gel fibrils, thus reducing the TFA- availability for
competitive encapsulation. This interaction between anions and
fibrils was evidenced by broadening of the 19F NMR signals
corresponding to the TFA− in the gel, as compared to the
solutions containing either 1 or 2 alone. No significant changes
in the proportion of FA encapsulated in 2 were observed
between 2⊂Gel and 2 in solution, as TFA− is not a competing
guest for 2.
Fitting the guest uptake curves to an asymptotic exponential
model allowed calculation of the initial rate of guest uptake or
diffusion (see SI Section 5.3), allowing quantitative comparison
−
between samples. The diffusion of the guests (FA or ReO4 ) in
1⊂Gel (6.30 ± 0.22 % h-1 and 5.44 ± 0.20 % h-1 respectively for
the initial rates of diffusion) was slower than in 2⊂Gel (14.61 ±
0.28 % h-1 for FA). In 1⊂Gel, the rates of diffusion for ReO4− and
This article is protected by copyright. All rights reserved.

10.1002/anie.201900429
Angewandte Chemie International Edition
COMMUNICATION
FA were similar. These observations suggest that the rate of
diffusion of small molecules within these gels is mainly
influenced by the structure of the gel network, as observed in the
TEM (SI, Section 4.6), rather than by the chemical structure of
the diffusing species. We inferred that the difference in
nanostructures between gels, such as thinner fibrils with higher
surface area, led to greater physisorption and therefore slower
diffusion of guests.
and 7 times slower respectively in 1⊂Gel and 2⊂Gel (1.31 ±
0.20 % h-1 and 2.11 ± 0.11 % h-1), meaning that the MOCs
remain localized in the gel matrix on a timescale that allowed the
smaller guests to diffuse through the sample. The system
therefore allowed for MOC segregation in separate gel layers, as
required for selective guest separation.
With guest separation in mind, we designed a three-layered
system composed of 1⊂Gel and 2⊂Gel, separated by a buffer
layer of peptide gel devoid of MOCs (Fig. 4a). The presence of
each MOC in their respective layers was confirmed by spatial
kini/diff = 6.30 0.22 %.h-1
a)
100
80
1
mapping of the sample by slice-selective H NMR (Fig. 4b).[28]
The gray regions in Fig. 4b detail the spatial partitioning of the
proton signals corresponding to cages 1 and 2 within the gel
matrix. 1H NMR signals assigned to 1 (blue spectrum) were only
found in layer 1, and signals for 2 (purple spectrum) were only
found in layer 2. The observation of color leaching into the buffer
layer was attributed to the strong visible absorbance of MOCs
-
ReO4
60
kini/ReO4- = 1.6 0.05 %.h-1
40
ReO4- uptake in solution
ReO4- uptake in gel
20
ReO4- diffusion in gel
0
1
even at trace concentrations (Fig. 2a-b). H NMR signals of the
peptide only were detected there, indicating that the MOCs
remained segregated mostly in their original layers and were not
present at concentrations above the NMR detection threshold in
the buffer layer (SI, Section 5.4).
0
100
Time (h)
200
b)
100
80
60
40
20
0
kini/diff = 14.61 0.28 %.h-1
kini/FA = 7.23 0.15 %.h-1
After the tri-layered gel formation,
a
mixture of
FA
tetrabutylammonium perrhenate and 1-fluoroadamantane in
CD3CN was added on top, and the diffusion of the guests
through the different gel layers was followed by slice-selective
19F NMR (Fig. 4c). Due to the faster diffusion and uptake of FA
FA uptake in solution
FA uptake in gel
FA diffusion in gel
−
in 2⊂Gel, relative to that of ReO4 in 1⊂Gel, maximum guest
encapsulation was achieved in 12 h for the former, and in 62 h
for the latter (Fig. 4c). Afterwards, each MOC-encapsulated
guest could be observed specifically in its respective layer.
While free FA was observed in both layers, likely in similar
proportions, the presence of both FA⊂2 and free FA in layer 2
signaled a clear enrichment of the compound in this layer. Over
0
100
Time (h)
200
Figure 3. a) ReO4− uptake kinetics by 1 in solution (light blue diamond) and by
1⊂Gel (dark blue dots) and diffusion of ReO4− in 1⊂Gel (black circles). b) FA
uptake kinetics by 2 in solution (pink diamond) and by 2⊂Gel (purple dots) and
diffusion of FA in 2⊂Gel (black circles). Dotted lines represent the asymptotic
fitting from which the initial rates (kini) were deduced.
–
80% of the encapsulated TFA– was displaced by ReO4 from
–
MOC 1’s cavity and the remaining ReO4 was inferred to be
A 5-fold difference between the initial rate of guest uptake for
1⊂Gel and 2⊂Gel (1.60 ± 0.05 % h-1 and 7.23 ± 0.15 % h-1
respectively) was obtained due to the different properties of the
hybrid MOC⊂Gel. Thus, temporal control of the encapsulation of
small guest molecules could be achieved for this system.
The diffusion of larger species, such as the MOCs
themselves, was shown to be much slower than that of the
smaller guests. The initial rate of diffusion of the MOCs were 4
spread across both layers, resulting in an estimated enrichment
up to a ratio 9:1 of this compound in layer 1 compared to layer 2
(Fig. 4c and S72-73). The potential of this type of system
towards selective chemical separation was thus demonstrated.
The investigation of MOCs with greater binding affinity for more
technologically relevant guests will be explored next, to further
optimize the extent of separation achievable by these systems.
This article is protected by copyright. All rights reserved.

10.1002/anie.201900429
Angewandte Chemie International Edition
COMMUNICATION
1H NMR mapping
c) 19
F NMR
a)
b)
Time / h
TFA− ⊂ 1
1
12
24
62
−
ReO4
TFA−
−
ReO4 ⊂ 1
δ/ppm
1
2
12
24
62
FA
FA ⊂ 2
δ/ppm
δ/ppm
Figure 4. a) Photo of the three-layered gel and b) 2D mapping of the 1H NMR spectra for the three-layered gel, showing the presence of MOC 1 in layer 1
(1⊂Gel), the peptide alone in the buffer gel layer, and MOC 2 in layer 2 (2⊂Gel). c) 19F NMR spectra of layer 1 (top, blue) and layer 2 (bottom, purple) showing
respectively the decrease of the encapsulated TFA− peak (▲) and the increase of the both the encapsulated (■) and free (●) FA over time after addition of mixed
FA and ReO4− (1 equiv. each).
15465; c) Y. Hisamatsu, S. Banerjee, M. B. Avinash, T.
Govindaraju, C. Schmuck, Angew. Chem. Int. Ed. 2013, 52,
12550-12554; d) E. Borré, J.-F. Stumbé, S. Bellemin-
In conclusion, we have demonstrated the formation of hybrid
MOC⊂gel nanostructured materials made of a self-assembled
tripeptide and one of two distinct Fe4L4 cages. These gels allow
for the spatial separation of chemically-distinct phases from one-
solvent systems. The hierarchically nested supramolecular
assemblies allow for selective, chemical segregation by means
of guest encapsulation. The gel nanostructure is influenced by
the presence of the cages, thus providing new means to tune
the diffusion kinetics and, as a consequence, the uptake of small
molecules in the embedded MOCs. Future efforts will focus
upon the extension of this chemical platform to biocompatible
materials able to perform time-controlled guest release.
Laponnaz, M. Mauro, Angew. Chem. Int. Ed. 2016, 55, 1313-
1317; e) C. N. Zhu, T. Bai, H. Wang, W. Bai, J. Ling, J. Z. Sun,
F. Huang, Z. L. Wu, Q. Zheng, ACS Applied Materials &
Interfaces 2018, 10, 39343-39352; f) T. Hiratani, O. Kose, W.
Y. Hamad, M. J. MacLachlan, Materials Horizons 2018, 5,
1076-1081.
a) B. O. Okesola, D. K. Smith, Chem. Soc. Rev. 2016, 45,
4226-4251; b) T. N. Plank, L. P. Skala, J. T. Davis, Chem.
Commun. 2017, 53, 6235-6238; c) J. R. Hiscock, M. R.
Sambrook, N. J. Wells, P. A. Gale, Chem. Sci. 2015, 6, 5680-
5684.
a) J. Mayr, C. Saldías, D. Díaz Díaz, Chem. Soc. Rev. 2018,
47, 1484-1515; b) D. J. Cornwell, B. O. Okesola, D. K. Smith,
Angew. Chem. Int. Ed. 2014, 53, 12461-12465; c) G. B.
Demirel, R. von Klitzing, ChemPhysChem 2013, 14, 2833-
2840; d) G. Yu, X. Zhao, J. Zhou, Z. Mao, X. Huang, Z. Wang,
B. Hua, Y. Liu, F. Zhang, Z. He, O. Jacobson, C. Gao, W.
Wang, C. Yu, X. Zhu, F. Huang, X. Chen, J. Am. Chem. Soc.
2018, 140, 8005-8019.
[2]
[3]
Acknowledgements
The authors gratefully acknowledge funding from the Italian
Ministry of University and Research through the Scientific
Independence of young Researchers (SIR) program (‘‘HOT-
SPOT’’ project; grant no. RBSI14A7PL to S.M.).This project has
received funding from the European Union's Horizon 2020
research and innovation program under the Marie Sklodowska-
Curie grant agreement No 642192 and was supported by the UK
Engineering and Physical Sciences Research Council (EPSRC
EP/P027067/1). The authors thank Duncan Howe and the NMR
facility at the University of Cambridge for setting the slice-
selective experiment.
[4]
a) R. Chakrabarty, P. S. Mukherjee, P. J. Stang, Chem. Rev.
2011, 111, 6810-6918; b) Y. Sakata, R. Yamamoto, D. Saito,
Y. Tamura, K. Maruyama, T. Ogoshi, S. Akine, Inorg. Chem.
2018, 57, 15500-15506; c) W. M. Bloch, J. J. Holstein, B.
Dittrich, W. Hiller, G. H. Clever, Angew. Chem. Int. Ed. 2018,
57, 5534-5538; d) D. Luo, X.-Z. Wang, C. Yang, X.-P. Zhou, D.
Li, J. Am. Chem. Soc. 2018, 140, 118-121.
a) H. Li, P. Yang, P. Pageni, C. Tang, Macromol. Rapid
Commun. 2017, 38, 1700109; b) P. Sutar, T. K. Maji, Chem.
Commun. 2016, 52, 8055-8074; c) N. Hosono, S. Kitagawa,
Acc. Chem. Res. 2018, 51, 2437-2446; d) H. L.-K. Fu, V. W.-
W. Yam, Chem. Lett. 2018, 47, 605-610.
a) W. Zheng, G. Yang, N. Shao, L.-J. Chen, B. Ou, S.-T. Jiang,
G. Chen, H.-B. Yang, J. Am. Chem. Soc. 2017, 139, 13811-
13820; b) L. Li, Y. Cong, L. He, Y. Wang, J. Wang, F.-M.
Zhang, W. Bu, Polymer Chemistry 2016, 7, 6288-6292; c) S. V.
Wegner, F. C. Schenk, S. Witzel, F. Bialas, J. P. Spatz,
Macromolecules 2016, 49, 4229-4235.
a) C. Lu, M. Zhang, D. Tang, X. Yan, Z. Zhang, Z. Zhou, B.
Song, H. Wang, X. Li, S. Yin, H. Sepehrpour, P. J. Stang, J.
Am. Chem. Soc. 2018, 140, 7674-7680; b) X. Yu, Z. Wang, Y.
Li, L. Geng, J. Ren, G. Feng, Inorg. Chem. 2017, 56, 7512-
7518.
[5]
[6]
Keywords: self-assembly • metal-organic cages • low molecular
weight gelators • host-guest chemistry • chemical separation
[7]
[1]
a) C. D. Jones, J. W. Steed, Chem. Soc. Rev. 2016, 45, 6546-
6596; b) D. Spitzer, L. L. Rodrigues, D. Straßburger, M.
Mezger, P. Besenius, Angew. Chem. Int. Ed. 2017, 56, 15461-
This article is protected by copyright. All rights reserved.

10.1002/anie.201900429
Angewandte Chemie International Edition
COMMUNICATION
[8]
a) W. Zheng, L.-J. Chen, G. Yang, B. Sun, X. Wang, B. Jiang,
G.-Q. Yin, L. Zhang, X. Li, M. Liu, G. Chen, H.-B. Yang, J. Am.
Chem. Soc. 2016, 138, 4927-4937; b) M. Mauro, Eur. J. Inorg.
Chem. 2018, 2018, 2090-2100; c) J. Uchida, M. Yoshio, S.
Sato, H. Yokoyama, M. Fujita, T. Kato, Angew. Chem. Int. Ed.
2017, 56, 14085-14089.
a) J. Feng, L. Zeng, K. Chen, H. Fang, J. Zhang, Z. Chi, C.-Y.
Su, Langmuir 2016, 32, 12184-12189; b) A. V. Zhukhovitskiy,
J. Zhao, M. Zhong, E. G. Keeler, E. A. Alt, P. Teichen, R. G.
Griffin, M. J. A. Hore, A. P. Willard, J. A. Johnson,
Macromolecules 2016, 49, 6896-6902; c) J. A. Foster, R. M.
Parker, A. M. Belenguer, N. Kishi, S. Sutton, C. Abell, J. R.
Nitschke, J. Am. Chem. Soc. 2015, 137, 9722-9729.
a) A. Carné-Sánchez, G. A. Craig, P. Larpent, T. Hirose, M.
Higuchi, S. Kitagawa, K. Matsuda, K. Urayama, S. Furukawa,
Nat. Commun. 2018, 9, 2506; b) D. Nam, J. Huh, J. Lee, J. H.
Kwak, H. Y. Jeong, K. Choi, W. Choe, Chem. Sci. 2017, 8,
7765-7771.
a) N. Hosono, K. Omoto, S. Kitagawa, Chem. Commun. 2017,
53, 8180-8183; b) T.-H. Chen, L. Wang, J. V. Trueblood, V. H.
Grassian, S. M. Cohen, J. Am. Chem. Soc. 2016, 138, 9646-
9654; c) Y. Gu, E. A. Alt, H. Wang, X. Li, A. P. Willard, J. A.
Johnson, Nature 2018, 560, 65-69.
[17]
[18]
[19]
A. Lampel, R. V. Ulijn, T. Tuttle, Chem. Soc. Rev. 2018, 47,
3737-3758.
A. V. Vargiu, D. Iglesias, K. E. Styan, L. J. Waddington, C. D.
Easton, S. Marchesan, Chem. Commun. 2016, 52, 5912-5915.
D. Iglesias, M. Melle-Franco, M. Kurbasic, M. Melchionna, M.
Abrami, M. Grassi, M. Prato, S. Marchesan, ACS Nano 2018,
12, 5530-5538.
[9]
[20]
[21]
[22]
[23]
L. Peraro, J. A. Kritzer, Angew. Chem. Int. Ed. 2018, 57,
11868-11881.
A. M. Garcia, M. Kurbasic, S. Kralj, M. Melchionna, S.
Marchesan, Chem. Commun. 2017, 53, 8110-8113.
A. Méndez-Ardoy, J. R. Granja, J. Montenegro, Nanoscale
Horizons 2018, 3, 391-396.
P. W. J. M. Frederix, G. G. Scott, Y. M. Abul-Haija, D.
Kalafatovic, C. G. Pappas, N. Javid, N. T. Hunt, R. V. Ulijn, T.
Tuttle, Nat. Chem. 2014, 7, 30-37.
A. M. Garcia, D. Iglesias, E. Parisi, K. E. Styan, L. J.
Waddington, C. Deganutti, R. De Zorzi, M. Grassi, M.
Melchionna, A. V. Vargiu, S. Marchesan, Chem 2018, 4, 1862-
1876.
a) A. M. Castilla, M. A. Miller, J. R. Nitschke, M. M. J.
Smulders, Angew. Chem. Int. Ed. 2016, 55, 10616-10620; b) J.
L. Bolliger, T. K. Ronson, M. Ogawa, J. R. Nitschke, J. Am.
Chem. Soc. 2014, 136, 14545-14553.
R. Orbach, I. Mironi-Harpaz, L. Adler-Abramovich, E. Mossou,
E. P. Mitchell, V. T. Forsyth, E. Gazit, D. Seliktar, Langmuir
2012, 28, 2015-2022.
B. Lekprasert, V. Korolkov, A. Falamas, V. Chis, C. J. Roberts,
S. J. B. Tendler, I. Notingher, Biomacromolecules 2012, 13,
2181-2187.
a) A. B. Grommet, J. B. Hoffman, E. G. Percástegui, J.
Mosquera, D. J. Howe, J. L. Bolliger, J. R. Nitschke, J. Am.
Chem. Soc. 2018, 140, 14770-14776; b) A.-C. Pöppler, S.
Frischkorn, D. Stalke, M. John, ChemPhysChem 2013, 14,
3103-3107.
[10]
[11]
[24]
[25]
[12]
[13]
P. Sutar, V. M. Suresh, K. Jayaramulu, A. Hazra, T. K. Maji,
Nat. Commun. 2018, 9, 3587.
[26]
[27]
[28]
a) Y. Takashima, Y. Shojima, T. Sekine, M. Osaki, Y.
Kobayashi, H. Yamaguchi, T. Sekito, K. Hatano, K. Nakajima,
A. Harada, Chem. Lett. 2018, 47, 1255-1257; b) J. Liu, O. A.
Scherman, Adv. Funct. Mater. 2018, 28, 1800848.
a) H. L. Ozores, M. Amorín, J. R. Granja, J. Am. Chem. Soc.
2017, 139, 776-784; b) D. Preston, J. J. Sutton, K. C. Gordon,
J. D. Crowley, Angew. Chem. Int. Ed. 2018, 57, 8659-8663; c)
D. P. August, G. S. Nichol, P. J. Lusby, Angew. Chem. Int. Ed.
2016, 55, 15022-15026; d) C. G. P. Taylor, W. Cullen, O. M.
Collier, M. D. Ward, Chem. Eur. J. 2017, 23, 206-213; e) S.
Kusaba, M. Yamashina, M. Akita, T. Kikuchi, M. Yoshizawa,
Angew. Chem. Int. Ed. 2018, 57, 3706-3710.
[14]
[15]
[16]
S. Ganta, D. K. Chand, Inorg. Chem. 2018, 57, 3634-3645.
M. Amit, S. Yuran, E. Gazit, M. Reches, N. Ashkenasy, Adv.
Mater. 2018, 30, 1707083.
This article is protected by copyright. All rights reserved.

10.1002/anie.201900429
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Cages in gels: FeII L4 metal-organic
Marion Kieffer,ǂ Ana M. Garcia,ǂ Cally
J. E. Haynes, S. Kralj, D. Iglesias,
Jonathan R. Nitschke* and Silvia
Marchesan*
4
cages were incorporated in a D,L-tripeptide
self-assembled gel, modulating the gel
viscoelasticity, and thus the diffusion rate
of molecular guests through the material.
Two different cages were incorporated into
spatially separated gel layers to enable the
separation of a mixture of guests by
selective encapsulation within the two
cages.
Page No. – Page No.
Embedding and positioning of two
FeII L4 cages in supramolecular
4
tripeptide gels for selective chemical
segregation.
This article is protected by copyright. All rights reserved.