Effect of Stereochemistry on Chirality and Gelation Properties of Supramolecular Self-Assemblies

Article abstract of DOI:10.1002/chem.202004533

Although chiral nanostructures have been fabricated at various structural levels, the transfer and amplification of chirality from molecules to supramolecular self-assemblies are still puzzling, especially for heterochiral molecules. Herein, four series o

Full text of DOI:10.1002/chem.202004533

Accepted Article
Accepted Article
Title: Effect of Stereochemistry on the Supramolecular Self-Assembly
Chirality and Gelation Property
Authors: Minggao Qin, Yaqian Zhang, Chao Xing, Li Yang, Changli
Zhao, Xiaoqiu Dou, and Chuan Liang Feng
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To be cited as: Chem. Eur. J. 10.1002/chem.202004533
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01/2020

10.1002/chem.202004533
Chemistry - A European Journal
Effect of Stereochemistry on the Supramolecular Self-
Assembly Chirality and Gelation Property
Minggao Qin1, Yaqian Zhang1, Chao Xing1, Li Yang1, Changli Zhao1, Xiaoqiu Dou1,
Chuanliang Feng1,*
State Key Lab of Metal Matrix Composites, School of Materials Science and
Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240,
China
*Corresponding author
Tel: +86-021-54747651; E-mail: clfeng@sjtu.edu.cn
Abstract
Although chiral nanostructures have been fabricated at various structural levels,
the transfer and amplification of chirality from molecules to supramolecular self-
assemblies are still puzzling, especially for heterochiral molecules. Herein, four series
of C2-symmetrical dipeptide-based derivatives bearing various amino acid sequences
and different chiralities are designed and synthesized. The transcription and
amplification of molecular chirality to supramolecular assemblies are achieved. The
results show that the supramolecular chirality is only determined by the amino acid
adjacent to the benzene core and irrespective of the absolute configuration of C-
terminal amino acid. In addition, the molecular chirality also has a significant influence
on their gelation behaviors. For the diphenylalanine-based gelators, the homochiral
gelators can be gelled through conventional heating-cooling process, while heterochiral
gelators form translucent stable gels under sonication. And the racemic gels possess
higher mechanical properties than that of pure enantiomers. All these results contribute
to an increasing knowledge over control the generation of specific chiral
supramolecular structures and the development of new optimized strategies to achieve
functional supramolecular organogel through heterochiral and racemic systems.
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Introduction
Chirality is a ubiquitous phenomenon in nature from the microscopic to the
macroscopic scale.[1-4] Usually, chiral molecular units can decide both molecular
conformations and supramolecular biological functions.[5, 6] Inspired by the specific
chirality in life processes, the design and fabrication of chiral nanostructures as well as
their applications in the fields of asymmetric catalysis[7, 8], enantiomer discrimination
or sensor[9, 10], biological effects[11, 12], and optical materials[13] have been tremendously
reported. However, the establishment of clear rules for achieving an accurate
knowledge on the chiral amplification in self-assembling systems is still
challengeable.[14-17] Revealing the fundamental discipline about the chiral amplification
from simple molecules towards supramolecular assembled nanostructures would be of
significance in guiding us in construction chiral supramolecular materials.[18]
To date, various chiral nanostructures such as helical ribbons,[19-21] twisted
nanofibers,[22-25] rolled-up nanotubes,[26-28] and even super-helix[29-31] have been
constructed. For two-component co-assembly systems, the chiral amplification is
usually obedient to the following rules: (i) sergeants-and-soldiers (S&S) effect,[32] (ii)
majority-rules (MR) effect,[33] and (iii) diluted MR effect,[34] a combination of the above
two effects. In comparison, the situation is more sophisticated for self-assembly of
single component. In most cases, left-handed chiral nanostructures drive from peptides
composed of L-amino acids, whereas D-amino acid derivatives are prone to self-
assemble into right-handed twist or helix.[31, 35] However, it is still difficult to predict
the self-assembled supramolecular chirality based on a known peptide sequence which
contains more than one chiral center.[15-17] Recently, some intriguing investigations on
chiral amplification phenomenon are reported.[36-38] For example, Xu and co-workers
investigated the self-assembly chirality of three pairs of short tetrapeptide enantiomers，
and found that the handedness of the supramolecular nanofibrils was determined by the
chirality of the hydrophilic Lys head at the C-terminal, while the morphological
handedness could not be changed by altering the molecular chirality of hydrophobic Ile
residues.[16]
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Apart from the effect of molecular chirality on its self-assembled handedness,
chirality is proved to be not a pre-requisite but an effective parameter to regulate
gelation properties.[39-41] It has been widely accepted that homochiral peptide-based
gelators are more prone to gelate compared with heterochiral molecules, results in
thermally and mechanically robust homochiral self-assemblies.[42] The investigation of
D-amino acids, especially the combination of L- and D-amino acids is largely
overlooked. It is only in last few years that heterochiral molecules have attracted more
and more attention due to their unusual self-assembling behaviors and great potential
biological applications.[43-45]
Herein, based on C2 symmetrical molecular system, a rule of chiral transfer and
amplification from molecules to supramolecular assemblies is established, as well as
the effect of stereochemistry on gelation property is investigated. 16 molecules in which
two dipeptide arms with different sequences and chiralities connected to para-
disubstituted phenyl group are design and synthesized (Scheme 1). For this system, the
supramolecular chirality is just determined by the chirality of amino acid close to the
benzene core, not related to the terminal one. In addition, for the diphenylalanine-based
gelators, the homochiral gelators can be gelled through conventional heating-cooling
process and heterochiral gelators form translucent stable gels under sonication, which
has been rarely reported. This work not only deepens our fundamental understanding
on the transfer and amplification of molecular chirality to supramolecular chirality, but
also provides an easy accessible approach to fabricate chiral organogels for potential
applications.
Results and discussion
In this study, 16 molecules are designed and synthesized according to the reported
literatures(Scheme 1)[10]. All the synthesized compounds were characterized by 1H and
13C NMR spectra, high-resolution mass (Figure S4-S19), as well as their melting points
(Table S1) and FT-IR spectra (Figure S22).
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Scheme 1. Molecular structures of 16 molecules in which two dipeptide arms with different
amino acid sequences and chiralities conjugated to para-disubstituted phenyl group; F:
phenylalanine, A: alanine, L and D represent L- and D-amino acids.
Molecular chirality effect on self-assembled handedness
All the gelators were initially dissolved in ethanol through heating, allowing them
to self-assemble when cooling down under room temperature. SEM images showed
micrometer-long twisted fibers assembled from the as-prepared dipeptide-based
derivatives (Figure 1). Left-handed nanofibers (M) separately assembly from LFLF,
LFLA, LALF, and LALA, while right-handed nanofibers (P) were obtained from DFDF,
DFDA, DADF, and DADA. Obviously, the molecular chirality played a decisive role
in determining the supramolecular chirality. The results were accordance with the
previous reports that L-type amino acid derivatives are preferred to generate left-handed
twist or helix, and vice-versa.[31] More intriguing, all the heterochiral gelators with L-
amino acid adjacent to phenyl core and D-amino acid at terminal (LFDF, LFDA, LADF,
and LADA) possessed left-handed nanofibers. On the contrary, the remaining four
heterochiral enantiomeric molecules (DFLF, DFLA, DALF, and DALA) revealed right-
handedness.
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Figure 1. SEM images of supramolecular self-assemblies. Left-handed (M) nanofibers
assembled from (a1) LFLF, (a2) LFDF, (b1) LFLA, (b2) LFDA, (c1) LALF, (c2) LADF, (d1)
LALA, and (d2) LADA, and right-handed (P) nanofibers assembled from (a3) DFDF, (a4)
DFLF, (b3) DFDA, (b4) DFLA, (c3) DADF, (c4) DALF, (d3) DADA, and (d4) DALA were
presented. Scale bars: 500 nm for c2, c4 and d1-d4, 1 μm for the other cases.
With changing the chirality of the amino acid near to the benzene core, nanofibers
with reversed handedness were formed. On the contrary, the helicity would not change
with altering the chirality of the C-terminal amino acids. The above SEM results clearly
indicated that the supramolecular chirality was solely determined by the chirality of the
amino acid adjacent to the benzene core, irrespective of the absolute configuration of
the terminal amino acid. This finding was contradictory to some preceding reports that
the supramolecular chirality was dictated by the C-terminal chirality which was called
“C-terminal rule”.[46-48] In fact, the gelators in those systems were amphiphilic
molecules and upon self-assembly the C-terminal hydrophilic head group residues were
located on the surface of the self-assembled aggregates. It could be anticipated that
terminal noncovalent interactions among gelators or solvents play a profound effect on
controlling the supramolecular morphology, as well as handedness.[16] Here, the
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prepared non-amphiphilic and the use of organic solvent were not suitable to this “C-
terminal rule”.
Even though the changes of amino acids sequence were not found to prevent the
impartation of chirality onto the nanofiber handedness, subtle differences were
observed. For Phe-Phe enantiomers, homochiral LFLF and DFDF respectively showed
uniform left and right-handed nanofibers with similar diameter and helical pitch.
However, the helix was not distinct for heterochiral LFDF and DFLF and only a few
nanofibers showed helix structure, demonstrating the vital effect of amino acid chirality.
The homologous phenomenon was also occurred for Phe-Ala enantiomers. Interestingly,
the helix were noticeable for all four Ala-Phe enantiomers. Homochiral LALF and
DADF showed single twisted, while heterochiral LADF and DALF presented
superhelix composed of single helix. Compared with the other three systems, the
nanofibers exhibited smaller sizes for Ala-Ala enantiomers due to their smaller amino
acid residues.
Figure 2. CD spectra of self-assembled membranes obtained from solutions evaporation
on quartz plates under room temperature: (a) LFLF, LFDF DFDF, DFLF; (b) LFLA, LFDA,
DFDA, DFLA; (c) LALF, LADF, DADF, DALF; (d) LALA, LADA, DADA, DALA.
It is well-known that circular dichroism (CD) spectra appear when the
chromophoric moieties of chiral molecules are organized into an appropriate orientation.
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The inherent chirality present in the dipeptide-based gelators and the specific stacking
modes of the amide carbonyl and benzene groups allowed the aggregated state to be
studied by CD.
Initially, molecular chirality was characterized using a 1.0 mm quartz cuvette with
concentration of 0.1 mg/mL, and their corresponding UV-Vis spectra were shown in
Figure S20. The expected mirror-imaged CD spectra were acquired from the
enantiomers in those four systems. Meanwhile, all the UV-Vis spectra possessed an
absorption at around 248 nm due to the benzene chromophores. Upon self-assembly,
an apparent red-shift of UV-Vis absorption and a new weak peak at around 290 nm were
occurred (Figure S21), indicating the existence of intense intermolecular π-π
interactions.[49]
For Phe-Phe system (Figure 2a), the CD spectrum of LFDF displayed bisignate
Cotton effect with a positive dichroic signal at 265 nm followed by a negative CD peak
at 231 nm (sign: +/-). In contrast, DFLF showed perfect mirror images to LFDF with a
negative signal at 265 nm and a positive signal at 231 nm (sign: -/+), indicating that the
helical sense of the LFDF assemblies switched to opposite for DFLF. Similarly, the CD
spectrum of LFLF possessed a positive Cotton effect at around 265 nm and a negative
signal at around 213 nm (sign: +/-), which was opposite to the case of DFDF (negative
minimum at 265 nm and positive maximum at about 215 nm (sign: -/+)). Notably, the
occurrence of zero crossing located at around 245 nm corresponding to the maximum
UV absorption, indicating that the strong exciton coupled aromatic chromophores were
in a helical arrangement.[50, 51] That was, stronger interactions were existed within
heterochiral chromophores than that of homochiral ones. On the other hand, compared
with the CD spectra of self-assemblies, no exciton coupling occurred around 248 nm in
solution state for all the four enantiomers (Figure S20a), indicating that tight π-π
stacking between the chromophores in self-assemblies might give rise to the formation
of chiral helical nanofibers.
For the Phe-Ala (Figure 2b), the homochiral derivatives (LFLA and DPDA) and
heterochiral derivatives (LFDA and DFLA) also showed mirror-image relationships to
each other, respectively. Both LFLA and LFDA presented positive bisignate Cotton
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effect with a positive dichroic signal at around 260 nm followed by a negative CD peak
at 218 nm (sign: +/-) while DFDA and DFLA exhibited a negative dichroic signal at
262 nm and a positive one at 218 nm (sign: -/+), revealing distinctly opposite helicity.
Similarly to Phe-Phe, all enantiomers of Phe-Ala showed split CD signals with a
crossover at 252 nm. However, different to Phe-Phe derivatives which had almost
equally strong splitting Cotton effects, the CD spectra of Phe-Ala derivatives possessed
much weaker intensity around 262 nm than that of at 206 nm. It could be attribute to
different orientation of the chromophores transition dipole moments existing in the Phe-
Ala. Thus, for Phe-Phe, the exciton coupling most likely came from two identical
chromophores of the benzene residues of the diphenylalanine, while for Phe-Ala, it
might be due to the interaction between the benzene core and the benzene of
phenylalanine adjacent to the core.
For Ala-Phe derivatives (Figure 2c), distinct differences of the CD spectra were
occurred between homochiral (LALF, DADF) and heterochiral (LADF, DALF)
enantiomers, suggesting the formation of two different molecular stacking models. The
CD spectrum of the LALF displayed negative, negative, and positive Cotton signals at
218, 242, and 292 nm, respectively. Nevertheless, these three CD bands of DADF
became positive, positive, and negative, indicating the formation of self-assemblies
with opposite handedness. The Cotton signs at around 244 nm were associated with
intramolecular transitions from the amide linkage to the central aryl group.[52] Moreover,
CD signals appeared at higher wavelengths at 277, 292 and 303 nm could be assigned
to the chiral scattering of light as a result of the interaction of the light with the chiral
nanostructures.[51]
For the Ala-Ala molecules, the molecular CD spectra were shown in Figure S20g.
Clearly, homochiral enantiomers LALA and DADA showed two main bands at 227 and
252 nm with opposite Cotton effects, and similar Cotton signals at 224 and 256 nm
appeared in CD spectra of heterochiral enantiomers LADA and DALA. In comparison
with the molecular CD signals at 227 and 252 nm, the CD curves of LALA and DADA
assemblies also displayed the characteristic CD absorption at 227 nm (Figure 2d). A
red-shift from 252 to 262 nm of LALA/DADA was observed, which was resulted from
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the J-aggregation among molecules induced by H-bond interactions among the
carboxyl groups. In view of heterochiral enantiomers LADA and DALA, besides the
red-shifted peak at 262 nm, a blue-shift appeared from 224 to 218 nm due to the H-
aggregation among molecules. Signals with positive or negative Cotton effects at 300
nm indicated the formation of helical superstructures with preferred handedness.[53] The
peak at 262 nm was mainly due to intermolecular π-π* transitions of the central aryl
group reported by previous study.[30]
As systematically demonstrated above, it revealed the chirality transformation
from molecular scale into supramolecular level accompanied by the chirality
amplification during the self-assembly process. More importantly, the handedness of
the self-assembled nanostructures could be estimated and controlled based on a certain
chirality of the molecule. The chiroptical activities of these self-assembled nanofibers
were further determined by vibrational circular dichroism (VCD), which indicated the
involvement of specific parts of the molecule configuration influenced by chiral
supramolecular aggregation.[54] We conducted the VCD measurements by dropping the
solution on a CaF2 wafer followed by drying under ambient temperature overnight.
Figure 3. VCD spectra of membranes obtained from solutions evaporation on CaF2 plates
under room temperature: (a) LFLF, LFDF DFDF, DFLF; (b) LFLA, LFDA, DFDA, DFLA; (c)
LALF, LADF, DADF, DALF; (d) LALA, LADA, DADA, DALA.
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For Phe-Phe-based self-assembled systems (Figure 3a), LPLP and LPDP exhibited
a (-/+) VCD signal of C=O stretching band between 1750 and 1600 cm-1, whereas the
VCD signal of the band switched to a totally opposite (+/-) pattern for DPDP and DPLP
assemblies. The VCD patterns indicated the opposite handedness of nanofibers
assembled from LPLP/LPDP and DPDP/DPLP, which were in good accordance with
the SEM and CD results. Moreover, a strong C=O…H-N hydrogen-bonding network
was inferred from the vibrational amide I stretching band at around 1636 cm-1. The
similar phenomena were occurred among Phe-Ala, Ala-Phe and Ala-Ala-based
assemblies in Figure 3b, c and d, respectively. To be specific, the spectra of LPLP,
LPDA, LALP, LADP, LALA, and LADA all showed -/+ signals in the range of 1750-
1600 cm-1 with left-handed self-assembled helices. Whereas right-handed nanofibers
were formed from aggregation of DPDA, DPLA, DADP, DALP, DADA, and DALA,
whose VCD spectra presented perfect mirror images (with a (-/+) pattern) to their
corresponding enantiomers. These results suggested that the VCD signal patterns could
be inversed by changing the chirality of the amino acid that adjacent to the molecular
core, which further confirmed the crucial role of chirality of the specific amino acid in
determining the helicity of the self-assemblies.
FTIR can provide critical information about the hydrogen bonds networks,
especially in the region of 1800-1500 cm-1. The FTIR spectra of the products in their
molecular states and assembled states were checked, as shown in Figure S22 and S23,
respectively. Obviously, all the gelators show almost identical characteristic peaks at
approximately 1723, 1676, 1652 and 1544 cm-1. The peak at 1723 cm-1 is due to the
C=O stretching vibration of carboxylic group. While, 1676 and 1652 cm-1 of amide I
and amide II at 1540 cm-1 are attributed to the C=O stretching vibration and N-H
bending vibration of the amide groups. And then, the KBr disk technique FTIR was
used for the as-prepared self-assemblies, as shown in Figure S23a-d. Expectedly,
almost the same spectra for homochiral and heterochiral molecules, respectively.
Compared with the molecular states, the peaks of assemblies showed distinct shifts,
indicating that the hydrogen bonding was one of the main driving forces for self-
assembly. Besides, the multiple peaks emerged in amide I or II demonstrated the
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existence of complex hydrogen bonds.
A feasible mechanism was proposed in Scheme 2. During self-assembly, the
amide groups closed to the hydrophobic benzene core would be shielded from the
solvent environment, thus allowing strong intermolecular H-bond formation to occur.
Consequently, due to the directional hydrogen bonding and π-π stacking, 1D molecular
stacking further promoted the generation of nanofibers. Hence, the existence of specific
stereochemistry of chiral chain residues suspended to the medial amide group would
prefer to determine the handedness of the nanofibers. In comparison, the lateral amide
groups were insusceptible to the phenyl core, but presumably to be affected by the
adjacent hydrophilic carboxyl groups. This could explain the observation of various
twisted nanofibers with different morphologies, diameters or helical pitches.
Overall, comprehensive characterizations (SEM, CD, VCD and FTIR) and
interpretation of the nanostructures self-assembled from 16 C2-symmetrical molecules
with various amino acid sequences and chiral centres were performed. It was showed
that the chirality of amino acid proximal to benzene core determined the supramolecular
chirality of the self-assembled nanofibers. This principle on chiral transformation and
amplification was discrepant to the most previous literatures, in which the terminal
chirality was dominant in controlling the handedness of assembled nanostructures.
Even though the terminal amino acid chirality was insusceptible in regulating the
supramolecular chirality, it impacted the nanofiber diameters, degree of twists, and
helical pitches of the nanofibers. These results provided us a facile way to fabricate
nanofibers with controllable chirality and tailored sizes by altering partial chirality and
sequence of the involved amino acids.
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Scheme 2. Schematic illustration showed the decisive role of chirality of amino acid close
to benzene core (Amino acid 1) on the handedness of self-assembled nanofibers based
on four series of dipeptide-based derivatives.
Molecular chirality effect on gelation properties
Molecular chirality has been intensively proved to be a mysterious factor
controlling its gelation behaviors. In most cases, homochiral molecules are more likely
to be effective gelators than heterochiral ones, and racemates of the pure enantiomeric
gelator mixtures are normally inclined to form precipitates rather than gels. In rare
examples, all the enantiomers, diastereomers and racemates of a given dipeptide-based
derivatives could form stable gels. Due to its structural simplicity, ease of chemical
modification and biocompatibility, diphenylalanine (FF), a core recognition motifs of
Alzheimer’s β-amyloid polypeptide, has increasingly become subject of intense
investigation in both sciences of medicine and nanotechnology. Herein, the synthesized
LFLF, LFDF, DFDF, DFLF were utilized to investigate their gelation behaviours.
Meanwhile, the racemates of homochiral enantiomers mixtures (MFMF) and
heterochiral enantiomers mixtures (mFmF) were introduced. Noting that LFLF (DFDF)
and LFDF/DFLF are diastereomers.
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Figure 4. Photographs (a-c) showed gels formation results of LFLF, LFDF, DFDF, DFLF,
MFMF and mFmF under heating-cooling or sonication methods. In (d), Sus: suspension,
G: gel, Sol: solution, P: precipitate.
Homochiral enantiomers LFLF and DFDF formed into white opaque gels in
ethanol through traditional heating-cooling (HC) method (Figure 4a1 and a3).
Meanwhile, under the identical conditions, clear solutions were presented without any
gelation tendency for LFDF and DFLF (Figure 4b2 and b4), and some sediments
extracted from the solution were observed after 24 h (data not shown). It was not
surprisingly that no gelation occurred to heterochiral enantiomers. However,
homogeneous transparent organogels were obtained when LFDF or DFLF subjected to
sonication for 2 min (Figure 4a2 and a4). We suggested that sonication initially
accelerated the dissolution and dispersion of gelator molecules in ethanol, and then
reorganized the molecules. It resulted in enhanced π-π stacking between the aromatic
groups and the intermolecular hydrogen bonding, providing the driving force to form
extended supramolecular aggregates. In comparison, LFLF and DFDF exhibited white
suspensions under sonication even with longer processing time (Figure 4b1 and b3). It
demonstrated that the molecular chirality played a critical role in guiding their gelation
abilities. These unusual phenomena had rarely been reported that the homochiral and
heterochiral enantiomers gelled individually through heating-cooling and sonication.
Inspired by this, we were intrigued to explore the gelation possibility of racemates
under heating-cooling and sonication process. In Figure 4c1 and c4, MFMF displayed
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suspension and white gel after dealing with sonication and heating-cooling,
respectively. Semilucent organogel and precipitates were observed for mFmF (Figure
4c2 and c3). It was scarce that the racemates possessed similar gelation abilities with
their related pure enantiomers.[55-59] Obviously, our observation expand the design rules
to a more diverse toolbox of heterochiral peptides and even racemates, and opens the
way to exciting possibilities for the fabrication of supramolecular architectures and
functional materials.
To check how the different molecular chiralities were reflected in the macroscopic
properties of these organogels, rheological tests were carried out to measure their
mechanical rigidity. From a frequency sweep experiments with a constant strain 0.1%
(Figure 5a), all the prepared organogels revealed stronger storage moduli (G’) than
relevant loss moduli (G’’), and also G’ and G’’ values were weakly dependent on
angular frequency over the range discussed. These data indicated the formation of stable
organogels for all single gelators, as well as the enantiomeric mixtures. Furthermore, it
was found that the mechanical strength as indicated by G’ increased in sequence of
LFLF≈DFDF<MFMF<LFDF≈DFLF<mFmF (Figure 5b). From which three issues
could be inferred. Firstly, enantiomeric pairs (LFLF/DFDF or LFDF/DFLF) had nearly
equal storage moduli. Secondly, heterochiral enantiomeric pair possessed much higher
storage moduli (around 2000 Pa) than homochiral enantiomeric pair (about 700
Pa).Thirdly, the organogels strength formed from racemates were obviously enhanced
(about 1.5 times) compared with that of the gels formed by corresponding either pure
enantiomers. These data also suggested that the enantiomers in the mixtures co-
assembled into a new kind of network of mixed nanofibers, rather than self-sorting in
the racemates gels.[60] Thus, we can conclude that altering molecular chirality and
rearranging the D-amino acid in the appropriate position can be valuable approaches to
regulate the mechanical strength of supramolecular gels.
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Figure 5. (a) Frequency sweeps of dynamic shear modulus for organogels made from
LFLF, DFDF and MFMF after heating-cooling, and organogels made from LFDF, DFLF
and mFmF under sonication, respectively. (b) Comparison of corresponding mechanical
strength at a constant frequency of 6.29 rad/s.
The formation of gels was a synergetic effect of both gelator-gelator and gelator-
solvent interactions, and the gel mechanical rigidity was dependent on both the number
of crosslinks existed between fibrils in the network and the stiffness of the individual
fibrils themselves. Subsequently, the self-assembled nanostructures were checked by
scanning electron microscopy (SEM), which provides a visual way to estimate the
impact of peptide stereoisomers on self-assembly.
Compared with the soluble winding nanofibers formed in ethanol (1 mg/mL) of
homochiral enantiomers LFLF and DFDF (Figure 1a, c), stretching nanofibers in gel
state were preserved (Figure 6a, c). Even though a slight change in morphology was
emerged between solution and gel states, the supramolecular chirality remained the
same, where LFLF and DFDF formed left- and right-handed twisted nanofibers,
respectively. In contrast, distinct rigid nanofibers with much larger sizes were found in
the gels of LFDF and DFLF (Figure 6b, d). Transmission electron microscopy (TEM)
characterizations further confirmed the results displayed by SEM. Homochiral gelators
reliably self-assembled into thin nanotwists with width of 30-50 nm and an average of
helical pitches around 150-250 nm (insets of Figure 6a, b and S24a, c). Meanwhile,
more rigid and thicker nanofibers with 100-150 in diameters and 400-500 nm in helical
pitches were revealed (insets of Figure 6e, f and Figure S24b, d). As for the MFMF gels,
nanofibers intertwined into wheel hub-like nanostructures, which possessed smaller
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aspect ratio but larger sizes (Figure 6e). On account of mFmF gels, compact and
entangled nanofibers were observed. Worth noting that the disappearance of twist both
for MFMF and mFmF nanostructures further indicated the formation of co-assemblies.
Besides, the self-assembled nanostructures of the non-gel systems were also conducted
by SEM. No nanofibers but micro-scale worm-like aggregates were formed from
homochiral enantiomers under sonication, as well as their racemates (Figure S25),
which resulted in the occurrence of suspension rather than gels. The nanostructures of
LFDF, DFLF produced nanofibers, and mFmF presented large bundles of fibers after
heating-cooling (Figure S26).
Figure 6. Morphologies of nanofibers based on organogels in ethanol: (a) LFLF, (b) DFDF,
(c) MFMF, (d) LFDF, (e) DFLF, and (f) mFmF. Gels of a-c and d-f obtained by heating-
cooling and sonication, respectively. Insets in a-b and d-e were their corresponding TEM
images.
In view of the SEM results in concert with gelation behaviors and rheological
strength, we could speculate that the molecular chirality significantly affect the
intermolecular packing geometry, leading to distinct self-assembled nanostructures.
Ultimately, these subtle alteration in morphologies could account for the differences
observed in the corresponding macroscopic gelation behaviors. To better understand
the gelation driving forces within the individual assembled gels, ATR-FTIR and
temperature-dependent 1H-NMR were performed. On account of the identical gelation
16
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abilities of enantiomeric pairs, the investigation on gelation mechanism were focused
on LFLF, LFDF, MFMF and mFmF hereinafter.
FTIR spectra provide valuable information on the hydrogen bonding interactions.
Herein, ATR-FTIR of the LFLF, LFDF, MFMF and mFmF organogels prepared with
ethanol-D6, and their corresponding solution state in DMSO-D6, were detected
carefully. All gelators in the monomer state presented nearly identical characteristic
peaks at 1718, 1676, 1651 and 1543 cm-1 (Figure 7a and S27). In comparison, distinct
variations of spectra were obtained in their gel state. The peaks at around 1633 cm-1
attributed to the hydrogen bonded stretching frequency of the amide group close to
benzene core were presented in all gels, while the peak intensity for H-bonded amide
C=O located in the periphery was much stronger for LFLF and MFMF gels than that
within LFDF and mFmF gels. This indicated the existence of relative weaker hydrogen
bonding interactions formed from terminal amide group among heterochiral gelators
and their racemates. Meanwhile, the peaks in the range of 1750-1700 cm-1 belong to
C=O stretching vibration of terminal carboxyl groups displayed opposite shift tendency.
A small bathochromic-shift occurred for LFLF and MFMF gels from 1718 to 1715 cm-
1, while a significant hypochromatic shift happened to LFDF and mFmF gels from 1718
to 1730 cm-1. This result suggested that different intermolecular interactions originated
from carboxyl were existed among the gelators, which likely to play a critical role on
their gelation properties. Besides, compared with the single peak at 1541 cm-1 assigned
to amide N-H bending vibration in pure LFLF and LFDF gels, an obvious peak splitting
phenomenon along with red-shift was emerged. This might be due to the stronger and
multiple hydrogen bonds between enantiomers with opposite stereochemical centres in
the racemic mixtures.
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Chemistry - A European Journal
Figure 7. ATR-FTIR spectra and temperature-dependent 1H-NMR of LFLF, LFDF, MFMF
and mFmF gels in etanol-D6.
Apart from the different hydrogen bonds existed within the gels, it was rational to
anticipate that aromatic interactions could be affected simultaneously owing to various
chiralities. To verify this assumption, the temperature-dependent 1H-NMR experiments
were further carried out on ethanol-D6 gels. In the range of 7.8-7.0 ppm, two types of
aromatic protons assigned to benzene core (H1: around 7.737 ppm) and phenylalanine
residues (H2: around 7.260 ppm) were confirmed in the gel state at 300 K, respectively.
When increasing temperature, along with the sharpening of the peaks, the both relevant
peaks moved upfield gradually for all the four gels (Figure 7b and S28). Obviously,
both these two benzenes were involved in aromatic interactions during the gelation of
LFLF and MFMF. On the contrary, for LFDF and mFmF gels, H1 showed similar
upfield shift with that of LFLF and MFMF, while H2 exhibited downfield shift
unexpectedly. The different outcomes happened to phenylalanine residues were most
likely to be the result of various π-π stacking patterns, where LFLF and MFMF
preferred to adopt J-aggregation, while H-aggregation were dominant in LFDF and
mFmF gels.[61]
Conclusions
In summary, four series of dipeptide-based derivatives with various amino acid
sequences and chiral centres were designed and synthesized. The handedness of the
twisted nanofibers was merely dictated by the chirality of amino acid conjugated to
benzene core. The diameters and helical pitches could be facilely regulated by altering
the amino acid sequences and the stereochemistry of peripheral amino acid.
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Furthermore, it was find that homochiral and heterochiral enantiomers could form
organogels with the assistance of heating-cooling and sonication, respectively.
However, suspension or solution (precipitates) instead of gels would be observed when
reversing the processing methods. The decisive role of amino acid chirality on its
supramolecular chirality and gelation properties could be attributed to the various
hydrogen bonding, aromatic interactions and steric hindrance. The above observations
on chiral transformation and amplification would be significantly beneficial in guiding
us fabricate chiral nano-materials with desirable handedness and controllable sizes. In
addition, the investigation of gelation property of dipeptide-based gelators, especially
the heterochiral gelators and racemates would largely expand the potential applications
due to the unique nature of D-amino acids.
Experimental section
Materials:
BOC-L/D-phenylalanine (BOC-L/D-Phe-OH), BOC-L/D-alanine, L/D-phenylalanine
methyl ester hydrochloride (H-L/D-Phe-OMe·HCl), L/D-alanine methyl ester
hydrochloride, were purchased from J&K; 1-hydroxybenzotriazole (HOBt), N-(3-
himethylaminopropyl)-n'-ethylcarbodiimide
hydrochloride
(EDCI),
N;N-
diisopropylethylamine (DIEA), 1,4-benzenedicarbonyl chloride, trifluoroacetic acid
(TFA), dichloromethane (DCM), triethylamine (Et3N), methanol, sodium hydroxide
(NaOH), sodium bicarbonate (NaHCO₃), citric acid, sodium chloride (NaCl), those
chemicals were purchased from Aladdin. All the chemicals used without further
purification.
Synthesis of Dipeptide-based Derivatives
The synthesis of the target products mainly involves four steps described in Scheme S1
in Supporting Information. Take the preparation of LFLF as a typical example. Firstly,
conventional solution-phase approaches for dipeptide synthesis were utilized: Boc-L-
Phe-OH (2.66 g, 10 mmol), HOBt (1.76 g, 13 mmol), DIEA (5.56 g, 40 mmol) and H-
Phe-OMe·HCl (2.38g, 11 mmol) were dissolved in dry DCM (100 mL), and stirred
under ice water bath for 30 min. EDCI (3.84 g, 20 mmol) was then added and the
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10.1002/chem.202004533
Chemistry - A European Journal
mixture was further stirred for another 12 h. After washing successively with saturated
citric acid solution, NaHCO₃ solution and brine, the obtained organic phase was dried
over MgSO4. Purification through recrystallization (ethyl acetate/light petroleum)
afforded BOC-L-Phe-L-Phe-OMe (3.62 g, 85%) (1H-NMR in Figure S1). Secondly,
trifluoroacetic acid (TFA, 10.0 mL, 135 mmol) was added to a solution of BOC-L-Phe-
L-Phe-OMe (3.62 g, 8.5 mmol) in dry DCM (10 mL). The reaction was quenched by
adding an excess amount of methanol after 90 min. Evaporation of all solvents under
vacuum afforded H-L-Phe-L-Phe-OMe (2.69 g, 97%) (1H-NMR in Figure S2). Thirdly,
Et3N (5 mL, 36.45 mmol) was added to solution of H-L-Phe-L-Phe-OMe (2.69 g, 8.2
mmol) dissolved in dry CH2Cl2 (50 mL), following by adding 1,4-benzenedicarbonyl
dichloride (0.81 g, 4.0 mmol) dropwise. Precipitates formed overnight at room
temperature, which was filtered off and washed in ethanol and dried to give pure
product P-L-Phe-L-Phe-OMe (2.28 g, 71%) (1H-NMR in Figure S3). Finally, for the
hydrolysis, aqueous NaOH (30 mL, 2M) was added to a cooled suspension of P-L-Phe-
L-Phe-OMe (2.28 g, 2.9 mmol) in methanol (30 mL). The mixture was stirred for 24
hours at room temperature and acidified with 2 M HCl solution until pH value no more
than 3.0. The precipitate was collected and dried under vacuum to give the product
LFLF (1.82 g, 83%).
The other 15 molecules (LFDF, DFDF, DFLF, LFLA, LFDA, DFDA, DFLA, LALF,
LADF, DADF, DALF, LALA, LADA, DADA, and DALA) with various amino acid sequences
and chiral centres were synthesized in the same way for the synthesis of LFLF.
Hydrogel Preparation.
LFLF (4.0 mg mL−1) was suspended in ethanol with a septum-capped 5.0 mL glass vial
and heated until a transparent solution was obtained. The solution was turned into
organogel after cooling to room temperature. The gels from DFDF and MFMF gelators
could be obtained in the same way with LFLF gel. As for LFDF, DFLF and mFmF (4.0
mg mL−1), sonication were exerted for gel formation.
Characterization of self-assemblies
Field emission scanning electron microscopy (FE-SEM)
FE-SEM measurements were carried out using an FEI QUANTA 250 microscope.
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10.1002/chem.202004533
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Samples were prepared by depositing the as-prepared solution (0.1 wt%) or gels (0.4
wt%) on silicon slice, dried in air at room temperature overnight and sprayed with a
thin gold layer.
Transmittance electron microscopy (TEM)
A 4 μL aliquot of the sample was pipetted onto each grid. After 60 s adsorption the
excess was wiped away using filter paper. Grids were dried under infrared lamp for 5
min. Samples were examined using a Tecnai G2 Spirit Biotwin at an operating voltage
of 120 kV.
Circular dichroism (CD) spectroscopy
The CD spectra of self-assemblies were measured using a JASCO J-815 CD
spectrometer with bandwidth of 1.0 nm in the UV region (200-400 nm). For the CD of
the film, in order to keep the film thickness same, we chose the quartz slide with a
groove on it, and then fixed amount solution (100 mL) was added into the groove, and
dried at room temperature. The molecular solution and organogel were measured in 0.1
mm quartz cuvette. Measurements were repeated 3 times to reduce the noise near 200
nm, their average were plotted.
Vibrational circular dichroism (VCD) spectra
VCD spectra were obtained by BioTools using a ChiralIR-2X Fourier transform
VCD (FT-VCD) spectrometer equipped with an MCT detector and the Dual PEM
option for enhanced VCD baseline stability. VCD spectra were acquired at a resolution
of 4 cm-1 by co-adding 300 scans. The solution samples (at a concentration of 1.0 mg
mL-1) were dried under infrared lamp after coating on a CaF2 wafer that is subsequently
placed in a variable path length cell with CaF2 windows.
Rheology
The rheological properties of hydrogels were measured with a rotary rheometer
(KINEXUS LAB+, Malvern Company, UK). The measurements were performed using
a dynamic frequency sweep test with 0.1% strain over a range of frequencies (0.1-100
rad/s), a temperature controller was connected to the rheometer to maintain a
o
temperature of 25 C. Gels were freshly prepared by heating-cooling method or
sonication methods and directly poured on the rheometer. Data acquisition was repeated
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10.1002/chem.202004533
Chemistry - A European Journal
in triplicate, and average values were plotted.
Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR)
FTIR spectra were collected in transmission mode on a Thermofisher Nicolet iS5 FTIR
spectrometer. Samples dissolved in DMSO-D6 or organogels in ethanol-D6 were
placed on diamond ATR windows and covered with a Teflon spacer. For each sample
64 scans were collected from 1800 to 1500 cm-1 and averaged in order to obtain a good
signal-to-noise ratio. Spectra of DMSO-D6 or ethanol-D6 were collected as
background and subtracted from the sample spectra.
Acknowledgments
The authors thank the National Nature Science Foundation of China (NSFC 51833006),
the Innovation Program of Shanghai Municipal Education Commission
(201701070002E00061), the Science and Technology Commission of Shanghai
Municipality (STCSM, No. 19441903000, 19ZR1425400), and SJTU Trans-med
Awards Research (NO. WF540162603).
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
Key words: dipeptide, molecular chirality, self-assembly, chiral nanostructures,
supramolecular organogel
References
[1] M. Liu, L. Zhang and T. Wang, Chem. Rev. 2015, 11, 57304-7397.
[2] H. Liu, B. Pang, R. Garces, R. Dervisoglu, L. Chen, L. Andreas and K. Zhang, Angew. Chem. Int.
Ed. 2018, 57, 16323-16328.
[3] P. Duan, H. Cao, L. Zhang and M. Liu, Soft Matter 2014, 10, 5428-5448.
[4] A. Ajayaghosh, R. Varghese, S.J. George and C. Vijayakumar, Angew. Chem. Int. Ed. 2006, 45,
1141-1144.
[5] S. Goskulwad, D.D. La, M.A. Kobaisi, S.V. Bhosale, V. Bansal, A. Vinu, K. Ariga and S.V. Bhosale,
Sci. Rep. 2018, 8, 11220.
[6] D.J. van Dijken, P. Stacko, M.C.A. Stuart, W.R. Browne and B.L. Feringa, Chem. Sci. 2017, 8,
1783-1789.
[7] Z. Shen, Y. Sang, T. Wang, J. Jiang, Y. Meng, Y. Jiang, K. Okuro and T. Aida, Nat. Commun. 2019,
22
This article is protected by copyright. All rights reserved.

10.1002/chem.202004533
Chemistry - A European Journal
10, 3976.
[8] C. Hao, R. Gao, Y. Li, L. Xu, M. Sun, C. Xu and H. Kuang, Angew. Chem. Int. Ed. 2019, 58, 7371-
7374.
[9] Y. Zhang, M. Qin, C. Zhao, X. Dou, C. Xing, M. Sun, X. Ma, C. Feng, Carbon 2020, 165, 82-89.
[10] M. Qin, Y. Zhang, J. Liu, C. Xing, C. Zhao, X. Dou, C. Feng, Langmuir 2020, 36, 2524-2533.
[11] J.Y. Liu, F. Yuan, X.Y. Ma, D.I.Y. Auphedeous, C.L. Zhao, C.T. Liu, C.Y. Shen, C.L. Feng, Angew. Chem.
Int. Ed. 2018, 57, 6475-6479.
[12] H. Zheng, T. Yoshitomi, K. Yoshimoto, ACS App. Bio-Mater. 2018, 1, 538-543.
[13] A. Nitti, D. Pasini, Adv. Mater. 2020, 1908021.
[14] A.R. Palmans, E.W. Meijer, Angew. Chem. Int. Ed. 2007, 46 8948-8968.
[15] G. Liu, J. Sheng, H. Wu, C. Yang, G. Yang, Y. Li, R. Ganguly, L. Zhu, Y. Zhao, J. Am. Chem. Soc.
2018, 140, 6467-6473.
[16] M. Wang, P. Zhou, J. Wang, Y. Zhao, H. Ma, J.R. Lu, H. Xu, J. Am. Chem. Soc. 2017, 139, 4185-
4194.
[17] E.E. Greciano, J. Calbo, J. Buendia, J. Cerda, J. Arago, E. Orti, L. Sanchez, J. Am. Chem. Soc.
2019, 141, 7463-7472.
[18] X. Zhang, J. Zou, K. Tamhane, F.F. Kobzeff, J. Fang, Small 2010, 6, 217-20.
[19] X. Lu, Z. Guo, C. Sun, H. Tian, W. Zhu, J. Phy. Chem. B 2011, 115, 10871-10876.
[20] A. Sánchez-Ferrer, J. Adamcik, R. Mezzenga, Soft Matter 2012, 8, 149-155.
[21] Y. Zhao, W. Yang, D. Wang, J. Wang, Z. Li, X. Hu, S. King, S. Rogers, J.R. Lu, H. Xu, Small 2018,
14, 1703216.
[22] C. Zhou, Y. Ren, J. Han, X. Gong, Z. Wei, J. Xie, R. Guo, J. Am. Chem. Soc. 2018, 140, 9417-9425.
[23] Y. Sang, P. Duan and M. Liu, Chem. Commun. 2018, 54, 4025-4028.
[24] S.T. Wang, Y. Lin, R.K. Spencer, M.R. Thomas, A.I. Nguyen, N. Amdursky, E.T. Pashuck, S.C.
Skaalure, C.Y. Song, P.A. Parmar, R.M. Morgan, P. Ercius, S. Aloni and R.N. Zuckermann, ACS
nano 2017, 11, 8579-8589.
[25] C. Li, K. Deng, Z. Tang, L. Jiang, J. Am. Chem. Soc. 2010, 132, 8202-8209.
[26] H. Choi, K.J. Cho, H. Seo, J. Ahn, J. Liu, S.S. Lee, H. Kim, C. Feng, J.H. Jung, J. Am. Chem. Soc.
2017, 139, 17711-17714.
[27] Z. Huang, S.K. Kang, M. Banno, T. Yamaguchi, D. Lee, C. Seok, E. Yashima and M. Lee, Science
2012, 337, 1521-1526.
[28] X. Zhu, Y. Li, P. Duan, M. Liu, Chem. Eur. J. 2010, 16, 8034-8040.
[29] M. Qin, Y. Li, Y. Zhang, C. Xing, C. Zhao, X. Dou, Z. Zhang, C. Feng, Small 2020, e2004756.
[30] H. Jiang, Y. Jiang, J. Han, L. Zhang and M. Liu, Angew. Chem. Int. Ed. 2019, 58, 785-790.
[31] Y. Wang, W. Qi, R. Huang, X. Yang, M. Wang, R. Su and Z. He, J. Am. Chem. Soc. 2015, 137, 7869-
7880.
[32] A.J. Markvoort, H.M. ten Eikelder, P.A. Hilbers, T.F. de Greef and E.W. Meijer, Nat. Commun.
2011, 2, 509.
[33] H. Cao and S. De Feyter, Nat. Commun. 2018, 9, 3416.
[34] S.K. Jha, K.S. Cheon, M.M. Green and J.V. Selinger, J. Am. Chem. Soc. 1999, 121, 1665-1673.
[35] T. Tachibana, H. Kambara, J. Am. Chem. Soc. 1965, 87, 3015-3106.
[36] Q. Xing, J. Zhang, Y. Xie, Y. Wang, W. Qi, H. Rao, R. Su and Z. He, ACS Nano 2018, 12, 12305-
12314.
[37] X. Zhu, Y. Jiang, D. Yang, L. Zhang, Y. Li and M. Liu, Chem. Sci. 2019, 10, 3873-3880.
23
This article is protected by copyright. All rights reserved.

10.1002/chem.202004533
Chemistry - A European Journal
[38] Y. Li, A. Hammoud, L. Bouteiller and M. Raynal, J. Am. Chem. Soc. 2020, 142, 5676-5688.
[39] S. Marchesan, C.D. Easton, K.E. Styan, L.J. Waddington, F. Kushkaki, L. Goodall, K.M. McLean,
J.S. Forsythe, P.G. Hartley, Nanoscale 2014, 6, 5172-5180.
[40] K. Basu, A. Baral, S. Basak, A. Dehsorkhi, J. Nanda, D. Bhunia, S. Ghosh, V. Castelletto, I.W.
Hamley, A. Banerjee, Chem. Commun. 2016, 52, 5045-5048.
[41] K.J. Nagy, M.C. Giano, A. Jin, D.J. Pochan and J.P. Schneider, J. Am. Chem. Soc. 2011, 133, 14975-
14977.
[42] S. Basak, I. Singh, A. Ferranco, J. Syed and H.B. Kraatz, Angew. Chem. Int. Ed. 2017, 56, 13288-
13292.
[43] J. Zhou, X. Du, J. Li, N. Yamagata, B. Xu, J. Am. Chem. Soc. 2015, 137, 10040-10043.
[44] J. Shi, X. Du, D. Yuan, J. Zhou, N. Zhou, Y. Huang, B. Xu, Biomacromolecules 2014, 15, 3559-3568.
[45] M.T. Jeena, K. Jeong, E.M. Go, Y. Cho, S. Lee, S. Jin, S.W. Hwang, J.H. Jang, C.S. Kang, W.Y. Bang,
E. Lee, S.K. Kwak, S. Kim and J.H. Ryu, ACS Nano 2019, 13, 11022-11033.
[46] L. Zhang, J. Qin, S. Lin, Y. Li, B. Li and Y. Yang, Langmuir 2017, 33, 10951-10957.
[47] Y. Fu, B. Li, Z. Huang, Y. Li and Y. Yang, Langmuir 2013, 29, 6013-6017.
[48] K. Lv, L. Zhang, W. Lu and M. Liu, ACS Appl. Mate. Inter. 2014, 6, 18878-18884.
[49] X. Chen, Z. Huang, S.Y. Chen, K. Li, X.Q. Yu and L. Pu, J. Am. Chem. Soc. 2010, 132, 7297-7299.
[50] N. Berova, L. Di Bari and G. Pescitelli, Chem. Soc. Rev. 2007, 36, 914-931.
[51] H. Cao, X. Zhu and M. Liu, Angew. Chem. Int. Ed. 2013, 52, 4122-4126.
[52] G.F. Liu, L.Y. Zhu, W. Ji, C.L. Feng and Z.X. Wei, Angew. Chem. Int. Ed. 2016, 55, 2411-2415.
[53] G. Liu, X. Li, J. Sheng, P.Z. Li, W.K. Ong, S.Z.F. Phua, H. Agren, L. Zhu and Y. Zhao, ACS Nano 2017,
11, 11880-11889.
[54] J. Sadlej, J.C. Dobrowolski, J.E. Rode, Chem. Soc. Rev. 2010, 39, 1478-1488.
[55] K. McAulay, B. Dietrich, H. Su, M.T. Scott, S. Rogers, Y.K. Al-Hilaly, H. Cui, L.C. Serpell, A.M.
Seddon, E.R. Draper, D.J. Adams, Chem. Sci. 2019, 10, 7801-7806.
[56] R. Amemiya, M. Mizutani, M. Yamaguchi, Angew. Chem. Int. Ed. 2010, 49, 1995-1999.
[57] X. Caumes, A. Baldi, G. Gontard, P. Brocorens, R. Lazzaroni, N. Vanthuyne, C. Troufflard, M. Raynal,
L. Bouteiller, Chem. Commun. 2016, 52, 13369-13372.
[58] V. Caplar, L. Frkanec, N. Sijakovic Vujicic, M. Zinic, Chem. Euro. J. 2010, 16, 3066-3082.
[59] L. Wang, X. Jin, L. Ye, A.Y. Zhang, D. Bezuidenhout, Z.G. Feng, Langmuir, 2017, 33, 13821-13827.
[60] K. Nagy-Smith, P.J. Beltramo, E. Moore, R. Tycko, E.M. Furst and J.P. Schneider, ACS Cent. Sci.
2017, 3, 586-597.
[61] A. Ajayaghosh, C. Vijayakumar, R. Varghese and S.J. George, Angew. Chem. Int. Ed. 2006, 45,
456-460
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Table of Content
For C2-symmetrical dipeptide-based derivatives bearing various amino acid
sequences and different chiralities, their supramolecular chirality is only determined by
the amino acid adjacent to the benzene core and irrespective of the absolute
configuration of C-terminal amino acid.
25
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