Dou Et Al 2020 Supramolecular Hydrogels With Tunable Chirality For Promising Biomedical Applications
Dou Et Al 2020 Supramolecular Hydrogels With Tunable Chirality For Promising Biomedical Applications
Dou Et Al 2020 Supramolecular Hydrogels With Tunable Chirality For Promising Biomedical Applications
org/accounts Article
Cite This: Acc. Chem. Res. 2020, 53, 852−862 Read Online
of molecular units play a crucial role in a wide diversity of biochemical reactions (e.g.,
gene replication, molecular recognition, ion transport, enzyme catalysis, and so on).
However, the importance of supramolecular chirality and its potential biofunctions has
not yet been fully explored. Thus, generating chiral assembly to transfer nature’s chiral
code to artificial biomaterials is expected to be utilized for developing novel functional
biomaterials. As one of the most commonly used biomaterials, supramolecular hydrogels
have attracted considerable research interest due to their resemblance to the structure and
function of the native extracellular matrix (ECM). Therefore, the performance and
manipulation of chiral assembled nanoarchitectures in supramolecular hydrogels may
provide useful insights into understanding the role of supramolecular chirality in biology.
In this Account, recent progress on chiral supramolecular hydrogels is presented, including how to construct and regulate assembled
chiral nanostructures in hydrogels with controllable handedness and then use them to develop chiral hydrogels that could be applied
in biology, biochemistry, and medicine. First, a brief introduction is provided to present the basic concept related to supramolecular
chirality and the importance of supramolecular chirality in living systems. The chiral assemblies in supramolecular hydrogels are
strongly driven by noncovalent interactions between molecular building blocks (such as hydrogen bonding, π−π stacking,
hydrophobic, and van der Waals interactions). Consequently, the handedness of these chiral assemblies can be regulated by many
extra stimuli including solvents, temperature, pH, metal ions, enzymes, and photoirradiation, which is presented in the second
section. This manipulation of the chirality of nanoarchitectures in supramolecular hydrogels can result in the development of
potential biofunctions. For example, specific supramolecular chirality-induced biological phenomena (such as controlled cell
adhesion, proliferation, differentiation, apoptosis, protein adsorption, drug delivery, and antibacterial adhesion) are presented in
detail in the third section. Finally, the outlook of open challenges and future developments of this rapidly evolving field is provided.
This account that highlights the diverse chirality-dependent biological phenomena not only helps us to understand the importance of
chirality in life but also provides new ideas for designing and preparing chiral materials for more bioapplications.
Figure 1. Schematic representation of chiral supramolecular hydrogels assembled from molecular building blocks.
Figure 2. Schematic illustration of chirality regulation through different external stimuli. (a) Solvent-induced inversion of supramolecular chirality.
Left-handed (M) helical nanofibers formed in ethanol (EtOH) and acetonitrile (ACN). Right-handed (P) helical fibers formed in toluene,
dichloromethane (DCM), trichloromethane (TCM), and benzene. Reproduced from ref 14. Copyright 2018, American Chemical Society. (b)
Individual chiral molecules self-assemble into helical nanofibers and form chiral hydrogels upon decreasing the temperature from 90 to 20 °C. Circular
dichroism (CD) signals are obviously enhanced by the formation of helical nanofibers. Reproduced from ref 19. Copyright 2017, American Chemical
Society. (c) Right-handed (P) helical fibers formed in solution below pH 7.0. Meanwhile, left-handed (M) helical fibers formed in solution above pH
7.0. Reproduced from ref 22. Copyright 2019, Elsevier Ltd. (d) Varied chiral nanostructure assembled from L-amino acid derivatives (LPF and LPPG)
with different metal ions. Reproduced from ref 23. Copyright 2019, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
some diseases including prion Alzheimer’s disease, Creutzfeldt- and their promising biomedical applications (Figure 1). We
Jakob disease, and Parkinson’s disease. Inspired by these highly conclude by providing solutions to the remaining challenges in
sophisticated supramolecular chiral structures and their the design and preparation of chiral supramolecular hydrogels
corresponding biological events, a challenge and potential and offering perspectives on future developments in this rapidly
research direction for chemistry, materials science, and biology evolving field. This account is expected to open up a broad
has been to construct biomimetic supramolecular assemblies perspective for the development of chiral supramolecular
with tunable chirality. Hydrogels constructed by supramolecular hydrogels with desirable chirality and provide comprehensive
assemblies are one of the most attractive materials that resemble insight into the controllable chiral assemblies with specific use as
native ECM.8 In particular, unlike conventional polymeric biomaterials.
hydrogels made by covalently cross-linked polymers, supra-
molecular hydrogels are formed by noncovalent interactions 2. REGULATION OF CHIRALITY IN SUPRAMOLECULAR
such as hydrogen bonding, π−π stacking, the van der Waals HYDROGELS
force, or hydrophobic interaction. On account of the inherent The flexibility of supramolecular assemblies makes their chirality
reversibility of noncovalent interactions, supramolecular hydro- easy to regulate by many extra stimuli (Figure 2). In this section,
gels respond well to extra stimuli (e.g., temperature, solvent, pH, a number of external factors controlling the chirality of
enzymes, and light) and biochemical cues and can provide a assemblies are considered, such as solvent, light, temperature,
dynamic environment for cell growth.9 In this regard, the pH, and sonication, which are of key importance to supra-
performance and manipulation of chiral assembled nano- molecular assemblies. There are several reviews available that
architectures in supramolecular hydrogels may provide useful provide a further detailed and comprehensive understanding of
insights into mimicking the structure and functions of the regulation of supramolecular chirality.1,10−13
biosystems and understanding the role of supramolecular 2.1. Solvent
chirality in biology. Solvent is a basic medium for assembly and can modify the
In this Account, we introduce and discuss the construction spatial configuration of assembled nanostructures via solvent−
and regulation of chiral assemblies in supramolecular hydrogels solute interactions and consequently modulate the chirality of
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assemblies. Hence, the adjustment of solute−solvent inter- temperature due to the large difference between the periphery
actions can result in the modulation of chiral assembled and the center.
structures in supramolecular gels. For example, the polarity of Considering the biomedical applications, the chirality
the solvent is found to be the reason for the reversal of chirality regulation in supramolecular hydrogels by varying temperature
in alanine inferred gels (Figure 2a).14 The gel of LPA (L-alanine- is better done in a physiological range (20−42 °C) of
based gelator) in ethanol (EtOH) or acetonitrile (ACN) temperature so as to provide more possibilities for carrying
obtained via the heating−cooling process exhibits left-handed out biorelated functions.
(M) twisted ribbons. Right-handed (P) twisted ribbons are 2.3. pH Value
observed for LPA/toluene, LPA/dichloromethane (DCM),
LPA/trichloromethane (TCM), and LPA/benzene. For the Hydrogen bonding between the hydrogelator and water
DPA (D-alanine-based gelator), the right-handed (P) twisted molecules can be regulated by changing the pH of the solvent.
ribbons are achieved in EtOH and ACN via heating−cooling Such hydrogen bonding interactions may cause different
treatment. By contrast, left-handed (M) twisted ribbons are arrangements of molecules, leading to an inversion of helicity.
observed for DPA/toluene, DPA/DCM, DPA/TCM, and For example, Nafie with co-workers report the change in insulin
DPA/benzene. The basic component of the chiral reversal is fibrils from one handedness to another by a subtle pH change.21
that solvent polarity changes the hydrogen bonding among They find that the sign of the vibrational circular dichroism
amide/carboxylic groups, solvent−gelator interactions, and (VCD) is modulated by changing the pH of solution, with left-
consequently, the chirality of assemblies. Similarly, the handed helical filaments produced above pH 2 and right-handed
controlled morphology of chiral self-assembled nanostructures helical filaments below pH 2.
is also achieved by changing the solvent polarity. Interactions In addition, pH-controlled supramolecular chirality is
between gelators and solvents may transform the stacking model achieved by the coassembly of a chiral phenylalanine-based
of the molecules and hence self-assembled nanostructures. Liu et gelator (LPF/DPF) and a poly(acrylamide-co-diallyldimethyl-
al. report that trace amounts of water can trigger the gelation of ammonium chloride) (CPAM) solution.22 Achiral cationic
cationic amphiphiles containing pyridinium and long-chain CPAM can trigger chirality inversion at pH ≥7, while no change
glutamide and the formation of helical tapes or tubes.15 During in the handedness of nanostructures for LPF/DPF itself occurs
at pH <7 (Figure 2c). The reason is that electrostatic
gelation, water hydrates the cationic headgroup, leading to
interactions between CPAM and LPF/DPF change with the
intermolecular hydrogen bond formation with urea, tuning the
change in solvent pH, generating turbulence upon π−π stacking
extent of interdigitation of the alky chains among the gelators
and hydrogen bonding in LPF. Modulating chirality via
and thus generating different chiral structures. Interestingly,
changing the pH should be helpful in in situ or in vitro
with the continuous addition of water, various helical structures
biomedical research if the trigger pH is carried out within the
can transfer into nonhelical nanobelts. This disappearance of
physiological range of pH (i.e., 6−8).
chiral structures is due to the gel collapse as a result of
destabilization of the assembly held by hydrogen bonds. 2.4. Metal Ions
To obtain additional details about the precise control of Metal-ion-triggered supramolecular assembly based on metal
supramolecular architecture concerning molecular self-assem- coordination provides an effective method for the construction
bly, the reader may refer to some quoted references which are of hierarchical structures. Metal coordination has been used for
not for pure hydrogel systems but illustrate chirality modulation the regulation of the chiral structure due to the relative ease of
through various solvents in detail.16,17 Solvent-triggered chirality controlling supramolecular chirality. Our group finds that the
modulation provides an easy way to obtain the desired chiral handedness of helical nanofibers can be successfully regulated by
nanostructures in water−organic gels. Meanwhile, avoiding too using a series of metal ions, as shown in Figure 2d, illustrating the
much toxic organic solvent is also necessary to be considered for study of 1,4-benzene-dicarboxamide (C2) L-phenylalanine-
biological applications. based chiral supramolecular hydrogels.23 For example, the
2.2. Temperature addition of Al3+ can trigger the formation of right-handed
nanotwists; meanwhile, the left-handed twists can be observed
The thermal reversibility of the self-assembly is the basic feature upon addition of Tb3+. Similarly, the self-assembled structures of
of a chiral supramolecular hydrogel since the strengths of cholesterol-azopyridine (PAzPCC) gels are observed to show
noncovalent interactions are temperature-dependent. Heating metal-ion-regulated helix reversal through coordination bonds
molecules in water to be dissolved and cooling to gelation is a between metal cations and pyridine groups.24 Moreover, metal
common approach to preparing supramolecular hydrogels.18 ion coordination interactions between metal ions and carboxyl/
The most popular instances of this thermoregulation in chiral pyridine groups are used to regulate not only the ground-state
assemblies are reported in the supramolecular gels based on chirality but also the excited-state chirality and circularly
hydrogen bonding, in which circular dichroism (CD) signals are polarized luminescence (CPL) of supramolecular assemblies.25
silent in solution as the system temperature is increased (Figure Considering abundant metal-ion-triggered biological responses,
2b).19 Gelation-induced supramolecular chirality is sensitive to these metal-coordination-based chiral supramolecular hydrogels
sol−gel transformation caused by temperature change. More- are of interest in the detection of metal ions, the construction of
over, the pitch of chiral fibers can be tuned by the speed of chiral biomaterials, and so on.
temperature change. Microtwists from achiral X-shaped π-
conjugated molecules exhibit a larger pitch (about 18 μm) at 35 2.5. Other Factors
°C, and the helical pitch becomes smaller at lower temperature Due to the dynamic structure of supramolecular assemblies
(30, 25, 20, and 15 °C).20 This microtwist formation is due to based on relatively weak noncovalent interactions, some other
crystal growth kinetics. An imbalance of the crystal growth rate external stimuli can also be explored to regulate the chirality,
between the center and the edge causes the driving force for such as achiral additives. For example, two achiral bis(pyridinyl)
twisting. Twists with small pitch are produced at lower derivatives (BPy1 and BPy2) can control the handedness in
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Figure 3. (a) Illustration of the 3D cell culture in chiral supramolecular hydrogels. (b) Left column: fluorescence microscopy images of HUVECs in
L(D)PFEG hydrogels after 3 days of culture. Live cells are green, and dead cells are red. Right column: schematic diagram of different cell adhesion and
proliferation in the chiral hydrogels. (c) Quantitative date for HUVECs cultured in L(D)PFEG hydrogels until day 9. Reproduced from ref 31.
Copyright 2014, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. (d) Molecular structure of BA, BE, and BP. Helical direction of self-
assembled nanofibers can be tuned by the number of methylene units. (e) Influences of molecular chirality and supramolecular chirality of assembly on
cell adhesion. Reproduced from ref 32. Copyright 2018, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany.
coassembled nanofibers. The inversion of supramolecular interactions, especially hydrogen bonding and π−π stacking,
chirality of the C2 phenylalanine-based hydrogel is achieved and further cause the chirality inversion. Interestingly, through
simply by exchanging these two coassembled achiral BPy1 and the coassembly of achiral 1,4-bis(pyrid-4-yl)benzene (DPb) and
BPy2 molecules.26 As a participant in supramolecular assembly, chiral C2 L-phenylalanine-glycine (LPPG) derivative gelators,
BPy1 and BPy2 molecules can tune the intermolecular stoichiometry is found to be a key factor for modulating the
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Figure 4. (a) Schematic of chiral nanofibers induced by stem cell differentiation. (b) RT-qPCR quantification suggesting the greatest upregulation of
osteogenic markers (RUNX2, OPN, and BMP2 in the LPFEG hydrogels (abbreviated as L) and the greatest upregulation of adipogenic markers
(PPARG and ADN) in the DPFEG hydrogels (abbreviated as D). (c) Representative microcomputed tomography (μCT) images of bone regeneration
in rat cranial defects after MSC/hydrogel implantation. (d) Evaluations of total bone volume and (e) bone mineral density (BMD) of newly formed
bone tissue. (f) RT-qPCR results suggests Itgα5β1 inhibition leading to the downregulation of FAK, ERK, and YAP. (g) Illustration of cell
differentiation and gene expression induced by the chirality of nanofibers. Reproduced from ref 34. Copyright 2019, Wiley-VCH Verlag GmbH & Co.
KGaA, Weinheim, Germany.
supramolecular chirality inversion.27 This inversion is primarily nm biological window), is of great scientific significance and
due to the subtle balance between intermolecular hydrogen practical value in the field of biology.
bonding interactions and the π−π stacking of DPb and LPPG
molecules, in turn, the handedness of assembled nanofibers. 3. BIOMEDICAL APPLICATIONS OF
Interestingly, meso achiral cycloalkane-based bisamide SUPRAMOLECULAR HYDROGELS
molecules are reported to form chiral aggregates without the Chirality exists widely in living systems, which has been found to
addition of any additives, only under sonication.28 The reason is be closely related to many physiological processes. The
stochastic symmetry breaking induced by sonication. Addition- manipulation of the chirality of nanoarchitectures in supra-
ally, Xu et al. report the preparation of chiral peptide-based molecular hydrogels provides a promising way to develop
supramolecular hydrogels by using an enzyme trigger.29 potential functions of chiral biomaterials. On the basis of this,
Precursors are usually formed by coupling a hydrophilic segment tunable chiral motifs and sophisticated helical structures in the
such as a phosphate group onto an L- or D-peptide-based supramolecular hydrogels are very useful in biological research.
hydrogelators. These precursors can convert to chiral hydro- 3.1. Cell Adhesion and Proliferation
gelators upon elimination of the hydrophilic group by enzyme-
Cell adhesion plays an essential role in cell communication and
catalyzed bond cleavage and then self-assemble into chiral proliferation. C2-symmetric amino acid-based gelators are an
peptide hydrogels. alternative for achieving cell culture materials with both tunable
Moreover, photoirradiation is another noninvasive, simple, supramolecular chirality and good biocompatibility.8 A chiral
and quick trigger that is often used to adjust supramolecular hydrogel system for three-dimensional (3D) cell culture is
structures.30 Light-induced supramolecular assembly that is fabricated by two enantiomers of phenylalanine-based gelators
suitable for in vivo applications requires the light source to have (LPFEG and DPFEG; Figure 3).31 Compared to nanofibers
deep tissue penetration while being innocuous to cells. Because with right handedness (P-type), left-handed (M-type) helical
of reduced absorption, minimal scattering, and negligible nanofibers can enhance the adhesion and proliferation of human
autofluorescence, near-infrared (NIR) light (at wavelengths umbilical vein endothelial cells (HUVECs) and mouse
750−2500 nm) has advantages in deep tissue penetration, low embryonic fibroblast cell line (NIT3T3) because of increased
cytotoxicity, and high-resolution imaging. Consequently, the fibronectin adsorption on the left-handed helical fibers. Cell
chirality control in supramolecular hydrogels by NIR light, adhesion and proliferation on material surfaces are complex
especially NIR-II light (deeper penetration in the 1000−1400 processes that need the collaboration of various intracellular and
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Figure 5. (a) Molecular structure of peptide-based precursor (1P) and monomer (1). (b) Schematic representation of enzyme-instructed nanofibers
for targeting mitochondria and triggering cancer cell apoptosis. Reproduced from ref 36. Copyright 2016, American Chemical Society.
extracellular proteins. Due to the highly chiral selectivity of the formation of new bone in vivo (Figure 4c−e). Further
amino acids that constitute proteins, it is reasonably speculated molecular analysis reveals that the left-handed chirality of 3D
that hydrogel chirality influences cell adhesion and proliferation fibers promotes the clustering of the Itgα5 mechansensor while
through the stereospecific interaction between the chiral matrix righted-handedness weakens this effect, which directs hetero-
and proteins. geneous differentiation (Figure 4f,g). Molecular simulations
In addition, the chirality of helical nanofibers based on C2- demonstrate that diverse cell differentiation is initiated by
symmetric L-phenylalanine derivatives (BA, BE, and BP) can be different protein adsorptions on different chiral hydrogels. The
regulated by the number of methylene units (Figure 3d).32 interaction of cell surface proteins with extracellular compo-
Enhanced cell adhesion and proliferation on left-handed nents further induces a complex intracellular signaling cascade.
nanofibers compared to those on right-handed nanofibers are Interestingly, Zouani et al. find that even if the handedness of
observed, even though both nanofibers are derived from L- helical fibers is the same, different nanohelical shapes and
phenylalanine derivatives (Figure 3e). It clearly suggests that not pitches still show the ability to induce MSC differentiation.35
only molecular chirality but also supramolecular chirality has a The helical pitch of 63 nm (±5 nm) with silica ribbon leads to
significant impact on cell adhesion and growth. osteogenic differentiation. In contrast, no osteoblast is observed
3.2. Cell Differentiation on the twisted ribbon with 100 nm (±15 nm) periodicity. This
result provides a potential strategy to promote the osteogenic
Although molecular chirality and helical structures on two- differentiation of MSCs, which can be applied in the material to
dimensional (2D) surfaces have been demonstrated as indirect repair bone tissue.
regulators for stem cell differentiation,33 these 2D materials
cannot accurately mimic the biophysical properties and 3.3. Cell Apoptosis
architecture of natural ECM. We recently demonstrate the Fibrous nanostructures in the chiral hydrogels not only provide
possibility of induced cell differentiation in 3D chiral hydro- cell growth scaffolds but also can play apoptotic inducers to
gels.34 Mesenchymal stem cells (MSCs) are seeded into the 3D target cells. For example, Xu et al. establishes a series of enzyme-
hydrogels by mixing a cell suspension and a dimethyl sulfoxide instructed chiral nanofibers self-assembled from L- or D- peptide
(DMSO) solution of L(D)PFEG gelators. It is found that left- derivatives, exhibiting attractive abilities for inducing the
handed nanofibers (L) from LPFEG favor osteogenesis and apoptosis of cancer cells.36 Ectophosphatases (e.g., alkaline
right-handed nanofibers (D) from DPFEG favor adipogenesis phosphatase (ALP)) overexpressed on cancer cells can trans-
(Figure 4a,b, molecular structure of L(D)PFEG in Figure 3a). form peptide-based precursors (e.g., 1P in Figure 5a) into
Moreover, chiral hydrogels with left-handed fibers can promote nanofibers, which surround the cell membranes and are taken up
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Figure 6. (a) Molecular dynamic simulations of binding between L(D)PFEG and FnIII9-10 protein. (b) Binding structure of L(D)PFEG and FnIII9-10
in the equilibrium state. (c) The binding energy between LPFEG and FNIII9-10 is lower than that between DPFEG and FNIII9-10. Reproduced from
ref 34. Copyright 2019, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (d) Quartz crystal microbalance (QCM) experiments characterizing the
interactions between human serum albumin (HSA) and DPLG and LPLG assemblies. (e) Different protein adhesions based on HSA and gelator
molecule interactions. Reproduced from ref 41. Copyright 2014, American Chemical Society.
by the cancer cells. The normal cellular functions (e.g., lectivity between proteins and chiral molecules, we perform
homeostasis of mitochondria) are disrupted by these nanofibers, molecular dynamic (MD) simulations using fibronectin (FN) as
thus further inducing the death of cancer cells (Figure 5b). a protein model.34 The snapshots show that LPFEG can
Compared to L-peptide-based precursors, D-peptide-based recognize FnIII9-10, which acts as the key cell-adhesion domain
precursors show higher cytotoxicity against most cancer cells of Fn and achieves an equilibrium state within 500 ps, while
(e.g., Saos2), which may originate from the higher proteolytic DPFEG and FnIII9-10 cannot reach a stable binding until 1000
stability of D-peptide fibers compared to that of L-peptide fibers. ps (Figure 6a). Additionally, a greater stereoaffinity for FnIII9-
Moreover, it is found that D-peptide-based precursors are less 10 than for DPFEG is presented (Figure 6b), which is further
cytotoxic than L-peptide-based precursors against T98G cells. supported by the lower interaction energy of the LPFEG/
The reason may be ascribed to the different stereochemical FnIII9-10 complex (Figure 6c).
interactions between cancer cells and chiral assemblies, which Liu et al. utilize gelators containing L/D-pantolactone
may deserve further investigation in future research. Similar (abbreviated as L(D)PLG) to obtain the self-assembly with
results are also reported by Ulijn,37 Maruyama,38 and Yang.39 opposite supramolecular chirality.41 The protein adsorption on
The difference in anticancer activity between L- and D-peptide- these nanostructures is found to be closely related to their
based nanofibers encourages us to further explore the utilization supramolecular chirality (Figure 6d,e). Interestingly, DPLG self-
of chirality of supramolecular assemblies for tumor therapy. assembled nanofibers exhibit a stronger protein adhesive ability
3.4. Protein Adsorption than LPLG nanofibers, while there is no clear difference at the
molecular level.
As mentioned above, protein adsorption is a key mediator in
modulating many cell behaviors. Both molecular chirality and 3.5. Antibacterial Adhesion
supramolecular chirality have shown the ability to regulate The prevention of bacterial adhesion is an important research
protein adsorption onto material surfaces. Sun et al. prepare area, and various strategies have been explored to achieve it.42,43
chiral surfaces containing amino acid enantiomers, proving that Recently, on the basis of the understanding of chiral effects on
the stereoconfiguration of chiral units is an important factor microorganism adhesion, Wang et al. designed a series of chiral
governing the interaction between chiral molecules and surfaces modified with borneol-based polymers for antibacterial
peptides/proteins.40 It is found that the Aβ peptide binds adhesion.44 It was found that the polymers with the camphene-
much more strongly with S-cysteine-modified grapheme oxide type bicyclic structure of borneol exhibit excellent antibacterial
(S-Cys-GO) than with R-cysteine-modified grapheme oxide (R- capability because of several chiral centers located in the
Cys-GO). Compared with R-Cys-GO, S-Cys-GO provides more polymers. The antibacterial adhesion can be achieved through
hydrogen binding sites between the carboxylic/thiol groups and polymer surface stereochemistry. In particular, differences in
Aβ peptides. To gain more insight into the initial enantiose- antibacterial adhesion are found between poly-L-borneolacrylate
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Figure 7. (a) Chemical structures of gelators consisting of D-amino acids (blue) and naproxen (Npx, red). (b) TEM images of hydrogels of (1) Npx-ff,
(2) Npx-ffy, (3) Npx-ffk, (4) Npx-ffky, (5) ffk(Npx), and (6) ffk(Npx)y. Reproduced from ref 48. Copyright 2013, American Chemical Society.
Figure 8. (a) Handedness of CPL for the coassembly of LPF and coumarin derivatives (G), which can be regulated by changing coumarin derivatives
or incorporating metal ions into the coassembly. (b) CPL spectra of LPF/G1 (excitation wavelength: 320 nm). Reproduced from ref 25. Copyright
2019, American Chemical Society. (c) Schematic representation of the coassembly of LPF and 1NA/2/NA. CPL inversion is triggered by alternative
1NA and 2NA. (d) CPL spectra of LPF-1NA/2NA (excitation wavelength: 325 nm). Reproduced from ref 54. Copyright 2019, the Royal Society of
Chemistry.
■
In spite of the significant progress in chiral supramolecular
hydrogels, there are still some challenges to be solved. First, the
design of supramolecular gelators with purpose is still in the early AUTHOR INFORMATION
stage since the mechanism for chiral assembly has not yet been Corresponding Author
clearly revealed. It is difficult to predict the assembly of Chuanliang Feng − State Key Lab of Metal Matrix Composites,
molecules and the handedness of supramolecular structures. In School of Materials Science and Engineering, Shanghai Jiao Tong
particular, the modification of bioactive motifs on original University 200240 Shanghai, China; orcid.org/0000-0001-
gelators often disturbs the balance of intermolecular inter- 6137-5568; Email: [email protected]
actions, resulting in the disintegration of the supramolecular
structures. To better explore chiral hydrogels, a promising future Authors
direction is to utilize molecular dynamics (MD) simulations and Xiaoqiu Dou − State Key Lab of Metal Matrix Composites, School
time-dependent density functional theory (TDDFT) calcula- of Materials Science and Engineering, Shanghai Jiao Tong
tions for predicting the supramolecular chirality of assembly. It is University 200240 Shanghai, China
worth noting that superhelical structures consisting of initial Nabila Mehwish − State Key Lab of Metal Matrix Composites,
helical fibrils may bring about more precision, selectivity, and School of Materials Science and Engineering, Shanghai Jiao Tong
efficiency for their functions.55 The prediction of superhelical University 200240 Shanghai, China
860 https://dx.doi.org/10.1021/acs.accounts.0c00012
Acc. Chem. Res. 2020, 53, 852−862
Accounts of Chemical Research pubs.acs.org/accounts Article
Changli Zhao − State Key Lab of Metal Matrix Composites, (4) Tang, K. J.; Gan, H.; Li, Y.; Chi, L. F.; Sun, T. L.; Fuchs, H.
School of Materials Science and Engineering, Shanghai Jiao Tong Stereoselective Interaction Between DNA and Chiral Surfaces. J. Am.
University 200240 Shanghai, China Chem. Soc. 2008, 130, 11284−11285.
Jinying Liu − State Key Lab of Metal Matrix Composites, School (5) Hanein, D.; Geiger, B.; Addadi, L. Differential Adhesion of Cells to
of Materials Science and Engineering, Shanghai Jiao Tong Enantiomorphous Crystal-Surface. Science 1994, 263, 1413−1416.
(6) Yao, X.; Hy, Y. W.; Cao, B.; Peng, R.; Ding, J. D. Effects of Surface
University 200240 Shanghai, China
Molecular Chirality on Adhesion and Differentiation of Stem Cells.
Chao Xing − State Key Lab of Metal Matrix Composites, School of Biomaterials 2013, 34, 9001−9009.
Materials Science and Engineering, Shanghai Jiao Tong (7) Yeom, J.; Guimaraes, P. P. G.; Ahn, H. M.; Jung, B. K.; Hu, Q. Y.;
University 200240 Shanghai, China McHugh, K.; Mitchell, M. J.; Yun, C. O.; Langer, R.; Jaklenec, A. Chiral
Complete contact information is available at: Supraparticles for Controllable Nanomedicine. Adv. Mater. 2020, 32,
https://pubs.acs.org/10.1021/acs.accounts.0c00012 1903878.
(8) Dou, X. Q.; Feng, C. L. Amino Acids and Peptide-Based
Supramolecular Hydrogels for Three-Dimensional Cell Culture. Adv.
Author Contributions
Mater. 2017, 29, 1604062.
†
These authors contributed equally. (9) Lim, J. Y. C.; Lin, Q.; Xue, K.; Loh, X. J. Recent Advances in
Notes Supramolecular Hydrogels for Biomedical Applications. Mater. Today
Adv. 2019, 3, 100021.
The authors declare no competing financial interest. (10) Yue, B. B.; Zhu, L. L. Dynamic Modulation of Supramolecular
Chirality Driven by Factors from Internal to External Levels. Chem. - Asian
Biographies J. 2019, 14, 2172−2180.
Xiaoqiu Dou received her Ph.D. from Shanghai Jiao Tong University in (11) Xing, P. Y.; Zhao, Y. L. Controlling Supramolecular Chirality in
2015. Currently, she is an assistant professor at Shanghai Jiao Tong Multicomponent Self-Assembled Systems. Acc. Chem. Res. 2018, 51,
2324−2334.
University. Her research interest is stimuli-responsive and chiral
(12) Zhang, L.; Qin, L.; Wang, X. F.; Cao, H.; Liu, M. H. Supramolecular
supramolecular hydrogels for application in biomedical and bio- Chirality in Self-Assembled Soft Materials: Regulation of Chiral
technology fields. Nanostructures and Chiral Functions. Adv. Mater. 2014, 26, 6959−
Nabila Mehwish has been a doctoral student at Shanghai Jiao Tong 6964.
University since 2016. Her research interests include functional chiral (13) Lee, C. C.; Grenier, C.; Meijer, E. W.; Schenning, A. P. H. J.
assemblies. Preparation and Characterization of Helical Self-Assembled Nano-
fibers. Chem. Soc. Rev. 2009, 38, 671−683.
Changli Zhao received his Ph.D. from Shanghai Jiao Tong University (14) Wang, F.; Qin, M. G.; Peng, T.; Tang, X. H.; Dang-i, A. Y.; Feng,
in 2012. He is an assistant research fellow at Shanghai Jiao Tong C. L. Modulating Supramolecular Chirality in Alanine Derived
University. His research interests focus on metallic biomaterials and Assemblies by Multiple External Stimuli. Langmuir 2018, 34, 7869−
supramolecular biohydrogels. 7876.
Jinying Liu received his Ph.D. from Shanghai Jiao Tong University in (15) Liu, C. X.; Jin, Q. X.; Lv, K.; Zhang, L.; Liu, M. H. Water Tuned
the Helical Nanostructures and Supramolecular Chirality in Organo-
2019. He is an assistant research fellow at Henan University. His
gels. Chem. Commun. 2014, 50, 3702−3705.
research is focused on chiral self-assembly. (16) Borovkov, V. V.; Hembury, G. A.; Inoue, Y. The Origin of
Chao Xing is a Ph.D. student at Shanghai Jiao Tong University. His Solvent-Controlled Supramolecular Chirality Switching in a Bis(Zinc
research interests focus on supramolecular hydrogels with high Porphyrin) System. Angew. Chem., Int. Ed. 2003, 42, 5310−5314.
mechanical properties. (17) Mamiya, F.; Ousaka, N.; Yashima, E. Remote Control of the
Planar Chirality in Peptide-Bound Metallomacrocycles and Dynamic-
Chuanliang Feng received his Ph.D. from the University of Twente in to-Static Planar Chirality Control Triggered by Solvent-Induced 310-to-
2005. He is a full professor at Shanghai Jiao Tong University. His α-Helix Transitions. Angew. Chem., Int. Ed. 2015, 54, 14442−14446.
research mainly focuses on functionalized polymeric nanomaterials, (18) Dou, X. Q.; Li, P.; Zhang, D.; Feng, C. L. C2-Symmetric Benzene-
chiral biomaterials, and supramolecular hydrogels. Based Hydrogels with Unique Layered Structures for Controllable
■
Organic Dye Adsorption. Soft Matter 2012, 8, 3231−3238.
(19) Liu, G. F.; Li, X.; Sheng, J. H.; Li, P. Z.; Ong, W. K.; Phua, S. Z. F.;
ACKNOWLEDGMENTS
Agren, H.; Zhu, L. L.; Zhao, Y. L. Helicity Inversion of Supramolecular
The authors thank the National Nature Science Foundation of Hydrogels Induced by Achiral Substituents. ACS Nano 2017, 11,
China (NSFC 51833006), the Innovation Program of Shanghai 11880−11889.
Municipal Education Commission (201701070002E00061), (20) Chen, H. B.; Zhou, Y.; Yin, J.; Yan, J.; Ma, Y. G.; Wang, L.; Cao,
and the Science and Technology Commission of Shanghai Y.; Wang, J.; Pei, J. Single Organic Microtwist with Tunable Pitch.
Municipality (STCSM, no. 19441903000, 19ZR1425400) for Langmuir 2009, 25, 5459−5462.
their financial support. (21) Kurouski, D.; Lu, X.; Popova, L.; Wan, W.; Shanmugasundaram,
■
M.; Stubbs, G.; Dukor, R. K.; Lednev, I. K.; Nafie, L. A. Is
Supramolecular Filament Chirality the Underlying Cause of Major
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