Chiral Nanofibers Research Articles

Chiral Supramolecular Nanofibers Regulated Tumor-Derived Exosomes Secretion for Constructing an Anti-Tumor Extracellular Microenvironment.

Tumor-derived exosomes (TDEs) induced extracellular microenvironment has recently been validated to be critical for tumor progression and metastasis, however, remodeling it for oncotherapy still remains a major challenge due to difficulty in regulation of TDEs secretion. Herein, the supramolecular chiral nanofibers, composed of L/D-phenylalanine derivates (L/D-Phe) and linear hyaluronic acid (HA), are successfully employed to construct TDEs induced anti-tumor extracellular microenvironment. The left-handed L-Phe @HA nanofibers significantly inhibit TDEs secretion into extracellular microenvironment, which results in suppression of tumor proliferation and metastasis in vitro and vivo. Biological assays and theoretical modeling reveal that these results are mainly attributed to strong adsorption of the key exosomes transporters (Ras-related protein Rab-27A and synaptosome-associated protein 23) on left-handed L-Phe @HA nanofibers via enhanced stereoselective interaction, leading to degradation and phosphorylated dropping of exosomes transporters. Subsequently, transfer function of exosomes transporters is limited, which causes remarkable inhibition of TDEs secretion. These findings provide a promising novel insight of chiral functional materials to establish an anti-tumor extracellular microenvironment via regulation of TDEs secretion.

Supramolecular gelators enabling chiral organogels for naked-eye enantiodifferentiation with wide accessibility and applicability

Techniques to acquire chiral information from molecules are essential for deciphering important biological processes and improving the performance of industrial chiral materials. Herein, we report novel supramolecular gelators that enable widely accessible chiral supramolecular organogels for simple naked-eye enantiodifferentiation of specific enantiomers (left- or right-handedness) for wide-range substances. The supramolecular gelators featuring multiple hydrogen-bonding sites and large π-π conjugated groups are produced by complexing commercially available chiral tartaric acids and achiral 1-naphthylmethylamine. The highly polar and insoluble acid-amine complexes drive the aggregation of the supramolecular gelators, which further form chiral nanofibers due to chirality transfer from tartaric acid to the supramolecular nanofibers through multiple hydrogen-bonding between the hydroxyl groups of chiral tartaric acids and π-π stacking between 1-naphthylmethylamine molecules. At high concentrations, physical crosslinking of the chiral nanofibers creates a chiral gel structure that facilitates interactions between its chirally and non-covalently associated components and enantiomers, making the gel system particularly sensitive to specific types of enantiomers. Consequently, sensitive naked-eye detection of specific enantiomers of diverse substances is achieved via observing “gel-to-micelle” transitions, which occurs when the enantiomers generate complexes that disrupt chirality transfer in the co-assembly and destroy the hierarchical structures.

Ultrasound-Directed Symmetry Breaking and Spin Filtering of Supramolecular Assemblies from only Achiral Building Blocks.

Herein we describe the self-assembly of an achiral molecule into macroscopic helicity as well as the emergent chiral-selective spin-filtering effect. It was found that a benzene-1,3,5-tricarboxamide (BTA) motif with an aminopyridine group in each arm could coordinate with AgI and self-assemble into nanospheres. Upon sonication, symmetry breaking occurred and the nanospheres transferred into helical nanofibers with strong CD signals. Although the sign of the CD signals appeared randomly, it could be controlled by using the as-made chiral assemblies as a seed. Furthermore, it was found that the charge transport of the helical nanofibers was highly selective with a spin-polarization transport of up to 45 %, although the chiral nanofibers are composed exclusively from achiral building blocks. This work demonstrates symmetry breaking under sonication and the chiral-selective spin-filtering effect.

Ultrasound‐Directed Symmetry Breaking and Spin Filtering of Supramolecular Assemblies from only Achiral Building Blocks

AbstractHerein we describe the self‐assembly of an achiral molecule into macroscopic helicity as well as the emergent chiral‐selective spin‐filtering effect. It was found that a benzene‐1,3,5‐tricarboxamide (BTA) motif with an aminopyridine group in each arm could coordinate with AgI and self‐assemble into nanospheres. Upon sonication, symmetry breaking occurred and the nanospheres transferred into helical nanofibers with strong CD signals. Although the sign of the CD signals appeared randomly, it could be controlled by using the as‐made chiral assemblies as a seed. Furthermore, it was found that the charge transport of the helical nanofibers was highly selective with a spin‐polarization transport of up to 45 %, although the chiral nanofibers are composed exclusively from achiral building blocks. This work demonstrates symmetry breaking under sonication and the chiral‐selective spin‐filtering effect.

Synergistic Effect of Chiral Nanofibers Amplifying the Orbit Angular Momentum To Enhance Optomagnetic Coupling.

Manipulating magnetic bits by photon in spintronics, opto-magnetic coupling, is lagging far behind what we could expect. To investigate the issue, one should face the problem to find photon dependence of spin dynamics and spin manipulation. In this work, through introducing chiral orbit in organic crystals, circularly polarized photon can manipulate spin via the channel of photon-orbit-spin interactions. Under the stimulus of the magnetic field, strong spin polarization will feed back to the change in polarized state of light. Moreover, twisting several chiral nanofibers into a thick one, a more pronounced opto-magnetic coupling is clearly observed due to the chirality generated larger chiral orbit. Meanwhile, spin dynamics (or spin response times) inside the aggregated thick chiral fiber can be further tuned by circularly polarized light. Hopefully, this study can deepen the understanding of organic chiral spin-photonics and enhance the application of organic functional crystals in the future.

Controlling supramolecular filament chirality of hydrogel by co-assembly of enantiomeric aromatic peptides

Supramolecular chirality plays an indispensable role in living and synthetic systems. However, the generation and control of filament chirality in the supramolecular hydrogel of short peptides remains challenging. In this work, as the first example, we report that the heterodimerization of the enantiomeric mixture controls the alignment, chirality, and stiffness of fibrous hydrogels formed by aromatic building blocks. The properties of the resulting racemic hydrogel could not be achieved by either pure enantiomer. Cryo-EM images indicate that the mixture of L and D enantiomers forms chiral nanofibers, the percentage of which can be readily controlled through stoichiometric co-assembly of heterochiral enantiomers. 2D NOESY NMR and diffusion-ordered NMR spectroscopy reveal that heterodimerization of enantiomers plays a crucial role in the formation of chiral nanofibers. Further mechanistic studies unravel the mechanism of supramolecular chirality formation in this two-component system. Molecular dynamics simulations confirm that the intermolecular hydrogen bond and π–π interaction of heterodimers play important roles in forming a chiral hydrogel. Furthermore, regulation of the adhesion and morphology of mammalian cells is achieved by tuning the relative ratio of L and D enantiomers at the same concentration. This work illustrates a novel strategy to control the supramolecular chirality of aromatic peptide hydrogels for materials science.Graphical

Chirality-influenced antibacterial activity of methylthiazole- and thiadiazole-based supramolecular biocompatible hydrogels

Chiral stereochemistry is a unique and fundamental strategy that determines the interaction of bacteria cells with chiral biomolecules and stereochemical surfaces. The interaction between bacteria and material surface (molecular chirality or supramolecular chirality) plays a significant role in modulating antibacterial performance. Herein, we developed inherent chiral antibacterial hydrogels by modifying the carboxyl groups of our previously reported supramolecular gelator (LPF-left handed phenylalanine gelator and DPF- right handed phenylalanine gelator) with 2-amino-5-methylthiazole (MTZ) and 5-amino-1,3,4-thiadiazole-2- thiol (TDZ). The new L/D-gelator molecules initiate self-assembly to form hydrogels through non-covalent interactions (Hydrogen bonding and π-π interactions) verified by FTIR and CD spectroscopy. Morphological studies of the xerogels revealed left and right-handed chiral nanofibers for the gelators' L-form and D-form, respectively. The resulting hydrogels exhibited inherent antibacterial activity against Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria, with TDZ hydrogels showing more significant antibacterial activity than MTZ hydrogels. Interestingly, the D-form (having right-handed nanofibers) of both hydrogels (MTZ and TDZ) exhibited higher antibacterial activities compared with the left-handed nanofibrous hydrogels (L-form) attributed to the stereoselective interaction of the chiral helical nanofiber. Moreover, the amplification of chirality moving from a molecular to a supramolecular level essentially improved the antibacterial action. Our results provide deep insight into the development of unique supramolecular chiral antimicrobial agents and hint at the potentiality of right-handed nanofibers (D-form) having enhanced antibacterial activity. Statement of significanceChiral stereochemistry plays a significant role in many biological processes, which determines the interaction of bacteria cells with chiral biomolecules. The interaction between bacteria and material surface (molecular chirality or supramolecular chirality) plays a significant role in modulating antibacterial performance. Here, we deigned and synthesized unique inherent biocompatible supramolecular chiral hydrogel. From this study we concluded that the D-form (having right-handed nanofibers) of hydrogels exhibited higher antibacterial activities compared with the left-handed nanofibrous hydrogels (L-form) attributed to the stereoselective interaction of the chiral helical nanofiber. Additionally, this study also explored the amplification of chirality moving from a molecular to a supramolecular level essentially improved the antibacterial action.

Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/d-phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

Controlling Helical Pitch of Chiral Supramolecular Nanofibers Composed of Two Amphiphiles

Abstract In a previous work, we demonstrated that an amidoamine amphiphile with a stearyl group as the alkyl chain (C18AA) and 12-hydroxystearic acid (HSA) can produce hydrogels consisting of self-assembled chiral nanofibers with a homogeneous helical structure. In this work, we investigate the effect of introducing a double bond into the alkyl chain, i.e., substituting the oleyl group for a stearyl group, on the formation of the hydrogel and the structure of the chiral nanofibers. Combining the amphiphile with the oleyl group (OleylAA) and HSA produced hydrogels, although the self-assembled chiral nanofibers in the hydrogels had a different composition, helical pitch, and diameter than those formed by C18AA and HSA mixtures. Further, we demonstrate that the chiral nanofibers can be used as a soft template for preparing chiral Au nanowires.

Facile formation of chiral nanofibers with excellent electrochemical performance via self-assembly of carbon dots and cysteine molecules.

Novel chiral nanofibers with a strong chiroptical response have been facilely synthesized via self-assembly of negatively charged carbon dots (CDs) and cysteine molecules. Besides a strong chiroptical response, the chiral hybrid nanofibers also exhibit excellent catalytic performance in lithium-oxygen batteries.

A self-assembled photoresponsive gel consisting of chiral nanofibers.

A novel compound based on a glutamic acid skeleton, containing azobenzene as a photoresponsive group and ureidopyrimidinone (UPy) as a connection site, was designed and synthesized. The monomer is capable of forming an organogel in nonpolar organic solvents and different types of nanostructures in other solvents. The state of the gel and the chirality of the nanostructures could both be adjusted by subsequent light irradiation at different wavelengths. The helical nanofiber-like morphology was verified in the internal structure of the gel. The performance of this gel was investigated by a series of methods, such as UV–vis absorption spectroscopy, circular dichroism, scanning electron microscopy and rheological techniques. This work provides a new method for facile synthesis of chiro-optical gels.

Self‐Assembly of 1D Helical Nanostructures into Higher Order Chiral Nanostructures in Supramolecular Systems

AbstractChirality and hierarchy are two important aspects of biological systems. Investigation of the hierarchical self‐assembly of chiral supramolecular nanostructures leads not only to biomimics but also provides deep understanding of the self‐assembly and function in biological systems. While it is generally well‐known how small molecules can self‐assemble into nanostructures like chiral nanofibers, nanobelts, nanotubes and nanotwists, it is still less frequently investigated how these nanostructures can be further assembled into higher ordered chiral nanostructures. In this review, we mainly focus on how these 1D helical nanostructure can be further assembled into higher ordered or complex chiral nano/microstructures such as nanospirals, super‐nanohelices, helical nanotubes, nanoflowers, toroids, microflowers, microtubular flowers and dendritic chiral nanotwists. Moreover, some applications including asymmetric catalysis, cell adhesion, chiral optics and chiral recognition based on these nanostructures are discussed.

Alanine-Based Chiral Metallogels via Supramolecular Coordination Complex Platforms: Metallogelation Induced Chirality Transfer.

Chiral self-assemblies constantly attract great interest because of their potential to provide insight into biological systems and materials science. Herein we report on the efficient preparation of alanine-based chiral metallacycles, rhomboids 1D and 1L and hexagons 2D and 2L using a Pt(II) ← pyridyl directional bonding approach. The metallacycles are subsequently assembled into nanospheres at low concentration, that generate chiral metallogels at high concentration driven by hydrogen bonding, hydrophobic and π-π interactions. The gels consist of microscopic chiral nanofibers with well-defined helicity, as confirmed by circular dichroism (CD) and scanning (SEM) and transmission electron (TEM) microscopies. Given these results, we expect this technique will not only unlock interesting new approaches to understand homochirality in nature but also allow the design of versatile soft materials containing chiral supramolecular cores.

All-Atom Molecular Dynamics Simulations of Peptide Amphiphile Assemblies That Spontaneously Form Twisted and Helical Ribbon Structures.

Self-assembly of peptide amphiphiles (PAs) has been an active research area as the assemblies can be programmed into variously shaped nanostructures. Although cylindrical micelles are common structures, gold-binding peptide conjugates can self-assemble into chiral nanofibers with single or double helices. When gold nanoparticles bind to the helices, the resulting chiral nanoparticle assemblies have a collective plasmonic circular dichroism signal that can serve as nanoscale circular polarizers or chiroptical sensors. A better atomic-level understanding of the factors which lead to helical PA assemblies is therefore of significant importance. In this study we show that all-atom molecular dynamics simulations can describe the spontaneous structural transformation from a planar assembly of PAs to a twisted assembly or to a helical ribbon. The twist angle and the helical diameter calculated from the simulations closely match the experimental results, with the oxidation of a single Met residue in each PA leading to a change from bilayer to monolayer assemblies with significantly different ribbon properties. A secondary structure analysis shows how a combination of β-sheet formation near the hydrophobic core of the micelle and PPII structures from proline-rich C-terminus regions favors helix formation. The simulations presented here demonstrate the capability of predicting self-assembly in chiral structures, protocols that can easily be applied to the assembly of other amphiphilic molecules.

Self-Assembly of Hierarchical Chiral Nanostructures Based on Metal-Benzimidazole Interactions: Chiral Nanofibers, Nanotubes, and Microtubular Flowers.

Controlled hierarchical self-assembly of synthetic molecules into chiral nanoarchitectures to mimic those biological chiral structures is of great importance. Here, a low-molecular-weight organogelator containing a benzimidazole moiety conjugated with an amphiphilic l-glutamic amide has been designed and its self-assembly into various hierarchical chiral nanostructures is investigated. Upon gel formation in organic solvents, 1D chiral nanostructure such as nanofiber and nanotube are obtained depending on the solvents. In the presence of transition and rare earth metal ions, hierarchical chiral nanostructures are formed. Specifically, the addition of TbCl3 , EuCl3 , and AgNO3 leads to nanofiber structures, while the addition of Cu(NO3 )2 , Tb(NO3 )3 , or Eu(NO3 )3 provides the microflower structures and microtubular flower structures, respectively. While Eu(III) and Tb(III)-containing microtubular flowers keep the chirality, the Cu(II)-coordinated microflowers lose chirality. More interestingly, the nanofibers formed by the gelator coordinated with Eu(III) or Tb(III) ions show not only the supramolecular chirality but also the circularly polarized luminescence.

Polar Self-Assembled Subphthalocyanine Materials

Subphthalocyanines (SubPcs)1 are singular cone-shaped molecules with unique physicochemical properties that render them promising light-harvesting and/or donor units for photovoltaic and light-emitting applications. We were very interested in studying if such molecules could be organized in columnar stacks, both in solution2 and liquid-crystalline phases3 by hydrogen-bonding and p-p stacking interactions. The columnar aggregation of these non-planar molecules with axial dipole moments represents in itself a challenging task. Our motivation comes from the possibility of obtaining supramolecular chiral nanofibers and condensed phases that can be aligned in the presence of electric fields, yielding nanomaterials with permanent polarization and unusual ferroelectric and piezoelectric properties. Figure 1

Polar Self-Assembled Subphthalocyanine Columnar Stacks

Subphthalocyanines (SubPcs) are singular cone-shaped molecules with unique physicochemical properties that render them promising light-harvesting and/or donor units for photovoltaic and light-emitting applications. We were very interested in studying if such molecules could be organized in columnar stacks, both in solution and liquid-crystalline phases by hydrogen-bonding and p-p stacking interactions. The columnar aggregation of these non-planar molecules with axial dipole moments represents in itself a challenging task. Our motivation comes from the possibility of obtaining supramolecular chiral nanofibers and condensed phases that can be aligned in the presence of electric fields, yielding nanomaterials with permanent polarization and unusual ferroelectric and piezoelectric properties. Figure 1

Self-assembled chiral nanofibers from ultrathin low-dimensional nanomaterials.

Despite many developed methods, it still remains a challenge to provide a simple and general strategy for the controlled preparation of chiral nanostructures. Here we report a facile and universal approach for the high-yield and scalable preparation of chiral nanofibers based on the self-assembly of various ultrathin one-dimensional and two-dimensional nanomaterials in vigorously stirred polymeric solutions. The obtained chiral nanofibers can be further transformed to same-handed chiral nanorings. As a proof-of-concept application, chiral MoS(2) and multiwalled carbon nanotube nanofibers were used as promising active layers for flexible nonvolatile data storage devices. Impressively, the chiral MoS(2) nanofiber-based memory device presents a typical nonvolatile flash memory effect with excellent reproducibility and good stability. Our method offers a general route for the preparation of various functional chiral nanostructures that might have wide applications.

Dye-sensitized photoelectrochemical cell on plasmonic Ag/AgCl @ chiral TiO2 nanofibers for treatment of urban wastewater effluents, with simultaneous production of hydrogen and electricity

The feasibility of simultaneous production of hydrogen and electricity with simultaneous contaminants removal from “actual” urban wastewater within a dye-sensitized photoelectrochemical cell (DSPC) is demonstrated for the first time. The photoanode in the DSPC was a novel nanostructured plasmonic Ag/AgCl @ chiral TiO2 nanofibers (Ag and AgCl nanoparticles supported on chiral TiO2 nanofibers). The electrolyte in the DSPC was actual wastewater to which an estrogen (17-β-ethynylestradiol, EE2) and a heavy metal (Cu2+) were added. The contaminants in the wastewater rather than I−/I3− (usual electrolyte in conventional DSPCs) acted as electrons’ bridges for the stabilization of charges in this DSPC. Almost total removal of total organic carbon (TOC), Cu2+, EE2, and 70% removal of total nitrogen (TN) were achieved under visible-light irradiation. A relatively high solar energy conversion efficiency (PCE 3.09%) was recorded and approximately 98% of the electricity was converted to H2 after the consumption of dissolved oxygen (DO), Cu2+ and TN. This performance was attributed to the “symbiotic” relationship between the TiO2 chiral nanofibers and the plasmonic effect of Ag nanoparticles at the photoanode, although Ag may act as a recombination site which may hinder the generation of electricity. The dye N719 in this study exhibited a temporary sensitization effect, and a more efficient sensitizer is expected to be studied in the future. This study opens up new opportunities for producing renewable energy from wastewater treatment processes including organic and inorganic matter as viable resources.

Differential self-assembly and tunable emission of aromatic peptide bola-amphiphiles containing perylene bisimide in polar solvents including water.

We demonstrate the self-assembly of bola-amphiphile-type conjugates of dipeptides and perylene bisimide (PBI) in water and other polar solvents. Depending on the nature of the peptide used (glycine-tyrosine, GY, or glycine-aspartic acid, GD), the balance between H-bonding and aromatic stacking can be tailored. In aqueous buffer, PBI-[GY]2 forms chiral nanofibers, resulting in the formation of a hydrogel, while for PBI-[GD]2 achiral spherical aggregates are formed, demonstrating that the peptide sequence has a profound effect on the structure formed. In water and a range of other polar solvents, self-assembly of these two PBI-peptides conjugates results in different nanostructures with highly tunable fluorescence performance depending on the peptide sequence employed, e.g., fluorescent emission and quantum yield. Organogels are formed for the PBI-[GD]2 derivative in DMF and DMSO while PBI-[GY]2 gels in DMF. To the best of our knowledge, this is the first successful strategy for using short peptides, specifically, their sequence/structure relationships, to manipulate the PBI nanostructure and consequent optical properties. The combination of controlled self-assembly, varied optical properties, and formation of aqueous and organic gel-phase materials may facilitate the design of devices for various applications related to light harvesting and sensing.