Self‐Assembly of Pyridinium‐Tailored Anthracene Amphiphiles into Supramolecular Hydrogels

The mixing of a polyacid cross‐linker with a pyridinium‐functionalized anthracene amphiphile afforded a supramolecular hydrogel through a self‐assembly process that was primarily driven by π‐stacking and electrostatic interactions.     

Inversion of the Supramolecular Chirality of Nanofibrous Structures through Co‐Assembly with Achiral Molecules

To understand the behavior of chiral nanostructures, it is of critical importance to study how achiral molecules regulate the chirality of such nanostructures and what the main driving forces for the regulation processes are. In this work, the supramolecular chirality of helical nanofibers consisting of phenylalanine‐based enantiomers is inverted by achiral bis(pyridinyl) derivatives through co‐assembly. This inversion is mainly mediated by intermolecular hydrogen bonding interactions between the achiral additives and the chiral molecules, which may induce stereoselective interactions and different reorientations for the assembled molecules, as confirmed by calculations. This work not only exemplifies a feasible method to invert the helicity of chiral nanostructures by the addition of achiral molecules, but also provides a method to explore their functions in environments where chiral and achiral molecules are in close proximity.     

Optically Active Liquid Crystalline Polyoxometalates via Electrostatic Encapsulation with Cholesterol‐Containing Amphiphile

A novel cholesterol‐containing amphiphile was designed and prepared in the study, which is a room‐temperature ionic liquid crystal over a broad temperature range with pronounced chiroptical properties. Four types of inorganic polyoxometalates (PMs) with different numbers of charges were encapsulated by the chiral amphiphile. The incorporation of chiral organic cations triggers achiral PMs in the complexes to show induced chirality through intermolecular interactions, as demonstrated by circular dichroism spectroscopy. The electrostatic encapsulation with mesomorphic promoters provides the inorganic PMs with liquid crystalline behavior, characterized by differential scanning calorimetry, polarized optical microscopy, and X‐ray diffraction. The strategy applied herein represents a unique example of liquid crystalline PM complexes with optical activity.     

Control of Stem‐Cell Behavior by Fine Tuning the Supramolecular Assemblies of Low‐Molecular‐Weight Gelators

Controlling the behavior of stem cells through the supramolecular architecture of the extracellular matrix remains an important challenge in the culture of stem cells. Herein, we report on a new generation of low‐molecular‐weight gelators (LMWG) for the culture of isolated stem cells. The bola‐amphiphile structures derived from nucleolipids feature unique rheological and biological properties suitable for tissue engineering applications. The bola‐amphiphile‐based hydrogel scaffold exhibits the following essential properties: it is nontoxic, easy to handle, injectable, and features a biocompatible rheology. The reported glycosyl‐nucleoside bola‐amphiphiles (GNBA) are the first examples of LMWG that allow the culture of isolated stem cells in a gel matrix. The results (TEM observations and rheology) suggest that the supramolecular organizations of the matrix play a role in the behavior of stem cells in 3D environments.     

Cyclodextrin‐Based Supramolecular Assemblies and Hydrogels: Recent Advances and Future Perspectives

The application of cyclodextrin (CD)‐based host–guest interactions towards the fabrication of functional supramolecular assemblies and hydrogels is of particular interest in the field of biomedicine. However, as of late they have found new applications as advanced functional materials (e.g., actuators and self‐healing materials), which have renewed interest across a wide range of fields. Advanced supramolecular materials synthesized using this noncovalent interaction, exhibit specificity and reversibility, which can be used to impart reversible cross‐linking, specific binding sites, and functionality. In this review, various functional CD‐based supramolecular assemblies and hydrogels will be outlined with the focus on recent advances. In addition, an outlook will be provided on the direction of this rapidly developing field.

     

Hydrogels Composed of Organic Amphiphiles and α‐Cyclodextrin: Supramolecular Networks of Their Pseudorotaxanes in Aqueous Media

Mixtures of N‐alkyl pyridinium compounds [py‐N‐(CH₂)_nOC₆H₃‐3,5‐(OMe)₂]⁺(X^?) ( 1b Cl: n=10, X=Cl; 1c Br: n=12, X=Br) and α‐cyclodextrin (α‐CD) form supramolecular hydrogels in aqueous media. The concentrations of the two components influences the sol–gel transition temperature, which ranges from 7 to 67 °C. Washing the hydrogel with acetone or evaporation of water left the xerogel, and ¹³C CP/MAS NMR measurements, powder X‐ray diffraction (XRD), and scanning electron microscopy (SEM) revealed that the xerogel of 1b Cl (or 1c Br) and α‐CD was composed of pseudorotaxanes with high crystallinity. ¹³C{¹H} and ¹H NMR spectra of the gel revealed the detailed composition of the components. The gel from 1b Cl and α‐CD contains the corresponding [2]‐ and [3]pseudorotaxanes, [ 1b? (α‐CD)]Br and [ 1b? (α‐CD)₂]Br, while that from 1c Br and α‐CD consists mainly of [3]pseudorotaxane [ 1c? (α‐CD)₂]Br. 2D ROESY ¹H NMR measurements suggested intermolecular contact of 3,5‐dimethoxyphenyl and pyridyl end groups of the axle component. The presence of the [3]pseudorotaxane is indispensable for gel formation. Thus, intermolecular interaction between the end groups of the axle component and that between α‐CDs of the [3]pseudorotaxane contribute to formation of the network. The supramolecular gels were transformed into sols by adding denaturing agents such as urea, C₆H₃‐1,3,5‐(OH)₃, and [py‐N‐nBu]⁺(Cl^?).     

Self‐Assembly of DNA–Oligo(p‐phenylene‐ethynylene) Hybrid Amphiphiles into Surface‐Engineered Vesicles with Enhanced Emission

Surface‐addressable nanostructures of linearly π‐conjugated molecules play a crucial role in the emerging field of nanoelectronics. Herein, by using DNA as the hydrophilic segment, we demonstrate a solid‐phase “click” chemistry approach for the synthesis of a series of DNA–chromophore hybrid amphiphiles and report their reversible self‐assembly into surface‐engineered vesicles with enhanced emission. DNA‐directed surface addressability of the vesicles was demonstrated through the integration of gold nanoparticles onto the surface of the vesicles by sequence‐specific DNA hybridization. This system could be converted to a supramolecular light‐harvesting antenna by integrating suitable FRET acceptors onto the surface of the nanostructures. The general nature of the synthesis, surface addressability, and biocompatibility of the resulting nanostructures offer great promises for nanoelectronics, energy, and biomedical applications.     

Rational Design of Heat‐Set and Specific‐Ion‐Responsive Supramolecular Hydrogels Based on the Hofmeister Effect

Smart supramolecular hydrogels have been prepared from a bolaamphiphilic L ‐valine derivative in aqueous solutions of different salts. The hydrogels respond selectively to different ions and are either reinforced or weakened. In one case, in contrast to conventional systems, the hydrogels are formed upon heating of the system. The use of the hydrogels in the controlled release of an entrapped dye is described as a proof of the potential applications of these systems. The responsive hydrogels were rationally designed by taking into account the noticeable effect of different ions from the Hofmeister series in the solubility of the hydrogelator, which was assessed by using NMR experiments. On the one hand, kosmotropic anions such as sulfate produce a remarkable solubility decrease in the gelator, which is associated with gel reinforcement, as measured by rheological experiments. On the other hand, chaotropic species such as perchlorate weaken the gel. A dramatic effect was observed in the presence of guanidinium chloride, which boosted the solubility of the gelator, in accordance with its chaotropic behaviour reported in protein science. In this case, a direct interaction of the guanidinium species with the carbonyl groups of the hydrogelator is detected by ¹³C NMR spectroscopy. The weakening of this interaction upon a temperature increase allows for the preparation of heat‐set hydrogelating systems.     

Time‐Resolved Assembly of Cluster‐in‐Cluster {Ag12}‐in‐{W76} Polyoxometalates under Supramolecular Control

We report the time‐resolved supramolecular assembly of a series of nanoscale polyoxometalate clusters (from the same one‐pot reaction) of the form: [H_(10+m)Ag₁₈Cl(Te₃W₃₈O₁₃₄)₂]_n, where n=1 and m=0 for compound 1 (after 4 days), n=2 and m=3 for compound 2 (after 10 days), and n=∞ and m=5 for compound 3 (after 14 days). The reaction is based upon the self‐organization of two {Te₃W₃₈} units around a single chloride template and the formation of a {Ag₁₂} cluster, giving a {Ag₁₂}‐in‐{W₇₆} cluster‐in‐cluster in compound 1 , which further aggregates to cluster compounds 2 and 3 by supramolecular Ag‐POM interactions. The proposed mechanism for the formation of the clusters has been studied by ESI‐MS. Further, control experiments demonstrate the crucial role that TeO₃^2?, Cl^?, and Ag⁺ play in the self‐assembly of compounds 1 – 3 .     

Mixing Biomimetic Heterodimers of Nucleopeptides to Generate Biocompatible and Biostable Supramolecular Hydrogels

As a new class of biomaterials, most supramolecular hydrogels formed by small peptides require the attachment of long alkyl chains, multiple aromatic groups, or strong electrostatic interactions. Based on the fact that the most abundant protein assemblies in nature are dimeric, we select short peptide sequences from the interface of a heterodimer of proteins with known crystal structure to conjugate with nucleobases to form nucleopeptides. Being driven mainly by hydrogen bonds, the nucleopeptides self‐assemble to form nanofibers, which results in supramolecular hydrogels upon simple mixing of two distinct nucleopeptides in water. Moreover, besides being biocompatible to mammalian cells, the heterodimer of the nucleopeptides exhibit excellent proteolytic resistance against proteinase K. This work illustrates a new and rational approach to create soft biomaterials by a supramolecular hydrogelation triggered by mixing heterodimeric nucleopeptides.     

Self‐Assembly of Amphiphilic Janus Dendrimers into Mechanically Robust Supramolecular Hydrogels for Sustained Drug Release

Compounds that can gelate aqueous solutions offer an intriguing toolbox to create functional hydrogel materials for biomedical applications. Amphiphilic Janus dendrimers with low molecular weights can readily form self‐assembled fibers at very low mass proportion (0.2 wt %) to create supramolecular hydrogels (G′?G′′) with outstanding mechanical properties and storage modulus of G′>1000 Pa. The G′ value and gel melting temperature can be tuned by modulating the position or number of hydrophobic alkyl chains in the dendrimer structure; thus enabling exquisite control over the mesoscale material properties in these molecular assemblies. The gels are formed within seconds by simple injection of ethanol‐solvated dendrimers into an aqueous solution. Cryogenic TEM, small‐angle X‐ray scattering, and SEM were used to confirm the fibrous structure morphology of the gels. Furthermore, the gels can be efficiently loaded with different bioactive cargo, such as active enzymes, peptides, or small‐molecule drugs, to be used for sustained release in drug delivery.     

Pyrene‐Based Fluorescent Supramolecular Hydrogel: Scaffold for Energy Transfer

The self‐assembled gelation of an amino‐acid‐based low molecular weight gelator having a pyrene moiety at the N terminus and a bis‐ethyleneoxy unit linked with succinic acid at the C terminus is reported. This amphiphile is capable of gelating binary mixtures (1/3 v/v) of CH₃CN/water, DMSO/water, and DMF/water, and the minimum gelation concentration (MGC) varied from 0.2 to 0.3 % w/v. The sodium salt of the amphiphile efficiently gelates water with an MGC of 1.5 % w/v. The participation of different noncovalent interactions in supramolecular gelation by formation of fibrillar networks was investigated by spectroscopic and microscopic methods. High mechanical strength of the supramolecular gels is indicated by storage moduli on the order of 10³ Pa. The hydrogel was utilized for energy transfer, whereby inclusion of only 0.00075 % w/v of acridine orange resulted in about 50 % quenching of the fluorescence intensity of the gel through fluorescence resonance energy transfer.     

Molecular and Supramolecular Networks on Surfaces: From Two‐Dimensional Crystal Engineering to Reactivity

The invention of the scanning tunneling microscope has led to the visualization of molecules in real space on atomically flat conductive substrates. This has boosted research into supramolecular chemistry on surfaces. In this Review, we highlight recent developments in the design and functionality of supramolecular surface patterns, with special attention paid to those networks which are chiral or contain a high degree of porosity as well as to the reactivity, which is one of the most important recent developments in supramolecular surface chemistry.     

Multistimuli‐Responsive,Moldable Supramolecular Hydrogels Cross‐Linked by Ultrafast Complexation of Metal Ions and Biopolymers

A new type of multistimuli‐responsive hydrogels cross‐linked by metal ions and biopolymers is reported. By mixing the biopolymer chitosan (CS) with a variety of metal ions at the appropriate pH values, we obtained a series of transparent and stable hydrogels within a few seconds through supramolecular complexation. In particular, the CS–Ag hydrogel was chosen as the model and the gelation mechanism was revealed by various measurements. It was found that the facile association of Ag⁺ ions with amino and hydroxy groups in CS chains promoted rapid gel‐network formation. Interestingly, the CS–Ag hydrogel exhibits sharp phase transitions in response to multiple external stimuli, including pH value, chemical redox reactions, cations, anions, and neutral species. Furthermore, this soft matter showed a remarkable moldability to form shape‐persistent, free‐standing objects by a fast in situ gelation procedure.     

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

Supramolecular hydrogels are a class of self‐assembled network structures formed via non‐covalent interactions of the hydrogelators. These hydrogels capable of responding to external stimuli are considered to be smart materials due to their ability to undergo sol–gel and/or gel–sol transition upon subtle changes in their surroundings. Such stimuli‐responsive hydrogels are intriguing biomaterials with applications in tissue engineering, delivery of cells and drugs, modulating tissue environment to promote innate tissue repair, and imaging for medical diagnostics among others. This review summarizes the recent developments in stimuli‐responsive supramolecular hydrogels and their potential applications in regenerative medicine. Specifically, various structural aspects of supramolecular hydrogelators involved in self‐assembly, the role of external stimuli in tuning/controlling their phase transitions, and how these functions could be harnessed to advance applications in regenerative medicine are focused on. Finally, the key challenges and future prospects for these versatile materials are briefly described.     

Surfactant‐Encapsulated Polyoxometalates as Immobilized Supramolecular Catalysts for Highly Efficient and Selective Oxidation Reactions

A type of interesting immobilized supramolecular catalysts based on surfactant‐encapsulated polyoxometalates has been developed for oxidation reactions. Through a sol‐gel process with tetraethyl orthosilicate, hydroxyl‐terminated surfactant‐encapsulated polyoxometalate complexes have been covalently and uniformly bound to a silica matrix with unchanged complex structure. The formed hybrid catalysts possess a defined hydrophobic nano‐environment surrounding the inorganic clusters, which is conducive to compatibility between the polyoxometalate catalytic centres and organic substrates. The supramolecular synergy between substrate adsorption, reaction, and product desorption during the oxidation process has been found to have an obvious influence on the reaction kinetics, with the activity of the catalyst being greatly improved. The supramolecular catalysts performed effectively in the selective oxidation of several different kinds of organic compounds, such as alkenes, alcohols, and sulfides, and the main products were the corresponding epoxides, ketones, sulfoxides, and sulfones. More significantly, the catalyst could be easily recovered by simple filtration, and the catalytic activity was well retained for at least five cycles. Finally, the present strategy has proved to be a general route for the fabrication of supramolecular hybrid catalysts containing common polyoxometalates suitable for various purposes.