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.     

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.

     

Anion-Responsive Fluorescent Supramolecular Gels

Three novel bis-urea fluorescent low-molecular-weight gelators (LMWGs) based on the tetraethyl diphenylmethane spacer—namely, L1, L2, and L3, bearing indole, dansyl, and quinoline units as fluorogenic fragments, respectively, are able to form gel in different solvents. L2 and L3 gel in apolar solvents such as chlorobenzene and nitrobenzene. Gelator L1 is able to gel in the polar solvent mixture DMSO/H₂O (H₂O 15% v/v). This allowed the study of gel formation in the presence of anions as a third component. An interesting anion-dependent gel formation was observed with fluoride and benzoate inhibiting the gelation process and H₂PO₄⁻, thus causing a delay of 24 h in the gel formation. The interaction of L1 with the anions in solution was clarified by ¹H-NMR titrations and the differences in the cooperativity of the two types of NH H-bond donor groups (one indole NH and two urea NHs) on L1 when binding BzO⁻ or H₂PO₄⁻ were taken into account to explain the inhibition of the gelation in the presence of BzO⁻. DFT calculations corroborate this hypothesis and, more importantly, demonstrate considering a trimeric model of the L1 gel that BzO⁻ favours its disruption into monomers inhibiting the gel formation.     

An Easy Access to Organic Salt‐Based Stimuli‐Responsive and Multifunctional Supramolecular Hydrogels

By exploiting orthogonal hydrogen bonding involving supramolecular synthons and hydrophobic/hydrophilic interactions, a new series of simple organic salt based hydrogelators derived from pyrene butyric acid and its β‐alanine amide derivative, and various primary amines has been achieved. The hydrogels were characterised by microscopy, table‐top rheology and dynamic rheology. FTIR, variable‐temperature ¹H NMR and emission spectroscopy established the role of various supramolecular interactions such as hydrogen bonding and π–π stacking in hydrogelation. Single‐crystal X‐ray diffraction (SXRD) studies supported the conclusion that orthogonal hydrogen bonding involving amide–amide and primary ammonium monocarboxylate (PAM) synthons indeed played a crucial role in hydrogelation. The hydrogels were found to be stimuli‐responsive and were capable of sensing ammonia and adsorbing water‐soluble dye (methylene blue). All the hydrogelators were biocompatible (MTT assay in RAW 264.7 cells), indicating their suitability for use in drug delivery.     

High‐Fidelity Noncovalent Synthesis of Hydrogen‐Bonded Macrocyclic Assemblies

A hydrogen‐bonded cyclic tetramer is assembled with remarkably high effective molarities from a properly designed dinucleoside monomer. This self‐assembled species exhibits an impressive thermodynamic and kinetic stability and is formed with high fidelities within a broad concentration range.     

Supramolecular Assemblies by Charge‐Transfer Interactions between Donor and Acceptor Chromophores

We have collated various supramolecular designs that utilize organic donor–acceptor CT complexation to generate noncovalently co‐assembled structures including fibrillar gels, micelles, vesicles, nanotubes, foldamers, conformationally restricted macromolecules, and liquid crystalline phases. Possibly inspired by nature, chemists have extensively used hydrogen bonding as a tool for supramolecular assemblies of a diverse range of abiotic building blocks. As a structural motif, CT complexes can be compared to hydrogen‐bonded complexes in its directional nature and complementarities. Additional advantages of CT interactions include wider solvent tolerance and easy spectroscopic probing. Nevertheless the major limitation is their low association constant. This article shows different strategies have evolved over the years to overcome this drawback by reinforcing the CT interactions with auxiliary noncovalent forces without hampering the alternate stacking mode. Emerging reports on promising CT complexes in organic electronics are intimately related to various supramolecular designs that one can postulate based on donor–acceptor CT interactions.     

Self‐Sorting Supramolecular Polymerization: Helical and Lamellar Aggregates of Tetra‐Bay‐Acyloxy Perylene Bisimide

A new perylene bisimide (PBI), with a fluorescence quantum yield up to unity, self‐assembles into two polymorphic supramolecular polymers. This PBI bears four solubilizing acyloxy substituents at the bay positions and is unsubstituted at the imide position, thereby allowing hydrogen‐bond‐directed self‐assembly in nonpolar solvents. The formation of the polymorphs is controlled by the cooling rate of hot monomer solutions. They show distinctive absorption profiles and morphologies and can be isolated in different polymorphic liquid‐crystalline states. The interchromophoric arrangement causing the spectral features was elucidated, revealing the formation of columnar and lamellar phases, which are formed by either homo‐ or heterochiral self‐assembly, respectively, of the atropoenantiomeric PBIs. Kinetic studies reveal a narcissistic self‐sorting process upon fast cooling, and that the transformation into the heterochiral (racemic) sheetlike self‐assemblies proceeds by dissociation via the monomeric state.     

Self‐Assembled Supramolecular Nanocarrier Hosting Two Kinds of Guests in the Site‐Isolation State

Hyperbranched polyethylenimine (HPEI) was simply mixed with a solution of amphiphilic calix[4]arene (AC4), which possesses four phenol groups and four aliphatic chains, in chloroform. This resulted in the novel supramolecular complex HPEI–AC4 through the noncovalent interaction of the amino groups of HPEI with the phenol groups of AC4. The formed HPEI–AC4 supramolecular complexes were characterized by ¹H NMR spectroscopy and dynamic light scattering. The cationic water‐soluble dye methyl blue (MB) and the anionic water‐soluble dye methyl orange (MO) were used as the model guests to test the performance of HPEI–AC4 as a supramolecular nanocarrier. It was found that HPEI–AC4 could accommodate the anionic water‐soluble MO guests into the HPEI core. The MO encapsulation capacity of HPEI–AC4 was pH sensitive, which reached maximum loading under weakly acidic conditions. The loaded MO molecules could be totally released when the pH value was reduced to be around 4.5 or raised to be around 9.5, and this process was reversible. HPEI–AC4 could not only accommodate the anionic MO with the HPEI core but could also simultaneously load the cationic MB molecules using the formed AC4 shell, thereby realizing the site isolation of the two kinds of functional units. The amount of MO and MB encapsulated by HPEI–AC4 could be controlled by varying the ratio of hydroxyl groups of AC4 to amino groups of HPEI.     

The Power of Confocal Laser Scanning Microscopy in Supramolecular Chemistry: In situ Real-time Imaging of Stimuli-Responsive Multicomponent Supramolecular Hydrogels

Multicomponent supramolecular hydrogels are promising scaffolds for applications in biosensors and controlled drug release due to their designer stimulus responsiveness. To achieve rational construction of multicomponent supramolecular hydrogel systems, their in-depth structural analysis is essential but still challenging. Confocal laser scanning microscopy (CLSM) has emerged as a powerful tool for structural analysis of multicomponent supramolecular hydrogels. CLSM imaging enables real-time observation of the hydrogels without the need of drying and/or freezing to elucidate their static and dynamic properties. Through multiple, selective fluorescent staining of materials of interest, multiple domains formed in supramolecular hydrogels (e. g. inorganic materials and self-sorting nanofibers) can also be visualized. CLSM and the related microscopic techniques will be indispensable to investigate complex life-inspired supramolecular chemical systems.     

Carboxylate‐Driven Supramolecular Assemblies of Protonated meso‐Aryl‐Substituted Dipyrrolylpyrazoles

Dipyrrolylpyrazole (dpp) derivatives possessing an aryl ring at the pyrazole 4‐position were synthesized. Upon protonation, modified dpp derivatives formed a variety of assembled structures through complexation with carboxylates, as observed by single‐crystal X‐ray and synchrotron XRD analyses. In particular, the complexation of protonated dpp species possessing long alkyl chains with dicarboxylates resulted in highly ordered assembled structures, the packing modes of which as lamellar structures were controlled by the lengths of the spacer units between two carboxylate moieties. The charge‐carrier transporting properties of the solid materials were also controlled by bound anions, including dicarboxylates.     

Sequential Assembly of Mutually Interactive Supramolecular Hydrogels and Fabrication of Multi-Domain Materials

A two-component self-sorting hydrogel based on acylhydrazide and carboxylic acid derivatives of 1,3:2,4-dibenzylidene-d -sorbitol (DBS-CONHNH₂ and DBS-COOH) is reported. A heating–cooling cycle induces the self-assembly of DBS-CONHNH₂, followed by the self-assembly of DBS-COOH induced by decreasing pH. Although the networks are formed sequentially, there is spectroscopic evidence of interactions between them, which impact on the mechanical properties and significantly enhance the ability of these low-molecular-weight gelators (LMWGs) to form gels when mixed. The DBS-COOH network can be switched “off” and “on” within the two-component gel through a pH change. By using a photo-acid generator, the two-component gel can be prepared combining the thermal trigger with photo-irradiation. Photo-patterned self-assembly of DBS-COOH within a pre-formed DBS-CONHNH₂ gel under a mask yields spatially controlled multi-domain gels. Different gel domains can have different functions, for example, controlling the rate of release of heparin incorporated into the gel, or directing gold nanoparticle assembly. Such photo-patterned multi-component hydrogels have potential applications in regenerative medicine or bio-nano-electronics.     

Intramolecular Interactions of a Phenyl/Perfluorophenyl Pair in the Formation of Supramolecular Nanofibers and Hydrogels

A new system for the incorporation of a phenyl/perfluorophenyl pair in the structure of a peptide hydrogelator was developed. The strategy is based on the idea that the integration of an end‐capped perfluorophenyl group and a phenylalanine with a phenyl moiety in the side chain forms an intramolecular phenyl/perfluorophenyl pair, which can be used to promote the formation of the supramolecular nanofibers and hydrogels. This work illustrates the importance of structure‐hydrogelation relationship and provides new insights into the design of self‐assembly nanobiomaterials.     

Polyoxometalate-Based Photochromic Supramolecular Hydrogels with Highly Ordered Spherical and Cylindrical Micellar Nanostructures

Polyoxometalates (POMs) have attracted much attention in the field of photochromic materials. However, POM-based photochromic supramolecular hydrogels with high transparency and good photochromic properties are seldom reported. In this work, a homogenous, optically transparent, injectable, and photochromic supramolecular hydrogel was fabricated through the coassembly of ammonium heptamolybdate (Mo₇) and an imidazolium-based zwitterionic amphiphile (3-(1-hexadecyl-3-imidazolio)propanesulfonate (C₁₆IPS)). The balance between electrostatic attraction and repulsion of Mo₇ clusters and zwitterionic amphiphiles enables them to coassemble into a homogenous and transparent supramolecular hydrogel. By adjusting the molar ratio of C₁₆IPS/Mo₇, ordered spherical micelle-based hydrogels and aligned wormlike micelle-based hydrogels can be obtained. The incorporation of Mo₇ into hydrogels endows these hydrogels with excellent photochromic properties. Specifically, after coassembly with C₁₆IPS, the photochromic ability of hydrogels is significantly enhanced compared with that of a pure aqueous solution of Mo₇. These hydrogels exhibit great potential applications as photochromic materials for the recording of rewritable information.     

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^?).     

Supramolecular Proteoglycan Aggregate Mimics: Cyclodextrin‐Assisted Biodegradable Polymer Assemblies for Electrostatic‐Driven Drug Delivery

Self‐assembled, noncovalent polymeric biodegradable materials mimicking proteoglycan aggregates were synthesized from inclusion complexes of cationic surfactants with γ‐cyclodextrin and the natural anionic polymer hyaluronan. The amorphous structure of this ternary system was proven by X‐ray diffraction and thermal analysis. Light‐scattering measurements showed that there was a competition between hyaluronic acid and the surfactant for the cyclodextrin cavity. These self‐assembled supramolecular matrices were loaded with both hydrophilic and lipophilic drug substances for dissolution studies. The release of the entrapped drugs was found to be controlled by cations in the surrounding media and by biodegradation. Slow drug release in an ion‐free medium became faster in physiological salt solution in which the macroscopic polymer matrix was disassembled. In contrast, the enzymatic degradation of hyaluronan was hindered in the polymeric matrix. The supramolecular systems consisting of γ‐cyclodextrin as a macrocyclic host, a cationic surfactant guest, and hyaluronic acid as the anionic polymer electrostatically cross‐linked by the inclusion complex of the first two was found to be a novel drug‐delivery system for the controlled release of traditional drugs such as curcumin and ketotifen and proteins such as bovine serum albumin.     

Hierarchical Self‐Assembly of Supramolecular Hydrophobic Metallacycles into Ordered Nanostructures

We describe herein the hierarchical self‐assembly of discrete supramolecular metallacycles into ordered fibers or spherical particles through multiple noncovalent interactions. A new series of well‐defined metallacycles decorated with long alkyl chains were obtained through metal–ligand interactions, which were capable of aggregating into ordered fibroid or spherical nanostructures on the surface, mostly driven by hydrophobic interactions. In‐depth studies indicated that the morphology diversity was originated from the structural information encoded in the metallacycles, including the number of alkyl chains and their spatial orientation. Interestingly, the morphology of the metallacycle aggregates could be tuned by changing the solvent polarity. These findings are of special significance since they provide a simple yet highly controllable approach to prepare ordered and tunable nanostructures from small building blocks by means of hierarchical self‐assembly.     

Construction of Chemical‐Responsive Supramolecular Hydrogels from Guest‐Modified Cyclodextrins

A methodology for preparing supramolecular hydrogels from guest‐modified cyclodextrins (CDs) based on the host–guest and hydrogen‐bonding interactions of CDs is presented. Four types of modified CDs were synthesized to understand better the gelation mechanism. The 2D ROESY NMR spectrum of β‐CD‐AmTNB (Am=amino, TNB=trinitrobenzene) reveals that the TNB group was included in the β‐CD cavity. Pulsed field gradient NMR (PFG NMR) spectroscopy and AFM show that β‐CD‐AmTNB formed a supramolecular polymer in aqueous solution through head‐to‐tail stacking. Although β‐CD‐AmTNB did not produce a hydrogel due to insufficient growth of supramolecular polymers, β‐CD‐CiAmTNB (Ci=cinnamoyl) formed supramolecular fibrils through host–guest interactions. Hydrogen bonds between the cross‐linked fibrils resulted in the hydrogel, which displayed excellent chemical‐responsive properties. Gel‐to‐sol transitions occurred by adding 1‐adamantane carboxylic acid (AdCA) or urea. ¹H NMR and induced circular dichroism (ICD) spectra reveal that AdCA released the guest parts from the CD cavity and that urea acts as a denaturing agent to break the hydrogen bonds between CDs. The hydrogel was also destroyed by adding β‐CD, which acts as the competitive host to reduce the fibrils. Furthermore, the gel changed to a sol by adding methyl orange (MO) as a guest compound, but the gel reappeared upon addition of α‐CD, which is a stronger host for MO.     

Porphyrin–Phthalocyanine/Pyridylfullerene Supramolecular Assemblies

The synthesis and photophysical properties of several porphyrin (P)–phthalocyanine (Pc) conjugates (P–Pc; 1 – 3 ) are described, in which the phthalocyanines are directly linked to the β‐pyrrolic position of a meso‐tetraphenylporphyrin. Photoinduced energy‐ and electron‐transfer processes were studied through the preparation of H₂P–ZnPc, ZnP–ZnPc, and PdP–ZnPc conjugates, and their assembly through metal coordination with two different pyridylfulleropyrrolidines ( 4 and 5 ). The resulting electron‐donor–acceptor hybrids, which were formed by axial coordination of compounds 4 and 5 with the corresponding phthalocyanines, mimicked the fundamental processes of photosynthesis; that is, light harvesting, the transduction of excited‐state energy, and unidirectional electron transfer. In particular, photophysical studies confirmed that intramolecular energy‐transfer resulted from the S₂ excited state as well as from the S₁ excited state of the porphyrins to the energetically lower‐lying phthalocyanines, followed by an intramolecular charge‐transfer to yield P–Pc^.+ ? C₆₀^.?. This unique sequence of processes opens the way for solar‐energy‐conversion processes.