Dramatic Specific‐Ion Effect in Supramolecular Hydrogels

We report on a pronounced specific‐ion effect on the intermolecular and chiral organization, supramolecular structure formation, and resulting materials properties for a series of low molecular weight peptide‐based hydrogelators, observed in the presence of simple inorganic salts. This effect was demonstrated using aromatic short peptide amphiphiles, based on fluorenylmethoxycarbonyl (Fmoc). Gel‐phase materials were formed due to molecular self‐assembly, driven by a combination of hydrogen bonding and π‐stacking interactions. Pronounced morphological changes were observed by atomic force microscopy (AFM) for Fmoc‐YL peptide, ranging from dense fibrous networks to spherical aggregates, depending on the type of anions present. The gels formed had variable mechanical properties, with G′ values between 0.8 kPa and 2.4 kPa as determined by rheometry. Spectroscopic analysis provided insights into the differential mode of self‐assembly, which was found to be dictated by the hydrophobic interactions of the fluorenyl component, with comparable H‐bonding patterns observed in each case. The efficiency of the anions in promoting the hydrophobic interactions and thereby self‐assembly was found to be consistent with the Hofmeister anion sequence. Similar effects were observed with other hydrophobic peptides, Fmoc‐VL and Fmoc‐LL. The effect was found to be less pronounced for a less hydrophobic peptide, Fmoc‐AA. To get more insights into the molecular mechanism, the effect of anions on sol–gel equilibrium was investigated, which indicates the observed changes result from the specific‐ion effects on gels structure, rather than on the sol–gel equilibrium. Thus, we demonstrate that, by simply changing the ionic environment, structurally diverse materials can be accessed providing an important design consideration in nanofabrication via molecular self‐assembly.     

Surfactant‐Free Self‐Assembly of Nanocrystals into Ellipsoidal Architectures

A simple approach to control the self‐assembly of ZnS nanocrystals into well‐defined, uniform, three‐dimensional, micrometer‐scale, solid ellipsoidal structures with rattle‐type, multishelled, and hollow architectures is presented. There is no surfactant or small molecule to assist the self‐assembly of the nanocrystals. A possible mechanism of the controlled self‐assembly is proposed. The growth process can be divided into two stages: 1) the formation of ellipsoidal architectures via oriented aggregation, the growth kinetics of which is primarily attributed to the charge–charge, charge–dipole, and dipole–dipole interactions of preformed ZnS nanocrystals; and 2) Ostwald ripening, which results in multishelled, rattle‐type, and hollow structures. This self‐assembly concept is also applicable to other metal sulfides.     

Spontaneous Stepwise Self‐Assembly of a Polyoxometalate–Organic Hybrid into Catalytically Active One‐Dimensional Anisotropic Structures

An inorganic–organic hybrid surfactant with a hexavanadate cluster as the polar head group was designed and observed to assemble into micelle structures, which further spontaneously coagulate into a 1D anisotropic structure in aqueous solutions. Such a hierarchical self‐assembly process is driven by the cooperation of varied noncovalent interactions, including hydrophobic, electrostatic, and hydrogen‐bonding interactions. The hydrophobic interaction drives the quick formation of the micelle structure; electrostatic interactions involving counterions leads to the further coagulation of the micelles into larger assemblies. This process is similar to the crystallization process, but the specific counterions and the directional hydrogen bonding lead to the 1D growth of the final assemblies. Since most of the hexavanadates are exposed to the surface, the 1D assembly with nanoscale thickness is a highly efficient heterogeneous catalyst for the oxidation of organic sulfides with appreciable recyclability.     

Construction of Supramolecular Self‐Assembled Microfibers with Fluorescent Properties through a Modified Ionic Self‐Assembly (ISA) Strategy

Highly ordered supramolecular microfibers were constructed through a simple ionic self‐assembly strategy from complexes of the N‐tetradecyl‐N‐methylpyrrolidinium bromide (C₁₄MPB) surface‐active ionic liquid and the small methyl orange (MO) dye molecule, with the aid of patent blue VF sodium salt. By using scanning electron microscopy and polarized optical microscopy, the width of these self‐assembled microfibers is observed to be about 1 to 5 μm and their length is from tens of micrometers to almost a millimeter. The ¹H NMR spectra of the microfibers indicates that the supramolecular complexes are composed of C₁₄MPB and MO in equal molar ratio. The electrostatic, hydrophobic, and π–π stacking interactions are regarded as the main driving forces for the formation of microfibers. Furthermore, through characterization by using confocal fluorescence microscopy, the microfibers were observed to show strong fluorescent properties and may find potential applications in many fields.     

Engineering the Ionic Self‐Assembly of Polyoxometalates and Facial‐Like Peptides

The self‐assembly behavior of polyoxometalates (PMs) and facial‐like cationic peptides carrying lysine residues were systematically investigated. Circular dichroism and UV/Vis spectra demonstrated that the multivalent electrostatic attractions between polyanionic PMs and short peptides with protonated lysine residues initiated the conformational transition of peptide molecules from random‐coil to β‐sheet state, and subsequently the co‐assembly. TEM and atomic force microscopy (AFM) measurements showed that uniform nanofibers formed with decreasing size of the PMs or increasing the intermolecular forces of the peptides, such as through hydrogen‐bonding, hydrophobic, and/or π–π interactions. Additionally, the stability of the nanostructures can be improved by rational suppression of the electrostatic repulsion of the shell peptides covering the surface of the nanostructures. These results provide new insight into understanding the ionic self‐assembly of peptides and PMs and controlling their final morphology.     

Biocatalytic Self‐Assembly of Supramolecular Charge‐Transfer Nanostructures Based on n‐Type Semiconductor‐Appended Peptides

The reversible in situ formation of a self‐assembly building block (naphthalenediimide (NDI)–dipeptide conjugate) by enzymatic condensation of NDI‐functionalized tyrosine ( NDI‐Y ) and phenylalanine‐amide ( F‐NH₂ ) to form NDI‐YF‐NH₂ is described. This coupled biocatalytic condensation/assembly approach is thermodynamically driven and gives rise to nanostructures with optimized supramolecular interactions as evidenced by substantial aggregation induced emission upon assembly. Furthermore, in the presence of di‐hydroxy/alkoxy naphthalene donors, efficient charge‐transfer complexes are produced. The dynamic formation of NDI‐YF‐NH₂ and electronic and H‐bonding interactions are analyzed and characterized by different methods. Microscopy (TEM and AFM) and rheology are used to characterize the formed nanostructures. Dynamic nanostructures, whose formation and function are driven by free‐energy minimization, are inherently self‐healing and provide opportunities for the development of aqueous adaptive nanotechnology.     

Ultrasound‐Driven Secondary Self‐Assembly of Amphiphilic β‐Cyclodextrin Dimers

The controlled secondary self‐assembly of amphiphilic molecules in solution is theoretically and practically significant in amphiphilic molecular applications. An amphiphilic β‐cyclodextrin (β‐CD) dimer, namely LA‐(CD)₂, has been synthesized, wherein one lithocholic acid (LA) unit is hydrophobic and two β‐CD units are hydrophilic. In an aqueous solution at room temperature, LA‐(CD)₂ self‐assembles into spherical micelles without ultrasonication. The primary micelles dissociates and then secondarily form self‐assemblies with branched structures under ultrasonication. The branched aggregates revert to primary micelles at high temperature. The ultrasound‐driven secondary self‐assembly is confirmed by transmission electron microscopy, dynamic light scattering, ¹H NMR spectroscopy, and Cu²⁺‐responsive experiments. Furthermore, 2D NOESY NMR and UV/Vis spectroscopy results indicate that the formation of the primary micelles is driven by hydrophilic–hydrophobic interactions, whereas host–guest interactions promote the formation of the secondary assemblies. Additionally, ultrasonication is shown to be able to effectively destroy the primary hydrophilic–hydrophobic balances while enhancing the host–guest interaction between the LA and β‐CD moieties at room temperature.     

Redox‐responsive Fluorescent Nanoparticles Based on Diselenide‐containing AIEgens for Cell Imaging and Selective Cancer Therapy

A fluorescent, diselenide‐containing 9,10‐distyrylanthracene (DSA) derivative (SeDSA) with aggregation‐induced emission (AIE) characteristic was successfully synthesized and SeDSA nanoparticles (NPs) were prepared through a nanoprecipitation method. SeDSA could coassemble with an antitumor prodrug, diselenide‐containing paclitaxel (SePTX), which could be obtained by precipitation, to form SeDSA‐SePTX Co‐NPs (Co‐NPs). Molecular dynamics (MD) simulations reveal that the driving forces for the self‐assembly behaviors of SeDSA NPs and SePTX NPs are π–π interactions and hydrophobic interactions, respectively, while the driving forces for Co‐NPs include hydrophobic interactions between SeDSA and SePTX, π–π interactions between SeDSA molecules and hydrophobic interactions between SePTX molecules. Meanwhile, Se‐Se bonds play a crucial role in balancing the intramolecular forces. These diselenide‐containing nanoparticles (SeDSA NPs, SePTX NPs and Co‐NPs) exhibit a high stability under physiological conditions and excellent reduction‐sensitivity in the presence of the redox agent glutathione (GSH) because of the selenium‐sulfur exchange reaction between diselenide and GSH. Both SeDSA NPs and Co‐NPs show strong orange fluorescence emissions on the account of the AIE feature of SeDSA and they were easily internalized by HeLa and HepG2 cells. Distinctively, the Co‐NPs combine the advantage of SeDSA and SePTX for cell imaging and antineoplastic activity, and exhibit selectivity of cytotoxicities between neoplasia cells and normal cells. This study highlights the development of diselenide‐containing AIEgens as a unique approach to prepare uniform and stable fluorescent nanoparticles for the application in cell imaging and tumor treatment.     

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.     

A Hot‐Segment‐Based Approach for the Design of Cross‐Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self‐Assembly

The design of inhibitors of protein–protein interactions mediating amyloid self‐assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self‐assembly. Here we present a hot‐segment‐linking approach to design a series of mimics of the IAPP cross‐amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self‐ and cross‐seeded IAPP self‐assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer’s disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self‐assembly and pathogenic interactions of other proteins as well.     

Light‐ and Solvent‐Controlled Self‐Assembly Behavior of Spiropyran–Polyoxometalate–Alkyl Hybrid Molecules

A molecular photochromic spiropyran–polyoxometalate–alkyl organic–inorganic hybrid has been synthesized and fully characterized. The reversible switching of the hydrophobic spiropyran fragment to the hydrophilic merocyanine one can be easily achieved under light irradiation at different wavelengths. This switch changes the amphiphilic feature of the hybrid, leading to a light‐controlled self‐assembly behavior in solution. It has been shown that the hybrid can reversibly self‐assemble into vesicles in polar solvents and irreversibly into reverse vesicles in non‐polar solvents. The sizes of the vesicles and the reverse vesicles are both tunable by the polarity of the solvent, with the hydrophobic interactions being the main driving force.     

Nanoscale polyoxometalate‐based inorganic/organic hybrids

The latest advances in the area of polyoxometalate (POM)‐based inorganic/organic hybrid materials prepared by self‐assembly, covalent modification, and supramolecular interactions are presented. This Review is composed of five sections and documents the effect of organic cations on the formation of novel POMs, surfactant encapsulated POM‐based hybrids, polymeric POM/organic hybrid materials, POMs‐containing ionic crystals, and covalently functionalized POMs. In addition to their role in the charge‐balancing, of anionic POMs, the crucial role of organic cations in the formation and functionalization of POM‐based hybrid materials is discussed. DOI 10.1002/tcr.201100002     

SAXS study on complexes formed by anionic poly(sodium methacrylate‐co‐N‐isopropylacrylamide) gels with cationic surfactants

Small‐angle X‐ray scattering (SAXS) has been used to study the nanostructures of complexes formed by slightly crosslinked anionic copolymer gels of poly(sodium methacrylate‐co‐N‐isopropylacrylamide) [P(MAA/NIPAM)] interacting with cetylpyridinium bromide (CPB), and alkyltrimethylammonium bromide (C_nTAB, 10 ≤n ≤ 18), respectively. Both the charge density of polyelectrolyte gels and the surfactant alkyl tail length could induce the phase structure transition from Pm3n space group cubic to hexagonal close packing of spheres (HCP), while the different polar groups of pyridinium and trimethylammonium with the same hydrophobic cetyl chain in surfactants had no significant effects on the structures of complexes formed with the same gels. The highly ordered structures were shown to be formed by the self‐assembly of ionic surfactants inside the anionic gel network, driven by both electrostatic and hydrophobic interactions. Freeze drying the water‐equilibrated complexes could collapse the formed ordered structures. However, the highly ordered structures could be restored after the dried complexes were reswollen by water under the same conditions, indicating that the highly ordered water‐equilibrated complexes were thermodynamically stable. Copyright © 2000 John Wiley & Sons, Ltd.     

Taking Advantage of Hydrophobic Fluorine Interactions for Self‐Assembled Quantum Dots as a Delivery Platform for Enzymes

Self‐assembly of nanoparticles provides unique opportunities as nanoplatforms for controlled delivery. By exploiting the important role of noncovalent hydrophobic interactions in the engineering of stable assemblies, nanoassemblies were formed by the self‐assembly of fluorinated quantum dots in aqueous medium through fluorine–fluorine interactions. These nanoassemblies encapsulated different enzymes (laccase and α‐galactosidase) with encapsulation efficiencies of ≥74 %. Importantly, the encapsulated enzymes maintained their catalytic activity, following Michaelis–Menten kinetics. Under an acidic environment the nanoassemblies were slowly disassembled, thus allowing the release of encapsulated enzymes. The effective release of the assayed enzymes demonstrated the feasibility of this nanoplatform to be used in pH‐mediated enzyme delivery. In addition, the as‐synthesized nanoassemblies, having a diameter of about 50 nm, presented high colloidal stability and fluorescence emission, which make them a promising multifunctional nanoplatform.     

Cation‐Driven Self‐Assembly of a Gold(I)‐Based Metallo‐Tweezer

A combination of self‐complementary π–π‐stacking interactions and metallophilic interactions triggered the self‐assembly of a new digold(I) metallo‐tweezer in the presence of several types of M⁺ ions. Titrations by fluorescence spectroscopy enabled the determination of the association constants of the resulting inclusion duplex complexes.     

Salt Responsive Morphologies of ssDNA‐Based Triblock Polyelectrolytes in Semi‐Dilute Regime: Effect of Volume Fractions and Polyelectrolyte Length

A comprehensive study is reported on the effect of salt concentration, polyelectrolyte block length, and polymer concentration on the morphology and structural properties of nanoaggregates self‐assembled from BAB single‐strand DNA (ssDNA) triblock polynucleotides in which A represents polyelectrolyte blocks and B represents hydrophobic neutral blocks. A morphological phase diagram above the gelation point is developed as a function of solvent ionic strength and polyelectrolyte block length utilizing an implicit solvent ionic strength method for dissipative particle dynamics simulations. As the solvent ionic strength increases, the self‐assembled DNA network structures shrinks considerably, leading to a morphological transition from a micellar network to worm‐like or hamburger‐shape aggregates. This study provides insight into the network morphology and its changes by calculating the aggregation number, number of hydrophobic cores, and percentage of bridge chains in the network. The simulation results are corroborated through cryogenic transmission electron microscopy on the example of the self‐assembly of ssDNA triblocks.     

Superhydrogels of Nanotubes Capable of Capturing Heavy‐Metal Ions

Self‐assembly regulated by hydrogen bonds was successfully achieved in the system of lithocholic acid (LCA) mixed with three organic amines, ethanolamine (EA), diethanolamine (DEA), and triethanolamine (TEA), in aqueous solutions. The mixtures of DEA/LCA exhibit supergelation capability and the hydrogels consist of plenty of network nanotubes with uniform diameters of about 60 nm determined by cryogenic TEM. Interestingly, the sample with the same concentration in a system of EA and LCA is a birefringent solution, in which spherical vesicles and can be transformed into nanotubes as the amount of LCA increases. The formation of hydrogels could be driven by the delicate balance of diverse noncovalent interactions, including electrostatic interactions, hydrophobic interactions, steric effects, van der Waals forces, and mainly hydrogen bonds. The mechanism of self‐assembly from spherical bilayer vesicles into nanotubes was proposed. The dried hydrogels with nanotubes were explored to exhibit the excellent capability for capturing heavy‐metal ions, for example, Cu²⁺, Co²⁺, Ni²⁺, Pb²⁺, and Hg²⁺. The superhydrogels of nanotubes from the self‐assembly of low‐molecular‐weight gelators mainly regulated by hydrogen bonds used for the removal of heavy‐metal ions is simple, green, and high efficiency, and provide a strategic approach to removing heavy‐metal ions from industrial sewage.     

Entropically Driven Self‐Assembly of Bolaamphiphilic Perylene Dyes in Water

The specific hydrophobic effect involved in the self‐assembly of a bolaamphiphilic perylene bisimide (PBI) dye bearing oligoethylene glycol (OEG) chains has been identified. In pure water, the self‐assembly is entropically driven and enthalpically disfavored, as explored by optical spectroscopy and isothermal titration calorimetry studies. Besides strong π–π interactions between the PBI units that are primarily of enthalpic nature, the major contribution to the self‐assembly is the gain of entropy by release of confined water molecules from the hydration shell of the hydrophilic OEG moieties. Both contributions favor self‐assembly, but their countervailing thermodynamic parameters are reflected in an uncommon temperature dependence, which can be inverted upon gradual addition of an organic cosolvent that makes the π–π interaction increasingly dominant.     

Controlling Aqueous Self‐Assembly Mechanisms by Hydrophobic Interactions

We report an innovative template‐assisted synthetic protocol for the selective functionalization of terminal triple bonds in oligophenyleneethynylenes (OPE) by pre‐organization in aqueous solution. By this approach, three new OPE‐based bolaamphiphiles substituted with hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOx) chains of different length have been synthesized. The chain length was observed to strongly influence the aqueous supramolecular polymerization: bolaamphiphiles with longer hydrophilic chains aggregate into spherical nanoparticles in a stepwise fashion, whereas 2D anisotropic platelets are formed cooperatively if shorter PEtOx chains are used. Our results demonstrate that hydrophobic interactions can be strong enough to trigger cooperative effects in aqueous self‐assembly processes.     

Access to Metastable Gel States Using Seeded Self‐Assembly of Low‐Molecular‐Weight Gelators

Here we report on how metastable supramolecular gels can be formed through seeded self‐assembly of multicomponent gelators. Hydrazone‐based gelators decorated with non‐ionic and anionic groups are formed in situ from hydrazide and aldehyde building blocks, and lead through multiple self‐sorting processes to the formation of heterogeneous gels approaching thermodynamic equilibrium. Interestingly, the addition of seeds composing of oligomers of gelators bypasses the self‐sorting processes and accelerates the self‐assembly along a kinetically favored pathway, resulting in homogeneous gels of which the network morphologies and gel stiffness are markedly different from the thermodynamically more stable gel products. Importantly, over time, these metastable homogeneous gel networks are capable of converting into the thermodynamically more stable state. This seeding‐driven formation of out‐of‐equilibrium supramolecular structures is expected to serve as a simple approach towards functional materials with pathway‐dependent properties.