Alkyl-π Functional Molecular Gels: Control of Elastic Modulus and Improvement of Electret Performance.

The development of optoelectronically-active soft materials is drawing attention to the application of soft electronics. A room-temperature solvent-free liquid obtained by modifying a π-conjugated moiety with flexible yet bulky alkyl chains is a promising functional soft material. Tuning the elastic modulus (G') is essential for employing optoelectronically-active alkyl-π liquids in deformable devices. However, the range of G' achieved through the molecular design of alkyl-π liquids is limited. We report herein a method for controlling G' of alkyl-π liquids by gelation. Adding 1 wt % low-molecular-weight gelator formed the alkyl-π functional molecular gel (FMG) and increased G' of alkyl-π liquids by up to seven orders of magnitude while retaining the optical properties. Because alkyl-π FMGs have functional π-moieties in the gel medium, this new class of gels has a much higher content of π-moieties of up to 59 wt % compared to conventional π-gels of only a few wt %. More importantly, the gel state has a 23 % higher charge-retention capacity than the liquid, providing better performance in deformable mechanoelectric generator-electret devices. The strategy used in this study is a novel approach for developing next-generation optoelectronically-active FMG materials.

Simple Strategy for Benzo[g]chromene Synthesis via a Photochemical Intramolecular Cyclization Reaction.

Photochemical reactions are often a desirable strategy for organic synthesis because they do not require toxic and expensive reagents and produce less waste than thermal reactions. Herein, a facile photochemical strategy is described to synthesize benzo[g]chromene derivatives. This strategy utilizes the photoredox reaction of quinones, which allows C-H bond oxidation in the vicinity of the photoexcited quinone carbonyl group. The reaction mechanism was investigated using 1H NMR analysis. The intramolecular cyclization reaction proceeded via the formation of 1,3-dioxole compounds as intermediates by the photoredox reaction of p-quinone, followed by re-cyclization. The synthesized benzo[g]chromene derivatives are important heterocyclic skeletons with useful biological and pharmacological properties.

Bovine Serum Albumin Hydrogel Formation: pH Dependence and Rheological Analyses.

In vitro evaluation of the physical properties of biopolymer-based hydrogels can help in understanding certain phenomena, such as liquid-liquid phase separation. The formation of bovine serum albumin (BSA) hydrogels was investigated in the pH range of 1.0 to 4.0. Hydrogels were formed in the pH range of 3.0 to 4.0, whereas viscous solutions were formed in the pH range of 1.5 to 2.5. Unexpectedly, formation of BSA hydrogel was observed in extremely acidic condition (pH 1.0). The circular dichroism spectra of BSA solutions were recorded at pH values of 1.0, 2.0, 3.0, and 7.0, and α-helix contents were determined from the ellipticity data at 222 nm. The α-helix content decreased with a decrease in pH, and this decrease was associated with the partial denaturation (F-isoform) and the denaturation (E-isoform) of BSA. However, the α-helix contents at pH 1.0 and 3.0 were similar. BSA hydrogels at pH 1.0 and 3.5 showed similar dynamic viscoelastic properties, further supporting the stereo structural change of BSA from the denatured E-isoform to the partially denatured F-isoform at pH 1.0. The study also focused on measuring viscoelasticity, a fundamental physical property of hydrogels, using traditional rheometer and with minimal sample volume. A highly reproducible procedure for measuring the viscoelastic properties of hydrogels was established using sample volumes of 200 and 350 µL.

Multiple Stimuli-Responsive Supramolecular Gel Formed from Modified Adenosine.

Urea derivatives 1 and 2, synthesized from adenosine, were designed as low-molecular-weight gelators. Hydrophobic groups have been introduced into all or part of the hydroxy groups of the hydrophilic ribose moiety of 1 and 2 to control the solvophilicity of the molecules and their aggregates. Compound 2 selectively formed supramolecular gels in halogenated solvents such as chloroform and 1,2-dichloroethane. The supramolecular gel of 2 and chloroform was thermally stable and its gel-to-sol phase transition temperature was higher than the boiling point of chloroform. The physical properties of the supramolecular gel were investigated by determining its viscoelastic properties using a rheometer. The supramolecular gel realized multiple stimuli-responsive reversible gel-sol phase transitions. The supramolecular gel showed reversible phase transition by repeated warming-cooling cycles accompanying with the gel-sol transitions. The supramolecular gel could undergo five repeated mechano-responsive gel-sol transitions. Gel-to-sol phase transition could also be achieved by adding various anions to the supramolecular gel, such as tetrabutylammonium fluoride. Regelation was realized by adding boron trifluoride etherate to the fluoride ion containing sol. Addition of methanol to the supramolecular gel also induced gel-to-sol phase transition. Regelation was realized by adding molecular sieves 4 Å to the suspension.

On-demand gelation of ionic liquids using photoresponsive organometallic gelators.

The reversible formation of ionic liquid gels, or ionogels, upon external stimuli could improve their versatility and expand their application scope in electronic, biomedical, and micro-engineering systems. Herein, we developed organometallic compounds that release low-molecular-weight gelators upon photoirradiation, which facilitate the on-demand photogelation of ionic liquids (ILs). The chemical formulae of the gelator-coordinated complexes are [Ru(C5H5)L]X (L = C6H5NHCONHC12H25; X = PF6, B(CN)4). Each of the complexes were ILs that are easy to synthesize and miscible in ILs. By adding a small amount of the complex, various ILs were transformed to gels upon UV photoirradiation. The PF6 salt allowed the photogelation of ILs with coordinating substituents, whereas the B(CN)4 salt allowed the photogelation of non-coordinating ILs, albeit the reaction was slower. These gels underwent the reverse reaction and liquefied back when heated, and the photogelation was repeatable for ILs with coordinating cations.

Inhibition of BACE1 and amyloid ß aggregation by polyketide from Streptomyces sp.

Alzheimer's disease (AD) causes cognitive impairment in the elderly and is a severe problem worldwide. One of the major reasons for the pathogenesis of AD is thought to be due to the accumulation of amyloid beta (Aß) peptides that result in neuronal cell death in the brain. In this study, bioassay-guided fractionation was performed to develop seed compounds for anti-AD drugs that can act as dual inhibitors of BACE1 and Aß aggregation from secondary metabolites produced by Streptomyces sp. To improve the solubility, the crude extracts were methylated with trimethylsilyl (TMS) diazomethane and then purified to yield polyketides 1-5, including the new compound 1. We synthesized the compounds 6 and 7 (original compounds 2 and 3, respectively), and their activities were evaluated. KS-619-1, the demethylated form of 4 and 5, was isolated and evaluated for its inhibitory activity. The IC50 values for BACE1 and Aß aggregation were found to be 0.48 and 1.1 µM, respectively, indicating that KS-619-1 could be a lead compound for the development of therapeutic agents for AD.

Formation of pH-Responsive Supramolecular Hydrogels in Basic Buffers: Self-assembly of Amphiphilic Tris-Urea.

An amphiphilic tris-urea compound (1) containing hydrophilic resorcinol units was designed and synthesized. Compound 1 formed supramolecular hydrogels in basic buffers, such as glycine-NaOH, phosphate-NaOH, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES)-NaOH, and borate-NaOH. The optimum pH range of the buffer solution for gelation was 10-11 and insoluble suspensions or solutions were formed when the pH was outside this range. When the borate-NaOH buffer was used, supramolecular hydrogels were formed over a wide pH range (7.5-11.0). The thermal stabilities and viscoelastic properties of the supramolecular hydrogels were determined from the gel-to-sol phase transition temperatures and rheological properties, respectively. The supramolecular hydrogel formed from compound 1 and the borate-NaOH buffer exhibited a pH-responsive reversible gel-to-sol phase transition property. Gel-to-sol phase transition could be achieved by adding NaOH and regelation of the sol was realized by adding an appropriate amount of boric acid. Increasing the amount of the acid resulted in a gel-to-sol phase transition.

Effect of Alkyl Chain Length of N-Alkyl-N'-(2-benzylphenyl)ureas on Gelation.

Urea derivatives that were substituted with a 2-benzylphenyl group and an alkyl group functioned as low molecular weight gelators for various organic solvents and ionic liquids. Urea derivatives with long alkyl chains were effective for the gelation of polar solvents. However, they were not suitable for the gelation of non-polar solvents, whereas urea derivatives with short alkyl chains were effective. Ionic liquids were similar to polar solvents in that urea derivatives with long alkyl chains were the most effective gelators. The physical properties of the formed supramolecular gels were analyzed by dynamic viscoelasticity measurements using a rheometer.

Enzymatic Hydrolysis-Responsive Supramolecular Hydrogels Composed of Maltose-Coupled Amphiphilic Ureas.

Maltose is a ubiquitous disaccharide produced by the hydrolysis of starch. Amphiphilic ureas bearing hydrophilic maltose moiety were synthesized via the following three steps: I) construction of urea derivatives by the condensation of 4-nitrophenyl isocyanate and alkylamines, II) reduction of the nitro group by hydrogenation, and III) an aminoglycosylation reaction of the amino group and the unprotected maltose. These amphiphilic ureas functioned as low molecular weight hydrogelators, and the mixtures of the amphipathic ureas and water formed supramolecular hydrogels. The gelation ability largely depended on the chain length of the alkyl group of the amphiphilic urea; amphipathic urea having a decyl group had the highest gelation ability (minimum gelation concentration=0.4 mM). The physical properties of the supramolecular hydrogels were evaluated by measuring their thermal stability and dynamic viscoelasticity. These supramolecular hydrogels underwent gel-to-sol phase transition upon the addition of α-glucosidase as a result of the α-glucosidase-catalyzed hydrolysis of the maltose moiety of the amphipathic urea.

Urea Derivatives as Functional Molecules: Supramolecular Capsules, Supramolecular Polymers, Supramolecular Gels, Artificial Hosts, and Catalysts.

Urea, which has both hydrogen bond acceptor and donor moieties, is an ideal structure for a supramolecular synthon. Various supramolecules having ureido group(s) have been widely developed. This article summarizes recent developments of urea derivatives that exhibit various functions: i) supramolecular capsules that form discrete urea-urea intermolecular hydrogen bonds, ii) supramolecular polymers that form continuous urea-urea intermolecular hydrogen bonds, iii) supramolecular gels that form continuous urea-urea intermolecular hydrogen bonds, iv) artificial host molecules based on the molecular recognition ability of the ureido group, and v) catalytic reactions developed by utilizing the molecular recognition ability of the ureido group.

Amphoteric Homotropic Allosteric Association between a Hexakis-Urea Receptor and Dihydrogen Phosphate.

Conformationally flexible hexakis-urea 1 was synthesized efficiently by condensing hexakis(aminomethyl)benzene with 4-nitrophenyl-(3,5-di-tert-butylphenyl)carbamate. The hexakis-urea 1 is unexpectedly soluble in organic solvents of low polarity due to intramolecular hydrogen bonding. The hexakis-urea 1 recognizes chloride, bromide, and acetate in a 1:2 host-guest ratio and in a positive allosteric manner in CDCl3 . The ability of 1 to recognize dihydrogen phosphate is a unique outcome, and the structure of the associated complex, which contains four dihydrogen phosphate ions, was clarified by single-crystal X-ray structural analysis. However, in solution, a complex with three dihydrogen phosphate ions was identified. The dihydrogen phosphate association in CDCl3 proceeds in an amphoteric allosteric manner; in a positive allosteric manner (K1 K3 ) in the subsequent step.

Gelation and luminescence of lanthanide hydrogels formed with deuterium oxide.

Gel formations and efficient lanthanide luminescence appeared in deuterium oxide (D2O) medium instead of light water (H2O), and their solvation possibilities by using luminescence lifetimes were discussed. The lanthanide ions in the hydrogel of 1 obtained by H2O (abbreviated as H2O-Ln1; Ln = Eu, Tb, and Gd) in our previous report act as the coupling part between neighbor molecules for the bundle structure. Here, D2O also acts as a medium to form the lanthanide-hydrogel of 1, and increases intensities of luminescence for Tb, because a soft crystalline state reducing resonance thermal relaxation is realized. The gel-formation and luminescence band positions of Ln1 in D2O corresponded to those in H2O. From the observation of luminescence lifetimes in H2O and D2O, the number of coordinating water molecules on Eu and Tb were estimated to be around 3 or 4 for both. The luminescence intensity of Eu1 did not increase even in D2O, due to a blue shift of the excited triplet state of 1, as compared to that in H2O.

Enzymatic hydrolysis-induced degradation of a lactose-coupled supramolecular hydrogel.

Amphiphilic urea 1 with a hydrophilic lactose group was prepared as a low-molecular-weight hydrogelator, which formed a transparent supramolecular hydrogel. Enzymatic hydrolysis of the lactose moiety using ß-galactosidase allowed a gel-to-sol phase transition of the supramolecular hydrogel. A ß-galactosidase inhibitor enables us to control the time course of this phase transition.

Synthesis of a Bis-Urea Dimer and Its Effects on the Physical Properties of an Amphiphilic Tris-Urea Supramolecular Hydrogel.

The successful development of stiff supramolecular gels is an important goal toward their practical application. One approach to stiffen supramolecular gels is to introduce covalent cross-links. The bis-urea dimer 2, having a structure similar to that of the low-molecular-weight gelator 1, was synthesized. Supramolecular hydrogels were formed from mixtures of 1 and 2 in appropriate ratios, with 2 acting as a covalent cross-linker to connect the fibrous aggregates formed by the self-assembly of 1. The introduction of these covalent cross-links greatly influenced the dynamic viscoelasticity of the supramolecular hydrogels. In the supramolecular hydrogel of 1 mixed with 5 % 2, the storage modulus was 1.35 times higher than that of the supramolecular hydrogel of 1 alone, and the crossover strain was extended from 5 % to over 20 %. The supramolecular hydrogel of 1 and 2 was free-standing and supported 13 times its own weight.

Organic Dye Adsorption by Amphiphilic Tris-Urea Supramolecular Hydrogel.

The development of an effective adsorbent for cleansing polluted water is required for environmental purification. In this respect, a supramolecular hydrogel constructed by the self-assembly of small molecules could be a strong candidate. Adsorption experiments of organic dyes were performed using supramolecular hydrogels of amphiphilic tris-urea 1. Cationic organic dyes were adsorbed efficiently; indeed, the adsorption of methylene blue was as high as 4.19 mol equivalents relative to 1. Two luminescence peaks were observed in the rhodamine 6G-adsorbed supramolecular hydrogels, and their ratios varied with the amount of dye adsorbed. Fluorescence microscopy images of the supramolecular hydrogel at lower dye levels exhibited fibrous fluorescence consistent with the fibrous aggregates of 1. According to these results, adsorption may proceed gradually, that is, occurring initially on the fibers and later in the aqueous spaces of the supramolecular hydrogel.

Supramolecular gel electrophoresis of large DNA fragments.

Pulsed-field gel electrophoresis is a frequent technique used to separate exceptionally large DNA fragments. In a typical continuous field electrophoresis, it is challenging to separate DNA fragments larger than 20 kbp because they migrate at a comparable rate. To overcome this challenge, it is necessary to develop a novel matrix for the electrophoresis. Here, we describe the electrophoresis of large DNA fragments up to 166 kbp using a supramolecular gel matrix and a typical continuous field electrophoresis system. C3 -symmetric tris-urea self-assembled into a supramolecular hydrogel in tris-boric acid-EDTA buffer, a typical buffer for DNA electrophoresis, and the supramolecular hydrogel was used as a matrix for electrophoresis to separate large DNA fragments. Three types of DNA marker, the λ-Hind III digest (2 to 23 kbp), Lambda DNA-Mono Cut Mix (10 to 49 kbp), and Marker 7 GT (10 to 165 kbp), were analyzed in this study. Large DNA fragments of greater than 100 kbp showed distinct mobility using a typical continuous field electrophoresis system.

Development of C3-Symmetric Tris-Urea Low-Molecular-Weight Gelators.

This article describes recent developments in C3 -symmetric tris-urea low-molecular-weight gelators and their applications. The C3 -symmetric tris-ureas are excellent frameworks to form supramolecular polymers through noncovalent interactions. In organic solvents, hydrophobic tris-ureas form supramolecular gels. Amphiphilic tris-ureas form supramolecular gels in aqueous media. Functional supramolecular gels were prepared by introducing appropriate functional groups into the outer sphere of tris-ureas. Supramolecular hydrogels obtained from amphiphilic tris-ureas were used in the electrophoresis of proteins. These electrophoreses results showed several unique characteristics compared to typical electrophoreses results obtained using polyacrylamide matrices.

Self-Assembled Boronic Ester Cavitand Capsules with Various Bis(catechol) Linkers: Cavity-Expanded and Chiral Capsules.

Two molecules of cavitand tetraboronic acid and four molecules of various bis(catechol) linkers self-assemble into capsules through the formation of eight dynamic boronic ester bonds. Each capsule has a different cavity size depending on the linker used, and shows particular guest encapsulation selectivity. A chiral capsule made up of the cavitand and a chiral bis(catechol) linker was also constructed. This capsule induces supramolecular chirality with respect to a prochiral biphenyl guest by diastereomeric encapsulation through the asymmetric suppression of rotation around the axis of the prochiral biphenyl moiety.

Reinforcement of guest selectivity through the self-assembly of host molecules: selective recognition of lithium ions by dimerizable tricarboxylic acids.

C3-Symmetric tricarboxylic acids form dimers through intermolecular hydrogen bonds in nonpolar organic solvents. These dimers recognize lithium ions with high selectivities through the formation of 1 : 1 host-guest complexes between the collapsed dimeric assemblies and guest molecules.

Photoresponsive self-assembled hexameric capsules based on calix[4]resorcinarenes bearing azobenzene dendron conjugates as side chains.

We synthesized calix[4]resorcinarenes bearing various azobenzene dendron conjugates as side chains, wherein the azobenzene moiety is a photoresponsive unit and the dendron moiety is a capsule-destabilizing unit, and then studied the photoresponsive properties of their self-assembled hexameric capsules in conjunction with guest encapsulation in H2O-saturated CDCl3. It was found that correlation between the trans-to-cis photoisomerization of the azobenzene dendron side chains of hosts and the consequent capsule destabilization leading to guest release largely depends on the nature of the dendron moieties, such as their steric bulkiness or hydrophilicity.