Beyond Sol-Gel: Molecular Gels with Different Transitions.

The existence of sol-gel transitions is one of the most manifest properties of molecular gels. These transitions reflect their nature since they correspond to the association or dissociation of low weight molecules through non-covalent interactions to form the network constitutive of the gel. Most described molecular gels undergo only one gel-to-sol transition upon heating, and the reverse sol-to-gel transition upon cooling. It has been long observed that different conditions of formation could lead to gels with different morphologies, and that gels can undergo a transition from gel to crystals. However, more recent publications report molecular gels which exhibit additional transitions, for instance gel-to-gel transitions. This review surveys the molecular gels for which, in addition to sol-gel transitions, transitions of different nature have been reported: gel-to-gel transitions, gel-to-crystal transition, liquid-liquid phase separations, eutectic transformations, and synereses.

Development of Thixotropic Molecular Oleogels Comprising Alkylanilide Gelators by Using a Mixing Strategy.

Molecular oleogels have the potential to be used as materials in healthcare applications. However, their design and synthesis are complex, thus requiring simple and effective methods for their preparation. This paper reports on alkylanilides that are low molecular-weight organogelators, which when appropriately mixed with different alkyl chain lengths could result in the formation of mixed molecular gels that exhibit excellent gel-forming ability and mechanical properties. In addition, the single and mixed molecular organogel systems were found to be applicable as single and mixed molecular oleogel systems capable of gelling oils such as olive oil and squalane. This has been found to be true, especially in molecular oleogel systems consisting of squalane, which is used as solvents in healthcare. The mixed squalene-molecular oleogel systems showed an increase in the critical (minimum) gelation concentration from 1.0 to 0.1 wt.% in the single system and an improvement in the thixotropic behavior recovery time. The thixotropic behavior of the molecular oleogels in the mixed system was quantitatively evaluated through dynamic viscoelasticity measurements; however, it was not observed for the single-system molecular oleogels. Scanning electron microscopy of the xerogels suggested that this behavior is related to the qualitative improvement of the network owing to the refinement of the mesh structure. These mixed molecular oleogels, composed of alkylanilides displaying such thixotropic behavior, could be used as candidates for ointment-base materials in the healthcare field.

Polymeric Hydrogelator-Based Molecular Gels Containing Polyaniline/Phosphoric Acid Systems.

To expand the range of applications of hydrogels, researchers are interested in developing novel molecular hydrogel materials that have affinities for the living body and the ability to mediate electrical signals. In this study, a simple mixing method for creating a novel composite molecular gel is employed, which combines a hydrophilic conductive polymer, a polyaniline/phosphoric acid complex, and a polymer hydrogelator as a matrix. The composite hydrogel showed an improved gel-forming ability; more effective mechanical properties, with an increased strain value at the sol-gel transition point compared to the single system, which may be sufficient for paintable gel; and a better electrochemical response, due to the electrically conducting polyaniline component. These findings demonstrate the applicability of the new composite hydrogels to new potential paintable electrode materials.

N-Alkylhydantoins as New Organogelators and Their Ability to Create Thixotropic Mixed Molecular Organogels.

The author reported molecular organogels using N-alkylhydantoins as new low-molecular-weight gelators for the first time, and thixotropic mixed molecular organogels using a set of N-alkylhydantoin gelators with different alkyl chain lengths. These homologous compounds with different alkyl chains are found to form macroscopic crystals or solution states in polar solvents, but form homogeneous organogels in non-polar solvents, such as n-octane and squalane. Although there is no significant increase in the minimum gelation concentration of the mixed molecular gels using squalane as a solvent, these mixed molecular organogels show improved mechanical properties, especially in their thixotropic behavior, which is not observed in the single N-alkylhydantoin gels. Furthermore, they exhibit reversible thixotropic behavior with quick recovery of the gel state in a minute by quantitatively measuring dynamic viscoelasticity measurements of rheometry of mixed molecular gels. Based on the morphological observations of the xerogels, the self-assembling fibers of the gelators become finer, indicating an increase in the density of the mesh structure inside the gel, which could explain its thixotropic behavior. These thixotropic mixed molecular gels may be applicable to ointment base materials, because they are gelled with squalane oil.

Sucralose hydrogels: Peering into the reactivity of sucralose versus sucrose under lipase catalyzed trans-esterification.

Sucralose differs from sucrose only by virtue of having three Cl groups instead of OH groups. Its intriguing features include being noncaloric, noncariogenic, ∼600 times sweeter than sucrose, stable at high temperatures/acidic pH's, and void of disagreeable aftertastes. These properties are attractive as food additive, one of which is as hydrogel obtainable via the technique of molecular gelation using a sucralose-derived low-molecular weight gelator (LMWG). Such hydrogels are highly responsive to external stimuli like temperature, because the LMWGs self-assemble via non-covalent interactions and could thus be utilized in applications like control-release. We found that sucralose to be unreactive under lipase biocatalysis, unlike sucrose. Hence, the aim of this work was (i) to use computational simulations to further understand sucralose's lack of enzymatic reactivity and (ii) to synthesize the sucralose-based amphiphiles using conventional chemical synthesis and systematically study their tendency towards hydrogelation. Sucrose and sucralose were docked with a high-resolution atomic structure of lipase B from Candida antarctica, modeling the esterification transition state with an active site serine. In extended molecular dynamics simulations, sucrose remained in the active site due to multiple sugar-protein hydrogen bonds. The oxygen-to-chlorine substitutions in sucralose disrupted this hydrogen bonding network. Consistent with observed lack of enzymatic conversion, in multiple simulations, sucralose would rapidly dissociate from the active site. The sucralose-based LMWGs were subsequently synthesized using base-catalyzed conventional chemical synthesis. Three of the sucralose-based amphiphiles (SL-5, SL-6 and SL-7) proved to be successful hydrogelators. The gelators also showed the ability to gel selected beverages. The LMWGs gelled quantities of water and beverage up to 71 and 55 times their weight, respectively, and remain thermally stable up to 144 °C.

A Molecular Shape Recognitive HPLC Stationary Phase Based on a Highly Ordered Amphiphilic Glutamide Molecular Gel.

Chiral glutamide-derived lipids form self-assembled fibrous molecular gels that can be used as HPLC organic phases. In this study, HPLC separation efficiency was improved through the addition of branched amphiphilic glutamide lipids to the side chains of a terminally immobilized flexible polymer backbone. Poly(4-vinylpyridine) with a trimethoxysilyl group at one end was grafted onto the surface of porous silica particles (Sil-VP15, polymerization degree = 15), and the pyridyl side chains were quaternized with a glutamide lipid having a bromide group (BrG). Elemental analysis indicated that the total amount of the organic phase of the prepared stationary phase (Sil-VPG15) was 38.0 wt%, and the quaternization degree of the pyridyl groups was determined to be 32.5%. Differential scanning calorimetric analysis of a methanol suspension of Sil-VPG15 indicated that the G moieties formed a highly ordered structure below the phase transition temperature even on the silica surface, and the ordered G moieties exhibited a gel-to-liquid crystalline phase transition. Compared with a commercially available octadecylated silica column, the Sil-VPG15 stationary phase showed high selectivity toward polycyclic aromatic hydrocarbons, and particularly excellent separations were obtained for geometrical and positional isomers. Sil-VPG15 also showed highly selective separation for phenol derivatives, and bio-related molecules containing phenolic groups such as steroids were successfully separated. These separation abilities are probably due to multiple interactions between the elutes and the highly ordered functional groups, such as the pyridinium and amide groups, on the highly ordered molecular gel having self-assembling G moieties.

Designing Supramolecular Gelators: Challenges, Frustrations, and Hopes.

This article is a personal account of the author, who serendipitously entered the field of supramolecular gels nearly two decades ago. A supramolecular synthon approach in the context of crystal engineering was utilized to develop a working hypothesis to design supramolecular gelators derived from simple organic salts. The activity not only provided a way to occasionally predict gelation, but also afforded clear understanding of the structural landscape of such supramolecular materials. Without waiting for an ab initio approach for designing a gel, a large number of supramolecular gelators derived from organic salts were designed following the working hypothesis thus developed. Organic salts possess a number of advantages in terms of their ease of synthesis, purification, high yield and stability and, therefore, are suitable for developing materials for various applications. Organic salt-based gel materials for containing oil spills, synthesizing inorganic nanostructures and metal nanoparticles, sensing hazardous gas and dissolved glucose, adsorbing dyes, and facilitating drug delivery in self-delivery fashion have been developed. The journey through the soft world of gelators which was started merely by serendipity turned out to be rewarding, despite the challenges and frustrations in the field.

Deamidation of pseudopeptidic molecular hydrogelators and its application to controlled release.

HYPOTHESIS: The incorporation of a succinic acid-derived moiety in amino acid derivatives would favor an intramolecular catalysis of a deamidation reaction. Such reaction would permit controlled disassembly of molecular hydrogelators and the use of the hydrogels for controlled release of actives. EXPERIMENTAL: Low molecular weight hydrogelators containing a succinic acid-derived moiety were prepared by conventional organic synthesis procedures. Hydrogels were examined by electron microscopy and 1HNMR studies were carried out to evaluate the solubility in water of the hydrogelators and the deamidation reaction. Liberation of Rose Bengal entrapped in the hydrogels was monitored by UV-Vis spectroscopy. FINDINGS: Molecular hydrogels formed by pseudopeptidic derivatives of l-valine suffer a thermal deamidation reaction, leading to partial disassembly. The succinic acid-derived moiety present in the gelators is responsible of intramolecular catalysis of a deamidation reaction. Such neighboring group effect is reminiscent of biochemical processes such as protein deamidation and self-excision of inteins. It has been found that the thermodynamic equilibrium of the deamidation reaction is regulated by the efficiency of hydrogelation. As a proof of concept, the thermally promoted deamidation is applied to controlled release of Rose Bengal.

Radiation-Responsive Esculin-Derived Molecular Gels as Signal Enhancers for Optical Imaging.

Recent interest in detecting visible photons that emanate from interactions of ionizing radiation (IR) with matter has spurred the development of multifunctional materials that amplify the optical signal from radiotracers. Tailored stimuli-responsive systems may be paired with diagnostic radionuclides to improve surgical guidance and aid in detecting therapeutic radionuclides otherwise difficult to image with conventional nuclear medicine approaches. Because light emanating from these interactions is typically low in intensity and blue-weighted (i.e., greatly scattered and absorbed in vivo), it is imperative to increase or shift the photon flux for improved detection. To address this challenge, a gel that is both scintillating and fluorescent is used to enhance the optical photon output in image mapping for cancer imaging. Tailoring biobased materials to synthesize thixotropic thermoreversible hydrogels (a minimum gelation concentration of 0.12 wt %) offers image-aiding systems which are not only functional but also potentially economical, safe, and environmentally friendly. These robust gels (0.66 wt %, ∼900 Pa) respond predictably to different types of IRs including ß- and γ-emitters, resulting in a doubling of the detectable photon flux from these emitters. The synthesis and formulation of such a gel are explored with a focus on its physicochemical and mechanical properties, before being utilized to enhance the visible photon flux from a panel of radionuclides as detected. The possibility of developing a topical cream of this gel makes this system an attractive potential alternative to current techniques, and the multifunctionality of the gelator may serve to inspire future next-generation materials.

Low-Molecular-Weight Gelators as Base Materials for Ointments.

Ointments have been widely used as an efficient means of transdermal drug application for centuries. In order to create ointments suitable for various new medicinal drugs, the creation of ointment base materials, such as gels, has attracted much research attention in this decade. On the other hand, the chemical tuning of low-molecular-weight gelators (LMWGs) has been increasingly studied for two decades because LMWGs can be tailored for different purposes by molecular design and modification. In this review, several series of studies related to the creation of ointment base materials with enhanced properties using existing and newly-created LMWGs are summarized.

Functionality-Oriented Derivatization of Naphthalene Diimide: A Molecular Gel Strategy-Based Fluorescent Film for Aniline Vapor Detection.

Modification of naphthalene diimide (NDI) resulted in a photochemically stable, fluorescent 3,4,5-tris(dodecyloxy)benzamide derivative of NDI (TDBNDI), and introduction of the long alkyl chains endowed the compound with good compatibility with commonly found organic solvents and in particular superior self-assembly in the solution state. Further studies revealed that TDBNDI forms gels with nine of the 18 solvents tested at a concentration of 2.0% (w/v), and the critical gelation concentrations of five of the eight gels are lower than 1.0% (w/v), indicating the high efficiency of the compound as a low-molecular mass gelator (LMMG). Transmission electron microscopy, scanning electron microscopy, and confocal laser scanning microscopy studies revealed the networked fibrillar structure of the TDBNDI/methylcyclohexane (MCH) gel. On the basis of these findings, a fluorescent film was developed via simple spin-coating of the TDBNDI/MCH gel on a glass substrate surface. Fluorescence behavior and sensing performance studies demonstrated that this film is photochemically stable, and sensitive and selective to the presence of aniline vapor. Notably, the response is instantaneous, and the sensing process is fully and quickly reversible. This case study demonstrates that derivatization of photochemically stable fluorophores into LMMGs is a good strategy for developing high-performance fluorescent sensing films.

Dicyclohexylammonium bromoacetate: a low molecular mass organogelator with a one-dimensional secondary ammonium monocarboxylate (SAM) synthon.

The asymmetric unit of the title salt, C12H24N(+)·C2H2BrO2(-), contains a dicyclohexylammonium cation connected to a bromoacetate anion by means of an N-H...O hydrogen bond. In the crystal, the ion pairs assemble via N-H...O interactions, forming zigzag infinite chains parallel to the c axis with the (...H-N-H...O-C-O...)n motif that is considered to be a prerequisite for ensuring gelation properties of secondary ammonium monocarboxylate salts. The title salt was characterized by FT-IR, X-ray powder diffraction (XRPD), TG-DTA and (1)H NMR spectroscopy in solution. Gelation experiments revealed that dicyclohexylammonium bromoacetate forms molecular gels with dimethylformamide and dimethyl sulfoxide. Scanning electron microscopy (SEM) was used to reveal morphological features of dried gels.