Self-Assembly of Unconventional Low-Molecular-Mass Amphiphiles Containing a PEG Chain.

The design and synthesis of biocompatible surfactants are important for a wide range of applications in cosmetics, personal care products, and nanomedicine. This feature article summarizes our studies over the past 8 years on the design, synthesis, surface activity, and self-assembly of a series of unconventional low-molecular-mass amphiphiles containing a poly(ethylene glycol) (PEG) tail or spacer and different ionic or zwitterionic headgroups, including carboxylate, sulfonate, and quaternary ammonium salts. Despite having a so-called polar PEG chain as a tail or spacer, these ionic amphiphiles are found to have a tendency to adsorb at the air/water interface and self-assemble in pH 7.0 buffers at 298 K in the same way that conventional hydrocarbon tail surfactants do. However, they are observed to be relatively less surface-active compared to hydrocarbon tail surfactants. Although these amphiphilic molecules have less surface activity, they do self-assemble in aqueous buffer at 298 K, producing a range of microstructures, including spherical micelles, disclike micelles, and vesicles. In fact, our group is the first to report the self-assembly of PEG-tailed ionic amphiphiles in water at room temperature. Some of these molecules are also found to gel various organic liquids on heat-cool treatment or by ultrasound irradiation. We think that the present article will arouse general interest among researchers working toward the development of new biocompatible amphiphiles and soft materials.

Poly(vinyl alcohol)-induced thixotropy of an l-carnosine-based cytocompatible, tripeptidic hydrogel.

The generally poor mechanical stability of hydrogels limits their use as functional materials for many biomedical applications. In this work, a poly(vinyl alcohol) (PVA) embedded hybrid hydrogel of a ß-amino acid-containing Fmoc-protected tripeptide was produced at physiological pH (7.4) and room temperature. The hydrogel system was characterized by a number of techniques, including UV-vis, fluorescence, circular dichroism, FT-IR spectroscopy, electron microscopy, and rheology. While the tripeptide-based pure hydrogel was found to be unstable after ca. half an hour, addition of PVA, a water soluble polymer, increased the temporal and mechanical stability of the hydrogel. A rheological step-strain experiment demonstrates that the peptide-polymer hydrogel is thixotropic. Results from a fluorescence probe study and transmission electron microscopy reveal that addition of PVA increases both the fibre diameter and entanglement. Circular dichroism spectra of the hydrogels confirm the formation of aggregates with supramolecular chirality. The thixotropic nature of the hydrogel has been exploited to entrap and release doxorubicin, an anticancer drug, under physiological conditions. Furthermore, an MTT assay of the Fmoc-tripeptide using AH927 cells confirmed its cytocompatibility, which broadens the utility of the hybrid gel for biomedical applications.

l-Carnosine-Derived Fmoc-Tripeptides Forming pH-Sensitive and Proteolytically Stable Supramolecular Hydrogels.

A series of ß-amino acid containing tripeptides has been designed and synthesized in order to develop oligopeptide-based, thermoreversible, pH-sensitive, and proteolytically stable hydrogels. The Fmoc [N-(fluorenyl-9-methoxycarbonyl)]-protected tripeptides were found to produce hydrogels in both pH 7 and 2 buffers at a very low concentration (<0.2% w/v). It has been shown that the Fmoc group plays an important role in the gelation process. Also a dependence of gelation ability on hydrophobicity of the side chain of the Fmoc-protected α-amino acid was observed. The effect of the addition of inorganic salts on the gelation process was investigated as well. Spectroscopic studies indicated formation of J-aggregates through π-π stacking interactions between Fmoc groups in solution as well as in the gel state. In the gel phase, these self-assembling tripeptides form long interconnected nanofibrils leading to the formation of 3-dimensional network structure. The hydrogels were characterized by various techniques, including field emission electron microscopy, transmission electron microscopy, atomic force microscopy, rheology, Fourier transform IR, circular dichroism (CD), and wide-angle X-ray diffraction (WAXD) spectroscopy. The CD studies and WAXD analyses show an antiparallel ß-sheet structure in the gel state. l-Phenylalanine and l-tyrosine containing tripeptides formed helical aggregates with handedness opposite to those containing l-valine and l-leucine residues. The mechanical stability of the hydrogels was found to depend on the hydrophobicity of the side chain of the tripeptide as well as on the pH of the solution. Also, the tripeptides exhibit in vitro proteolytic stability against proteinase K enzyme.

Ultrasound-Induced Gelation of Organic Liquids by L-Cysteine-Derived Amphiphile Containing Poly(ethylene glycol) Tail.

Amphiphile containing l-cysteine covalently linked with poly(ethylene glycol) (PEG) chain (PEG360-Cys) was observed to produce transparent gel at room temperature in polar aprotic solvents not only by heating-cooling (HC) but also when subjected to ultrasound (US). It was observed that a suspension of PEG360-Cys when treated with US readily formed gel at much lower critical gelation concentration. US irradiation has been established to control the gel properties at the molecular level. The morphological change of the organogels produced by the HC and US methods was confirmed from scanning as well as transmission electron microscopy. The organogels produced by the two external stimuli (HC and US) were characterized in detail by FTIR spectroscopy, differential scanning calorimetry, and rheology to shed light on the molecular packing during gelation. It is important to note that the US-induced organogels showed almost 13-fold increase in gel strength compared to the organogels obtained by the HC method. Further, US-induced gels were found to be thermally more stable than the heat-set gels. All these studies clearly demonstrate that hydrogen-bonding interaction is the main driving force for both the gelation processes, but the mode of hydrogen bonding at the molecular level is different.

Understanding the role of H-bonding in self-aggregation in organic liquids by fatty acid amphiphiles with a hydrocarbon tail containing different H-bonding linker groups.

In this work, we have designed and synthesized a series of fatty acid amphiphiles that have the same structural skeleton but different hydrogen-bonding (H-bonding) functional groups in the hydrocarbon chain. To examine the importance of the H-bonding interaction on the formation of a one-dimensional (1D) aggregate in organic solvents, we have compared the gelation behavior of these amphiphiles in some common organic solvents at room temperature. Despite the structural similarity, the amphiphiles were observed to exhibit different gelation behavior. The organogels were characterized using conventional techniques such as field emission scanning electron microscopy, X-ray diffraction, and rheology. A systematic analysis of the FT-IR and (1)H NMR spectral data, gel melting temperatures, and mechanical strengths of the organogels in a given solvent suggested the importance of H-bonding as well as van der Waals interaction in the gelation process. In this study, we have made an attempt to estimate qualitatively the relative contribution of H-bonding and van der Waals interactions between gelator molecules forming organogels. The results suggest that strong and weaker H-bonding affects the gelation ability of gelators. However, when the H-bonding interaction is weak, an increase in van der Waals interactions can result in gelation, but when both H-bonding and van der Waals interactions are weak, that is, when the amphiphiles are liquid and semisolid, no gelation is observed. It is concluded that a balance between H-bonding and van der Waals interactions is necessary for physical gelation.

Thermoreversible as well as thermoirreversible organogel formation by L-cysteine-based amphiphiles with poly(ethylene glycol) tail.

We report here the gelation behavior of two novel L-cysteine-based amphiphiles bearing a poly(ethylene glycol) tail. The amphiphiles were found to form transparent organogels in both apolar and aprotic polar solvents at reasonably low concentrations. In chloroform, dichloromethane, and benzene solvents, the organogels are formed at room temperature without the requirement of heating-cooling cycle due to strong hydrogen-bonding interaction between gelator molecules. The swelling kinetics, however, becomes faster on heating. Unlike most organogels of low-molecular-mass gelators, these organogels do not exhibit a gel-to-sol transition on heating but instead become rigid when heated. Surprisingly, in polar solvents, the gelation required a heating-cooling cycle, and the sol-to-gel transition was found to be reversible. The gelation abilities of the amphiphiles were correlated with the hydrogen-bonding parameters of the solvents. Intermolecular H-bonding interaction was found to be the major driving force for the organogelation. The morphology of the organogels was investigated by the use of optical as well as electron microscopy and was found to be dependent on the nature of solvent. The mechanical strengths of the organogels were studied by rheological measurements.

Integration of Macro-Cross-Linker and Metal Coordination: A Super Stretchable Hydrogel with High Toughness.

The development of multifunctional hydrogels with high strength and stretchability is one of the most important topics in soft-matter research owing to their potential applications in various fields. In this work, a dual physically cross-linked network was designed for the fabrication of ultrastretchable tough hydrogels. The hydrogels were prepared through in situ polymerization of acrylic acid and acrylamide in the presence of positively charged quaternary poly(ethylene imine) (Q-PEI) and micelle-forming Pluronic F127 diacrylate, thus introducing electrostatic interactions between the positively charged Q-PEI and negatively charged poly(acrylic acid-co-acrylamide). For further mechanical reinforcement, Ca2+ and Cu2+ ions were introduced into the hydrogel network to construct coordination bonds, significantly enhancing tensile strength as well as stretchability. The hydrogel prepared with Ca2+ ion coordination bonds was found to be stretchable to 108 times its original length and exhibited a maximum toughness of 177 MJ·m-3, representing one of the most robust systems with both extraordinary toughness and superstretchability prepared to date. The hydrogels also exhibited excellent recovery of dimensions and reproducibility in terms of mechanical properties, providing a promising ultrastretchable soft-matter system with outstanding mechanical strength.