Reversible Sol-gel Transition Research Articles

A "keto-enol tautomerization"-based response mechanism: a novel approach to stimuli-responsive supramolecular gel.

A novel approach to stimuli-responsive gel termed the "keto-enol tautomerization"-based response mechanism was proposed. By tautomerization, vinyl ketone-based gelator G3 can be self-assembled into an organogel (OG3) accompanied by strong AIE. OG3 shows reversible dual-channel response for S(2-). The response process is based on the reversible deprotonation of the enol moiety in the tautomerized gelator G3′.

Photoresponsive supramolecular gels based on amphiphiles with azobenzene and maltose or polyethyleneglycol polar head

Photoresponsive supramolecular gelators have been synthesized using PEG or d-maltose as polar head. Incorporation of azobenzene photoresponsive moieties allows controlling the supramolecular gel structure, including a reversible gel–sol transition using light as external stimulus.

Electrochemically induced reversible formation of carboxymethyl chitin hydrogel and tunable protein release

Carboxymethyl chitin was synthesized through a “green” and homogeneous way in NaOH–urea solvent. Reversible sol–gel transition of carboxymethyl chitin hydrogel can be realized by an electrochemical method.

Supramolecular hydrogels: synthesis, properties and their biomedical applications.

As a novel class of three-dimensional (3D) hydrophilic cross-linked polymers, supramolecular hydrogels not only display unique physicochemical properties (e.g., water-retention ability, drug loading capacity, biodegradability and biocompatibility, biostability) as well as specific functionalities (e.g., optoelectronic properties, bioactivity, self-healing ability, shape memory ability), but also have the capability to undergo reversible gel-sol transition in response to various environmental stimuli inherent to the noncovalent cross-linkages, thereby showing great potential as promising biomaterial scaffolds for diagnosis and therapy. In this Review, we summarized the recent progress in the design and synthesis of supramolecular hydrogels through specific, directional noncovalent interactions, with particular emphasis on the structure-property relationship, as well as their wide-ranging applications in disease diagnosis and therapy including bioimaging, biodetection, therapeutic delivery, and tissue engineering. We believe that these current achievements in supramolecular hydrogels will greatly stimulate new ideas and inspire persistent efforts in this hot topic area in future.

Supramolecular hybrid hydrogel based on host-guest interaction and its application in drug delivery.

In this work, we developed a simple, novel method for constructing gold nanocomposite supramolecular hybrid hydrogels for drug delivery, in which gold nanocrystals were utilized as building blocks. First, methoxypoly(ethylene glycol) thiol (mPEG-SH, molecular weight (MW)=5 K) capped gold nanocrystals (nanospheres and nanorods) were prepared via a facile one-step ligand-exchange procedure. Then, the homogeneous supramolecular hybrid hydrogels were formed, after adding α-cyclodextrin (α-CD) into PEG-modified gold nanocrystal solutions, due to the host-guest inclusion. Both gold nanoparticles and inclusion complexes formed between α-CD and PEG chain provided the supra-cross-links, which are beneficial to the gelation formation. The resulting hybrid hydrogels were fully characterized by a combination of techniques including X-ray diffraction, rheology studies, and scanning electron microscopy. Meanwhile, the hybrid hydrogel systems demonstrated unique reversible gel-sol transition properties at a certain temperature caused by the temperature-responsive reversible supramolecular assembly. The drug delivery applications of such hybrid hydrogels were further investigated in which doxorubicin was selected as a model drug for in vitro release, cytotoxicity, and intracellular release studies. We believe that the development of such hybrid hydrogels will provide new and therapeutically useful means for medical applications.

Large red-shifted fluorescent emission via intermolecular π-π stacking in 4-ethynyl-1,8-naphthalimide-based supramolecular assemblies.

Two low molecular weight gelators containing 4-ethynyl-1,8-naphthalimide groups with large conjugated structure via different length of alkyl chains were synthesized and fully characterized. The gelation properties, structural character, and fluorescence of the gels were investigated via methods of scanning electron microscopy, X-ray diffraction, and spectral studies. The gelators have high fluorescence quantum yields in both solution and solid state. Interestingly, the wavelength of the fluorescent emission in the reversible sol-gel transition process of the gels has a large red-shift of 80 nm in DMF, which is extremely sparse for 1,8-naphthalimide derivatives in the literature. The intermolecular π-π stacking between naphthalimide is suggested to be the main driving force for the gel formation and fluorescent variation by means of temperature-dependent (1)H NMR study and theoretical calculation.

An electric field responsive drug delivery system based on chitosan–gold nanocomposites for site specific and controlled delivery of 5-fluorouracil

A novel drug delivery system based on an electric field and pH dual-stimuli responsive chitosan–gold nanocomposite (CGNC) is reported in the present study for site specific controlled delivery of the anticancer drug 5-fluorouracil (5-FU). At a higher pH of the solution CGNC encapsulates the drug molecules in its 3D-network and releases the drug at a relatively lower pH due to its reversible gel–sol transition properties. A sulphorhodamine B cytotoxicity assay showed that the chitosan–gold nanocomposite–fluorouracil conjugate (CGNC–FU) has higher cytotoxicity than 5-FU to the cervical cancer cells, SiHa. Drug release from CGNC has been controlled by applying a weak, external DC electric field. The drug delivery system is illustrated to be effective for the loading and delivery of 5-FU. The encapsulation efficiency of CGNC was found to be 36% and about 63% of the drug was released by applying the electric field. The biocompatibility of CGNC was demonstrated by growing SiHa cells successfully on a CGNC film electrodeposited on an indium tin oxide (ITO) coated glass plate. SiHa cells grown on a CGNC–FU conjugate modified ITO plate showed less viability and further application of an electric field of 1.5 V for the release of 5-FU led to the complete death of the cells. A highlight of the present drug delivery system is that the drug release can be controlled externally.

A thermally responsive cationic nanogel-based platform for three-dimensional cell culture and recovery

Thermo-sensitive nanogels have attracted great interest due to their versatile biological applications, but little research has been carried out to study their abilities in three-dimensional (3D) cell culture and recovery. A new insight is reported into exploring a low-charged thermosensitive cationic nanogel, poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-co-2-dimethylaminoethyl methacrylate) (P(NIPAM-HEMA-DMAEMA) or PNHD), for 3D cell culture. The positively charged DMAEMA moieties of the PNHD nanogels facilitate cellular attachment, and the low charge density renders those nanogels minimally cytotoxic. The volume phase transition temperatures (VPTTs) of the synthesized PNHD nanogels can be tailored by adjusting monomer feeds during the course of polymerization. Dynamic rheological measurements confirm the fully reversible sol–gel transition for 50 mg mL−1 PNHD nanogels. At room temperature, PNHD nanogels are in their dispersion states, allowing them to be thoroughly mixed with inoculated cells. Above their gelation temperatures, hydrogels containing a mixture of cells and nanogels are formed in situ. The increase in viable cells with culture time suggests that the in situ formed hydrogels support cell proliferation. Recovery of these cultured cells can be simply achieved by cooling the mixed hydrogels below their gelation temperature. The spherical shape of the released cells indicates their 3D growth in the absence of a physical scaffold. The released cells are not only alive, but also retain the capability of migration.

Tunable temperature-responsive supramolecular hydrogels formed by prodrugs as a codelivery system.

Taking advantage of the strong hydrophobicity of the anticancer drug camptothecin (CPT), the CPT molecule was conjugated to a class of low-molecular-weight (MW) poly(ethylene glycol) (PEG) chains (MW = 500, 1000, and 2000), forming an amphiphilic prodrug. The CPT-PEG prodrug formed stable hydrogels based on a combination of the partial inclusion complexation between one end of the PEG blocks and α-CD and the hydrophobic aggregation of CPT groups. Meanwhile, the formed hydrogels could be loaded with water-soluble drug 5-fluorouracil (5-FU), which is always combined with CPT drugs to enhance their anticancer activity. Moreover, the hydrogel systems demonstrate unique structure-related reversible gel-sol transition properties at a certain temperature due to the reversible supramolecular assembly, and the gel-sol transition temperature could be modulated by varying the length of the PEG chain and the concentrations of α-CD, demonstrating the possibility of achieving on-demand gel-sol transitions. The structure-related reversible gel-sol transition properties were proved by rheological property, XRD, DSC, and SEM measurements. The different controlled release profiles of two different anticancer drugs showed significant temperature-dependent properties. This easily prepared supramolecular hydrogel with excellent biocompatibility and tunable temperature responsiveness has significant potential for controlled drug release applications.

Reversible Sol–Gel Transition of Oligo(p-phenylenevinylene)s by π–π Stacking and Dissociation

Methyl sulfide terminated trans-oligo(p-phenylenevinylene) derivatives (OPVn, n is the number of phenyl rings) were synthesized, and reversible sol-gel transition was observed in a variety of organic solvents. Investigations with UV-vis, fluorescence, and (1)H NMR spectroscopy revealed that aromatic π-π stacking and van der Waals forces were important in the formation of the gels, with the former being the main driving force for sol-gel transition. The π-conjugation length showed a key influence on self-assembly and gelation property: the gel-to-sol transition temperature (Tgel) increased with π-conjugation length. The gels of OPV4-7 can self-assemble into one-dimensional fibers with different sizes and shapes, depending on their π-conjugation length. On the basis of X-ray diffraction measurements and spectroscopic data, a self-assembly model was proposed. Our observation may be useful for designing functional π-gelators based on π-π stacking.

Anion-activated, thermoreversible gelation system for the capture, release, and visual monitoring of CO2.

Carbon dioxide (CO2) is an important green house gas. This is providing an incentive to develop new strategies to detect and capture CO2. Achieving both functions within a single molecular system represents an unmet challenge in terms of molecular design and could translate into enhanced ease of use. Here, we report an anion-activated chemosensor system, NAP-chol 1, that permits dissolved CO2 to be detected in organic media via simple color changes or through ratiometric differences in fluorescence intensity. NAP-chol 1 also acts as a super gelator for DMSO. The resulting gel is transformed into a homogeneous solution upon exposure to fluoride anions. Bubbling with CO2 regenerates the gel. Subsequent flushing with N2 or heating serves to release the CO2 and reform the sol form. This series of transformations is reversible and can be followed by easy-to-discern color changes. Thus, NAP-chol 1 allows for the capture and release of CO2 gas while acting as a three mode sensing system. In particular, it permits CO2 to be detected through reversible sol-gel transitions, simple changes in color, or ratiometric monitoring of the differences in the fluorescence features.

A glucose-based diblock copolymer: synthesis, characterization and its injectable/temperature-sensitive behaviors

To be more biocompatible, poly(N-isopropyl acrylamide) (PNIPAM) hydrogel, as a typical temperature-sensitive hydrogel, is expected to be linked with other materials of excellent biocompatibility. For this propose, poly(N-isopropyl acrylamide)-block-poly(3-O-allyl-α-D-glucose) (PNIPAM-b-POAG), a new diblock copolymer, was successfully synthesized from N-isopropyl acrylamide (NIPAM) and 3-O-allyl-1,2:5,6-di-O-isopropynylene-α-D-glucose (OAIG) via reversible addition-fragmentation chain transfer (RAFT) polymerization in the presence of cumyl dithiobenzoate (CDB). PNIPAM-b-POAG was characterized byFourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, and gel permeation chromatography (GPC). The critical micelle concentration (CMC) of the copolymer was 0.045 mg/ml measured by fluorescence spectroscopy. The copolymer solution exhibited a reversible sol-gel phase transitions with the increase or decrease of temperature. An in situ gel formed rapidly after subcutaneously injecting the copolymer solution into a Sprague Dawley (SD) rat, which indicated the copolymer has a good injectable property. The in vitro release result showed that methylene blue (MB) as a model was sustainably released by the temperature-sensitive PNIPAM-b-POAG diblock copolymer at 37 °C within 120 h. The copolymer showed no apparent cytotoxicity on L929 cells by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The novel temperature-sensitive hydrogel is a promising candidate for drug delivery.

Multistimuli Responsive and Electroactive Supramolecular Gels Based on Ionic Liquid Gemini Guest.

Electroactive supramolecular gels with multistimuli responsiveness were fabricated through host-guest interactions between a host polymer containing β-cyclodextrin (CD) and an ionic liquid (IL) type asymmetric gemini guest, which contains both ferrocene (Fc) and bis(trifluoromethyl-sulfonyl)imide (TFSI-) as the respective α- and ω-guest groups. Owing to the multiple stimuli-responsiveness of the host-guest interactions, reversible sol-gel phase transition could be triggered by various stimuli, including temperature, electrochemical/chemical redox and anion-exchange reactions. Due to the intrinsically conductive properties of the IL gemini guest, the sol-gel transition behavior could be electrochemically controlled by the applied voltage, without using additional supporting electrolyte.

Fabrication of Reversible Phase Transition Polymer Gels toward Metal Ion Sensing

We report the synthesis of a new type of triple stimuli-responsive, i.e., thermo-, pH-, and metal ion-responsive copolymers based on poly(N-vinylimidazole-co-methacrylic acid) (poly(VI-co-MAA)) and their application as metal ion sensors. The copolymers exhibit reversible sol–gel phase transition behavior in aqueous media. The sol-to-gel transition temperature (Tsol–gel) can be shifted in the range of 20–80 °C, by varying monomer ratio and feeding glycerol content, by adjusting the copolymer concentration in aqueous solution, by tuning the pH of the solution, or by adding various divalent metal ions. Metal ion sensors were designed upon an inverse opal photonic film loaded with aqueous solution of poly(VI-co-MAA), which allows the easy reorganization of various divalent metal ions by combining the diversity of Tsol–gel of the copolymers on different metal ions and flexible reflection spectra of the film. In addition, a fluorescent reversible sol–gel transition system was established by in situ generation of nanocrystals in the copolymer matrix. These extensions may provide the multiresponsive copolymers great flexibility for applications in biomedical, optical, and sensory fields.

Stimuli-induced gel-sol transition of supramolecular hydrogels based on β-cyclodextrin polymer/ferrocene-containing triblock copolymer inclusion complexes

A novel kind of host-guest hydrogel possessing gel–sol phase transformation in response to temperature, oxidizing agent and glucose was prepared by ferrocene (Fc)-containing pluronic F127 and β-cyclodextrin (β-CD) linear polymer, which was synthesized in aqueous alkali by using native β-CD and epichlorohydrin in the presence of toluene. Because of the reversible association–dissociation of Fc-β-CD inclusions and F127 micelles, the gel-sol transition was easily observed. Two-dimension nuclear overhauser effect spectroscopy (2D NOESY), nuclear magnetic resonance (NMR), TEM (transmission electron microscopy) and TGA (thermogravimetric analysis) measurements were used to clarify the inclusion complexes of Fc-β-CD. The results showed that the formation of inclusion complexes affected the micelle size and stabilized the hydrogels. The rheological properties of solution and hydrogels were measured. The viscosity of hydrogel was enhanced markedly, to about 90 times higher than that of Fc-F127-Fc solution at the same concentration. Due to the coactions of PPO aggregation and Fc-β-CD inclusion, the gelation temperature of hydrogel was lower than that of Fc-F127-Fc solution. The reversible gel-sol transition and multi-sensitive supramolecular hydrogels may potentially be used in injectable hydrogel for drug delivery.

Thermal and photo reversible gel–sol transition of azobenzene based liquid crystalline organogel

Abstract Azobenzene based photoresponsive gelator, 1,2-bis[4-(4-(10-decyloxy)phenylazo)]-benzoylhydrazine showing selective gelation in alcoholic solvent is described. Whilst their thermodynamic behaviors are investigated by polarized optical microscopy and differential scanning calorimetry, the related layer arrangement is measured by X-ray diffraction techniques in which the organogel shows monotropic liquid crystalline phase. Present work shows that the non-liquid crystalline gelator can be converted into liquid crystalline organogel in the presence of alcoholic solvent in which the trans-cis isomerization of the azobenzene moiety disrupts the entanglement of gel fibers of self-assembly resulting in gel–sol transition. The present result also shows that the organogel is capable of the thermal and photo induced transition from gel–sol and vice versa.

Redox- and pH-responsive polymer gels with reversible sol–gel transitions and self-healing properties

Redox- and pH-responsive polymer gel with self-healing property was prepared by crosslinking of benzhydrazide-containing polytriazole with a disulfide-containing dialdehyde.

Tryptophan containing covalently cross-linked polymeric gels with fluorescence and pH-induced reversible sol–gel transition properties

pH-reversible covalently cross-linked polymeric gels from a side-chain polymer with multi-amino groups and a difunctional aldehyde cross-linker have been prepared by employing dynamic covalent chemistry in the form of reversible imine (CN) bond formation. Two different series of dual pH- and thermo-responsive amino acid based copolymers with primary amine groups located at different positions and various chemical compositions are synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization of tert-butyl carbamate (Boc)-tryptophan methacryloyloxyethyl ester (Boc-Trp-HEMA) with 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and N,N-(dimethylamino)ethyl methacrylate (DMAEMA) respectively, followed by Boc-group expulsion. The pH-induced thermoresponsive properties of the copolymers have been observed with the high content of thermoresponsive MEO2MA/DMAEMA segments (∼80%) in the copolymer. The tryptophanyl moiety present in the copolymer chain provided florescence characteristics, which were studied by florescence spectroscopy. Copolymers with free amino groups were employed for cross-linking with a difunctionalized aldehyde cross-linker, 4-formylphenyl 4′-formylbenzoate (FPFB), to form dynamic covalent gels through the formation of CN bonds in the network. Rheological measurements have been conducted with various ratios of CHO/NH2 from 1 to 0.33 for homopolymer gels and copolymer gels with different amino acid contents (20–80%), which showed a plateau of storage modulus (G′) over a wide range of angular frequencies indicating the independent nature of G′ with respect to angular frequency, and the mechanical properties of dynamic gels are a function of cross-linking density. The pH-dependent reversible sol–gel transition has also been investigated.

A simple structural hydrazide-based gelator as a fluoride ion colorimetric sensor.

A 4-nitrobenzohydrazide derivative, N-(3,4,5-octyloxybenzoyl)-N'-(4'-nitrobenzoyl)hydrazine (C8), was synthesized. It could form stable gels in some of the tested organic solvents. The wide-angle X-ray diffraction analysis showed that the xerogels exhibited a layered structure. SEM images revealed that the molecules self-assembled into fibrous aggregates in the xerogels. FT-IR studies confirmed that the intermolecular hydrogen bonding between C=O and N-H groups was the major driving force for the formation of self-assembling gel processes. The gel is utilized for a 'naked eye' detection of fluoride ions, through a reversible gel-sol transition, which is associated with a color change from colorless to red. An extended conjugated system formed through the phenyl group and a five-membered ring based on intramolecular hydrogen bonding between the oxygen atom near the deprotonation nitrogen atom and the other NH, which is responsible for the dramatic color change upon addition of fluoride ions.

Tb(3+)-containing supramolecular hydrogels: luminescence properties and reversible sol-gel transitions induced by external stimuli.

A dual-responsive green-light-emitting supramolecular metal hydrogel (G-gel) was prepared by the reaction of a simple hydrazide-functionalized benzimidazole ligand (L) with Tb(NO3)3. The green luminescence of gelator L is enhanced in the G-gel due to the coordination effect between L and Tb(3+). In addition, the G-gel shows different luminescence when in a semisolid state (gel) and in a solid state (xerogel). Remarkable reversible sol-gel transitions induced by temperature or pH were observed for this G-gel.