Molecular Hydrogels Research Articles

Exploiting Enzymatic (Reversed) Hydrolysis in Directed Self‐Assembly of Peptide Nanostructures

Enzyme-catalyzed reactions can be exploited to control molecular self-assembly under physiological conditions by converting nonassembling precursors into self-assembly building blocks. Two complementary approaches based on aromatic short-peptide derivatives that form molecular hydrogels are demonstrated. Firstly, it is shown that esterase-directed self assembly via hydrolysis of hydrophobic N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-peptide methyl esters give rise to formation of transparent hydrogels composed of defined peptide nanotubes. The internal and external diameters of these tubes are highly tunable, depending on the amino acid composition and chain length of the building blocks. Secondly, protease-directed self-assembly of Fmoc-peptide esters is achieved via amide-bond formation (reversed hydrolysis) for combinations of Fmoc-threonine and leucine/phenylalanine methyl esters, producing fibrous hydrogels. Upon treatment with an esterase, these systems revert back to solution, thus providing a two-stage solution-gel-solution transition.

Enzymatic hydrogelation to immobilize an enzyme for high activity and stability.

This article describes a new way to immobilize an enzyme by enzymatic hydrogelation to facilitate catalysis in the organic solvent to attain high activity and stability. A self-immobilized acid phosphatase (AP) in a molecular hydrogel created by the enzymatic hydrogelation had shown higher activities in several organic solvents than those of free AP in the same solvents. The high activities of AP(gel) in organic solvents are mainly due to the cooperative effect of the amphiphilic nanofibers in the hydrogel and the phase transfer between the organic solvent and the water in the hydrogel. This approach provides a useful method to immobilize enzymes for biotransformation in organic solvents.

Bisphosphonate-containing supramolecular hydrogels for topical decorporation of uranium-contaminated wounds in mice

Purpose: Personnel experiencing accidents that involve radionuclides or victims of potential malicious radioactive attacks may suffer injuries with wounds contaminated by radionuclides. The current treatment for contamination from uranium in external injuries is the use of saline solution to wash the wounds, which has the drawback of further spreading of the contaminants due to the flow of water. To minimize the cost of storage of contaminated liquids and to improve the efficiency of treatment, we propose the use of hydrogels as a form of decorporation agent.Methods: Mice with uranium-contaminated wounds on their backs were treated with bisphosphonate or diethylene triamine pentaacetic acid (DTPA) containing supramolecular hydrogels. Survival rates of the treated mice and changes in the body weight of the mice were observed and compared to those of mice without hydrogel treatment. Distribution of uranium in the mice was also explored as proof of the effectiveness of the hydrogel treatment.Results: The survival rate of the hydrogel-treated mice was significantly higher than that of the mice without treatment. The body weights of the hydrogel-treated mice showed significant recovery after 10 days while the body weight of mice without hydrogel treatment continuously decreased. The amount of uranyl ions in the organs (mainly concentrated in the kidney) of the hydrogel-treated mice was much smaller than that of the mice without hydrogel treatment.Conclusions: By incorporating uranium chelating agents, we developed new supramolecular hydrogels that could effectively and conveniently decorporate uranium ions from the contaminated wound sites of mice, with the highest efficacy achieved by our pamidronate-based molecular hydrogel.

Water‐Soluble Fluorescent Ag Nanoclusters Obtained from Multiarm Star Poly(acrylic acid) as “Molecular Hydrogel” Templates

Water‐Soluble Fluorescent Ag Nanoclusters Obtained from Multiarm Star Poly(acrylic acid) as “Molecular Hydrogel” Templates

Conjugates of naphthalene and dipeptides produce molecular hydrogelators with high efficiency of hydrogelation and superhelical nanofibers

Here we report a new class of molecular hydrogelators based on the conjugates of dipeptide and (naphthalen-2-yloxy)acetic acid. They form hydrogels efficiently—the lowest concentration for them to gel water is 0.07 wt%. Two hydrogelators show the ability to form helical nanofibers within the hydrogels, and the chirality of the hydrogelators apparently dictates the handedness of the nanofibers—D-peptide and L-peptide afford left-handed and right-handed self-assembled nanofibers in the hydrogels, respectively. Moreover, MTT assay of the viability of cells indicates that these molecular hydrogelators are biocompatible.

Molecular hydrogel-immobilized enzymes exhibit superactivity and high stability in organic solvents

This communication describes the use of a molecular hydrogel to immobilize enzymes for catalyzing reactions in an organic solvent to attain superactivity and exceptional stability.

Molecular Hydrogels from Bile Acid Analogues with Neutral Side Chains: Network Architectures and Viscoelastic Properties. Junction Zones, Spherulites, and Crystallites: Phenomenological Aspects of the Gel Metastability

Structural and rheological properties of hydrogels made up of neutral bile acid derivatives are studied. Complementary scattering, diffraction, and microscopy techniques provide a precise structural description of the network architecture and its variation as a function of concentration, aging time, composition of the solvent, and type of gelator. Two derivatives (TH and PH) are considered as presenting favorable scattering features to approach the issue of the competition between gelation versus crystallization. PH and TH fibers are semirigid cylinders with monodisperse cross-sections (R(0) = 92 and 80 A, respectively) involving 25 or 12 molecules per cross-sectional repeating unit along the fiber axis. Bundles are cross-links in the networks, and a scattering protocol is developed to determine the nodal and fibrillar fractions in the networks. The effects of alcoholic mixtures, dimethylsulfoxide, and temperature on the network properties are analyzed in terms of the bending modulus of the fibers, the degree of nonaffine character of the regime of deformation, and the dispersion degree of the nodal heterogeneities. It is shown that fibers are semirigid and the scaling laws of the elasticity of the gels with the concentration (exponent (5)/(2)) also support the theoretical context. Head-to-tail molecular arrangements are shown to be similar in the solid and gel phases. Birefringent textures show that spherulitic microdomains coexist in the network texture and are the seeds for a slow crystallization process. The whole pattern might be more general for numerous other self-assembled fibrillar networks found in molecular gels.

Self-Assembled Networks of Ribbons in Molecular Hydrogels of Cationic Deoxycholic Acid Analogues

Aqueous gels derived from three cationic 24-nor 3,12-dihydroxy cholane (DC) derivatives with N-methyl-2-pyrrolidinone (NMP), N-methylmorpholine (NMM), and 1,4-diazabicyclo[2.2.2]octane (DABCO) at the side chain positions have been exhaustively characterized by small-angle neutron-scattering experiments. Although the molecular structures differ slightly by the heterocycle grafted to the steroid core, the derived gels exhibit a range of structural behaviors at the nanoscale that depart from those observed with simple deoxycholate systems. The NMM-DC aggregates are ribbons with a bimolecular thickness of t = 37 A and an anisotropy of the section b/a approximately 0.1. DABCO-DC exhibits a remarkable transition from ribbons (t = 29.5 A, b/a = 0.18) to thicker cylindrical fibers (R approximately 59 A), involving four original ribbons, upon a concentration increase. The NMP-DC system forms thick cylindrical fibers (R approximately 68 A) with steroid molecules organized in a specific morphology. Bilayered or interdigited structures are formed and favored by the presence of multiple polar interaction centers in the DC molecules. Secondary aggregation mechanisms are invoked in the formation of bundles having a lower cross-sectional anisotropic symmetry and exhibiting Bragg peaks corresponding to molecular length periodicities. The relations between the structural information and the rheological properties are discussed.

Structure and Dynamics of a Molecular Hydrogel Derived from a Tripodal Cholamide

Tripodal cholamide 1 is a supergelator of aqueous fluids. A variety of physical techniques, including cryo-transmission electron microscopy (TEM), circular dichroism (CD), steady-state fluorescence, time-resolved fluorescence, and dynamic light-scattering, were employed to understand the structure and dynamics of the gel. Fluorescent probes [ANS (8-anilinonaphthalene-1-sulfonic acid) and pyrene] reported two critical aggregation concentrations (CAC(1) and CAC(2)) of 1 in predominantly aqueous media, with the minimum gel concentration (MGC) being close to CAC(2). Fluorescence lifetime measurements with pyrene revealed ineffective quenching of pyrene fluorescence by oxygen, possibly caused by slower Brownian diffusion due to the enhanced viscosity in the gel phase. The study of the gelation kinetics by monitoring the ultrafast dynamics of ANS revealed a progressive increase in the aggregate size and the microviscosity of the aqueous pool encompassed by the self-assembled fibrillar network (SAFIN) during the gelation. The striking difference between microviscosity and bulk (macroscopic) viscosity of the gel is also discussed.

A Pilot Study Evaluating Sodium Hyaluronate as a Carrier For Freeze-dried Demineralized Bone Powder.

Freeze-dried demineralized bone (FDDB) is widely used in orthopaedic and neurosurgery. However, it is difficult to deliver the FDDB by itself and surgeons have been seeking a convenient and easy-to-use form of FDDB. This study was designed to evaluate sodium hyaluronate (HA) as a carrier or delivery vehicle. HA is a viscous and biocompatible high molecular weight hydrogel. It was tested as a viscous carrier to facilitate the delivery of freeze-dried demineralized bone into a bony defect. The natural bone forming properties of FDDB were evaluated in an athymic mouse model and shown to be as active when dispersed in HA as compared to a saline control. Particle sizes in the range studied (125-850 microm) had no effect on FDDB efficacy. All exhibited active bone formation. Similarly, two different carrier viscosities were formulated to achieve both a malleable putty and a more flowable paste. These, too, both exhibited active bone formation. The use of a pH 7.4 buffer in the HA formulation gave optimum results in the model. Additional studies are underway to further evaluate the surgical efficacy of FDDB suspended in HA.

Chemical Modifications of Heparin.1: Reaction of Partially N-Desulfated Heparin with Glutaraldehyde

Purified glutaraldehyde was allowed to react with the primary amino groups generated by mild acidolysis of glucosamine N-sulfamino resi dues present in heparinic acid. The reaction yielded high molecular mass heparinoids (HMMHEP) or hydrogels, depending on experimental conditions. It was shown that a selected HMMHEP exhibited a higher anticoagulant activ ity than the starting heparin or the parent partially N-desulfated heparin. This HMMHEP degraded slowly in vitro in an aqueous medium buffered at pH = 7.4. Moreover, HMMHEP was biologically active after i.v. injection but not after s.c. and i.m. injections. Hydrogels also degraded slowly to yield biologi cally active higher molecular mass heparinoid. These findings suggested that neither N-desulfation nor coupling of glutaraldehyde adducts affected in a large extend the activity of the parent heparin.