G4-quartet·M(+) borate hydrogels.

The ability to modulate the physical properties of a supramolecular hydrogel may be beneficial for biomaterial and biomedical applications. We find that guanosine (G 1), when combined with 0.5 equiv of potassium borate, forms a strong, self-supporting hydrogel with elastic moduli >10 kPa. The countercation in the borate salt (MB(OH)4) significantly alters the physical properties of the hydrogel. The gelator combination of G 1 and KB(OH)4 formed the strongest hydrogel, while the weakest system was obtained with LiB(OH)4, as judged by (1)H NMR and rheology. Data from powder XRD, (1)H double-quantum solid-state magic-angle spinning (MAS) NMR and small-angle neutron scattering (SANS) were consistent with a structural model that involves formation of borate dimers and G4·K(+) quartets by G 1 and KB(OH)4. Stacking of these G4·M(+) quartets into G4-nanowires gives a hydrogel. We found that the M(+) cation helps stabilize the anionic guanosine-borate (GB) diesters, as well as the G4-quartets. Supplementing the standard gelator mixture of G 1 and 0.5 equiv of KB(OH)4 with additional KCl or KNO3 increased the strength of the hydrogel. We found that thioflavin T fluoresces in the presence of G4·M(+) precursor structures. This fluorescence response for thioflavin T was the greatest for the K(+) GB system, presumably due to the enhanced interaction of the dye with the more stable G4·K(+) quartets. The fluorescence of thioflavin T increased as a function of gelator concentration with an increase that correlated with the system's gel point, as measured by solution viscosity.

A G4·K⁺ hydrogel stabilized by an anion.

Supramolecular hydrogels derived from natural products have promising applications in diagnostics, drug delivery, and tissue engineering. We studied the formation of a long-lived hydrogel made by mixing guanosine (G, 1) with 0.5 equiv of KB(OH)4. This ratio of borate anion to ligand is crucial for gelation as it links two molecules of 1, which facilitates cation-templated assembly of G4·K(+) quartets. The guanosine-borate (GB) hydrogel, which was characterized by cryogenic transmission electron microscopy and circular dichroism and (11)B magic-angle-spinning NMR spectroscopy, is stable in water that contains physiologically relevant concentrations of K(+). Furthermore, non-covalent interactions, such as electrostatics, π-stacking, and hydrogen bonding, enable the incorporation of a cationic dye and nucleosides into the GB hydrogel.

Self-Assembly of Metallo-Nucleoside Hydrogels for Injectable Materials That Promote Wound Closure.

Injectable hydrogels are increasingly being used as scaffolds for in situ tissue engineering and wound healing. Most of these injectable hydrogels are made from polymers, and there are fewer examples of such soft materials made via self-assembly of low-molecular weight gelators. We report the room-temperature synthesis of a functional hydrogel formed by mixing cytidine (C) with 0.5 equiv each of B(OH)3 and AgNO3. The structural basis for this supramolecular hydrogel (C-B-C·Ag+) involves orthogonal formation of cytidine borate diesters (C-B-C) and Ag+-stabilized C-C base pairs, namely, the C·Ag+·C dimer. The C-B-C·Ag+ hydrogels, which can have high water content (at least 99.6%), are stable (no degradation after 1 year in the light), stimuli-responsive, and self-supporting, with elastic moduli of up to 104 Pa. Incorporation of Ag+ ions into the gel matrix endows the C-B-C·Ag+ hydrogel with significant antibacterial capability. Importantly, the rapid switching between the sol and gel states for this supramolecular hydrogel, as a response to shear stress, enables 3D printing of a flexible medical patch made from the C-B-C·Ag+ hydrogel. The C-B-C·Ag+ hydrogel was used to promote the closure of burn wounds in a mouse model.

Supramolecular hydrogels for environmental remediation: G4-quartet gels that selectively absorb anionic dyes from water.

Binary mixtures of guanosine (G 1) and 8-aminoguanosine (8AmG 2) form stable, transparent supramolecular hydrogels with stoichiometric concentrations of either K+ or Ba2+ salts. These hydrogels selectively bind anionic dyes.

G-Quartet hydrogels for effective cell growth applications.

Functional G-quartet hydrogels formed from natural guanosine cross linked with benzene-1,4-diboronic acid and Mg2+ support cell growth with no visible signs of gel degradation.

A G4·K(+) hydrogel that self-destructs.

A G4-quartet based hydrogel formed by self-assembly of borate esters of 5'-deoxy-5'-iodoguanosine (5'-IG 2) undergoes in situ cyclization to give 5'-deoxy-N3,5'-cycloguanosine (5'-cG 3). Formation of 5'-cG 3 causes self-destruction of the gel. This intramolecular cyclization can be used to release nucleoside analogs that have been pre-incorporated into the gel network.