Hierarchical Self‐Assembly of Amphiphilic β‐C‐Glycosylbarbiturates into Multiresponsive Alginate‐Like Supramolecular Hydrogel Fibers and Vesicle Hydrogel

Abstract

Ordered molecular self-assembly of glycoamphiphiles has been regarded as an attractive, practical and bottom-up approach to obtain stable, structurally welldefined, and functional mimics of natural polysaccharides. This study describes a versatile and rational design of carbohydrate-based hydrogelators through N,N'-substituted barbituric acid-mediated Knoevenagel condensation onto unprotected carbohydrates in water. Amphiphilic N-substituted β-C-maltosylbarbiturates self-assembled into pH-and calcium-triggered alginate-like supramolecular hydrogel fibers with a multistimuli responsiveness to temperature, pH and competitive metal chelating agent. In addition, amphiphilic N,N'-disubstituted β-C-maltosylbarbiturates formed vesicle gels in pure water that were scarcely observed for glycohydrogelators. Finally, barbituric acid worked as a multitasking group allowing chemoselective ligation onto reducing-end carbohydrates, structural diversity, stimuli-sensitiveness, and supramolecular interactions by hydrogen bonding.

Supramolecular carbohydrate-based hydrogels from oxidative hydroxylation of amphiphilic β-C-glycosylbarbiturates and α-glucosidase-induced hydrogelation

“…Briefly, the syntheses of GlcB and MalB were performed through the Knoevenagel condensation in water by reacting chemo-selectively N,N′-alkyl barbituric acid derivatives with unprotected Glc and Mal at the reducing-end anomeric position, as already reported. 18 Next, H 2 O 2 -mediated oxidative hydroxylation of GlcB and MalB in water led successfully to GlcB(OH) and MalB(OH), respectively, with moderate to good yields (54-72%) as shown in Table 1. While thin-layer chromatography analyses indicated an almost complete reaction, a chromatographic separation step was required, lowering the yields in isolated products.…”

“…1), which feature a maltose disaccharide linked through an N-monosubstituted barbiturate to a C18 saturated aliphatic chain and a C18 mono-unsaturated C18:1 (cis-9) chain, respectively, were able to hierarchically selfassemble into supramolecular hydrogels either under strong acidic conditions or by adding calcium ions. 18 We found, with others, [28][29][30] that the hydrophobic-hydrophilic balance is a determinant parameter for exhibiting hydrogelation and since oxidative hydroxylation brings an additional hydroxyl function, we decided to screen a library of synthetic amphiphilic β-C-glycosylbarbiturates GlcB(OH) and MalB(OH) for their hydrogelation abilities (Scheme 2).…”

“…[12][13][14] Very recently, we tackled these problems by reporting an efficient and versatile green synthetic method to construct glyco-hydrogelators through the Knoevenagel condensation of N,N′-substituted barbituric acids with protecting group-free carbohydrates in water. 18 The resulting sodium salt of N-monosubstituted β-C-glycosylbarbiturates led to entangled nanostructured hydrogels either under strong acidic conditions or by adding calcium ions at neutral pH (Fig. 1).…”

Aggressive strategies for regenerating intervertebral discs: stimulus-responsive composite hydrogels from single to multiscale delivery systems

“…186 Sodium citrate was able to degrade the hydrogel network through chelation, completing the application mechanism of Ca 2+ -sensitive hydrogels. Multiscale delivery systems based on ion-sensitive composite hydrogels are advantageous because ions are not only able to respond to the complexation mechanism of metal chelates, such as Yao et al 187 who assembled amphiphilic N -substituted β- C -maltosyl barbiturates into pH- and Ca 2+ -sensitive ALG supramolecular composite hydrogels with multiple stimulus responses of temperature, pH and Ca 2+ . Additionally, ionic nanocomplexes can be assembled into multiscale delivery systems, such as agarose-based composite hydrogels based on manganese oxide (MnO 2 ) nanoparticles, which trigger the catalytic decomposition of H 2 O 2 mediated by MnO 2 nanoparticles under NIR conditions to release oxygen.…”

Incorporation of PEG Diacrylates (PEGDA) Generates Hybrid Fmoc-FF Hydrogel Matrices

“…Hydrogels (HGs) are hydrophilic materials structurally characterized by a three-dimensional (3D) network originated by the macroscopic organization of polymer chains or of supramolecular elements [ 1 , 2 , 3 ]. The ability of these matrices to retain a large amount of aqueous fluid (~95/99%) confers on them a non-Newtonian flow behavior associated with a self-supporting tendency.…”