Water‐Soluble (Poly)acylhydrazones: Syntheses and Applications

Abstract

Acylhydrazone-based (macro)molecules display an increasingly broad spectrum of applications, from small therapeutic molecules and metal-ions probes to self-healing films and biorelevant dynamic polymers. The acylhydrazone function is indeed of prime interest since its unique design combines hydrogen bonds, pH-dependent reversibility, ability to undergo molecular exchanges, and a possible polyvalency. However, a key parameter of its use in aqueous media is the associated water-solubility of the resulting (macro)molecule. This property can indeed become a limitation for applications requiring high concentrations or no organic cosolvent. This review first focuses on describing the acylhydrazone function, its properties, and its relevancy in dynamic combinatorial chemistry. Then it details the synthesis strategies (molecular design, cosolvent, reaction conditions) reported in the literature to ensure a sufficient solubilization of both single-bond and multiple-bond acylhydrazone (macro)molecules, together with their various applications.

Structure‐Activity Relationships in Nucleic‐Acid‐Templated Vectors Based on Peptidic Dynamic Covalent Polymers

“…We reported a synthetic methodology for making peptide bisaldehydes BisAld n and complementary N‐aminooxy, C‐hydrazide arginine‐rich peptides OxArg n Hyd , which both take part in the formation of peptide‐based dynamic covalent polymers (DCPs). The approach is versatile and will enable inserting different sequences in the future [21] . For now, we have explored arginine‐rich DCPs that are formed in situ by nucleic acid‐templated polymerization.…”

“…The approach is versatile and will enable inserting different sequences in the future. [21] For now, we have explored arginine‐rich DCPs that are formed in situ by nucleic acid‐templated polymerization. Compared to the robotic screening of polymers for transfection applications, which require cumbersome work, [22] our methodology based on templated self‐assembly simply involves mixing of appropriate building blocks at room temperature in a slightly acidic saline buffer.…”

Photocurable acylhydrazone covalent adaptable networks with fast dynamic exchange and tunable viscoelastic properties

“…However, acylhydrazone compounds also exhibit a lower exchange rate and better acid resistance ( pH > 4 stable) due to the mesomeric effect and hydrogen bonding caused by the amide bond adjacent to the imine bond. [45][46][47] Therefore, acylhydrazones are promising for the production of CANs that are more creep and acid resistant compared to imine CANs.…”