Supramolecular hydrogels derived from 2 : 1-[α/aza]-pseudopeptides: design, structural analysis and self-assembly in solution, solid, and gel states

Abstract

Synthesis of innovating supramolecular hydrogels based on low molecular weight gelators (LMWGs < 2000 Da) has gained significant interest within the scientific research community due to their wide-ranging potential applications. Most supramolecular hydrogels, induced by a self-assembly process, are stabilized via non-covalent interactions. Recently, our research group has investigated the gelation properties of new low molecular weight hydrogelators (LWMHGs) based on Fmoc-functionalized 2 : 1-[α/aza]-azapeptides. This study presents the synthesis and characterization of two Fmoc-N-functionalized 2 : 1-[α/aza]-trimers: Fmoc-FazaFA (1) and Fmoc-D-FazaFA (2). Both molecules have demonstrated their capability to form hydrogels at pH 7.0 and 10.0, and the analysis of their monomeric states in solution using spectroscopic techniques (including NMR and FTIR) and in the crystal state (using X-ray diffraction) revealed a β-turn conformation. Molecular dynamics simulations were used for 3D model determination. Additionally, the structure of both molecules in the gel state was examined by circular dichroism (CD) experiments. The findings have confirmed that intermolecular hydrogen bonding and π-stacking between the aromatic moieties are the primary driving forces behind the self-assembly and hydrogelation phenomena. Rheology measurements validated the solid-like behavior of both hydrogels (G′ > G′′ within the studied frequency range). Finally, the self-assembly is emphasized through the fibrous structure observed by SEM imaging.