A structure–gelation ability study in a short peptide-based ‘Super Hydrogelator’ system

The development of small molecules that can efficiently gel water is of great interest for researchers in the field of self-assembly. We recently found that a short peptide-based molecule (Nap-GFFpY-OMe) could form hydrogels at a minimum gelation concentration of 0.01 wt% after enzymatic conversion, which was the most efficient small molecular hydrogelator reported up to now. In order to study the relationship between the chemical structure and the gelation ability for these short peptide-based gelators, we designed and synthesized a small library of compounds with similar chemical structures to Nap-GFFpY-OMe. They have different capping groups for the amine on glycine (G), different numbers of glycines, different numbers of phenylalanines (F), and different groups at the C-terminus of the peptides. Based on the results, we concluded that the compounds were ‘super gelators’ when their amine capping group was naphthalene, the number of G residues was odd (one and three), the number of F residues was two, and the C-terminus of the peptide was a methyl ester. We found that 10 compounds within the library could form hydrogels and the hydrogels were characterized by rheology, transmission electron microscopy (TEM), and fluorescence spectroscopy. The cytotoxicity of all the precursors of the gelators were also evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and we found that three precursors possessed obviously bigger IC50 values than their corresponding minimum gelation concentrations (MGCs). This study not only suggests the potential applications of our gel system in biomedical fields, but also provides useful information for the molecular design of short peptide-based hydrogelators with excellent gelation abilities.