Acid⋅⋅⋅Amide Supramolecular Synthon for Tuning Amino Acid‐Based Hydrogels’ Properties

Abstract

AbstractSupramolecular hydrogels formed by the self‐assembly of N‐Fmoc‐l‐phenylalanine derivatives are gaining relevance for several applications in the materials and biomedical fields. In the challenging attempt to predict or tune their properties, we selected Fmoc‐pentafluorophenylalanine (1) as a model efficient gelator, and studied its self‐assembly in the presence of benzamide (2), a non‐gelator able to form strong hydrogen bonds with the amino acid carboxylic group. Equimolar mixtures of 1 and 2 in organic solvents afforded a 1 : 1 co‐crystal thanks to the formation of an acid⋅⋅⋅amide heterodimeric supramolecular synthon. The same synthon occurred in the transparent gels formed by mixing the two components in 1 : 1 ratio in aqueous media, as revealed by structural, spectroscopic, and thermal characterizations performed on both the co‐crystal powder and the lyophilized hydrogel. These findings revealed the possibility of modulating the properties of amino acid‐based hydrogels by involving the gelator in the formation of a co‐crystal. Such a crystal engineering‐based approach is shown also to be useful for the time‐delayed release of suitable bioactive molecules, when involved as hydrogel coformers.