Unravelling Non-Peptidic Analogues as Phe-Phe Mimetics: Insights into Synthesis, Self-Assembly, Structural Analysis,...

The diphenylalanine (FF) and its derivatives are widely studied for their self-assembly, mechanical strength, and diverse applications in materials and the biomedicine field. To develop a stable, and synthetically accessible nonpeptidic FF mimic, 14 aromatic derivatives of l-phenylalanine (A1 to A7) and l-phenylglycine (G1 to G7) were designed and synthesized to investigate the structure-property relationships. The systematic variation of aromatic groups, electronic substitution, and C-terminal protection enabled control of the intermolecular interactions. The morphological study revealed that rigid derivatives formed rod-like structures through strong π-π stacking, whereas the flexible derivatives produced fibrillar morphologies. The C-terminal modification promoted plate-like assemblies, while the electronic effects led to microplate formation. Here, the N-terminal phenylacetyl protection enhances the molecular flexibility of derivative A2, enabling it to mimic the morphological and optical behavior of FF-dipeptide while offering enhanced stability and highlighting a robust nonpeptidic platform for bioinspired nanomaterials.