Molecular simplicity, supramolecular complexity: amphiphilic peptide-based gelators as hydrogel materials

Low-molecular-weight gelators (LMWGs) are small organic molecules capable of self-assembling into fibrous networks through non-covalent interactions (hydrogen bonding, π–π stacking, and hydrophobic effects), giving rise to a versatile class of supramolecular materials. Upon triggering (by pH change or solvent variation), these molecules can immobilize large amounts of solvent, forming gels that behave as soft solids. Owing to their biocompatibility, modularity, and structural simplicity, supramolecular gels have found applications across diverse fields, ranging from biomedical and environmental technologies to catalysis, and cosmetic formulations. The rational design of LMWGs capable of self-assembling into supramolecular architectures represents a crucial challenge in modern soft matter chemistry, as even minor molecular modifications can drastically alter their self-assembly and macroscopic behaviour. This PhD work focused on amino acid-derived amphiphilic and bolaamphiphilic molecules as minimalistic, bioinspired building blocks for supramolecular gels. Through a combined experimental and structural approach, this research aimed to elucidate how subtle molecular modifications (such as variations in the aromatic core, chain length, or molecular symmetry) affect aggregation, gelation, and the transition between crystalline and gel states. The research was organized into two main sections: the first explored Boc-protected Dopa (3,4-dihydroxyphenylalanine) derivatives as model systems for correlating molecular packing and supramolecular behaviour, while the second addressed families of amphiphilic and bolaamphiphilic derivatives of Dopa, phenylalanine, and tyrosine, to establish structure–property relationships across a broader molecular framework. Comprehensive characterization by rheology, electronic circular dichroism (ECD), scanning electron microscopy (SEM) and single-crystal X-ray diffraction revealed that small structural changes profoundly impact supramolecular organization. The results highlighted the delicate balance between solubility, π–π stacking, and hydrogen bonding in determining whether molecular aggregation leads to stable gels or ordered crystalline materials. Overall, this work provides an integrated structure-property framework for understanding and predicting the self-assembly behaviour of peptide-based LMWGs.