Cold Atmospheric Plasma-Driven Structural Transformation of Self-Assembled Fmoc-Trp and Fmoc-Phe into Supramolecular Aggregated Assemblies

Supramolecular chemistry plays a key role in the design of functional nanomaterials, and the self-assembly behavior of amino acids modified with the Fmoc group has gained significant attention for its potential in nanotechnology and biomedicine. This study investigates the self-assembly behavior of <i>N</i>-9-fluorenylmethoxycarbonyl(Fmoc)-modified amino acids and the impact of cold atmospheric plasma (CAP) on their transformation from 2D into 3D supramolecular aggregates. Fmoc-phenylalanine (Fmoc-F), a derivative of phenylalanine, primarily relies on π-π stacking interactions to form structures while Fmoc-tryptophan (Fmoc-W), a derivative of tryptophan, engages in both π-π stacking and hydrogen bonding due to the presence of an indole ring with a nitrogen atom, leading to stronger and more stable aggregates. Upon CAP treatment, Fmoc-F forms 3D aggregates containing β-sheet moieties binding to thioflavin T (dye) at concentrations as low as 10 μM, whereas Fmoc-W aggregates at 68 μM. These differences in aggregation behaviors can be attributed to the distinct molecular interactions of the two derivatives. The rapid treatment time and nonthermal properties of CAP regulate and direct the self-assembly process, promoting the formation of complex 3D structures, with fluorescence spectra revealing aggregation-induced quenching (ACQ). Characterization techniques confirm the formation of supramolecular assemblies, offering valuable insights into the design of Fmoc-amino acid-based materials for applications in biomimetic materials, cationic dye binding, drug delivery, and tissue engineering.