The incorporation of fluorine into amino acids is an important strategy to produce tailored building blocks with unique properties for peptide-based materials. Phenylalanine is frequently modified due to its role in cation–π interactions and the formation of amyloid fibres. Previous studies have utilized gas-phase vibrational spectroscopy to study interactions between canonical amino acids. In this study, we employ a combination of cryogenic gas-phase infrared spectroscopy and density functional theory to study the interactions in proton-bound dimers of side-chain fluorinated phenylalanines. Our findings reveal how the position and number of fluorine atoms affect the interactions and structures of the dimers. Monofluorinated phenylalanines adopt charge-solvated structures in which the two amino acids interact via their ammonium and amine functions (NH3+⋯NH2). The dimer with the perfluorinated side chain forms multiple charge-solvated and salt-bridged structures with varying interaction types. These structural changes are attributed to the significant reduction of electron density in the aromatic systems.
