Fluorinated hybrid organic–inorganic nanomaterials have attracted interest for applications ranging from biomedicine to superhydrophobic surfaces. However, few examples of fluorinated hybrid nanoparticles (F-NPs) establish a clear relationship between the structure of the fluorinated component and the properties of the hybrid system. This gap limits understanding of structure–property correlations and hinders the development of F-NPs with tailored functionalities. Here, we report the design, synthesis, and characterization of gold NPs passivated with fluorinated thiolates (F-NP2), combining high fluorine content with excellent dispersibility in both organic and aqueous solvents. The gold core measures approximately 2 nm, while the hydrodynamic diameter is around 12 nm, consistent with SAXS data. Electron Spin Resonance (ESR) studies reveal an exceptionally strong interaction between a hydrophobic radical probe and the NP coating, surpassing previously reported systems and indicating a high capacity for hosting hydrophobic, drug-like molecules. Molecular dynamics simulations support this behavior, showing a highly folded fluorinated segment and limited shielding by the polar mPEG550 end, which also explains reversible aggregation at high NP concentrations observed via dynamic light scattering. Finally, preliminary 19F MRI data acquired at 7 T demonstrate a good signal-to-noise ratio, suggesting that these F-NPs may serve as sensitive fluorine-based tracking agents for biomedical applications.
