A ¹⁹F‐ATCUN Peptide NMR Probe for Selective Cu²⁺ or Ni²⁺ Sensing in Complex Biological Media

We report the design and synthesis of ratiometric 19F-ATCUN (Xxx-Zzz-His) peptide probes for the selective and reversible detection of Ni2⁺ and Cu2⁺ by 19F NMR spectroscopy. In contrast to fluorescence-based approaches, 19F NMR enables background-free detection in biological media, due to the absence of fluorine in native biomolecules. The probes remain stable and functional in complex cell media (DMEM), enabling the detection of Cu2⁺ and Ni2⁺ by 19F NMR with a limit of detection (LOD) of 4 µM and quantification (LOQ) of 10 µM, relevant for studying copper-related pathologies.