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

Abstract

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.

Keywords: 19F NMR probe; ATCUN motif; biological copper sensor; ratiometric detection; trifluoromethylation.