Copper(ii) complexes for cysteine detection using ¹⁹F magnetic resonance

Cysteine plays an essential role in maintaining cellular redox homeostasis and perturbations in cysteine concentration are associated with cardiovascular disease, liver disease, and cancer. ¹⁹F MRI is a promising modality for detecting cysteine in biology due to its high tissue penetration and negligible biological background signal. Herein we report fluorinated macrocyclic copper complexes that display a ¹⁹F NMR/MRI turn-on response following reduction of the Cu(ii) complexes by cysteine. The reactivity with cysteine was studied by monitoring the appearance of a robust diamagnetic ¹⁹F signal following addition of cysteine in conjunction with UV-vis and EPR spectroscopies. Importantly, complexes with-CH₂CF₃ tags display good water solubility. Studies with this complex in HeLa cells demonstrate the applicability of these probes to detect cysteine in complex biological environments.