Cysteine responsive copper(II) based ¹⁹F MRI probes

Cysteine plays an important role upholding cellular homeostasis by maintaining a proper redox environment. Perturbations in cysteine concentration may lead to cardiovascular and liver disease, and cancer, making cysteine an important amino acid to detect and monitor. In order to detect cysteine in vitro and in vivo it is advantageous to choose an imaging tool with high tissue penetration, low background noise, and less radiation, which led us to ¹⁹F MRI. Herein we report a series of copper complexes with fluorine moieties appended to the macrocycle cyclam for use of ¹⁹F MRI detection of cysteine. In this study, an efficient “turn-on” response was observed upon reduction of the Cu(II) complexes by cysteine. This response was characterized using UV/Vis absorption spectroscopy, NMR, EPR, and ¹⁹F MRI. Early biological results suggest that these probes can detect cysteine in red blood cells, opening the doors for further animal studies.