Hypoxia-Responsive 19F MRI Probes with Improved Redox Properties and Biocompatibility

F-19 magnetic resonance imaging (MRI), an emerging modality in biomedical imaging, has shown promise for in vitro and in vivo preclinical studies. Here we present a It series of fluorinated Cu(II)ATSM derivatives for potential use as F-19 magnetic resonance agents for sensing cellular hypoxia. The synthesized complexes feature a hypoxia-targeting Cu2+ coordination core, nine equivalent fluorine atoms connected via a variable-length poly(ethylene glycol) linker. Introduction of the fluorine moiety maintains the planar coordination geometry of the,Cu2+ center, while the linker length modulates the Cu2+/+ reduction potential, F-19 NMR relaxation properties, and lipophilicity. In.particular, the F-19 NMI. relaxation properties were quantitatively evaluated by the Solomon-Bloembergen model, revealing a regular pattern of relaxation enhancement tuned by the distance between Cu2+ and F atoms. Finally, the potential utility of these complexes for sensing reductive environments was demonstrated using both F-19 MR phantom imaging and F-19 NMR, including experiments in intact live cells.