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

F 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 series of fluorinated Cu(II)ATSM derivatives for potential use as F magnetic resonance agents for sensing cellular hypoxia. The synthesized complexes feature a hypoxia-targeting Cu 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 Cu center, while the linker length modulates the Cu reduction potential, F NMR relaxation properties, and lipophilicity. In particular, the F NMR relaxation properties were quantitatively evaluated by the Solomon-Bloembergen model, revealing a regular pattern of relaxation enhancement tuned by the distance between Cu and F atoms. Finally, the potential utility of these complexes for sensing reductive environments was demonstrated using both F MR phantom imaging and F NMR, including experiments in intact live cells.