Elevated levels of reactive oxygen species and peroxidase expression are often associated with inflammation and inflammatory diseases. We developed two novel Co(II) complexes that can be used to detect oxidative activity associated with inflammation using F magnetic resonance imaging (MRI). These agents display a large change inF chemical shift upon oxidation from Co(II) to Co(III), facilitating selective visualization of both species using chemical shift selective pulse sequences. This large chemical shift change is attributed to a large magnetic anisotropy in the high spin Co(II) complexes. Importantly, the differing reactivity of the two agents allows for detection of either HO production and/or the activity of peroxidase enzymes, providing two useful platforms for F MR hot spot imaging of oxidative events associated with biological inflammation.

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, theF 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 andF NMR, including experiments in intact live cells.

A fluorinated, air-stable cobalt(ii) complex serves as a turn-on F magnetic resonance imaging (MRI) tracer for reactive oxygen species including HO. Upon oxidation with HO, the complex converts from paramagnetic high spin Co to diamagnetic low spin Co resulting in a chemical shift change and enhancement in F NMR signal. Further, the oxidation can be reversed in the presence of reductant NaSO. The turn-on response is demonstrated by F MRI, characterized by a ∼2-3 fold enhancement in signal.

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 addition to UV-vis and EPR spectroscopies. Importantly, complexes with -CH2CF3 tags display excellent water solubility. Studies with this complex in HeLa cells demonstrate the applicability of these probes to detect cysteine in complex biological environments.