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.

Two azobenzenesulfonamide molecules with thermally stable cis configurations resulting from fluorination of positions ortho to the azo group are reported that can differentially regulate the activity of carbonic anhydrase in the trans and cis configurations. These fluorinated probes each use two distinct visible wavelengths (520 and 410 or 460 nm) for isomerization with high photoconversion efficiency. Correspondingly, the cis isomer of these systems is highly stable and persistent (as evidenced by structural studies in solid and solution state), permitting regulation of metalloenzyme activity without continuous irradiation. Herein, we use these probes to demonstrate the visible light mediated bidirectional control over the activity of zinc-dependent carbonic anhydrase in solution as an isolated protein, in intact live cells and in vivo in zebrafish during embryo development.

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.

Highly fluorinated, water-soluble transition metal complexes serve as both 19F and PARACEST magnetic resonance imaging agents.