¹⁹F PARASHIFT Probes for Magnetic Resonance Detection of H₂O₂ and Peroxidase Activity

Abstract

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.

Molecular Magnetic Resonance Imaging Using a Redox-Active Iron Complex

“…13,14 For agents detected by magnetic resonance spectroscopy, changes in the relaxation times or chemical shift of the observed nuclei are detected. 15,16 A large number of biochemically responsive agents have been proposed over the last two decades, 17,18 such as agents that respond to enzymatic activity, 4,19 pH change, 5,20,21 metal ion or neurotransmitter flux, 22–25 changes in redox homeostasis, 3,12,16,26,27 and reactive oxygen species (ROS). 6,8,15 However, very few biochemically activated agents have been shown to be effective in vivo, and none have been translated to human clinical trials.…”

Copper(ii) complexes for cysteine detection using 19F magnetic resonance

“…30, 31 Paramagnetic metal centers can be used to modulate 19 F signal, which has been exploited in a number of transition metal and lanthanide complexes. 32–44…”

A ratiometric19F MR-based method for the quantification of Ca2+using responsive paramagnetic probes

“…Thus exploiting the relaxation properties, chemical shift and chemical exchange variations led to the development of responsive systems to measure tissue pO 2 , and detect ions, pH and enzymatic activity via various triggering mechanisms. 7,11,12 Monitoring of fluctuations in the concentration of endogenous metal ions is a particularly interesting application because of their role and relevance in the signalling and regulation of numerous biological processes. By using responsive, 13 or so-called smart contrast agents (SCAs), a functional MRI (fMRI) method that operates at the 1 H frequency demonstrated considerable potential for the assessment of neuronal activity by detecting the intracellular and extracellular calcium concentrations.…”