Development of MRI Contrast Agent H2O2 Sensors and Superoxide Dismutase Mimics to Visualize and Treat in vivo Oxidative Stress

Abstract - Oxidative stress has been implicated in a wide variety of lethal and debilitating health conditions. The lack of sensors capable of imaging in vivo oxidative stress, however, precludes us from fully understanding what roles reactive oxygen species play in disease progression. The Goldsmith laboratory has developed a series of Mn(II) complexes with redox-active quinol ligands that are stable enough in water to serve as contrast agents for magnetic resonance imaging (MRI). These complexes react rapidly with H₂O₂ with turn-on responses in the T₁-derived relaxivity but do not display significant responses to O₂. The sensor with the largest turn-on in relaxivity has been used for in vivo and ex vivo cardiac imaging and can detect the oxidative stress induced by the anti-cancer drug doxorubicin. The Mn(II) complexes were also found to catalytically degrade superoxide. This activity is believed to rely at least partly on the redox activity of the quinols, and a Zn(II) complex with one of the quinol ligands displays catalytic activity that is comparable to its Mn(II) analog.