Adding a Second Quinol to a Redox-Responsive MRI Contrast Agent Improves Its Relaxivity Response to H₂O₂

The overproduction of reactive oxygen species has been linked to a wide array of health disorders. The ability to noninvasively monitor oxidative stress in vivo could provide substantial insight into the progression of these conditions and, in turn, could facilitate the development of better diagnosis and treatment options. A mononuclear Mn(II) complex with the redox-active ligand N,N'-bis(2,5-dihydroxybenzyl)-N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine (H₄qtp2) was made and characterized. A previously prepared Mn(II) complex with a ligand containing a single quinol subunit was found to display a modest T₁-derived relaxivity response to H₂O₂. The introduction of a second redox-active quinol both substantially improves the relaxivity response of the complex to H₂O₂ and reduces the cytotoxicity of the sensor but renders the complex more susceptible to transmetalation. The addition of H₂O₂ partially oxidizes the quinol subunits to para-quinones, concomitantly increasing the r₁ from 5.46 mM^-1 s^-1 to 7.17 mM^-1 s^-1. The oxidation of the ligand enables more water molecules to coordinate to the metal ion, providing an explanation for the enhanced relaxivity. That the diquinol complex is only partially oxidized by H₂O₂ is attributed to its activity as an antioxidant; the complex can both catalytically degrade superoxide and serve as a hydrogen atom donor.