An Overly Anionic Metal Coordination Environment Eliminates the T1-Weighted Response of Quinol-Containing MRI Contrast Agent Sensors to H2O2

Abstract A previously reported quinol- and Mn(II)-containing MRI contrast agent sensor for H2O2 has the drawback of releasing the metal ion upon oxidation of the organic ligand. The release of potentially neurotoxic Mn(II) limits the sensor’s in vivo applicability. We prepared N,N’-bis(2,5-dihydroxybenzyl)ethanediamine-N,N’-diacetic acid (H6qc1) as a substitute ligand that could potentially remain bound to the metal ion after oxidation of the quinol portions to more weakly metal-binding para-quinones. The carboxylic acid groups deprotonate at ambient pH, providing a more anionic coordination environment that stabilizes its Mn(II) complex in water. Although the more anionic coordination sphere doesn’t introduce air sensitivity, it does render the metal center more susceptible to oxidation by hydrogen peroxide, as evidenced by electron paramagnetic resonance. The oxidation of the metal to less paramagnetic Mn(III) is proposed to lower the r1 enough to completely counter any increase in T1-weighted relaxivity that would result from improved aquation.