Influence of structure on the reduction of nitroxide MRI contrast-enhancing agents by ascorbate

With an eye toward the design of new nitroxide-based magnetic resonance imaging (MRI) contrast agents, the effect of ring size and the presence of proximate polar groups on the rate of reduction of cyclic nitroxides by the biologically relevant reducing agent ascorbate ion have been determined. To the extent that reduction by ascorbate ion is indicative of the behavior of nitroxides toward other in vivo reducing agents, our results indicate that saturated five-membered cyclic nitroxides are to be preferred over smaller or larger ring sizes or acyclic nitroxides. Proximate polar groups tend to enhance the susceptibility toward reduction by ascorbate.