Dendrimeric-Containing Nitronyl Nitroxides as Spin Traps for Nitric Oxide: Synthesis, Kinetic, and Stability Studies

The in-vivo in-situ spin-trapping of NO • with iron chelates is limited in its ability to localize NO • at defined cellular compartments. Nitronyl nitroxides, such as 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline 3-oxide 1-oxyl, have been found to react with NO • . The resulting nitroxide, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolidine 1-oxyl, exhibits an EPR spectrum that is characteristically distinct from the parent nitroxide. However, nitronyl nitroxides are unstable in biologic milieu. This limits their ability to in vivo identify NO • at specific tissue compartments. Herein, we report on the preparation of a family of dendrimer-containing nitronyl nitroxides, which were developed to spin-trap NO • . Once synthesized, we determined their rate of reaction with NO • and their capacity to spin-trap NO • and estimated the stability of dendrimer-linked nitronyl nitroxides under various experimental paradigms. For the largest of the dendrimeric nitronyl nitroxides prepared, the reaction with NO • changed the EPR spectrum from one that was broad to that with a major component with narrow and defined spectral lines. These compounds promise to be excellent biological spin-trapping agents for NO • .