Nitroxides as potential contrast enhancing agents for MRI application: influence of structure on the rate of reduction by rat hepatocytes, whole liver homogenate, subcellular fractions, and ascorbate.

With an eye toward the development of nitroxides as potential contrast enhancing agents for MRI applications, we have compared the rates of reduction of 24 nitroxides of diverse structures by rat whole liver homogenate, hepatocytes, subcellular fractions, and ascorbate (10 eq excess). Our results indicate that five-membered ring nitroxides and alpha-carboxy alpha-aryl tert-butyl nitroxides are significantly more resistant toward bioreduction than six-membered ring and heterocyclic-substituted nitroxides in all systems. In the case of six-membered ring nitroxides the presence of either negatively charged or positively charged groups increases the susceptibility toward ascorbate reduction. The presence of carboxylate groups tends to enhance the resistance of all the nitroxides toward reduction by liver homogenate, hepatocytes, and subcellular fractions. trans-Azethoxyl nitroxides exhibited the best overall resistance toward bioreduction. The T1 relaxants of selected nitroxides were measured and found to be similar.