Liponitroxides: EPR study and their efficacy as antioxidants in lipid membranes

A series of lipid-functionalized nitroxides having a pyrroline nitroxide moiety linked either to a glycerol or to a steroid unit has been synthesized, and their inclusion inside phospholipid bilayers has been investigated by Electron Paramagnetic Resonance (EPR) spectroscopy. The antioxidant behavior of these nitroxides has been studied in azo-initiator induced lipid peroxidation by means of the Thiobarbituric Acid Reactive Species (TBARS) assay; a correlation with their penetration depth within the bilayer has been found. The possible mechanisms involved in the antioxidant action have been considered, discussed and alternative pathways have been suggested for the synthesized liponitroxides due to their different localization. The steroid derivative is limited to scavenging radicals that are generated in the aqueous phase, while the glycerolipids can also act as chain breaking antioxidants.