Nitroxides as Building Blocks for Nanoantioxidants

Nitroxides are an important class of radical trapping antioxidants whose promising biological activities are connected to their ability to scavenge peroxyl (ROO center dot) radicals. We have measured the rate constants of the reaction with ROO center dot (k(inh)) for a series of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) derivatives as 5.1 x 10(6), 1.1 x 10(6), 5.4 x 10(5), 3.7 x 10(5), 1.1 x 10(5), 1.9 x 10(5), and 5.6 x 10(4) M-1 s(-1) for -H, -OH, -NH2, -COOH, -NHCOCH3, -CONH(CH2)(3)CH3, and.O substituents in the 4 position, with a good Marcus relationship between log (k(inh)) and E degrees for the R2NO center dot/R2NO+ couple. Newly synthesized Pluronicsilica nanoparticles (PluS) having nitroxide moieties covalently bound to the silica surface (PluS-NO) through a TEMPOCONH-R link and coumarin dyes embedded in the silica core, has k(inh) = 1.5 x 10(5) M-1 s(-1). Each PluS-bound nitroxide displays an inhibition duration nearly double that of a structurally related "free" nitroxide. As each PluS-NO particle bears an average of 30 nitroxide units, this yields an overall approximate to 60-fold larger inhibition of the PluS-NO nanoantioxidant compared to the molecular analogue. The implications of these results for the development of novel nanoantioxidants based on nitroxide derivatives are discussed, such as the choice of the best linkage group and the importance of the regeneration cycle in determining the duration of inhibition.