rganic radicals can be sufficiently stabilized with adequate steric shielding of unpaired electron. Among very few examples of stable organic radicals is nitroxide, for which stability is also imparted by a three-electron bonding in the NO moiety. Because of their stability, nitroxides have a wide range of applications in chemistry, biochemistry and biomedicine. Note, however, that applications of nitroxides are rather limited, as they undergo fast reduction to the diamagnetic hydroxylamines.
n the search for stable polyradicals that are promising building blocks for preparation of organic polymer magnets ("plastic magnets"), we prepared and studied numerous nitroxides di- and polyradicals. Among examples are high-spin nitroxide diradicals with conformationally-restricted structures, in which nitroxides are annelated to -phenylene forming tricyclic benzobisoxazine-like structures () and an annelated nitroxide diradical, analogue of the = 1 aminyl diradical (), which is stable in the solid state and in solution at ambient conditions. . Conformationally-constrained nitroxide polyradical scaffolds, such as calixarene nitroxide radicals with fixed cone and 1,3 alternate conformations, were prepared and studied. The 1,3-alternate nitroxide diradical and tetraradical provide unique polyradical scaffolds for dissection of the through-bond and through-space intramolecular exchange couplings.
o explore feasibility of high-spin nitroxide di- and polyradicals ( > 1/2) in biological and medical applications, we prepared a triplet ground state ( = 1) pegylated nitroxide diradical and, in collaboration with Professors Gareth and Sandra Eaton, we investigated the effect of water on its magnetic properties (). This project has evolved to the synthesis of nitroxides for applications, in particular, development of biostable organic radicals as contrast agents (ORCAs) for magnetic resonance imaging and as spin labels for biophysical applications.
Since the 1960s, the chemistry of nitroxideshas been widely investigateddue to their unique physical and chemical properties., Nitroxide radicals have been commonly utilized for spin trappingand spin labeling applications in electron paramagnetic resonance(EPR) spectroscopy and for monitoringcellular redox processes. Nitroxides arealso effective antioxidants in biological systems due to their abilityto react with superoxide radicals. Superoxide,one of the main reactive oxygen species produced in the cell, is asignificant contributor to cellular levels of oxidative stress, a term which describes an imbalance in the concentrations of pro-and antioxidants. Oxidative stress results in cellular damage dueto the generation of peroxides and free radicals and has been implicatedin cardiovascular aging, Parkinson’sdisease, and Alzheimer’s disease. Nitroxides have shown significant potential assmall molecule antioxidants in mammalian cells due to their broaddistribution and ability to react with and detoxify harmful radicalspecies.−
Bohle --Nitroxide radicals : properties, synthesis and ..
Nitroxide radicals have a wide range of applications in organic synthesis, materials chemistry,, biophysics, and biomedicine. These applications rely on the stability, paramagnetic properties, and/or redox properties of the radicals at ambient conditions. While fast redox reactions of nitroxide radicals are favorable for many applications, fast in vivo reduction of paramagnetic nitroxide radicals to diamagnetic hydroxylamines by antioxidants, such as ascorbate (vitamin C) or enzymatic systems, hinder their applications in biomedicine.