Syntheses of nitroxide diradicals and tetraradicals

Nitroxides are one of the most widely investigated classes of stable free radicals in the chemical, biological and medical sciences owing to their potential applications such as antioxidants, spin-labels, co-oxidants, building blocks for practical organic magnets, controlled free-radical polymerization, EPR and NMR (MRI) based contrast reagents. Central to the progress on these investigations has been the understanding of the effects of orientation (bond torsions), distance, and structure of different coupling units controlling the spin-spin interaction between two and more nitroxide spin moieties. Attachment of nitroxides on a rigid framework, which limits the extent of conformational change, is a necessary step towards addressing these effects on spin-spin exchange qualitatively and quantitatively. Calix[4]arenes immobilized in a 1,3-alternate conformation are structurally rigid with a cylindrical inner tunnel and possess two cofacial pairs of aromatic rings oriented orthogonal along the cavity axis. From numerous X-ray studies, the distance between the cofacial pair of aromatic rings has been found to be 5--6 Å. This arrangement allows one to study the through-bond (spin polarization of the σ- and π-core) and through-space (overlap of the singly-occupied p-orbitals) mechanism of exchange coupling by attaching two or four nitroxide moieties respectively on the aromatic rings. The design principle, synthetic methods, EPR and magnetic studies for stable nitroxide radicals presented in Chapter 1 were used for the synthesis and characterization of the 1,3-alternate calix[4]arene nitroxide diradical and tetraradical described in Chapter 2. In order to minimize the effect of bond-torsions as in the above nitroxides and weaken the through-bond exchange coupling, so that the through-space exchange coupling mechanism remains significant, the 1,3-alternate calix[4]arene nitronylnitroxide diradical and tetraradical were synthesized and characterized (Chapter 3). With the desire of exploring the biological applications of such diradicals and tetraradicals based on rigid scaffolds, a calix[4]arene nitroxide tetraradical with hexapoly(ethylene)glycol was synthesized (Chapter 4). The observation of good water solubility for the tetraradical (\u3e50 mM) and the preliminary investigations of EPR properties, provide a foundation for a future synthesis of an octaradical on the same scaffold. Lastly, our interest in exploring the applications of high-spin nitroxides in biological media led us to synthesize and characterize a glucamine-functionalized nitroxide diradical (Chapter 5)