4,4-Dimethyl-4H-imidazole-5-carbaldehyde oxime 3-oxides 4 were prepared by oxidation and nitrosation of 4,5,5-trimethyl-2,5-dihydro-1H-imidazol-1-ols. The oximes 4 were converted to 5-cyano derivatives; the latter react with primary or secondary amines to form 5-(di)alkylamino-4H-imidazole 3-oxides 6. Treatment of 6 with AlkMgX and subsequent oxidation yielded stable nitroxides 4-(di)alkylamino-2,5-dihydroimidazole-1-oxyls 7, the pH-sensitive spin probes.

Four albumin-nitroxide conjugates were prepared and tested as metal-free organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI). Each human serum albumin (HSA) carrier bears multiple nitroxides conjugated via homocysteine thiolactones. These molecular conjugates retain important physical and biological properties of their HSA component, and the resistance of their nitroxide groups to bioreduction was retained or enhanced. The relaxivities are similar for these four conjugates and are much greater than those of their individual components: the HSA or the small nitroxide molecules. This new family of conjugates has excellent prospects for optimization as ORCAs.

Stable free radicals are widely used as molecular probes and labels in various biophysical and biomedical research applications of magnetic resonance spectroscopy and imaging. Among these radicals, sterically shielded nitroxides of pyrrolidine series demonstrate the highest stability in biological systems. Here, we suggest new convenient procedure for preparation of 3-carboxy-2,2,5,5-tetraethylpyrrolidine-1-oxyl, a reduction-resistant analog of widely used carboxy-Proxyl, from cheap commercially available reagents with the yield exceeding the most optimistic literature data. Several new spin labels and probes of 2,2,5,5-tetraethylpyrrolidine-1-oxyl series were prepared and reduction of these radicals in ascorbate solutions, mice blood and tissue homogenates was studied.

An alkoxyamine was prepared from a cyclic aldonitrone nitroxide. The resulting alkoxyamine containing an aldonitrone functional substituent is relatively stable but can react readily with vinyl monomers to form a cycloadduct that has a much higher C–ON homolysis rate. This type of in situ activation converts the aldonitrone alkoxyamine into an efficient controlling agent for nitroxide-mediated polymerization. Here we present a study on this reaction of C–ON bond homolysis and application of such an alkoxyamine as an in situ-activated initiator.