Synthesis and characterization of sterically and electrostatically shielded pyrrolidine nitroxide radicals

Two new pyrrolidine nitroxide radicals, cisgrans-2,5-bis(carboxymethyl)-2,5-diethylpyrrolidine 1-oxyl and 2-(carboxymethyl)-2,5,5-triethylpyrrolidine 1-oxyl, for potential applications as spin probes and labels are reported. Carboxymethyl and ethyl groups have been introduced in the a-positions of the nitroxide group in order to improve the stability of the radicals through steric and electrostatic shielding. The compounds were structurally characterized by X-ray crystallography and EPR spectroscopy. An ascorbic acid reduction assay proves that the newly synthesized radicals exhibit higher reductive stability than the well-known and commercially available nitroxide radicals 3-carboxy-PROXYL and 4-carboxy-TEMPO. (C) 2019 Elsevier B.V. All rights reserved.