Spirocyclic Pyrrolidinyl Nitroxides with Exo‐Methylene Substituents.

Nitroxides are stable organic radicals with exceptionally long lifetimes, which render them uniquely suitable as observable probes or polarising agents for spectroscopic investigation of biomolecular structure and dynamics. Radical‐based probes for biological applications are ideally characterized by both robustness towards reductive degradation and beneficial electron spin relaxation parameters. These properties are largely influenced by the molecular structure of the nitroxide scaffold, and also by the conformations it prefers to adopt. In this study we present the synthesis of the first nitroxides based on a spirocyclic pyrrolidine scaffold with an exocyclic methylene substituent. The conformations adopted by these nitroxides were evaluated by X‐ray crystallography, both with single nitroxide crystals and by inclusion of nitroxides in a microporous crystalline sponge. The kinetic and thermodynamic stability of the new nitroxides towards reduction was investigated by electron paramagnetic resonance (EPR) spectroscopy and cyclic voltammetry (CV). In combination with EPR measurements of electron spin relaxation properties, these results suggest that this new family of nitroxides can provide access to multifunctionalized probes and polarising agents suitable for use in biological environments at elevated temperatures. [ABSTRACT FROM AUTHOR]