The stability of nitroxides towards reduction was measured by CW X-band EPR spectroscopy as a function of decay of the characteristic triplet signal in the presence of sodium ascorbate (1.4 equivalents). These conditions permitted the observation of meaningful decay rates at nitroxide concentrations high enough to be reliably measured on a benchtop EPR spectrometer. The time-dependent decay curves of the novel nitroxides 5, 8 and cis,cis-9 are shown in Figure . To confirm our hypothesis, these novel nitroxides were compared with the non-methylated spirocyclohexyl nitroxides 10 and 11. The reduction kinetics of the well-established tetramethylsubstituted TEMPOL (12) and tetraethyl-substituted TEEPOL (13), moreover, were included as benchmarks for the piperidinyl nitroxides that are least and most resistant towards reduction, respectively. Second-order rate constants k were derived by fitting decay data to a second-order kinetic rate law (see the Supporting Information for more details), and are included in Figure . Deviations from ideal second-order behaviour were apparent, especially for rapidly reducing nitroxides, for which reliable rate constants could not be extracted. The non-ideal reduction kinetics are consistent with previous findings that the mechanism of nitroxide reduction by ascorbate is reversible and proceeds through a complex mechanism. The presence of functional groups is known to influence the reduction rate of nitroxides. In with previous studies, the presence of an alcohol vs a ketone functionality has a negligible impact on the rate of reduction for the spirocyclic piperidinyl nitroxides examined in this work. It is known that spirocyclohexyl-substituted piperidinyl nitroxides show slightly higher stability towards reduction than tetramethyl-substituted nitroxides, but not higher than tetraethyl-substituted radicals, a trend that is also clear from the decay curves in Figure . However, we were delighted to observe a significant decrease of almost one order of magnitude in the rate of reduction of dimethylated spirocyclohexyl nitroxide cis,cis-9 compared to non-methylated nitroxide 11. This effect can be ascribed to the conformational effect on the spirocyclohexyl rings caused by the additional steric pressure from the two methyl substituents in 9, causing the compound to prefer a closed conformation, similar to that observed in the solid-state X-ray crystal structure (Scheme 1B), that more effectively shields the radical from reducing agents.