Reduction kinetics and electrochemistry of tetracarboxylate nitroxides

Abstract

Tetracarboxylate pyrroline nitroxides undergo very fast reduction with ascorbate/glutathione (GSH), with second-order rate constants that are five orders of magnitude greater than those for gem-diethyl pyrroline nitroxides. For tetracarboxylate nitroxides, the electrochemical reduction potentials, measured by square wave voltammetry, are much less negative (by about 0.8 V), compared with the corresponding gem-diethyl nitroxides, while the oxidation potentials become more positive (by about 0.7 V). Electrochemical potentials correlate well via simple regressions with field/inductive parameters such as Swain/Lupton F-parameters (and/or Charton σ_I-parameters). Rates of reduction with ascorbate/GSH similarly correlate well for four pyrroline nitroxides, except for the slowest reducing gem-diethyl nitroxide. These results suggest that the electron withdrawing groups adjacent to the nitroxide moiety have a strong accelerating impact on the reduction rates, and thus they are not suitable for the design of hydrophilic nitroxides for in vivo applications.

Keywords:

• Electrochemistry
• electron paramagnetic resonance
• Hammett correlation
• nitroxide
• voltammetry

Disclosure statement

The authors declare no conflict of interest between the authors or with any institution in relation to the contents of this article.

Additional information

Funding

The authors thank the National Institutes of Health for support of this work through Grants NIBIB R01EB019950-02, NIGMS R01GM124310-01 and NIGMS U54GM087519-06.