Biologically Relevant Chemistry of Nitroxides - Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds - page 577

TEMPO and TEMPOL, the rate constant of the comproportionation reaction varies between 20 and
50 M − 1 s − 1 at physiological pH range 62,64

and, therefore, cannot greatly contribute toward recycling

of the nitroxides in the tissue.
(iv) Oxidation of hydroxylamine to the respective nitroxides 34,65,66 by biologically relevant oxidants such

as oxygen, 65 H 2 O 2 19 and metal ions 67 (Scheme 17.4).
These mechanisms can, at least partly, explain why a residual concentration of nitroxide in the µ M

range persisting in the tissue demonstrates significant protection in a catalytic manner.

17.5 Conclusions

Most reactions of nitroxides with biologically relevant paramagnetic species involve the oxidation or reduc-
tion of RNO • to RN + = O and RNOH respectively. Nitroxide reactions with NO 2 • ,CO 3 • − , • OH, HO 2 • ,
organic peroxyl radicals, Fe IV

= O and globin radical yield the oxoammonium cation, whereas nitroxide
oxidation of reduced transition metals, such as iron(II) or copper(I), leads to the formation of hydroxy-
lamine. The catalytic activity of nitroxide requires its rapid and continuous recycling, which enables it to
operate catalytically and induce biological effects even at extremely low residual levels. Accordingly, sev-
eral different mechanisms can underlie the recycling of the nitroxide antioxidant, including the reduction
of R 2 N + = O by reductants abundant in the cell and oxidation of the cellular pool of R 2 NOH by O 2 ,H 2 O 2 ,
and transition metal ions. Consequently, although most of the nitroxide administered is rapidly converted
into R 2 NOH, the low traces of R 2 NO • thus formed are still biologically effective.

Acknowledgements

This work was supported by the Israel Science Foundation of the Israel Academy of Sciences.

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