A novel metal-free low molecular weight superoxide dismutase mimic.
2-Ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazolidine (OXANOH), the one-electron reduction product of the stable nitroxide radical, 2-ethyl-2,5,5-trimethyl-3-oxazolidinoxyl (OXANO), is reportedly oxidized by superoxide, and its oxidation has been proposed as a method for assaying superoxide. We find that superoxide can both reduce OXANO and oxidize OXANOH. The respective rate constants, k1 and k2, were determined using two superoxide-generating systems (xanthine oxidase/xanthine as well as ionizing radiation). OXANOH oxidation and OXANO reduction are both inhibitable by superoxide dismutase, pH-dependent (4.5-9.3), and result in a steady state distribution of [OXANO] and [OXANOH], independent of their initial concentrations, i.e. the OXANO/OXANOH couple exhibits a metal-independent superoxide dismutase-like function. Thus it provides a prototype for future development of improved low molecular weight superoxide dismutase mimics which will also function in cellular hydrophobic (aprotic) compartments such as membranes.
Samuni
A
A
Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892.
Krishna
C M
CM
Riesz
P
P
Finkelstein
E
E
Russo
A
A
D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D010080:Oxazoles; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides
D010080:Oxazoles; D013481:Superoxides; C034590:2-ethyl-2,5,5-trimethyl-3-oxazolidinoxyl; C034589:2-ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazolidine; D013482:Superoxide Dismutase