Mechanism of reaction of a suggested superoxide-dismutase mimic, Fe(II)-N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine.
The interaction of a recently developed intracellular superoxide dismutase analogue, Fe(II)-N,N,N',N'-tetrakis(2- pyridylmethyl)ethylenediamine (Fe(II)-TPEN), with reactive oxygen species was investigated under in vitro conditions. The complex catalyzed the dismutation of enzyme- or radiolysis-generated superoxide with the production of H2O2; under steady-state conditions the equilibrium was strongly shifted toward Fe(III)-TPEN. Fe(II)-TPEN reacted with H2O2 to generate hydroxyl radicals in a Fenton reaction. The oxidized Fe(III)-TPEN was readily reduced by ascorbate or glutathione. Given the capacity to produce hydroxyl radicals and the reaction with cellular reductants it seems unlikely that Fe-TPEN may find widespread use as an intracellular superoxide dismutase substitute.
Iuliano
L
L
Institute of First Clinical Medicine, University La Sapienza, Rome, Italy.
Pedersen
J Z
JZ
Ghiselli
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A
Praticò
D
D
Rotilio
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Violi
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D001205:Ascorbic Acid / Q000737:chemistry; D002614:Chelating Agents; D003855:Deoxyribose / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000737:chemistry; D006878:Hydroxides; D010084:Oxidation-Reduction; D012459:Salicylates / Q000737:chemistry; D013057:Spectrum Analysis; D013482:Superoxide Dismutase; D013481:Superoxides / Q000737:chemistry*
D002614:Chelating Agents; D005029:Ethylenediamines; D005296:Ferrous Compounds; D005609:Free Radicals; D006878:Hydroxides; D012459:Salicylates; D013481:Superoxides; D003855:Deoxyribose; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine