Model compounds with superoxide dismutase activity: iron porphyrins and other iron complexes [proceedings].

The enzyme superoxide dismutase (EC 1.15.1.1) is essential to aerobic life (Fridovich, 1975; Halliwell, 1978). All superoxide dismutases are metalloproteins, containing manganese, iron or copper and zinc as the prosthetic groups. However, some simple metal complexes also react with the superoxide radical (02-'); for example, complexes of Cu(I1) with amino acids (Brigelius et al., 1974) and complexes of Mn(1I) with pyrophosphate (Kono etal . , 1976) or with quinolino compounds (Howie et al., 1977). Complexes of Cu(I1) 01 Mn(I1) with EDTA do not react with 02-. (Halliwell, 1975). In contrast, complexes of Fe(I1) or Fe(II1) with EDTA react rapidly with 02-* (Halliwell, 1975). By competition of Fe(I1)-EDTA with Nitro Blue Tetrazolium for 02-* generated in a xanthine/xanthine oxidase system at pH 10.1, a rate constant of about 3 x 105~-'*s' was calculated for the reaction of Fe(l1)-EDTA with 02-' at 20°C. Complexes of iron(I1) or iron(II1) with diethylenetriaminepenta-acetic acid also react with 02-. at pH10.1 (k 1 x 105~-' .s' at 20°C). Halliwell(l975) reported that haematin reacts with 02-* at pH 10, but under the conditions used this compound would have been extensively aggregated. 02-. is known to reduce iron(II1) protoporphyrin IX dimethyl ester in organic solvents (Hill et al., 1974). Certain protein-porphyrin complexes interact with 02-* in aqueous solution, including oxidized cytochrome c ( k 1.1 x 106~vl'.s-' at pH7.2: Koppenol et a/., 1976), horseradish peroxidase (k 1 x 10'-1 x 109~' . s ' at pH5; Sawada & Yamazaki, 1973), oxyhaemoglobin and methaemoglobin ( k 4 x lo3 and 6 x 1 0 3 ~ 1 . s L at pH7; Sutton et al., 1976). However, catalase does not react with 02-' at either pH7.8 or 10.2 (Halliwell, 1973). As part of an investigation into the relation between the structure of porphyrins and their reaction with 02-., we have studied the properties of various metal-ion complexes of the water-soluble porphyrin tetrakis-(4-N-methyl)pyridylporphine (Fig. 1). The spectral and aggregation properties of this compound are well-known (Pasternack eta/., 1977). The compound itself was found not to react with 02-' in a xanthine/xanthine oxidase system at pH1O.l, nor did its complexes with Zn(1I) or Cu(l1). The Co(ll1) derivative of tetrakis-(4-N-methyl)pyridylporphine reacted slowly with O2 -., but it could not be decided if the reaction was catalytic in our system. However, the iron(lI1)