MODEL SYSTEMS FOR OXIDATIVE DRUG-METABOLISM STUDIES - CATALYTIC BEHAVIOR OF WATER-SOLUBLE METALLOPORPHYRINS DEPENDS ON BOTH THE INTRINSIC ROBUSTNESS OF THE CATALYST AND THE NATURE OF SUBSTRATES

Sulfonated manganese and iron porphyrins have been used as catalysts i n attempts to mimick the oxidation of acetaminophen and two ellipticin e derivatives by horseradish peroxidase. Cofactors were potassium mono persulfate for the synthetic catalyst and hydrogen peroxide for the na tural enzyme. Hindered metalloporphyrins, i.e. with ortho positions of the meso-phenyl rings substituted with methyl groups [iron(III) and m anganese(III) derivatives of octasodium meso-tetrakis(3,5-disulfonatom esityl)porphyrin], were shown to be at least 10 times more robust than unsubstituted derivatives [iron(III) and manganese(III) derivatives o f tetrasodium meso-tetrakis(4-sulfonatophenyl)porphyrin] when activate d in the absence of substrate. The catalytic activity depends on the n ature of the substrate as shown by a decrease or an increase in reacti vity observed, respectively, in the oxidation of acetaminophen or elli pticine derivatives catalyzed by hindered metalloporphyrins compared w ith nonhindered ones. Only sterically hindered metalloporphyrins, even in the case of lowered reactivity, were allowed to mimick the behavio r of horseradish peroxidase when activated in the absence of substrate (stability toward autodegradation) and in the course of repeated infu sion of substrate (retained catalytic activity as time advances).