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 in attempts to mimick the oxidation of acetaminophen and two ellipticine derivatives by horseradish peroxidase. Cofactors were potassium monopersulfate for the synthetic catalyst and hydrogen peroxide for the natural enzyme. Hindered metalloporphyrins, i.e. with ortho positions of the meso-phenyl rings substituted with methyl groups [iron(III) and manganese(III) derivatives of octasodium mesotetrakis(3,5-disulfonatomesityl)porphyrin], were shown to be at least 10 times more robust than unsubstituted derivatives [iron(III) and manganese(III) derivatives of tetrasodium meso-tetrakis(4-sulfonatophenyl)porphyrin] when activated in the absence of substrate. The catalytic activity depends on the nature of the substrate as shown by a decrease or an increase in reactivity observed, respectively, in the oxidation of acetaminophen or ellipticine derivatives catalyzed by hindered metalloporphyrins compared with nonhindered ones. Only sterically hindered metalloporphyrins, even in the case of lowered reactivity, were allowed to mimick the behavior of horseradish peroxidase when activated in the absence of substrate (stability toward autodegradation) and in the course of repeated infusion of substrate (retained catalytic activity as time advances).