Chemical models of cytochrome p450 catalyzed insecticide metabolism. Application to the oxidative metabolism of carbamate insecticides

Cytochrome P450 (CP450) catalyzed oxidative metabolism of carbofuran (1), c arbaryl (2), and pirimicarb (3) has been modeled using biomimetic oxidation s catalyzed by iron(III) tetraarylporphyrins. Oxidation products of 1 were identified by comparison of HPLC retention times measured under standardize d conditions for metabolites synthesized and characterized by H-1 and C-13 NMR spectroscopy. Comparison of product distributions to in vivo metabolic profiles revealed that the H2O2/meso-tetrakis(pentafluorophenyl)porphyrin i ron(III) chloride [Fe(TF20PP)] system mimics the action of insect CP450s ag ainst carbofuran. The effectiveness of this system was further demonstrated by the biomimetic oxidation of other carbamate insecticides (2 and 3) moni tored by HPLC/electrospray MS. The predictive power of this biomimetic mode l was compared to that of knowledge-based expert systems. Although similar models were recently applied in pharmaceutical research, the usefulness of this approach has first been demonstrated for the prediction of metabolic p rofiles of agrochemicals.