Four recent studies in cytochrome P450 modelings: A stable iron porphyrin coordinated by a thiolate ligand; A robust ruthenium porphyrin-pyridine N-oxide derivatives system; Polypeptide-bound iron porphyrin; Application to drug metabolism studies

(1) A distinctive structural feature of P450 is the unusual thiolate coordination to heme. We have succeeded in the preparation of the first synthetic thiolato-iron porphyrin (SR complex) which retains its structure during catalytic oxidation. Experiments using SR complex have revealed that the thiolate ligand greatly accelerates the rate of the O-O bond cleavage and its heterolysis even in highly hydrophobic media. (2) Heteroaromatic N-oxides were found to be excellent oxidants in the presence of ruthenium porphyrin. 2,6-disubstituted pyridine N-oxides plus a catalytic amount of Ru porphyrin oxidized olefins and sulfides to afford epoxides and sulfoxides, respectively, in high yields. The system in the presence of hydrogen halide effectively oxidized unactivated alkanes and arenes to give alcohols (or ketones) and p-quinones in high yields with high selectivity and an extremely high catalyst turnover number (up to 1.2 X 10(5)). (3) A polypeptide-bound porphyrinatoiron complex was prepared. The polymer complex exhibited greater P450-like activity than non-bound Fe(TPP)Cl in the oxidation of olefin and aniline derivatives. (4) P450 mimics were applied to drug metabolism studies. These model systems were effective for one-step preparation of unstable metabolic intermediates, 'candidate metabolites', and for the discovery of novel modes of metabolism.