Cytochrome P450 (P450) is a family of heme-containing enzymes that catalyze various oxidation reactions in steroid biosynthesis, fatty acid metabolism, and detoxification of xenobiotic compounds, mainly via monooxygenase-type NADPH/NADH- and O2-dependent reactions. P450 has a unique structure which the thiolate group of cysteine residue coordinates to the heme iron. The strong electron-donation from the cysteinyl thiolate group to the heme iron in P450 causes distinct spectroscopic properties as well as unique reactivity. Since P450 can catalyze various chemically complicated reactions, which cannot be catalyzed by synthetic metal catalysts, much attention has been directed to the function of the axial alkylthiolate ligand. However, only a limited number of examples of heme alkylthiolate complexes have been reported due to instability of the Fe-S bond toward oxygen.1,2
We recently succeeded in the synthesis of a new air-stable P450 model complex with a hydrophobic distal heme pocket for the binding of a substate. The stable Fe-S bond and hydrophobic cavity could be made by the phenyl and tolyl groups introduced at the ortho-positions of the meso-phenyl groups. X-ray crystal structure of the model complex showed that dichloromethane used for the crystallization was taken into the hydrophobic cavity with anagostic interaction to the heme iron and C-Cl••π interaction with the phenyl group. In this presentation we will present the synthesis, structure, and spectroscopic property of this model complexes.