Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

Abstract

Oxometalloporphyrin Intermediates in Enzymatic ProcessesMetalloenzymes catalyze a host of biological oxidation reactions that are crucial to life processes. The cytochromes P450, an important family of heme-iron metalloenzymes, are oxidoreductases that activate molecular oxygen (O2) and incorporate one of the oxygen atoms into a wide variety of biological substrates, with concurrent two-electron reduction of the other oxygen atom to H 2 0.' The structure, biochemistry, molecular biology and the chemistry of cytochrome P450 and related model systems was extensively reviewed recently. 1 Cytochrome P450 enzymes have been isolated from numerous mammalian tissues (e.g. liver, kidney, lung, intestine and adrenal cortex), as well as insects, plants, yeast and bacteria, 2 and are known to catalyze hydroxylations, epoxidations, N-, S-and O-dealkylations, N-oxidations, sulfoxidations, and dehalogenations. 1 These oxygenation reactions play a central role in carcinogen activation, drug and xenobiotic detoxification, and steroid and prostaglandin metabolism. Surprisingly, the active site of the enzyme, known in detail from several X-ray crystal structures, is extraordinarily simple, with an iron protoporphyrin IX (3.1; Fig. 3.1) buried deep in a hydrophobic, substrate-binding pocket of 91 Biomimetic Oxidations Catalyzed by Transition Metal Complexes Downloaded from www.worldscientific.com by KAINAN UNIVERSITY on 02/20/15. For personal use only.

The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies

“…The principal features of the consensus mechanism of cytochrome P450 (19) are as outlined in Scheme 1: binding of substrate to the enzyme, sometimes accompanied by a spin-state change of the iron, to afford an enzyme-substrate adduct 3; reduction of the ferric cytochrome P450 by an associated reductase with an NADPH-derived electron to the ferrous cytochrome P450 4; binding of molecular oxygen to the ferrous heme to produce a ferrous cytochrome P450-dioxygen complex 5, similar to the situation in oxymyoglobin; a second one-electron reduction and protonation to arrive at the Fe(III)-hydroperoxy complex 6; protonation and heterolytic cleavage of the OOO bond in 6 with concurrent production of a water molecule to form a reactive iron-oxo intermediate 7; and, finally, oxygen atom transfer from this ironoxo complex 7 to the bound substrate to form the oxygenated product complex 8. Product dissociation completes the cycle.…”

“…For substrates with a very strong COH bond and a small steric size, both effects would push the reaction coordinate toward a tighter radical cage. Indeed, it has been shown that the effective lifetime of a radical intermediate can even be affected by the stereochemistry of the hydrogen abstraction event (19). Here, the pro-R hydrogen of ethyl benzene was hydroxylated with nearly complete retention of configuration at carbon whereas the pro-S hydrogen underwent significant racemization.…”

A novel chlorin derivative of Meso-tris(pentafluorophenyl)-4-pyridylporphyrin: synthesis, photophysics and photochemical properties

“…They are capable of catalyzing a wide range of oxidation reactions: from hydroxylation of alkanes and epoxidation of alkenes to drug oxidation and DNA cleavage. [1][2][3] More recently, porphyrins have attracted even more attention from researchers in various fields due to their phototherapeutic properties. [4][5][6] Photodynamic therapy (PDT) is a form of neoplastic diseases treatment using a photosensitizer, oxygen and light.…”

Modified silicas covalently bounded to 5,10,15,20-tetrakis(2-hydroxy-5-nitrophenyl)porphyrinato iron(III): synthesis, spectroscopic and EPR characterization. Catalytic studies

“…26 In this respect, initial assays in the oxidation of cyclohexane catalized by 1-SiN, 1-SiN(IPG) and 1-CPS gave very low yields of the products cyclohexanol and cyclohexanone ( III species in the oxidative processes. In addition, 1-SiN, 1-SiN(IPG) and 1-CPS showed to be efficient catalysts in the epoxidation of (Z)-cyclooctene by PhIO even after three successive recycling steps, making them promising catalysts for selective epoxidations.…”