Iron(II)/reductant(DH 2)-induced activation of dioxygen for the hydroxylation and ketonization of hydrocarbons; Mimics for the cytochrome P-450 hydroxylase/reductase system

Abstract

Several metal complexes Fe II(DPAH) 2 (DPAH 2 = 2,6-dicarboxyl pyridine), Fe II(PA) 2 (PAH = picolinic acid), Fe II(bpy) 2 2+, Fe II(OPPh 3) 4 2+, (Cl 8TPP)Fe IIIX (X=Cl, OH, SCH 2Ph) [Cl 8TPP = tetrakis (2,6-dichlorophenyl)porp Fe IIICl (TPP = tetraphenylporphyrin), and Cu I(tpy) 2 + (tpy = 2,2′–6,2″-terpyridine) in combination with one of several reductants [DH 2; PhNHNHPh (mimic of dihydroflavin), PhNHNH 2, ascorbic acid (H 2asc), and PhCH 2SH (model ligand for cysteine residue)] catalytically activate O 2 (1 atm) for the hydroxylation of saturated hydrocarbons (e.g. c-C 6H 12 → c-C 6H 11OH). This chemistry closely parallels that of cytochrome P-450 proteins, and both appear to involve a Fenton-like reactive intermediate), [L x FeOOH(DH)]. With cyclohexene as the substrate the dominant product is its ketone (as well as significant amounts of its hydroperoxide), 1,4-Cyclohexadiene (with two double-allylic carbon centers) undergoes dehydrogenation to give benzene, but also yields substantial amounts of phenol via ketonization of an allylic carbon. The 1:1 Fe II(bpy) 2 2+/(PhNHNH 2 or H 2asc), Fe IIPA 2/H 2asc, and (Cl 8TPP)Fe IIICl/PhNHNH 2 combinations initiate the autoxidation of 1,4-cyclohexadiene with turnover numbers (moles of product per mole of reductant) from 71 to 26, respectively (α-tocophenol reduces the turnover numbers by 20–80 %). With respect to aerobic biology, the present results indicate that dysfunctional transition metals (degradation products of metalloproteins) in combination with biological reductants activate O 2 for reaction with organic substrates. The level of activation is similar to that for Fenton reagents and cytochrome P-450 hydroxylases. Hence, dysfunctional transition metals, reductants, and O 2 are a hazardous combination within a biological matrix.