| The water-soluble iron porphyrins Fe-4-TMPyP [(5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin)iron(III)], Fe-2-TMPyP [(5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin)iron(III)], and FeTMPS [(5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-disulfonato-phenyl)porphyrin)iron(III)] were investigated as models for the Compound I species of heme monoxygenases such as cytochrome P450 and chloroperoxidase. Fe-4-TMPyP and FeTMPS are the first examples of chemically generated and characterized oxoiron(IV) porphyrin cation radicals in aqueous buffer at ambient temperatures. Mechanistic studies suggest the Fe-2-TMPyP oxoiron(IV) porphyrin cation radical forms transiently even though it is not directly detected. The Compound I species of these iron porphyrins are demonstrated to be reactive in a variety of reactions including C-H and O-H hydrogen atom abstraction, halide oxygen atom transfer, olefin epoxidation, sulfoxidation, and one electron transfer nitrite oxidation. From these results, the structure-reactivity relationship revealed water-soluble iron porphyrins with increasingly electron withdrawing porphyrin ligands are more reactive toward substrate reactions. Interestingly, this is opposite the trend observed for the well characterized water-soluble manganese porphyrins.;Upon mixing Fe-4-TMPyP with mCPBA, oxoFe(IV)-4-TMPyP porphyrin cation radical is detected by rapid-mixing stopped-flow spectrophotometry. This results in the formation of a new intermediate displaying a weak, blue shifted Soret at 402 nm and an absorbance at 673 nm, typical of porphyrin cation radicals. This intermediate subsequently transforms into the well characterized oxoFe(IV)-4-TMPyP. The oxoFe(IV)-4-TMPyP porphyrin cation was highly reactive toward C-H and O-H hydrogen bond abstraction reactions. Mapping the observed rate (7.5 x 103 M-1s-1 for 4-ethylbenzoic acid to 3.6 x 106 M-1s -1 for xanthene) constants onto the Bronsted-Evans-Polanyi relationship for similar substrates estimates the BDE for H-OFe(IV)-4-TMPyP to be around 100 kcal/mol. In general, a dramatic decrease in rate constant (1.0 to 2.5 orders of magnitude) is observed in moving from O-H bonds to C-H bonds.;OxoFe(IV)-4-TMPyP porphyrin cation radical is also highly reactive toward oxygen atom transfer reactions with bromide, chloride, dihydropyran, carbamazepine, and methionine. The halide oxygen atom transfer reactions with bromide and chloride were shown to be reversible. Kinetic determination of the equilibrium constant led to the determination of the oxidation potential of the Cpd I/Fe(III) couple (E = 1.21 V at pH 4.7). A comparison of bromide oxidation rates indicates water-soluble iron porphyrins with increasingly electron-withdrawing meso substituents are more reactive and follow expected structure-reactivity trends. It is suggested that the variability in intrinsic kinetic reactivity observed among oxoiron(IV) porphyrin cation radicals results from the effect of the electron-withdrawing porphyrin ligand in facilitating a spin state crossing. More generally, subtle charge and structural modulations may result in dramatic changes in Compound I reactivity.;OxoFe(IV)TMPS porphyrin cation radical exhibits high stability and long lifetimes in aqueous solvent. This high stability enabled the 1H NMR characterization of oxoFe(IV)TMPS porphyrin cation radical, diaqua Fe(III)TMPS porphyrin cation radical, and dimethoxy Fe(IV)TMPS. On the basis of these observations and comparisons with previously reported models, it is suggested the oxoFe(IV)TMPS porphyrin cation radical species is a S = 3/2 complex with low spin iron (S = 1) ferromagnetically coupled to an a2u porphyrin cation radical (S' = 1/2). |
