The iron(III) meso-tetramesitylporphyrin complex is a good biomimetic to study the catalytic reactions of cytochrome P450. All of the three most discussed reactive intermediates concerning P450 catalysis (namely, Cpd 0, Cpd I, and Cpd II) can be selectively produced, identified, and stabilized for many minutes in solution at low temperature by choosing appropriate reaction conditions. In this way, their reactivity against various substrates was determined by utilizing low-temperature rapid-scan UV/Vis spectroscopy. Since all reactive intermediates are derived from a single model complex, the results of these kinetic measurements provide for the first time a full comparability of the determined rate constants for the three intermediates. The rate constants reveal a significant dependence of the reactivity on the type of reaction (e.g., oxygenation, hydrogen abstraction, or hydride transfer), which closely correlates with the chemical nature of Cpds 0, I, and II. The detailed knowledge of the reactivity of these intermediates provides a valuable tool to evaluate their particular role in biological systems.

A rate‐fate fête: Direct kinetic studies on epoxidation and sulfoxidation reactions revealed that the oxygenating capability of [(TMP+.)FeIVO] is orders of magnitude higher than that of [FeIII(TMP)(m‐CPBA)]. Under catalytic turnover conditions, the relative ratio between the rate of OO bond heterolytic cleavage and the rate of oxygen transfer from the [FeIII(TMP)(m‐CPBA)] intermediate to the substrate, should be taken into consideration. m‐CPBA=m‐chloroperbenzoic acid, TMP=meso‐tetramesitylporphyrin.

The present study focuses on the formation and reactivity of hydroperoxo-iron(III) porphyrin complexes formed in the [Fe(III)(tpfpp)X]/H(2)O(2)/HOO(-) system (TPFPP=5,10,15,20-tetrakis(pentafluorophenyl)-21H,23H-porphyrin; X=Cl(-) or CF(3) SO(3)(-)) in acetonitrile under basic conditions at -15 °C. Depending on the selected reaction conditions and the active form of the catalyst, the formation of high-spin [Fe(III)(tpfpp)(OOH)] and low-spin [Fe(III)(tpfpp)(OH)(OOH)] could be observed with the application of a low-temperature rapid-scan UV/Vis spectroscopic technique. Axial ligation and the spin state of the iron(III) center control the mode of O-O bond cleavage in the corresponding hydroperoxo porphyrin species. A mechanistic changeover from homo- to heterolytic O-O bond cleavage is observed for high- [Fe(III)(tpfpp)(OOH)] and low-spin [Fe(III)(tpfpp)(OH)(OOH)] complexes, respectively. In contrast to other iron(III) hydroperoxo complexes with electron-rich porphyrin ligands, electron-deficient [Fe(III)(tpfpp)(OH)(OOH)] was stable under relatively mild conditions and could therefore be investigated directly in the oxygenation reactions of selected organic substrates. The very low reactivity of [Fe(III)(tpfpp)(OH)(OOH)] towards organic substrates implied that the ferric hydroperoxo intermediate must be a very sluggish oxidant compared with the iron(IV)-oxo porphyrin π-cation radical intermediate in the catalytic oxygenation reactions of cytochrome P450.

Compound I, an oxo-iron(IV) porphyrin π-cation radical species, and its one-electron-reduced form compound II are regarded as key intermediates in reactions catalyzed by cytochrome P450. Although both reactive intermediates can be easily produced from model systems such as iron(III) meso-tetra(2,4,6-trimethylphenyl)porphyrin hydroxide by selecting appropriate reaction conditions, there are only a few thermal activation parameters reported for the reactions of compound I analogues, whereas such parameters for the reactions of compound II analogues have not been investigated so far. Our study demonstrates that ΔH(≠) and ΔS(≠) are closely related to the chemical nature of the substrate and the reactive intermediate (viz., compounds I and II) in epoxidation and C-H abstraction reactions. Although most studied reactions appear to be enthalpy-controlled (i.e., ΔH(≠) > -TΔS(≠)), different results were found for C-H abstractions catalyzed by compound I. Whereas the reaction with 9,10-dihydroanthracene as a substrate is also dominated by the activation enthalpy (ΔH(≠) = 42 kJ/mol, ΔS(≠) = 41 J/Kmol), the same reaction with xanthene shows a large contribution from the activation entropy (ΔH(≠) = 24 kJ/mol, ΔS ≠) = -100 J/kmol). This is of special interest since the activation barrier for entropy-controlled reactions shows a significant dependence on temperature, which can have an important impact on the relative reaction rates. As a consequence, a close correlation between bond strength and reaction rate-as commonly assumed for C-H abstraction reactions-no longer exists. In this way, this study can contribute to a proper evaluation of experimental and computational data, and to a deeper understanding of mechanistic aspects that account for differences in the reactivity of compounds I and II.

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