Oxoiron(IV) porphyrin π-cation radical complexes with a chameleon behavior in cytochrome P450 model reactions

Abstract

There is an intriguing, current controversy on the involvement of multiple oxidizing species in oxygen transfer reactions by cytochromes P450 and iron porphyrin complexes. The primary evidence for the "multiple oxidants" theory was that products and/or product distributions obtained in the catalytic oxygenations were different depending on reaction conditions such as catalysts, oxidants, and solvents. In the present work, we carried out detailed mechanistic studies on competitive olefin epoxidation, alkane hydroxylation, and C=C epoxidation versus allylic C-H hydroxylation in olefin oxygenation with in situ generated oxoiron(IV) porphyrin pi-cation radicals (1) under various reaction conditions. We found that the products and product distributions were markedly different depending on the reaction conditions. For example, 1 bearing different axial ligands showed different product selectivities in competitive epoxidations of cis-olefins and trans-olefins and of styrene and para-substituted styrenes. The hydroxylation of ethylbenzene by 1 afforded different products, such as 1-phenylethanol and ethylbenzoquinone, depending on the axial ligands of 1 and substrates. Moreover, the regioselectivity of C=C epoxidation versus C-H hydroxylation in the oxygenation of cyclohexene by 1 changed dramatically depending on the reaction temperatures, the electronic nature of the iron porphyrins, and substrates. These results demonstrate that 1 can exhibit diverse reactivity patterns under different reaction conditions, leading us to propose that the different products and/or product distributions observed in the catalytic oxygenation reactions by iron porphyrin models might not arise from the involvement of multiple oxidizing species but from 1 under different circumstances. This study provides strong evidence that 1 can behave like a "chameleon oxidant" that changes its reactivity and selectivity under the influence of environmental changes.

A Systematic Account on Aromatic Hydroxylation by a Cytochrome P450 Model Compound I: A Low‐Pressure Mass Spectrometry and Computational Study

“…As such, in the gas-phase the [Fe IV (O)(TPFPP +• )] + complex will preferentially react via aromatic hydroxylation over aliphatic hydroxylation with substrates. Nam et al [22] Subsequent computational modelling showed that the axial ligand affects the electron affinity and O-H bond strength (bond dissociation energy, BDEOH) and hence affected the relative barriers of aliphatic versus aromatic hydroxylation. [14b,23] To gain further insight into the intricate details of the bifurcation processes, below we will show a molecular orbital and valence bond interpretation of the mechanisms, but first we will discuss the experimental reaction trends.…”

High‐Valent Iron(IV)—Oxo Complexes of Heme and Non‐Heme Ligands in Oxygenation Reactions

“…[48][49][50][51] The primary evidence for proposing the multiple-oxidants hypothesis was that products and/or product distributions derived from the catalytic oxidations by CYP 450 and iron porphyrin models were different depending on reaction conditions such as catalysts (e.g., CYP 450 and their mutants), oxidants (e.g., H 2 O 2 , peracids, and iodosylarenes), and axial ligands of iron porphyrin catalysts (e.g., ligating and nonligating anions). 44,49,51 However, as we have discussed in the previous section, iron(IV)-oxo porphyrin π-cation radicals can exhibit diverse reactivity patterns under different circumstances, leading us to postulate that the different products and/or product distributions observed in iron porphyrin-catalyzed oxygenation reactions do not arise from the involvement of multiple oxidizing species but from a single oxidant under different environmental circumstances. 44 More strong experimental evidence for excluding the possibility of a "second electrophilic oxidant" in oxygen atom transfer reactions was obtained from the reactivity studies of iron(III)-hydroperoxo species in nucleophilic and electrophilic reactions, by using in situ-generated mononuclear non-heme iron(III)-hydroperoxo complexes that have been well characterized with various spectroscopic techniques.…”

“…44,49,51 However, as we have discussed in the previous section, iron(IV)-oxo porphyrin π-cation radicals can exhibit diverse reactivity patterns under different circumstances, leading us to postulate that the different products and/or product distributions observed in iron porphyrin-catalyzed oxygenation reactions do not arise from the involvement of multiple oxidizing species but from a single oxidant under different environmental circumstances. 44 More strong experimental evidence for excluding the possibility of a "second electrophilic oxidant" in oxygen atom transfer reactions was obtained from the reactivity studies of iron(III)-hydroperoxo species in nucleophilic and electrophilic reactions, by using in situ-generated mononuclear non-heme iron(III)-hydroperoxo complexes that have been well characterized with various spectroscopic techniques. 52 In this study, non-heme iron(III)-hydroperoxo intermediates did not exhibit any reactivities in both nucleophilic (e.g., aldehyde deformylation) and electrophilic (e.g., oxidation of sulfide and olefin) reactions (Scheme 4), demonstrating that non-heme iron(III)-hydroperoxo species are sluggish oxidants and that the oxidizing power of the intermediates cannot compete with that of iron(IV)-oxo complexes.…”

Axial ligand tuning of a nonheme iron(IV)–oxo unit for hydrogen atom abstraction

“…Although there are several studies demonstrating that axial ligands affect the reactivities of iron(IV)-oxo centers in biomimetic Cpd I analogs (15,16), only one of these studies reported the effect of a range of ligands on reaction rates (15), but no clear correlation between reactivity and some property of the axial ligand was discerned. More recently, with the synthesis of the first nonheme iron(IV)-oxo complex, [Fe IV (O)(TMC) (NCCH 3 )] 2ϩ (where TMC is 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) (17), we found that the axial CH 3 CN ligand can be replaced with anions and that these anions affected the reactivity of the iron(IV)-oxo unit (18)(19)(20).…”