Ferryl Protonation in Oxoiron(IV) Porphyrins and Its Role in Oxygen Transfer

Abstract

Ferryl porphyrins, P−FeIV=O, are central reactive intermediates in the catalytic cycles of numerous heme proteins and a variety of model systems. There has been considerable interest in elucidating factors, such as terminal oxo basicity, that may control ferryl reactivity. Here, the sulfonated, water-soluble ferryl porphyrin complexes tetramesitylporphyrin, oxoFeIVTMPS (FeTMPS-II), its 2,6-dichlorophenyl analogue, oxoFeIVTDClPS (FeTDClPS-II), and two other analogues are shown to be protonated under turnover conditions to produce the corresponding bis-aqua-iron(III) porphyrin cation radicals. The results reveal a novel internal electromeric equilibrium, P−FeIV=O ⇆ P+−FeIII(OH2)2. Reversible pKa values in the range of 4–6.3 have been measured for this process by pH-jump, UV–vis spectroscopy. Ferryl protonation has important ramifications for C–H bond cleavage reactions mediated by oxoiron(IV) porphyrin cation radicals in protic media. Both solvent O–H and substrate C–H deuterium kinetic isotope effects are observed for these reactions, indicating that hydrocarbon oxidation by these oxoiron(IV) porphyrin cation radicals occurs via a solvent proton-coupled hydrogen atom transfer from the substrate that has not been previously described. The effective FeO–H bond dissociation energies for FeTMPS-II and FeTDClPS-II were estimated from similar kinetic reactivities of the corresponding oxoFeIVTMPS+ and oxoFeIVTDClPS+ species to be ~92–94 kcal/mol. Similar values were calculated from the two-proton P+−FeIII(OH2)2 pKaobs and the porphyrin oxidation potentials, despite a 230 mV range for the iron porphyrins examined. Thus, the iron porphyrin with the lower ring oxidation potential has a compensating higher basicity of the ferryl oxygen. The solvent-derived proton adds significantly to the driving force for C–H bond scission.

Direct visualization of a Fe(IV)–OH intermediate in a heme enzyme

“…This offers a different perspective on the utilization of these ferryl intermediates across the family of heme enzymes. It remains to be seen whether other members of the peroxidase family behave similarly, but there is recent evidence that the ferryl heme could be protonated under certain conditions in other histidine-ligated heme enzymes2728. The mechanisms of proton delivery are poorly understood.…”

Biomimetic Reactivity of Oxygen-Derived Manganese and Iron Porphyrinoid Complexes

“…93 The two-proton p K a values of sulfonated, water-soluble Fe IV (O) porphyrins were identified and it was found that the most basic Fe IV (O) complex had the largest C-H bond cleavage rates. For Fe IV (O)(TMPS •+ ), a KIE of 1.80 was observed with xanthene- d 2 , and a solvent KIE of 1.65 was seen with D 2 O, giving a combined substrate-solvent isotope effect of 2.2.…”

Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities

“…Non-heme porphyrin complexes such as 18 – 21 have also been synthesized by Groves (Figure 14) [105]. Unique about these systems is the existence of a proton-coupled hydrogen atom transfer equilibrium, which may be thought of as a formal two-proton, one-electron transfer step.…”