Effect of Porphyrin Ligands on the Regioselective Dehydrogenation versus Epoxidation of Olefins by Oxoiron(IV) Mimics of Cytochrome P450

Abstract

The cytochromes P450 are versatile enzymes involved in various catalytic oxidation reactions, such as hydroxylation, epoxidation and dehydrogenation. In this work, we present combined experimental and theoretical studies on the change of regioselectivity in cyclohexadiene oxidation (i.e., epoxidation vs dehydrogenation) by oxoiron(IV) porphyrin complexes bearing different porphyrin ligands. Our experimental results show that meso-substitution of the porphyrin ring with electron-withdrawing substituents leads to a regioselectivity switch from dehydrogenation to epoxidation, affording the formation of epoxide as a major product. In contrast, electron-rich iron porphyrins are shown to produce benzene resulting from the dehydrogenation of cyclohexadiene. Density functional theory (DFT) calculations on the regioselectivity switch of epoxidation vs dehydrogenation have been performed using three oxoiron(IV) porphyrin oxidants with hydrogen atoms, phenyl groups, and pentachlorophenyl (ArCl 5 ) groups on the meso-position. The DFT studies show that the epoxidation reaction by the latter catalyst is stabilized because of favorable interactions of the substrate with halogen atoms of the meso-ligand as well as with pyrrole nitrogen atoms of the porphyrin macrocycle. Hydrogen abstraction transition states, in contrast, have a substrate-binding orientation further away from the porphyrin pyrrole nitrogens, and they are much less stabilized. Finally, the regioselectivity of dehydrogenation versus hydroxylation is rationalized using thermodynamic cycles.

Reactivity Patterns of (Protonated) Compound II and Compound I of Cytochrome P450: Which is the Better Oxidant?

“…protonated CpdII. [27] These results are in line with those obtained by Abu-Omar and co-workers on manganese(V)-oxo versus manganese(IV)-hydroxo porphyrinoid cation radical systems that gave slightly better reactivity of CpdI than protonated CpdII models. [28] Geometrically, the hydrogen atom abstraction transition states by protonated CpdII are relatively central with C-H and O-H distances that are very close.…”

Manganese Catalysts for C−H Activation: An Experimental/Theoretical Study Identifies the Stereoelectronic Factor That Controls the Switch between Hydroxylation and Desaturation Pathways

“…For instance, the organic radical can move around the MnOH group. The orientation of the substrate in its initial approach to the catalyst,30 the dynamics of the system31 and the weak interactions between the catalyst, substrate and solvent32 may also have a critical influence on the final outcome of the reaction. Therefore, the accurate prediction of the final desaturation/hydroxylation ratio, which is not the goal of this paper, will require extremely computationally demanding calculations.…”

Strengths, Weaknesses, Opportunities and Threats: Computational Studies of Mn- and Fe-Catalyzed Epoxidations

“…They are also proposed as intermediaries resulting from the dismutation of H 2 O 2 in cytochrome P450 [47]. Abashkin and Burt conducted a DFT survey on the catalase-mimicking activity of Mn(salen)Cl [32], showing a viable route for the formation of oxo-Mn(salen)Cl from Mn(salen)Cl and H 2 O 2 .…”