Origin of the Enhanced Reactivity of μ-Nitrido-Bridged Diiron(IV)-Oxo Porphyrinoid Complexes over Cytochrome P450 Compound I

Abstract

μ-Nitrido-bridged diiron porphyrins and phthalocyanines are known to be efficient oxidants that are able to oxidize some of the strongest C−H bonds in nature, such as the one in methane. The origin of their catalytic efficiency is poorly understood, and in order to gain insight into the structural and electronic features of this chemical system, we performed a detailed and systematic study into their chemical properties and reactivities using density functional theory. Our work shows that μ-nitrido-bridged diiron porphyrins and phthalocyanines are highly active catalytic oxidants, which react with methane with very low reaction barriers and a rate-determining hydrogen-atom-abstraction step. Furthermore, the μ-nitridobridged diiron porphyrin and phthalocyanine complexes react with a free energy of activation that is more than 10 kcal mol −1 lower in energy than that found for cytochrome P450 Compound I, which is known to be one of the most efficient C−H hydroxylating agents in Nature. We have analyzed the electronic configuration of reactants and transition states in detail and have identified the key properties of the oxidants that lead to this rate enhancement. In particular, the potency of the oxidant is related to the orbital mixing patterns along the Fe−O axis, whereby the axial iron(IV)-nitrido group donates sufficient electron density to affect the pK a of the oxo group as well as the strength of the O−H bond formed in the iron(IV)-hydroxo complex. The studies confirm that μ-nitrido diiron-oxo complexes should react via oxygen atom transfer readily even with strong C−H bonds as in methane. The results are analyzed with orbital diagrams, valence bond, and thermochemical cycles and explain the intricate details of the mechanism and the properties of the oxidant.

Singlet versus Triplet Reactivity in an Mn(V)–Oxo Species: Testing Theoretical Predictions Against Experimental Evidence

“…49 The correlations of these parameters with the Hammett parameter σ P are shown in Figure 6. Thus, we calculated the one-electron ionization energy of all substrates ( IE SubZ ) and the one-electron reduction of [Mn(O)(H 8 Cz)(CN)] − ( EA MnO ).…”

The Equatorial Ligand Effect on the Properties and Reactivity of Iron(V) Oxo Intermediates

“…[6] To gain insight into the structure and reactivity of enzymatic intermediatesa nd understandt he effect of ligand features and their direct environment, al arge number of biomimetic modelsh ave been generated and investigated. [7] These studies have given insighti nto the effect of the ligand coordination, [8] spin-state ordering, [9] and hydrogen-bonding interactions [10] that affect the properties and reactivity of the oxidants. In particular, it was found that nonheme iron(IV) oxo is more reactive in the quintets pin state than in the triplet spin state, probably due to exchange stabilization of the products tructures.…”

Theoretical Identification of the Factors Governing the Reactivity of C−H Bond Activation by Non‐Heme Iron(IV)‐Oxo Complexes

“…Indeed, UB3LYP/LACV3P(Fe), 6‐311+G*(all atoms) calculated barriers for methane hydroxylation with 3, 3‐Ac and CpdI are in an ascending order: 15.7, 19.4 and 25.9 kcal/mol respectively. Interestingly, the calculated strength of the OH bond formed after hydrogenation of the metal‐oxo center in 3 , i. e. BDE OH ( 3 ) is highest at 86.7 kcal/mol followed by BDE OH ( 3‐Ac ) at 82.3 kcal/mol, and BDE OH ( CpdI ) at 79.6 kcal/mol . Hence, it can be inferred that a greater bond dissociation energy of the metal‐OH moiety ensures a lower energetic penalty for its formation, thus lowering the barrier for HAT process.…”

“…Notably, the bond dissociation energy of methane C−H bond is 104.9 kcal/mol. As evident from the thermochemical cycle, BDE OH can be split up into two major constituents: electron affinity of the oxidant (interpreted from E °) and proton affinity of the reduced oxidant (obtained from p K a ) . Hence, dissecting the bond dissociation energies revealed that electron‐push effect from the axial ligand to the oxo group has marked impact on the relative acidity of the metal‐hydroxo bond.…”