Computational Insights into Hydrogen Atom Transfer Mediators in C–H Activation Catalysis of Nonheme Fe(IV)O Complexes

This study presents a detailed density functional theory (DFT) investigation into the mechanism and energetics of C-H activations catalyzed by bioinspired Fe(IV)O complexes, particularly in the presence of <i>N</i>-hydroxy mediators. The findings show that these mediators significantly enhance the reactivity of the iron-oxo complex. The study examines three substrates with varying bond dissociation energies─ethylbenzene, cyclohexane, and cyclohexadiene─alongside the [Fe(IV)O(N4Py)]²⁺ complex. Mediators <i>N</i>-hydroxyphthalimide (NHPI) and <i>N</i>-hydroxyquinolinimide (NHQI) were chosen for their strong oxidative abilities. The results reveal that NO-H bond cleavage in <i>N</i>-hydroxy compounds occurs more readily than C-H bond cleavage in hydrocarbons, as supported by the Marcus cross-relation applied to H-abstraction. This leads to the rapid formation of aminoxyl radicals, which are more reactive than Fe(IV)O species, lowering the activation energy and enhancing the reaction rate. The C-H bond activation aligns with the Bell-Evans-Polanyi principle, correlating the activation energy with the substrate bond dissociation energy. The investigation reveals that the mediator pathway is favored both thermodynamically and kinetically. Additionally, distortion energy provides a compelling explanation for the observed reactivity trends, further highlighting NHQI's superior efficiency compared to NHPI. Additionally, quantum mechanical tunneling plays a significant role, as evidenced by the computed kinetic isotope effect, which matches experimental data.