Computational Insights\ninto Hydrogen Atom Transfer\nMediators in C–H Activation Catalysis of Nonheme Fe(IV)O Complexes

This study presents a detailed density\nfunctional theory\n(DFT)\ninvestigation into the mechanism and energetics of C–H activations\ncatalyzed by bioinspired Fe(IV)O complexes, particularly in the presence\nof <i>N</i>-hydroxy mediators. The findings show that these\nmediators significantly enhance the reactivity of the iron-oxo complex.\nThe study examines three substrates with varying bond dissociation\nenergiesethylbenzene, cyclohexane, and cyclohexadienealongside\nthe [Fe(IV)O(N4Py)]<sup>2+</sup> complex. Mediators <i>N</i>-hydroxyphthalimide (NHPI) and <i>N</i>-hydroxyquinolinimide\n(NHQI) were chosen for their strong oxidative abilities. The results\nreveal that NO–H bond cleavage in <i>N</i>-hydroxy\ncompounds occurs more readily than C–H bond cleavage in hydrocarbons,\nas supported by the Marcus cross-relation applied to H-abstraction.\nThis leads to the rapid formation of aminoxyl radicals, which are\nmore reactive than Fe(IV)O species, lowering the activation energy\nand enhancing the reaction rate. The C–H bond activation aligns\nwith the Bell–Evans–Polanyi principle, correlating the\nactivation energy with the substrate bond dissociation energy. The\ninvestigation reveals that the mediator pathway is favored both thermodynamically\nand kinetically. Additionally, distortion energy provides a compelling\nexplanation for the observed reactivity trends, further highlighting\nNHQI’s superior efficiency compared to NHPI. Additionally,\nquantum mechanical tunneling plays a significant role, as evidenced\nby the computed kinetic isotope effect, which matches experimental\ndata.