Quantum chemical studies of C–H activation reactions by high-valent nonheme iron centers

Activation of unactivated C–H bonds is an important process in nature and organic synthesis. Nature employs a wide range of metalloproteins to efficiently catalyze such reactions. Quantum chemistry can be used to explore the reactivity of such systems. Atomic level insight into the catalytic mechanisms can be gained through the calculation of reaction energies, barriers, isotope effects, and—where available—spectroscopic properties. This approach is illustrated for the case of the H-atom abstraction reaction performed by the quintet iron(IV)-oxo intermediate in the nonheme iron enzyme taurine-α-ketoglutarate dioxygenase (TauD). The careful analysis of the electronic structure of the reactant, transition state, and product indicates that the reaction involves a preparatory step in which an iron(III)-oxyl species is produced that is the active species in the actual C–H bond activation process.