Theoretical study on kinetic isotope effects in the C-H bond activation of alkanes by iron-oxo complexes

The C-H bond dissociation reactions of methane and ethane by the bare FeO⁺ complex, diiron and dicopper models of methane monooxygenase, and a compound I model of cytochrome P450 are discussed using density functional theory (DFT) calculations, with an emphasis on their kinetic isotope effects (KIEs). There are possible three types of transition states for the C-H bond dissociation. The first is an oxene insertion mechanism, in which a C-H bond is dissociated and C-O and O-H bonds are formed in a concerted manner via a three-centered transition state C···H···O-Fe which directly leads to a product alcohol. The second is a direct abstraction mechanism in which a linear transition state C···H···O-Fe leads to the dissociation into an Fe-OH intermediate and an alkyl radical species. The third mechanism involves a four-centered transition state C···H···O-Fe in its initial stages, which leads to a reaction intermediate involving OH and CH₃ ligands. DFT computations demonstrate that the second and third types of transition states are likely to occur in the activation of a C-H bond, The four-centered H atom abstraction can preferentially occur when the metal active center of catalysts and enzymes is coordinatively unsaturated (five-coordinate), whereas the direct abstraction should occur when the metal active center is six-coordinate. KIE values calculated with transition state theory are significantly dependent on temperature, substituents, and ways of abstraction.