Kinetic isotope effects in a C-H bond dissociation by the iron-oxo speciesof cytochrome P450

Kinetic isotope effects (KIEs) in the electronic process of the H-atom abst raction from substrate ethane by a compound I model of cytochrome P450 are discussed at the B3LYP level of density functional theory. Our calculations demonstrate that the transition State for the H-atom abstraction involves a linear (Fe)O . .H . . .C array and that, a resultant radical species with a spin density of nearly one is bound to an iron-hydroxo complex, followed by recombination and release of product ethanol. Although the reacting sys tem involves this carbon radical species in the course of the hydroxylation , in view of the energy profile of the reaction pathway it cannot be viewed as a stable reaction intermediate with a finite lifetime. The KIEs calcula ted with transition state theory are significantly dependent on temperature and substituents, falling in a range of 7-13 at 300 K.