Heme oxo-iron complexes are powerful oxygenation catalysts of environmentally benign hydroxylation processes. We have performed density functional theoretic calculations on a model system, that is, an oxo-iron-porphyrin (Por) complex [(Fe=O)Cl(Por)], and studied its reactivity toward a realistic substrate, namely, ethylbenzene. The calculations showed that the dominant reaction process in the gas phase is benzyl hydroxylation leading to 1-phenylethanol, with an energetic barrier of 9.1 kcal mol(-1), while the competing para-phenyl hydroxylation has a barrier 3.0 kcal mol(-1) higher in energy. This benzyl hydroxylation barrier is the lowest C-H hydroxylation barrier we have obtained so far for oxo-iron-porphyrin complexes. Due to electronic differences between the intermediates in the phenyl and benzyl hydroxylation processes, the phenyl hydroxylation process is considerably stabilised over the benzyl hydroxylation mechanism in environments with a large dielectric constant. In addition, we calculated kinetic isotope effects of the substitution of one or more hydrogen atoms of ethylbenzene by deuterium atoms and studied its effect on the reaction barriers. Thus, in a medium with a large dielectric constant, a regioselectivity change occurs between [H(10)]ethylbenzene and [D(10)]ethylbenzene whereby the deuterated species gives phenol products whereas the hydrogenated species gives mainly 1-phenylethanol products. This remarkable metabolic switching was analysed and found to occur due to 1) differences in strength between a C-H versus a C-D bond and 2) stabilisation of cationic intermediates in a medium with a large dielectric constant. We have compared our calculations with experimental work on synthetic oxo-iron-porphyrin catalysts as well as with enzyme-reactivity studies.