How do aldehyde side products occur during alkene epoxidation by cytochrome P450? Theory reveals a state-specific multi-state scenario where the high-spin component leads to all side products

A theoretical study of alkene epoxidation, by the high-valent iron-oxo species (Compound I) of cytochrome P450, reveals a multi-state scenario in which the different products are generated in a state specific manner. All the low-spin doublet state processes are effectively concerted epoxide producing pathways. By contrast, all the high-spin quartet processes are stepwise and either lead to epoxide that does not conserve the isomeric identity of the alkene (cis or trans), or/and to by-products such as suicidal complexes and aldehydes. The product/state inventory is the following:(a) The epoxide with conserved alkene stereochemistry is generated from the low-spin doublet states of Compound I in a nonsynchronous but effectively concerted pathways that involve carbon radical (with Fe^III and Fe^IV) and cationic intermediates.(b) The epoxide with scrambled alkene stereochemistry is obtained from the quartet high-spin radical intermediate (with Fe^IV).(c) The suicidal complex, with a C-N bond between the alkene and the porphyrin, is obtained from the high-spin cationic state that possesses one electron in the σ*_xy orbital (the antibonding Fe-N orbital made from d_xy and nitrogen σ-hybrids).(d) The aldehyde by-product is obtained from the high-spin cationic state that possesses one electron in the σ*_z2 orbital (the antibonding O-Fe-S orbital made from d_z2 and the oxo and sulfur σ-hybrids). Factors controlling the competition between these processes are discussed.