Regioelectronic factors in metabolic hydroxylation of aliphatic carbon atoms

Abstract

EHT calculations have been performed on model molecules acting as substrates for mammalian mono-oxygenases. C αH bonds are consistently found to have larger overlap populations compared with C βH and C γH bonds. It is known on the other hand that metabolic hydroxylation of aliphatic carbon atoms shows a marked regioselectivity for α-carbons. The quantum-mechanical results sustain the view that CH bonds of relatively high electronic density are preferred target sites for the cytochrome P-450-mediated oxygenation, and that the oxygen atom being activated is transformed into an electrophilic species capable of CH bond insertion.