Electron Transfer Control of Reductase versus Monooxygenase: Catalytic C–H Bond Hydroxylation and Alkene Epoxidation by Molecular Oxygen

[Image: see text] Catalytic oxidation of organic substrates, using a green oxidant like O(2), has been a long-term goal of the scientific community. In nature, these oxidations are performed by metalloenzymes that generate highly oxidizing species from O(2), which, in turn, can oxidize very stable organic substrates, e.g., mono-/dioxygenases. The same oxidants are produced during O(2) reduction/respiration in the mitochondria but are reduced by electron transfer, i.e., reductases. Iron porphyrin mimics of the active site of cytochrome P450 (Cyt P450) are created atop a self-assembled monolayer covered electrode. The rate of electron transfer from the electrode to the iron porphyrin site is attenuated to derive monooxygenase reactivity from these constructs that otherwise show O(2) reductase activity. Catalytic hydroxylation of strong C–H bonds to alcohol and epoxidation of alkenes, using molecular O(2) (with (18)O(2) incorporation), is demonstrated with turnover numbers >10(4). Uniquely, one of the two iron porphyrin catalysts used shows preferential oxidation of 2° C–H bonds of cycloalkanes to alcohols over 3° C-H bonds without overoxidation to ketones. Mechanistic investigations with labeled substrates indicate that a compound I (Fe(IV)=O bound to a porphyrin cation radical) analogue, formed during O(2) reduction, is the primary oxidant. The selectivity is determined by the shape of the distal pocket of the catalyst, which, in turn, is determined by the substituents on the periphery of the porphyrin macrocycle.