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

Abstract

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.

Electrochemical C–H oxygenation and alcohol dehydrogenation involving Fe-oxo species using water as the oxygen source

“…Electrochemical generation of iron-oxo species from reduced Fe–OH/OH 2 species has been demonstrated,6 especially in the context of molecular iron-based catalysts for electrochemical water oxidation 7,8. The investigation of analogous reactivity for electrochemical oxidation of organic molecules however has been limited to electroanalytical studies9 or to the mineralization of organic pollutants 10,11. On the other hand, stoichiometric one-electron oxidants, such as cerium( iv ) ammonium nitrate (CAN), have been used to promote catalytic oxidation of organic molecules by high-valent metal-oxo species using water as an oxygen-atom source 12,13.…”

Oxoiron(v) mediated selective electrochemical oxygenation of unactivated C–H and CC bonds using water as the oxygen source

“…Collman and coworkers 50 and Tanaka and coworkers 51 reported electrochemical epoxidation using Mn complexes (porphyrins and salen), but the mechanism involved the electrochemical generation of the chemical oxidant (H 2 O 2 and OCl À ), which would subsequently activate the metal complex in a process similar to chemical oxidation. Murray and coworkers 52 and recently Dey and coworkers 35 showed electrochemical reductive activation of O 2 bound to metal porphyrin complexes, which would subsequently form high-valent oxometal intermediates to catalyze oxidation reactions. The only example, which demonstrates the use of water as the O-atom source for epoxidation reactions has been recently reported by Manthiram and coworkers.…”

“…Recently, heterogenized iron porphyrins have been used to catalytically oxidize hydrocarbons, including unactivated C-H bonds using molecular O 2 at cathodic potentials. 35 However, the selective homogeneous electrochemical oxidation of unactivated C-H and C]C bonds in organic substrates using water as the O-atom source via the formation of high-valent oxoiron intermediates has been elusive. We have earlier demonstrated that the 5th generation biuret modied TAML, [Et 4 N] 2 [Fe-bTAML(Cl)], catalyzes the oxidation of 3 C-H bonds with unprecedented selectivity over 2 C-H bonds using NaOCl or mCPBA as the terminal oxidant.…”

Harnessing the Oxidative Power of Monooxygenases through Electrochemistry

“…P450 model complex (Fe-“picket-fence” porphyrin, FePf) atop an alkylthiol-derived self-assembled monolayer (SAM) modified electrode, yielding a new electrocatalyst for the hydroxylation and epoxidation of alkanes and olefins (Figure 1). 3 Unlike Cyt. P450 or synthetic porphyrin model complexes, electrocatalysis is achieved without the requirement of exogenous electron donors or strong chemical oxidants utilizing solely O 2 and electrochemically derived electrons.…”

“…P450 showing substrate hydroxylation by the electrocatalyst FePf immobilized on a SAM modified gold electrode as reported by Mukherjee and Dey. 3 Highlighted in yellow is the active catalytic intermediate responsible for substrate oxidation, compound 1.…”