Metal-Catalyzed Oxygenation Mechanisms

Oxygen is chemically stubborn in its ground state, and living systems rely on metal-containing enzymes to coax it into reacting selectively with organic molecules—a feat that synthetic chemists have spent decades trying to understand and replicate. At the heart of this work are the mechanisms by which iron, copper, and manganese centers bind and split dioxygen, generating short-lived high-valent intermediates that carry out otherwise difficult oxidations, such as the conversion of methane to methanol by methane monooxygenase or the hydroxylation of drug molecules by cytochrome P450 enzymes. A central challenge is characterizing these transient species—compound I intermediates, iron-oxo complexes, and their precursors—with enough precision to explain how proton and electron transfers are orchestrated in concert to avoid unwanted side reactions. Ongoing work pushes toward designing synthetic non-heme iron catalysts that mimic enzymatic selectivity, and toward resolving long-standing debates about which oxidant is actually responsible for bond activation in specific enzyme families.

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Keywords

Dioxygen ActivationMetalloenzymeOxygenation ReactionsProton-Coupled Electron TransferNon-Heme Iron CatalystsCytochrome P450 Enzymes