monooxygenation

Monooxygenation is a category of oxidation reactions in which a single atom of molecular oxygen is incorporated into a substrate, while the other oxygen atom is reduced to water. This contrasts with dioxygenation, in which two oxygen atoms are added to the substrate. Monooxygenation can occur in biological systems and in chemical synthesis, often yielding hydroxylated, epoxidized, or heteroatom-oxidized products such as alcohols, epoxides, sulfoxides, or N-oxides.

In biology, monooxygenases catalyze these transformations using O2 and a reducing agent. The major enzymatic families are cytochrome P450 enzymes and flavin-containing monooxygenases (FMOs). Cytochrome P450 enzymes activate oxygen at a heme iron center to form a reactive iron-oxo species that inserts one oxygen atom into the substrate, typically hydroxylating C-H bonds or epoxidizing double bonds. FMOs transfer oxygen to nucleophilic heteroatoms or to carbon atoms in less activated substrates, producing products such as alcohols and sulfoxides. Both systems rely on reducing equivalents supplied by cofactors like NADPH or NADH and on molecular oxygen as the oxidant.

Monooxygenation plays a central role in metabolism and pharmacology. In drug metabolism, it constitutes a major phase I transformation that increases polarity and facilitates excretion, though it can also yield reactive intermediates. In biotechnology, engineered monooxygenases enable selective, enantioselective oxidations and late-stage functionalization of complex molecules for synthesis and green chemistry applications.

Chemical monooxygenation also occurs without enzymes, using oxidants and catalysts that insert a single oxygen atom into substrates. Examples include epoxidations with peracids or metal-oxo catalysts, and hydrogen peroxide–mediated oxidations, which mimic certain enzymatic processes and are employed in organic synthesis and environmental chemistry.