hydroxylation

Hydroxylation is a chemical reaction that introduces a hydroxyl group (-OH) into an organic substrate. It increases polarity and water solubility, often enabling further metabolism or functionalization. Hydroxylation can be carried out chemically, using oxidants such as oxygen under catalytic conditions, or enzymatically, most notably by enzymes that insert oxygen into substrates.

In biology, oxidation is typically carried out by hydroxylases, including cytochrome P450 monooxygenases and non-heme iron or copper-dependent enzymes. In the canonical P450 mechanism, a high-valent iron-oxo species abstracts a hydrogen from the substrate, forming a radical that recombines with an oxygen rebound, yielding an alcohol and water after reduction.

Biological roles: hydroxylation is central to drug metabolism and detoxification in humans, enabling excretion. It also activates or inactivates signaling molecules and is essential for posttranslational modification, e.g., the formation of hydroxyproline and hydroxylysine in collagen, which requires prolyl and lysyl hydroxylases and cofactors such as Fe2+, O2, and vitamin C.

Regio- and stereoselectivity: hydroxylation can occur at benzylic, allylic, aliphatic, or aromatic positions. Enzymes often show high regioselectivity and, in some cases, stereoselectivity, producing a single hydroxyl isomer.

Industrial and research relevance: hydroxylation is used in drug development to tune activity and solubility, and as a biocatalytic method for converting hydrocarbons to alcohols under mild conditions. Isotopic labeling with 18O2 is used to study mechanisms and pathways.