Hydroxamic

Hydroxamic is an adjective used in chemistry to describe compounds that contain the hydroxamic functional group, defined by the structure R-CO-NHOH. This moiety consists of an acyl group linked to an N-hydroxylamine, and it is characteristic of the class of compounds known as hydroxamic acids.

The defining property of hydroxamic acids is their ability to act as bidentate ligands, coordinating metals through the carbonyl oxygen and the deprotonated hydroxylamine nitrogen. This feature underpins their roles as metal chelators in biological and chemical systems. In nature, several hydroxamate-containing molecules function as siderophores, which bacteria and fungi use to sequester ferric iron. Examples include desferrioxamines and ferrichromes, which form stable complexes with Fe3+ through multiple hydroxamate groups.

In medicine and pharmacology, hydroxamic acids are of interest both as metal-binding pharmacophores and as functional groups in drugs. They appear in histone deacetylase inhibitors (HDAC inhibitors) such as vorinostat and panobinostat, where the hydroxamic moiety helps coordinate the zinc ion in the enzyme’s active site. Hydroxamic acids also feature in certain matrix metalloproteinase inhibitors and other metalloproteinase-targeting agents.

Synthesis commonly involves converting activated carboxylic derivatives (such as acid chlorides or esters) into the hydroxamic acid via reaction with hydroxylamine, followed by suitable protection or deprotection steps as needed.

Safety considerations for hydroxamic acids include irritant properties and, in some cases, potential toxicity or reactivity of related hydroxylamine species; appropriate handling and disposal are advised.

See also: hydroxylamine, hydroxamic acid, siderophores, HDAC inhibitors, chelating agents.