hydroxamates

Hydroxamates are chemical compounds that contain the hydroxamate functional group, typically described by the structural motif R-C(=O)-NHO-R'. The group derives from hydroxamic acids and is a common feature in ligands that bind metals. In many cases, hydroxamates are found as part of larger molecules such as siderophores or drug candidates.

Coordination chemistry and structure: The hydroxamate unit can donate two oxygen atoms to a metal center, usually the carbonyl oxygen and the deprotonated N-hydroxyl oxygen, forming stable chelate rings. When a molecule contains multiple hydroxamate groups, it can act as a multidentate ligand, binding metals such as Fe3+ or Zn2+ with high affinity. Multihydroxamate ligands can be hexadentate, enabling strong, selective metal binding.

Natural occurrence and biosynthesis: Hydroxamate motifs are prominent in biological siderophores—microbial iron-chelating compounds. For example, desferrioxamine B contains three hydroxamate groups and functions as a potent iron chelator, helping microbes scavenge iron from the environment. Similar motifs appear in other bacterial and fungal metabolites used for metal acquisition.

Applications: In medicine, hydroxamates are used as chelating agents to treat metal overload conditions (e.g., deferoxamine), and as pharmacophores in enzyme inhibitors. The hydroxamic acid moiety is a key feature of several histone deacetylase inhibitors, such as vorinostat, where metal binding in the enzyme active site is important for activity. In analytical chemistry and industry, hydroxamates serve as ligands for metal separation, purification, and sensing.

Overview: Hydroxamates combine a distinctive chelating motif with versatile applications in biology, medicine, and chemistry, owing to their strong, multidentate metal-binding properties.