hydroxamatebased

Hydroxamate-based refers to compounds that contain the hydroxamic acid functional group, typically written as R-CO-NHOH. The hydroxamate moiety comprises a carbonyl group adjacent to an N-hydroxylamine, enabling strong bidentate coordination of metal ions through the carbonyl oxygen and the deprotonated hydroxylamine oxygen. This chelating capability makes hydroxamate-based molecules useful in coordination chemistry, biology, and medicine.

In nature, hydroxamate-based siderophores are produced by various bacteria and fungi to acquire iron. These molecules feature multiple hydroxamate groups that bind Fe3+ with high affinity and shuttle it into cells via specific receptor and transporter systems. Desferrioxamine B (deferoxamine) is a clinically used hydroxamate-based iron chelator derived from this chemistry.

In pharmacology, hydroxamate-based motifs appear in two major roles. As histone deacetylase inhibitors, the hydroxamate group coordinates zinc in the HDAC active site, preventing deacetylation and altering gene expression. Notable examples include vorinostat (SAHA), panobinostat, belinostat, and trichostatin A. Separately, hydroxamate ligands are employed as iron chelators in conditions of iron overload.

Beyond biology, hydroxamate ligands form stable metal complexes for catalysis, materials science, and imaging. They are used in siderophore mimics and drug-delivery constructs that exploit metal coordination chemistry for targeting or activation.

Research focuses on improving selectivity, bioavailability, and safety, whether optimizing HDAC-inhibitor profiles or designing hydroxamate-based siderophore mimics and metal complexes for therapeutic and industrial applications.