Theoretical Studies on Hydroxamic Acids

Hydroxamic acids find many applications in chemistry and biology and have been the subject of many experimental investigations. Theoretical studies are not as frequent. However, the smallest homolog, formohydroxamic acid (FHA), has been studied at various levels, including high-level ab initio and density functional with large basis sets. All studies indicate that it exists as the Z-amide tautomer and deprotonation occurs from the nitrogen. Many combined experimental and theoretical studies confirm these conclusions. The interaction of formohydroxamic acid with solvent molecules and its adducts with various compounds have also been theoretically investigated. The higher homologs have not been studied as much. Acetohydroxamic acid, also known as Lithostat, has also been investigated at various levels of theory and experiment. Interest in this compound arises from the fact that it is a known inhibitor of urease. Other investigated hydroxamic acids include benzohydroxamic acid, whose conformational properties have also been investigated. Because of their association with inhibition of the urease enzyme and matrix metalloproteinases, as well as their application as siderophores, the complexation chemistry of hydroxamic acids is very important. However, very few theoretical studies aimed at deciphering the complexation of hydroxamic acids have appeared in the literature. Studies on metal ion selectivity of hydroxamic acids reveal that the affinity toward Ni(II), the metal ion present in urease, is due to its electrophilic nature. However, several QSAR and docking studies have appeared in the literature relating to applications of hydroxamic acids as inhibitors.