3-Hydroxy-2-pyridinone (3,2-HOPO)

3,2-Hydroxypyridinone (3,2-HOPO) is a chemical scaffold used to develop high-affinity chelating agents for 'hard' metal ions, including iron (Fe3+) and various actinides like plutonium and uranium (1.1.3, 1.4.1). Unlike the clinically approved 3,4-hydroxypyridinone (deferiprone), 3,2-HOPO derivatives are primarily investigated for their superior ability to decorporate radionuclides and as bifunctional chelators in radiopharmaceuticals (1.2.2, 1.3.3). These molecules function by forming highly stable coordination complexes with metal ions, which prevents the metals from causing oxidative damage or depositing in tissues like bone and kidney (1.3.4, 1.4.2). In therapeutic applications, 3,2-HOPO-based agents are used to treat metal toxicity or to deliver therapeutic radionuclides, such as Thorium-227, to tumor sites (1.2.1, 1.3.3). While highly effective in preclinical models, the primary therapeutic challenges include ensuring selectivity over essential biological metals and managing potential renal clearance issues (1.2.4, 1.4.2).

Other names

3,2-HP3-hydroxypyridin-2-one1,2-dihydro-3-hydroxypyridin-2-one3,2-hydroxypyridinone

Chelation of hard metal ions (such as Fe3+, Pu4+, U(VI), and Th4+) through the formation of stable coordination complexes with the ortho-positioned hydroxyl and ketone oxygen atoms, facilitating their excretion or preventing their biological activity (1.1.2, 1.2.1).