Synthesis and iron chelating properties of hydroxypyridinone and hydroxypyranone hexadentate ligands

Dalton Transactions Pub Date: 2019-02-20 DOI: 10.1039/C8DT05014G

Abstract

Chelation therapy has become an important therapeutic approach for some diseases. In attempt to identify clinically useful chelators, four hexadentate ligands were synthesized by conjugating the corresponding bidentate ligands (3-hydroxypyridin-4-one (3,4-HOPO), 3-hydroxypyridin-2-one (3,2-HOPO), 1-hydroxypyridin-2-one (1,2-HOPO), and 3-hydroxypyran-4-one) each with a free amino group to a tripodal acid. Their pKa values and affinities for iron(III) were investigated. The pFe3+ values of the hexadentate pyridinones 1 (3,4-HOPO), 3 (3,2-HOPO) and 4 (1,2-HOPO), and the pyranone 2 was found to follow the sequence 1 > 4 ? 3 > 2, which is different to the pFe3+ value sequence of the corresponding bidentate forms (3,4-HOPO ? 3,2-HOPO > 1,2-HOPO > 3-hydroxypyranone). Hexadentate 3,4-HOPOs and 1,2-HOPOs have the greatest potential as iron scavenging agents.

Graphical abstract: Synthesis and iron chelating properties of hydroxypyridinone and hydroxypyranone hexadentate ligands
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