Mixed hydroxypyridinonate ligands as iron chelators

New ligands based on hydroxypyridinonate (HOPO) and other bidentate ligands are explored as iron(III) sequestering agents. These are based on the N,N' ,N"-tris[(3-hydroxy-1-methyl-2-oxo-1,2-didehydropyrid-4-yl)carboxamidoethyl ]amine (TREN-Me-3,2-HOPO) platform in which one Me-3,2-HOPO ligand group is substituted with either a 2-hydroxyisophthalamide (TREN-Me-3,2-HOPOIAM) or a 2,3-dihydroxyterephthalamide (TREN-Me-3,2-HOPOTAM) moiety. The ferric co mplexes have been prepared and structurally characterized by X-ray diffract ion: Fe[TREN-Me-3,2-HOPOIAM] crystallizes in the monoclinic space group C2/ c with cell parameters a = 18.1186(3) Angstrom, b = 17.5926(2) Angstrom, c = 25.0476(2) Angstrom, beta = 98.142(1)degrees, Z = 8. Fe[TREN-Me-3,2-HOPOT AM](-) crystallizes in the monoclinic space group C2/c with cell parameters a = 31.7556(12) Angstrom, b = 14.0087(6) Angstrom, c = 22.1557(9) Angstrom , beta = 127.919(1)degrees, Z = 8. The aqueous coordination chemistry of th ese ligands with both the ferric and ferrous redox states of iron has been examined using spectroscopic and electrochemical methods, giving log format ion constants of 26.89(3) (beta(110)), 31.16(6) (beta(111)) for the ferric TREN-Me-3,2-HOPOIAM complexes and 33.89(2) (beta(110)), 38.45(2) (beta(111) ) for the ferric TREN-Me-3,2-HOPOTAM complexes. For the reduced (ferrous) c omplexes values of 10.03(9) (beta(110)) and 13.7(2) (beta(110)) were observ ed for the Fe[TREN-Me-3,2-HOPOIAM](-) and Fe[TREN-Me-3,2-HOPOTAM](2-) compl exes, respectively. These data provide a complete description of metal-liga nd speciation as a function of pH and of redox activity. The ligands descri bed in this work are part of a new class of heteropodate ligands which expl oit the various chelating properties of several binding units within a sing le tripodal ligand and allow for systematic variation of the properties for medical or other applications.