title: Amido-3-hydroxypyridin-4-ones as iron(III) ligands.
abstract: The synthesis and physicochemical properties of a range of 2- and 6-amido-3-hydroxypyridin-4-ones are described. All the amido-substituted 3-hydroxypyridin-4-ones have lower pK(a) values than 1,2-dimethyl-3-hydroxypyridin-4-one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pK(a) values of the 3-hydroxy group in 1-nonsubstituted pyridinones are dramatically lower than those of the corresponding 1-alkyl analogues, indicating that a strong hydrogen bond exists between the 2-amido function and the 3-oxygen anion, which stabilises the anion. As a result of the decreased competition with protons, the pFe(3+) values of this group of molecules are higher than that of deferiprone. The distribution coefficients of these molecules are also increased despite the lack of a hydrophobic 1-alkyl substituent and this is ascribed to the intramolecular hydrogen bond. X-ray diffraction studies confirm the existence of the intramolecular hydrogen bond.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200 Thailand.
authors.forename: Sirivipa
authors.initials: S
authors.lastname: Piyamongkol
authors.forename: Yong M
authors.initials: YM
authors.lastname: Ma
authors.forename: Xiao L
authors.initials: XL
authors.lastname: Kong
authors.forename: Zu D
authors.initials: ZD
authors.lastname: Liu
authors.forename: Mutlu D
authors.initials: MD
authors.lastname: Aytemir
authors.forename: Dick
authors.initials: D
authors.lastname: van der Helm
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
mesh_terms: D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry*; D008024:Ligands; D008968:Molecular Conformation; D011728:Pyridones / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D014961:X-Ray Diffraction
chemical_list: D008024:Ligands; D011728:Pyridones; D007501:Iron