Amido-3-hydroxypyridin-4-ones as Iron(III) Ligands

作者：Piyamongkol Sirivipa; Ma Yong M; Kong Xiao L; Liu Zu D; Aytemir Mutlu D; van der Helm Dick; Hider Robert C^*

来源：Chemistry - A European Journal, 2010, 16(21): 6374-6381.

DOI：10.1002/chem.200902455

• acidity
• hydrogen bonds
• hydroxypyridinones
• inductive effects
• iron

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-non-substituted pyridinones are dramatical ly 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.

• 出版日期2010