Amido-3-hydroxypyridin-4-ones as iron(III) ligands.
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.
Piyamongkol
Sirivipa
S
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200 Thailand.
Ma
Yong M
YM
Kong
Xiao L
XL
Liu
Zu D
ZD
Aytemir
Mutlu D
MD
van der Helm
Dick
D
Hider
Robert C
RC
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
D008024:Ligands; D011728:Pyridones; D007501:Iron