Amido-3-hydroxypyridin-4-ones as iron(III) ligands

• Main Authors: Sirivipa Piyamongkol, Yong M. Ma, Xiao L. Kong, Zu D. Liu, Mutlu D. Aytemir, Dick Van Der Helm, Robert C. Hider
• Format: Journal
• Published: 2018
• Subjects: Chemistry
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77952734302&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/50671
• Institution: Chiang Mai University

The synthesis and physicochemical properties of a range of 2and 6-amido-3-hydroxypyridin-4-ones are described. All the amido-substituted 3-hydroxypyridin-4-ones have lower pKavalues than 1,2-dimethyl-3-hydr-oxypyridin-4-one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pKavalues of the 3-hydroxy group in 1-nonsubstituted pyridinones are dramatical- Iy 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 pFe3+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. © 2010 Wiley-VCH Verlag GmbH & Cu. KGaA. Weinheim.