- Evaluation of 4-hydroxy-6-methyl-3-pyridinecarboxylic acid and 2,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid as chelating agents for iron and aluminium
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4-Hydroxy-6-methyl-3-pyridinecarboxylic acid (DQ6) and the new compound 2,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ726) were evaluated for possible application for iron (Fe) and aluminium (Al) chelation therapy. Metal/ligand solution chemistry, cytotoxicity, octanol/water partitioning (Do/w), and chelation efficiency were studied. The solution chemistry of the two ligands with Fe(III) and Al(III) was investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations, UV-Vis spectrophotometry, and 1H NMR spectroscopy. DQ6 exhibited a high coordination efficiency towards Al(III). Fe(III)/DQ6, Al(III)/DQ726, and Fe(III)/DQ726 complexes were less stable. These results were confirmed by chelation efficiency measurements performed in an octanol/aqueous solution. Accordingly, the effects of the substitution at various ring positions of 4-hydroxy-3-pyridinecarboxylic acid were rationalised. Partitioning experiments at pH 7.4 showed both DQ6 and DQ726, and their Fe(III) and Al(III) complexes, to be hydrophilic. The toxicity of DQ6 and of DQ726 was investigated with human cancer cell lines and normal human primary cells: no cytotoxic effects were observed up to 0.1 mM, following a 3 days exposure. According to our results, DQ6 has the favourable properties to be a chelating agent for Al.
- Dean, Annalisa,Ferlin, Maria Grazia,Brun, Paola,Castagliuolo, Ignazio,Yokel, Robert A.,Venzo, Alfonso,Giorgio Bombi,Di Marco, Valerio B.
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- A tautomeric ligand enables directed C-H hydroxylation with molecular oxygen
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Hydroxylation of aryl carbon-hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/ pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from monoanionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon-hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.
- Li, Zhen,Wang, Zhen,Chekshin, Nikita,Qian, Shaoqun,Qiao, Jennifer X.,Cheng, Peter T.,Yeung, Kap-Sun,Ewing, William R.,Yu, Jin-Quan
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p. 1452 - 1457
(2021/06/30)
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- Synthesis and Structure of the N-Alkyl-2,6-dimethyl-4-oxopyridine-3-carboxylic Acids
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A range of N-alkyl-2,6-dimethyl-4-oxopyridine-3-carboxylic acids XV have been prepared via reactions of primary alkyl amines with differing 2,6-dimethyl-4-oxopyran-3-carboxylate esters IX.The quantity of desired product formed and the character of by-prod
- Venkatramani, Lalitha,Siripitayananon, Jintana,Helm, Dick van der
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p. 723 - 738
(2007/10/02)
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