1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid as new possible chelating agents for iron and aluminium.

doi:10.1039/b819148d

Paper

1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid as new possible chelating agents for iron and aluminium.

Published Feb 24, 2009 · Annalisa Dean, M. Ferlin, P. Brun

Dalton transactions

Q1 SJR score

19

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid (DQ2) were evaluated for possible application to iron (Fe) and aluminium (Al) chelation therapy. Metal/ligand solution chemistry, electrochemistry, cytotoxicity, octanol/water partitioning (D(o/w)), and chelation efficiency, were studied. The Fe(iii)/DQ716, Fe(iii)/DQ2, Al(iii)/DQ716, and Al(iii)/DQ2 solution chemistry was investigated in aqueous 0.6 mol kg(-1) (Na)Cl at 25 degrees C by means of potentiometric titrations, UV-vis spectrophotometry, and (1)H-NMR spectroscopy. DQ716 exhibited the highest coordination efficiency towards Fe(iii) and Al(iii) among all hydroxypyridinecarboxylic acids examined so far, whereas DQ2 complexes were significantly less stable. These results were confirmed by chelation efficiency measurements performed in an octanol-aqueous solution in the presence of those ligands and metals. Partitioning experiments at pH 7.4 showed both DQ716 and DQ2, and their Fe(iii) and Al(iii) complexes, to be hydrophilic. According to the voltammetric data, the free ligands (DQ716 and DQ2) and their metal complexes are not predicted to undergo redox cycling at in vivo conditions. The standard reduction potentials of these complexes, and the kinetics of their formation and dissociation, were obtained. The toxicity of DQ716 and of DQ2 was investigated with human cancer cell lines and normal human fibroblasts. Cytotoxic effects were observed only for DQ2 at 0.1 mM, following 3 d exposure. According to our results, DQ716 has the required favourable properties to be a chelating agent for Fe and Al.

In Vitro Study

Study Snapshot

DQ716 shows the highest coordination efficiency towards iron and aluminium, with potential for use in iron and aluminium chelation therapy, while DQ2 shows less stability and cytotoxicity.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid as new possible chelating agents for iron and aluminium.

Sign up to use Study Snapshot

References

Use of electrochemical transient techniques to obtain thermodynamic and kinetic data on aqueous Fe(III)-1,6-dimethyl-4-hydroxy-3-pyridinecarboxylate and Fe(III)-4-hydroxy-2-methyl-3-pyridinecarboxylate complexes.

Electrochemical transient techniques can rapidly obtain stability constants, E degrees values, and kinetic parameters for Fe(III) complexes with 1,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid at pH 2.3 and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid at pH 3.

Evaluation of 2-methyl-3-hydroxy-4-pyridinecarboxylic acid as a possible chelating agent for iron and aluminium.

DT2 shows potential as a chelating agent for iron and aluminium, with lower complexation efficiency than other available chelators but higher than its non-methylated analogue, and no cytotoxic activity observed in vitro.

Evaluation of 1-methyl-3,4-hydroxypyridinecarboxylic acids as possible bidentate chelating agents for iron(III): Metal–ligand solution chemistry

1-methyl-3,4-hydroxypyridinecarboxylic acids show lower complexation efficiency with iron(III) than other available chelators, but higher than their non-methylated analogs 3H4P and 4H3P.

Fenton chemistry and iron chelation under physiologically relevant conditions: Electrochemistry and kinetics.

Tight binding of iron(III) by hydroxypyridinones prevents redox cycling, making them effective in iron-chelation therapy.

Synthesis of 1,4-dihydro-2-methyl-4-oxo-nicotinic acid: Ochiai's route failed

The Ochiai's procedure failed to synthesize 1,4-dihydro-2-methyl-4-oxo-nicotinic acid, yielding the isomer 1,6-dihydro-2-methyl-6-oxo-nicotinic acid ethyl este

Citations

Altered fecal microbial and metabolic profile reveals potential mechanisms underlying iron deficiency anemia in pregnant women in China

Pregnant women with iron deficiency anemia have increased levels of Streptococci and catechol in their gut microbiome, suggesting that adjusting intestinal homeostasis with oral Streptococcus may improve iron supplementation outcomes.

Experimental and theoretical study on the coordination properties of quercetin towards aluminum(III), iron(III) and copper(II) in aqueous solution

Quercetin complexes with aluminum, iron, and copper in aqueous solution, showing no clear preference for any complexation site, while copper shows a preference for the 4,5 site.

Crystal structures of zinc(II) complexes with β-hydroxypyridinecarboxylate ligands: examples of structure-directing effects used in inorganic crystal engineering

The study reveals that hydroxypyridinecarboxylate derivatives can direct the crystal structure of zinc(II) complexes, resulting in various geometrical structures.

An NMR study on the 6,6'-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) interaction with Al(III) and Zn(II) ions.

The ligand forms complexes with Al(III) and Zn(II) ions differently, depending on their hard or borderline nature, potentially impacting ligand bioavailability and chelation treatments.

Iron chelating agents for iron overload diseases

New, more suitable iron chelating agents are urgently needed to improve life expectancy and quality of life for patients with iron overload diseases.

Evaluation of 1,2-dimethyl-3-hydroxy-4-pyridinecarboxylic acid and of other 3-hydroxy-4-pyridinecarboxylic acid derivatives for possible application in iron and aluminium chelation therapy

DT712 shows the strongest potential for iron chelation therapy, with better kinetic properties and no redox cycling expected in vivo.

Possible chelating agents for iron and aluminium - 4-hydroxy-5-methyl- and 4-hydroxy-1,5-dimethyl-3-pyridinecarboxylic acid

DQ715 is a chelator for both iron and aluminium ions, while DQ5 is more suitable as a selective Al chelator, both with low cytotoxicity and potential for use in iron and aluminium chelation therapy.

Hydroxypyri(mi)dine-based chelators as antidotes of toxicity due to aluminum and actinides.

Hydroxypyri(mi)dine-based chelators show potential as antidotes for aluminum and actinide toxicity due to excessive metal exposure, with potential applications in actinide scavenging.

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

DQ6 shows potential as a chelating agent for aluminium, with high coordination efficiency and no cytotoxic effects observed up to 0.1 mM exposure.