Methyl‐Hydroxypyridinecarboxylic Acids as Possible Bidentate Chelating Agents for Aluminium(III): Synthesis and Metal–Ligand Solution Chemistry

Abstract

In view of a possible application to aluminium chelation therapy, 1-methyl-3-hydroxy-4-pyridinecarboxylic acid (1M3H4P) and 1-methyl-4-hydroxy-3-pyridinecarboxylic acid (1M4H3P) were synthesized, and their chemical interactions with aluminium(III) were investigated in aqueous 0.6 m (Na)Cl at 25°C by means of potentiometric titrations. The qualitative and quantitative results obtained were confirmed by UV spectrophotometry and 1 H NMR spectroscopy. For both ligands, the species AlL 2+ , AlL 2 + , AlL 3 , and AlL 2 H -1 were identified, with logβ 1,1,0 = 7.66, logβ 1,2,0 = 14.27, logβ 1,3,0 = 19.099, and logβ 1,2,-1 = 7.00 for 1M3H4P, logβ 1,1,0 = 7.21, logβ 1,2,0 = 13.41, logβ 1,3,0 = 18.15, and logβ 1,2,-1 = 6.4 for

4-Hydroxy-3,5-pyridinedicarboxylic Acids: Synthesis, Complexation Properties Towards Fe(III), Al(III), Cu(II), Zn(II), Human Serum Albumin, and Cellular Toxicity

“…The pKa values increase by ca. 0.2 log units when passing from (Na)Cl 0.6 m to KCl 0.2 M ionic strength.The low pKa values for the phenolic-OH, based on the comparison with salicylic acid derivatives, was justified[20], and it agrees with values obtained for the other HPCs[4].…”

“…see [20]). Broadening can be attributed [20] to the formation of several isomers (up to 4 and 2 diastereoisomers can exist in solution for the bis-and tris-complexes, respectively) and to a relatively slow kinetics of interconversion between them.…”

Relationship between solid state structure and solution stability of copper(ii)–hydroxypyridinecarboxylate complexes

“…Chemicals HPCs were synthesized as described in ref. [16][17][18], except L5 and L6 which were synthesized according to the procedure reported in the next section. The CuCl 2 stock solution was prepared from CuCl 2 Á2H 2 O (Sigma-Aldrich) dissolved in doubly distilled water.…”

“…The protonation steps of the HPC ligands have been determined by pH-potentiometry, either in the present study (L5 and L6) or in previous ones (all other HPCs [16][17][18] ). The constants are collected in Table 1.…”

Iron Chelating Agents for Iron Overload Diseases

“…Numerous studies on the design, synthesis and complex formation equilibria of variously substituted hydroxypyridinecarboxylic acids have been presented by the group of Di Marco: these ligands are characterized by two coordinating groups (-OH and -COOH) in various positions (2,3; 3,2; 3,4; 4,3) and differently methylated. [50][51][52][53][54][55] A study of our group on bisphosphonate ligands showed their high efficiency as iron chelating agents, reaching pFe values higher than that of deferiprone. 56 To further improve bisphosphonate chelating properties the conjugation with other strong coordinating groups was proposed.…”