Synthesis, Physicochemical Properties, and Biological Evaluation of Hydroxypyranones and Hydroxypyridinones:  Novel Bidentate Ligands for Cell-Labeling

Abstract

The synthesis of a range of hydroxypyranones and hydroxypyridinones with potential for the chelation of indium(III) is described. The crystal structures of two of the indium complexes are presented. The distribution coefficients of the ligands and the corresponding iron(III), gallium(III), and indium(III) complexes are reported. Good linear relationships between the distribution coefficients of the iron and gallium complexes and iron and indium complexes were obtained. In contrast a nonlinear relationship was obtained between the distribution coefficient of the free ligand and the distribution coefficient of the three groups of complexes. This latter relationship was used to identify compounds with optimal cell labeling properties. Two such compounds both 6-(alkoxymethyl)-3-hydroxy-4H-pyran-4-ones have been compared with tropolone for their ability to label human leucocytes with 111In. The leucocyte labeling efficiencies of the selected ligands were greater and the in-vitro plasma stabilities were similar to that of 111In-tropolonate. These results suggest that the new bidentate ligands may offer advantages over those currently used for cell-labeling.

Comparative solution equilibrium studies of anticancer gallium(III) complexes of 8-hydroxyquinoline and hydroxy(thio)pyrone ligands

“…Lipophilicity data revealed higher lipophilicity of the thio ligands compared with the pyrone analogues as it is expected due to the nature of the sulfur atom as larger size and lower electronegativity. While the allo derivatives are in general somewhat more hydrophilic as the ortho position of the methyl group to the hydroxyl moiety can result in a more compact compound which may bring weaker interactions with the solvent water molecules, thus higher logP values [25]. Note that the logP value of thiomaltol is higher than reported earlier [26], which is most probably related to analysis under inert atmosphere; while the value of allomaltol is also somewhat higher, though other kind of method was used for the determination [25].…”

New Macrocycles with Planar Chirality—Synthesis and Determination of Absolute Configurations

“…[17] It is known that direct alkylation of hydroxypyridines may yield either N-alkylpyridones or alkoxypyridines, due to tautomeric equilibrium. [18] In our case, the main tautomeric form was 3-hydroxy-1H-pyridin-2-one (10), and its elongation with chloroacetonitrile gave the a,w-dinitrile 11, which was subsequently reduced with BMS to give the desired diamine 12 (Scheme 3).…”

Synthesis of Oxovanadium Complexes and Their Apoptosis-Inducing Activity in Leukemia Cells

“…An Annexin V-Fluorescein Staining Kit was obtained from Wako Pure Chemical Industries Ltd. The compounds 1a, 1b, 18) 6a-c, 19) 2a, 26) and 5-(chlorosulfonyl)-8-hydroxy-2-methylquinoline 20) were prepared according to the previously reported methods. Bis (1-ethyl-1,2-dihydro-2-oxo-3-pyridinolato) oxovanadium(IV) (2b) Complexes 2b and 2c were synthesized from 6b and 6c, respectively, according to the procedure used for the synthesis of 2a.…”

“…18) As shown in Chart 2, 1-alkyl-3-hydroxy-2-(1H)-pyridinones 6a-c were prepared by the reaction of 3-methoxy-2(1H)-pyridone with a corresponding alkyl iodide, followed by treatment with boron tribromide. 19) Reaction of 6a-c with VOSO 4 yielded 2a-c. 8-Hydroxyquinoline derivatives 7 were prepared from 8-hydroxy-2-methylquinoline by chlorosulfonation, followed by amidation (Chart 3).…”