Comparative solution studies and cytotoxicity of gallium(III) and iron(III) complexes of 3-hydroxy-2(1H)-pyridinones

E. Enyedy, János P. Mészáros, G. Spengler, Muhammad Hanif, Christian G. Hartinger

Research output: Contribution to journalArticle

Abstract

The stoichiometry and stability constants of the gallium(III) and iron(III) complexes of two alkoxycarbonylmethyl-3-hydroxy-2(1H)-pyridinone ligands were determined by means of pH-potentiometry, UV–Vis spectrophotometry and 1 H and 71 Ga NMR spectroscopy in aqueous solution. The cytotoxicity of one of the gallium(III) complexes was also measured in multidrug resistant/non-resistant human colon adenocarcinoma cell lines. Iron(III) forms complexes with the studied 3-hydroxy-2-pyridinones of higher stability than gallium(III), while the obtained pFe values are significantly lower (pFe: 14.95, 15.06; pH 7.4, c M = 1 µM, c L = 10 µM) compared to those of typical iron binders such as deferiprone or transferrin. The moderate gallium(III) and iron(III) binding ability of the compounds stands for lower solution complex stability compared to that of analogous bidentate non-substituted 3-hydroxy-2-pyridinone or 3-hydroxy-4-pyridinone (O,O) donor ligands. Tris-ligand complexes of the general formula [ML 3 ] (M = Ga, Fe) predominate at physiological pH for both ligands. No interaction with cell culture medium components was observed in the millimolar concentration range of gallium(III) complexes, however they can suffer significant decomposition at biologically relevant low concentrations leading to negligible cytotoxic activity. The redox potential of the studied iron–3-hydroxy-2-pyridinone complex (E 1/2 = −597 mV at pH 7.4) falls into the range that is typical of iron(III) complexes with conventional bidentate (O,O) donor-containing chelators.

Original languageEnglish
JournalPolyhedron
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Pyridones
Gallium
Cytotoxicity
gallium
Iron
iron
Ligands
ligands
potentiometric analysis
culture media
Spectrophotometry
spectrophotometry
Transferrin
Chelating Agents
Cell culture
cultured cells
Stoichiometry
Nuclear magnetic resonance spectroscopy

Keywords

  • Chelators
  • Cytotoxicity
  • Equilibrium
  • Oxygen-donor ligands
  • Solution stability

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Materials Chemistry

Cite this

Comparative solution studies and cytotoxicity of gallium(III) and iron(III) complexes of 3-hydroxy-2(1H)-pyridinones. / Enyedy, E.; Mészáros, János P.; Spengler, G.; Hanif, Muhammad; Hartinger, Christian G.

In: Polyhedron, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Mészáros, János P.

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AU - Hanif, Muhammad

AU - Hartinger, Christian G.

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N2 - The stoichiometry and stability constants of the gallium(III) and iron(III) complexes of two alkoxycarbonylmethyl-3-hydroxy-2(1H)-pyridinone ligands were determined by means of pH-potentiometry, UV–Vis spectrophotometry and 1 H and 71 Ga NMR spectroscopy in aqueous solution. The cytotoxicity of one of the gallium(III) complexes was also measured in multidrug resistant/non-resistant human colon adenocarcinoma cell lines. Iron(III) forms complexes with the studied 3-hydroxy-2-pyridinones of higher stability than gallium(III), while the obtained pFe values are significantly lower (pFe: 14.95, 15.06; pH 7.4, c M = 1 µM, c L = 10 µM) compared to those of typical iron binders such as deferiprone or transferrin. The moderate gallium(III) and iron(III) binding ability of the compounds stands for lower solution complex stability compared to that of analogous bidentate non-substituted 3-hydroxy-2-pyridinone or 3-hydroxy-4-pyridinone (O,O) donor ligands. Tris-ligand complexes of the general formula [ML 3 ] (M = Ga, Fe) predominate at physiological pH for both ligands. No interaction with cell culture medium components was observed in the millimolar concentration range of gallium(III) complexes, however they can suffer significant decomposition at biologically relevant low concentrations leading to negligible cytotoxic activity. The redox potential of the studied iron–3-hydroxy-2-pyridinone complex (E 1/2 = −597 mV at pH 7.4) falls into the range that is typical of iron(III) complexes with conventional bidentate (O,O) donor-containing chelators.

AB - The stoichiometry and stability constants of the gallium(III) and iron(III) complexes of two alkoxycarbonylmethyl-3-hydroxy-2(1H)-pyridinone ligands were determined by means of pH-potentiometry, UV–Vis spectrophotometry and 1 H and 71 Ga NMR spectroscopy in aqueous solution. The cytotoxicity of one of the gallium(III) complexes was also measured in multidrug resistant/non-resistant human colon adenocarcinoma cell lines. Iron(III) forms complexes with the studied 3-hydroxy-2-pyridinones of higher stability than gallium(III), while the obtained pFe values are significantly lower (pFe: 14.95, 15.06; pH 7.4, c M = 1 µM, c L = 10 µM) compared to those of typical iron binders such as deferiprone or transferrin. The moderate gallium(III) and iron(III) binding ability of the compounds stands for lower solution complex stability compared to that of analogous bidentate non-substituted 3-hydroxy-2-pyridinone or 3-hydroxy-4-pyridinone (O,O) donor ligands. Tris-ligand complexes of the general formula [ML 3 ] (M = Ga, Fe) predominate at physiological pH for both ligands. No interaction with cell culture medium components was observed in the millimolar concentration range of gallium(III) complexes, however they can suffer significant decomposition at biologically relevant low concentrations leading to negligible cytotoxic activity. The redox potential of the studied iron–3-hydroxy-2-pyridinone complex (E 1/2 = −597 mV at pH 7.4) falls into the range that is typical of iron(III) complexes with conventional bidentate (O,O) donor-containing chelators.

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KW - Oxygen-donor ligands

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