Comparative solution equilibrium and structural studies of half-sandwich ruthenium(II)(η6-toluene) complexes of picolinate derivatives

Jelena M. Poljarević, G. Tamás Gál, Nóra V. May, Gabriella Spengler, Orsolya Dömötör, Aleksandar R. Savić, Sanja Grgurić-Šipka, Éva A. Enyedy

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9 Citations (Scopus)

Abstract

Five Ru(II)(η6-toluene) complexes formed with 2-picolinic acid and its various derivatives have been synthesized and characterized. X-ray structures of four complexes are also reported. Complex formation processes of [Ru(II)(η6-toluene)(H2O)3]2+ organometallic cation with the metal-free ligands were studied in aqueous solution in the presence of chloride ions by the combined use of 1H NMR spectroscopy, UV–visible spectrophotometry and pH-potentiometry. Solution stability, chloride ion affinity and lipophilicity of the complexes were characterized together with in vitro cytotoxic and antiproliferative activity in cancer cell lines being sensitive and resistant to classic chemotherapy and in normal cells as well. Formation of mono complexes such as [Ru(η6-toluene)(L)(Z)]+/0 (L: completely deprotonated ligand; Z = H2O/Cl) with high stability and [Ru(η6-toluene)(L)(OH)] was found in solution. The pKa values (8.3–8.7) reflect the formation of low amount of mixed hydroxido species at pH 7.4 at 0.2 M KCl ionic strength. The complexes are fairly hydrophilic and show moderate chloride ion affinity and fast chloride-water exchange processes. The studied complexes exhibit no cytotoxic activity in human cancer cells (IC50 > 100 μM), only complexes formed with 2-picolinic acid (1) and its 3-methyl derivative (2) represented a moderate antiproliferative effect (IC50 = 84.8 (1), 79.2 μM (2)) on a multidrug resistant colon adenocarcinoma cell line revealing considerable multidrug resistant selectivity. Complexes 1 and 2 bind to human serum albumin covalently and relatively slowly with moderate strength at multiple binding sites without ligand cleavage.

Original languageEnglish
Pages (from-to)74-85
Number of pages12
JournalJournal of Inorganic Biochemistry
Volume181
DOIs
Publication statusPublished - Apr 2018

Keywords

  • Antiproliferative activity
  • Half-sandwich complexes
  • Speciation
  • Stability constants
  • X-ray crystal structures

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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