Synthesis, characterization, interactions with 9-MeG and cytotoxic activity of heterobimetallic RuII-PtII complexes bridged with 2, 2'-bipyrimidine

J Inorg Biochem. 2021 Jun:219:111435. doi: 10.1016/j.jinorgbio.2021.111435. Epub 2021 Mar 24.

Abstract

The complexes [(η6-bz)Ru(bpm)Cl]PF6, (1)PF6, [(η6-bz)ClRu(μ-bpm)PtCl2]PF6, (2)PF6, [(η6-cym)ClRu(μ-bpm)PtCl2]PF6, (3)PF6, [(η6-cym)ClRu(μ-bpm)PdCl2]PF6, (4)PF6, [Pt(bpm)(cbdca)], (5) and [(η6-cym)ClRu(μ-bpm)Pt(cbdca)]PF6, (6)PF6, (bz = benzene, bpm = 2,2'-bipyrimidine, cym = p-cymene, cbdcaH2 = 1,1-cyclobutanedicarboxylic acid),were synthesized and characterized by means of 1H NMR and high-resolution ESI mass spectrometry. The complexes were transformed to the corresponding chloride salts to become soluble in aqueous media, and to be studied regarding their biological properties. However, while the heterobimetallic complexes (3)Cl and (6)Cl were almost stable, (2)Cl and (4)Cl were decomposed. The interaction of 9-MeG (9-MeG = 9-methylguanine) with (3)Cl and (6)Cl revealed that it coordinates only to the platinum center through N7. Decomposition of the heterobimetallic complexes takes place after the coordination of 9-MeG, mainly forming the complex [Pt(bpm)(9-MeG-N7)Cl]+. Notably, the cytotoxic activity of (6)Cl in cancer cells was found to be moderate when compared to cisplatin, but higher in comparison with its corresponding monomers.

Keywords: 9-methylguanine; Cytotoxicity; Heterobimetallic; Hydrolysis; Platinum; Ruthenium.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cisplatin / pharmacology
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Cymenes / chemistry
  • Guanine / analogs & derivatives
  • Guanine / chemistry
  • HeLa Cells
  • Humans
  • Hydrolysis
  • MCF-7 Cells
  • Magnetic Resonance Spectroscopy / methods
  • Mice
  • NIH 3T3 Cells
  • Platinum / chemistry*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Ruthenium / chemistry*
  • Spectrometry, Mass, Electrospray Ionization / methods

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Cymenes
  • Pyrimidines
  • 4-cymene
  • 9-methylguanine
  • Platinum
  • Guanine
  • Ruthenium
  • Cisplatin