Synthesis, characterization and anti-cancer properties of water-soluble bis(PYE) pro-ligands and derived palladium(ii) complexes

Abstract

The two cationic palladium(II) complexes, [Pd(L_en)₂][OTf]₂ (4) and [Pd(L_phen)₂][OTf]₂ (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(II) with [H₂L_en][OTf]₂ (2) or [H₂L_phen][OTf]₂ (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2–5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2–4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2–5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC₅₀ values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis.