Synthesis, characterization, thermal properties and antiproliferative potential of copper(ii) 4′-phenyl-terpyridine compounds

Abstract

Reactions between 4′-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO₃C₆H₄CH₃)L(H₂O)₂](p-SO₃C₆H₄CH₃) (1), [Cu(OCOPh)₂L] (2), [Cu(o-OCOC₆H₄OH)₂L] (3), [Cu(m-OCOC₆H₄OH)₂L]·MeOH (4·MeOH) and [Cu(p-OCOC₆H₄OH)₂L]·2H₂O (5·2H₂O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N₃O₃ octahedral coordination geometries, which, in 2–5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular π⋯π stacking interactions could also be found in 2–5 (in the 3.569–3.651 Å range and involving solely the pyridyl rings). Medium–strong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H₂O₂. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage.