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]4·MeOH (·MeOH) and [Cu(p-OCOC6H4OH)2L]5·2H2O (·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.

Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction

“…2,2 :6 ,2 -terpyridine (TPY) has been recognized as a useful ligand for transition metal and rare earth metal ions in inorganic chemistry [22][23][24][25][26][27]. The terpyridine molecule serves as a tridentate, nearly coplanar, N 3 donor ligand, and, in some cases, also as a mono or bidentate ligand [28].…”

Targeting Cancer Resistance via Multifunctional Gold Nanoparticles

“…One way to overturn this drawback has been via the synthesis of novel compounds and their incorporation in innovative formulations that are suitable for the selective delivery to cancer cells, thus optimizing the therapeutic window and circumventing drug resistance to conventional chemotherapeutics. Among these novel compounds, we have been focusing on the study of the antiproliferative potential and respective mechanisms of action of coordination compounds associated with suitable targeted delivery platforms [1,2,3,4,5]. One such compound, [Zn(DION) 2 ]Cl 2 —ZnD (DION—1,10-phenanthroline-5,6-dione), showed a high cytotoxic potential toward cancer cell lines, with IC 50 values 2x and 70x lower than those of doxorubicin (DOX) and cisplatin, respectively [1].…”

Transition Metal Intercalators as Anticancer Agents—Recent Advances

“…Copper complexes most often initiate their cytotoxic effect through oxygen-dependent or -independent DNA cleavage. Here, DNA intercalation can assist the cleavage process by allowing close proximity of copper complexes to the double strand [46,47,48]. Copper is also capable of a large variety of coordination geometries, often producing very different species from reactions with very similar starting reagents[46,47].…”

“…For example a recent series of complexes of the type [Cu(4phterpy)(L) 2 ] or [Cu(4phterpy)(L)(H 2 O) 2 ](L) (where 4phterpy is 4’-phenyl-2,2’:6’,2”-terpyridine and L is one of p -toluenesulphonate, benzoate or o -, m - or p -hydroxybenzoate, Cu5 – 9 , Figure 8) were found to be cytotoxic to HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cells while exhibiting lower activity in normal human fibroblasts (Table 3) [48]. The model complex Cu9 induced apoptosis in HCT116 cells in a caspase-3 related mechanism; the higher cytotoxicity of Cu9 relative to the others was theorised to be due to its labile aqua ligands and charged nature, which could encourage cellular uptake by human copper transporters [50].…”