Copper(ii) complexes based on 5-methyl-1H-tetrazole and 2,2′-bipyridine, 1,10-phenathroline derivatives: synthesis, crystal structures and extended cytotoxicity study

Abstract

Three copper(II) complexes – [Cu₂(bipy)₂L₄] (1), [Cu₂(phen)₂L₄] (2) and [Cu₂(dmphen)₂L₄]·2H₂O (3) – were synthesized based on 5-methyltetrazole (HL) and 2,2′-bipyridine/1,10-phenanthroline derivatives. A crystallographic study revealed that complexes 1–3 have a binuclear structure with coordination polyhedron close to the square pyramid. Stability of the complexes in aqueous solution was studied by UV-Vis spectroscopy and conductometry. In vitro cytotoxicity study was carried out in 2D and 3D cell culture models and showed that complexes 2 and 3 possess cytotoxic activity against tumor cells (A549, Hep2, HepG2, MCF7) with LC₅₀ values exceeding those of the medical drug cisplatin. At the same time, being less active, compound 1 has a selectivity index of 3.1 to hepatocellular carcinoma (HepG2 cell line) compared to non-tumor MRC5 cells. The Hoechst/Propidium iodide staining assay and ROS generation assay on Hep2 cells indicated that the cytotoxic effects of the complexes involved apoptosis induction without ROS accumulation.