Comparative evaluation of the structure and antitumor mechanism of mononuclear and trinucleated thiosemicarbazone Cu(II) complexes

The ratio of ligand to Cu(II) ions has an essential effect on the geometrical configuration and anti-tumour activity of metal-based complexes. In this work, we synthesised two Cu(II) thiosemicarbazone complexes, namely, [Cu(L)(Cl)] (C1) and [Cu3(L)2(Cl)4] (C2), by controlling the ratio of Cu(II) ion to ligand, to evaluate their anti-tumour activity. The ability of C1 to catalyze hydrogen peroxide to produce reactive oxygen species (ROS) was significantly higher than that of Cu(II) ion. Moreover, the bridge of Cu(II) and two molecules generated a new complex (C2), which, in contrast to C1, enhanced the generation of Fenton-like-triggered ROS. Consequently, the produced ROS depleted reduced glutathione, caused oxidative cell stress and promoted apoptosis through mitochondrial apoptotic pathways. In addition, C2 exhibited better tumour suppression than C1 in a nude mouse tumour xenograft model.