EPR and electrochemical interpretation of bispyrazolylacetate anchored Ni(ii) and Mn(ii) complexes: Cytotoxicity and anti-proliferative activity towards human cancer cell lines

Two mononuclear NiIIand MnIIcompounds, [Ni(bdtbpza)2(CH3OH)4] (1) and [Mn(bdtbpza)2(CH3OH)2(H2O)2] (2), are afforded by employing a 'scorpionate' type precursor [bdtbpza = bis(3,5-di-t-butylpyrazol-1-yl)acetate]. The single crystal X-ray structure reveals that the central metal ion (NiIIfor 1 and MnIIfor 2) is surrounded by a pair of Oacetateatoms of two bis(pyrazol-1-yl)acetate units, while four OMeOHdonors for 1 and two OMeOHplus two Owaterfor 2 complete the first coordination sphere. Thus, both compounds exhibit a slightly distorted octahedral geometry possessing an O6coordination environment. EPR spectra of CuII-doped 1 and of 2 recorded on the polycrystalline solids and in organic solution confirm the octahedral geometry around the metal ions and the binding of six oxygen atoms. The electrochemical study of compounds 1 and 2 shows that one electron reduction of MnIIoccurs at a more negative potential than NiII, indicating a lower tendency of reduction for Mn than Ni. Both compounds displayed a high cytotoxic activity against A2780 ovarian carcinoma cells and no cytotoxic activity in normal primary human fibroblasts for concentrations up to 55 μM. Notwithstanding, compound 1 is found to be the most cytotoxic towards A2780 cancer cells. The cytotoxic activity of compound 1 is correlated with the induction of apoptosis associated with a higher mitochondria dysfunction and autophagy cell death. In addition, the compounds can induce oxidative damage leading to ROS accumulation. Overall, the data presented here demonstrate that 1 has potential for further in vivo studies aiming at its future application in ovarian cancer therapy.