Configuration change from cis to trans of isothiocyanato groups in nickel(II) species: Experimental verification and theoretical interpretation of reaction consequence and study on their bio-activity

Two new mononuclear Ni(II) complexes, namely [Ni(HL)(SCN)2(H2O)] (1) and [Ni(HL)(SCN)2(4,4′-bipy)] (2) [HL = 2-[(2-piperazin-1-yl-ethylimono)-methyl]phenol] have been synthesized and structurally characterized. The uncoordinated nitrogen atom of the piperazine moiety is protonated to provide electrical neutrality to the system. The configuration of the isothiocyanato ligands is different in the two complexes, cis located in 1 and trans in complex 2. The change of configuration of the isothiocyanato groups on addition of the neutral spacer 4,4-bipyridine to complex 1 has been monitored by conductometric and FTIR spectral studies and the most probable mechanistic pathway has been proposed. DFT calculations have been performed and the outcome corroborates well with the experimental facts. The anticancer activity of the two Ni(II) complexes has been evaluated in human cervical (HeLa) cancer and breast cancer (MCF-7) cell lines. The cytotoxic effects of these complexes were determined by an MTT assay. The fluorescent intensity obtained in HeLa cells reveals the generation of ROS by the complexes using DCFH-DA (2,7-dichlorofluorescein diacetate) dye. The apoptotic cell death was determined by fluorescent staining with acridine orange and ethidium bromide, which confirmed the presence of apoptotic cells. Further, flow cytometry analysis was done, suggesting an arrest of the cell cycle in the S phase of the HeLa cells. Although a detailed molecular mechanism for the anticancer activity of the two complexes was not ascertained, the experimental results suggest that both complexes are effective anticancer agents, with complex 2 seeming to be more promising. The result also indicates that the apoptotic cell death in the cancer cell might be triggered by the process of ROS generation with the complexes. Thermo gravimetric analysis of two complexes hints that NiO particles are the final product after decomposition of the complexes at 600 °C.