Cytotoxicity of Pd(ii) and Pt(ii) complexes of 2′,6′-di(thiazol-2-yl)-2,4′-bipyridine: insights into the mode of cell death and cell cycle arrest

Abstract

Square-planar complexes were synthesized by the reaction of 2′,6′-di(thiazol-2-yl)-2,4′-bipyridine with either Na₂[PdCl₄] or K₂[PtCl₄], and these were thoroughly structurally characterized using some analytical and spectroscopic techniques. Density functional theory computations, including natural bond orbital analysis, were used to complement the experimental work to gain insight into the natural charge and electronic arrangement of the metal ion, as well as the strength of the metal–ligand bonds. The Pd(II) complex exhibited exceptional cytotoxicity against the A549 and HCT-116 cell lines with IC₅₀ values of 60.1 ± 3.45 and 23.8 ± 1.48 μM, respectively. Unfortunately, the Pd(II) complex was harmful to the Vero normal cell line with an IC₅₀ value of 24.5 ± 2.13 μM. The Pt(II) complex is unstable and has a high likelihood of exchanging the chlorido ligand for solvent molecules such as DMSO. The fluorescent-stain photos of the treated HCT-116 cells with the Pd(II) complex showed increased apoptotic bodies, indicating both early (18%) and late apoptosis (32%), as well as a necrosis ratio of about 10%. Flow cytometric analysis demonstrated that a cell arrest was induced by the Pd(II) complex on HCT-116 cells in the G₂/M phase.