Self-assembled supramolecular hetero-bimetallacycles for anticancer potency by intracellular release

Two new tetracationic hetero-bimetallacycles, compounds 4 and 5, have been constructed from an N, N'-bis(4-(pyridin-4-ylethynyl)phenyl)pyridine-2,6-dicarboxamide ligand (1), and cis-blocked complexes [M(dppf)(OTf)₂] (dppf=1,1'-bis(diphenylphosphino)ferrocene; OTf=trifluoromethanesulfonate; M=Pd (2), Pt (3)) in CH₃NO₂/CH₂Cl₂ (1:1) solvent. Both complexes were isolated with adequate yields as triflate salts and were then characterized using ¹H, ¹³C, and ³¹P NMR spectroscopy, elemental analysis, UV/Vis spectroscopy, and high-resolution electrospray mass spectrometry (HR-ESMS). The molecular structure of 4 was determined by molecular mechanics force-field calculations. The cytotoxic effect of both new complexes were analyzed against T98G (brain tumor), KB (head and neck cancer), SNU-80 (thyroid cancer), and HEK-293 non-malignant cell lines. The cytotoxicity of complexes 4 and 5 were found to be considerably more effective against cancer cells than reference drug cisplatin. Annexin-V/PI staining, caspase-3/7 activity, and the reduction in mitochondrial membrane potential justify a significant level of apoptosis in complex-treated cells.