Synthesis, Structural Elucidation, and Cytotoxicity Studies of New Triazolyl Half‐Sandwich RuII, OsII, RhIII and IrIII Complexes

Herein, we report the synthesis of a series of nine novel cationic triazole‐based complexes C1–C9 and their anticancer assays against cervical cancer cells (Hela), kidney cancer cells (HEK293), lung cancer cells (A549), and leukemia cells (MT4). The complexes have the formula [MCl(Ar)L]+X−, where M is a platinum group metal‐based cation (RuII, OsII, RhIII, or IrIII), Ar is Cp* for Rh and Ir and p‐cymene for Ru and Os, L is the N∧N ${N^ \wedge N}$ ‐chelating ligands 1‐benzyl‐4‐(aminomethyl)‐1H‐1,2,3‐triazole (L1) and 1‐picolyl‐4‐phenyl‐1H‐1,2,3‐triazole (L2), and X− is Cl−, BF4−, or BPh4−. The reaction of ligands L1 and L2 with [Ru(p‐cymene)Cl2]2, [Os(p‐cymene)Cl2]2, [Rh(Cp*)Cl2]2, and [Ir(Cp*)Cl2]2 produced the nine cationic complexes (C1–C9) cumulatively. Normal kidney cell lines (BHK21) were included in the assays to assess the selectivity aspect of these complexes to cancer cells. In general, all the compounds displayed low cytotoxicity except for the ruthenium(II) complex C7 (with BPh4− as the counterion), which showed good activity against all the cancer cell lines (EC50 values as low as 9±1.8 μM. Complex C1 with EC50=16±0.5 μM against MT4 gave the highest selectivity towards cancer cells. C7 was also shown to interact with L‐histidine (L‐His), NADH, bovine serum album (BSA) and guanosine 5’‐monophosphate (5’‐GMP). Due to the observed non‐toxicity of most of the complexes against normal cells, selectivity against specific cancer cells, and interaction with imidazole containing biomolecules, this class of complexes may serve as templates in drug development for targeted therapeutics. An illustration of the synthesis of a series of triazole‐based complexes and their anticancer assays against cervical (HeLa) cells, kidney (HEK) cells, lung cancer (A549) cells and leukemia (MT4) cells that were studied in this work, and their possible mode of cytotoxicity. This class of complexes may serve as templates in drug development for targeted therapeutics.