Investigating the Cytotoxicity of Ru(II) Polypyridyl Complexes by Changing the Electronic Structure of Salicylaldehyde Ligands.

A novel class of Ru(II)-based polypyridyl complexes with an auxiliary salicylaldehyde ligand [Ru(phen) 2 (X-Sal)]BF 4 {X: H ( 1 ), 5-Cl ( 2 ), 5-Br ( 3 ), 3,5-Cl 2 ( 4 ), 3,5-Br 2 ( 5 ), 3-Br,5-Cl ( 6 ), 3,5-I 2 ( 7 ), 5-NO 2 ( 8 ), 5-Me ( 9 ), 4-Me ( 10 ), 4-OMe ( 11 ), and 4-DEA ( 12 ), has been synthesized and characterized by elemental analysis, FT-IR, and 1 H/ 13 C NMR spectroscopy. The molecular structure of 4 , 6 , 9 , 10 , and 11 was determined by single-crystal X-ray diffraction analysis which revealed structural similarities. DFT and TD-DFT calculations showed that they also possess similar electronic structures. Absorption/emission spectra were recorded for 2 , 3 , 10 , and 11 . All Ru-complexes, unlike the pure ligands and the complex lacking the salicylaldehyde component, displayed outstanding antiproliferative activity in the screening test (10 μM) against CCRF-CEM leukemia cells underlining the crucial role of the presence of the auxiliary ligand for the biological activity. The two most active derivatives, namely 7 and 10 , were selected for continuous assays showing IC 50 values in the submicromolar and micromolar range against drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells, respectively. These two compounds were investigated in silico for their potential binding to duplex DNA well-matched and mismatched base pairs, since they showed remarkable selectivity indexes (2.2 and 19.5 respectively) on PBMC cells.