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 1H/ 13C 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.
A panel of Ru(II)-based complexes with general formula [Ru(phen) 2(X-Sal)]BF 4 and distorted octahedral geometry was synthesized and characterized (elemental analysis and spectroscopic methods). All Ru-complexes, unlike pure ligands and complex lacking the salicylaldehyde auxiliary component, displayed outstanding antiproliferative activity against CCRF-CEM leukemia cells. The top two compounds showed remarkable IC 50 values (submicromolar on CCRF-CEM) and selectivity indexes (up to 19.5 on PBMC). In silico studies indicated they bind preferentially to the anticancer target duplex DNA mismatched base pairs.