The effect of halogenation of salicylaldehyde on the antiproliferative activities of {Δ/Λ-[Ru(bpy)2(X, Y-sal)]BF4} complexes

Ru(II) polypyridyl complexes are widely used in biological fields, due to their physico-chemical and photophysical properties. in this paper, a series of new chiral Ru(II) polypyridyl complexes (1-5) with the general formula {Delta/Lambda-(Ru(bpy)(2)(X,Y-sal)]BF4} (bpy = 2,2'-bipyridyl; X,Y-sal = 5-bromosalicylaldehyde (1), 3,5-dibromosalicylaldehyde (2), 5-chlorosalicylaldehyde (3), 3,5-dichlorosalicylaldehyde (4) and 3-bromo-5-chlorosalicylaldehy (5)) were synthesized and characterized by elemental analysis, FT-IR, and H-1/C-13 NMR spectroscopy. Also, the structures of complexes 1 and 5 were determined by X-ray crystallography; these results showed that the central Ru atom adopts a distorted octahedral coordination sphere with two bpy and one halogen-substituted salicylaldehyde. DFT and TD-DFT calculations have been performed to explain the excited states of these complexes. The singlet states with higher oscillator strength are correlated with the absorption signals and are mainly described as (MLCT)-M-1 from the ruthenium centre to the bpy ligands. The lowest triplet states (T-1) are described as (MLCT)-M-3 from the ruthenium center to the salicy!aldehyde ligand. The theoretical results are in good agreement with the observed unstructured band at around 520 nm for complexes 2, 4 and 5. Biological studies on human cancer cells revealed that dihalogenated ligands endow the Ru(II) complexes with enhanced cytotoxicity compared to monohalogenated ligands. in addition, as far as the type of halogen is concerned, bromine is the halogen that provides the highest cytotoxicity to the synthesized complexes. All complexes induce cell cycle arrest in G0/G1 and apoptosis, but only complexes bearing Br are able to provoke an increase in intracellular ROS levels and mitochondrial dysfunction.

Automated summary

Ru(II) polypyridyl complexes are widely used in biological fields due to their physico-chemical and photophysical properties. The authors synthesized and characterized a series of new chiral Ru(II) polypyridyl complexes and analyzed their structures. The study revealed that dihalogenated ligands enhance the cytotoxicity of Ru(II) complexes and bromine provides the highest cytotoxicity. All complexes induced cell cycle arrest and apoptosis, while only the complexes with bromine increased intracellular ROS levels and mitochondrial dysfunction.