Synthesis of ruthenium(II) complexes and characterization of their cytotoxicity in vitro, apoptosis, DNA-binding and antioxidant activity.

A new ligand DBHIP and its two ruthenium (II) complexes [Ru(bpy)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(phen)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The binding behaviors of the two complexes to calf thymus DNA were investigated by absorption spectra, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 have been determined to be 8.87+/-0.27 x 10(4)M(-1) (s=1.83) and 1.32+/-0.31 x 10(5)M(-1) (s=1.84). The results suggest that these complexes interact with DNA through intercalative mode. The cytotoxicity of DBHIP, complexes 1 and 2 has been evaluated by MTT assay. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O(2)(-)) and singlet oxygen ((1)O(2)) may play an important role. Crown Copyright (c) 2009. Published by Elsevier Masson SAS. All rights reserved.