Non-covalent DNA binding and cytotoxicity of certain mixed-ligand ruthenium(ii) complexes of 2,2′-dipyridylamine and diimines

Abstract

A series of mixed ligand ruthenium(II) complexes [Ru(Hdpa)2(diimine)](ClO4)2, 1-5 where Hdpa is 2,2'-dipyridylamine and diimine is 1,10-phenanthroline (phen) and a modified/extended 1,10-phenanthroline such as, 5,6-dimethyl-1,10-phenanthroline (5,6-dmp), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), 5-methyldipyrido[3,2-d:2',3'-f]quinoxaline (mdpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been isolated and characterized by analytical and spectral methods. The complex [Ru(Hdpa)2(phen)](PF6)2 1 has been structurally characterized and the coordination geometry around Ru(II) in it is described as distorted octahedral. 1H NMR spectral data reveal that 1-5 should have a C2 symmetry lying on the diimine plane due to the rapid flapping of the coordinated Hdpa ligands. The interaction of the complexes with calf thymus (CT) DNA has been explored by using absorption and emission spectral and viscometry and electrochemical techniques and the mode of DNA binding of the complexes has been proposed. The DNA binding affinity of the complexes decreases with decrease in number of planar aromatic rings in the co-ligand supporting the intercalation of the diimine co-ligands in between the DNA base pairs. Circular dichroic spectral studies reveal that the complexes 3-5 exhibit induced circular dichroism upon binding to CT DNA. Interestingly, upon interaction with CT DNA all the complexes show an increase in anodic current in the cyclic voltammograms suggesting that they are involved in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 5 alters the DNA superhelicity upon binding with supercoiled pBR322 DNA, which is consistent with its higher DNA binding affinity. Further, the cytotoxicities of the complexes against human cervical epidermoid carcinoma cell line (ME180) have been examined. Interestingly, 5 exhibits a cytotoxicity against ME180 higher than other complexes with potency approximately 8 times more than cisplatin for 24 h incubation but 4 times lower than cisplatin for 48 h incubation.

Effect of substitution and planarity of the ligand on DNA/BSA interaction, free radical scavenging and cytotoxicity of diamagnetic Ni(ii) complexes: A systematic investigation

“…10 shows the plot of the hydroxyl radical scavenging effect (%) and it is found that the inhibitory effect of the compounds tested with OH and O 2 -radicals are concentration dependent and their suppression ratio increases with increasing sample concentrations in the tested range. The IC 50 -, decreased in the order 8 > 7 > 6 > 5 > 4 > 3 > 2 > 1. However, the radical scavenging effects of nickel chelates are higher than that of the corresponding free ligands due to chelation with nickel ions in complexation that exert different and selective effects on scavenging radicals of the biological system.…”

“…49, 50 The overall order of interaction between the complexes and CT DNA as well as BSA decreased in the order 8 > 7 > 6 > 5.…”

“…Complexes 5-8 were dissolved in DMSO and blank samples containing the same amount of DMSO were taken as controls. The effects of the complexes on the viability of these cells evaluated after an exposure period of 48 h showed antitumour activity and their corresponding IC 50 values, related to inhibition of tumour cell growth at the 50% level, are noted.…”

“…The percentage activity was calculated by using the formula, % activity = [(A 0 -A C )/A 0 ] ¥ 100, where A 0 and A C represent the absorbance in the absence and presence of the test complex, respectively. The 50% activity (IC 50 ) is calculated from the result of percentage activity.…”

Synthesis, characterization and DNA binding and cleavage properties of ruthenium(II) complexes with various polypyridyls

“…[4][5][6] Several ruthenium complexes were found to be potent anticancer substances with remarkable activity and lower toxicity than platinum complexes. 7 In co-ordination chemistry, terpyridines are of special interest due to their ability to form stable complexes with many transition metal ions. Such complexes possess interesting photophysical, electrochemical and photochemical properties, allowing constructing extended supramolecular architectures.…”