In vitro cytotoxicity, cellular uptake, reactive oxygen species and cell cycle arrest studies of novel ruthenium(II) polypyridyl complexes towards A549 lung cancer cell line.

Ruthenium(II) polypyridyl complexes have displayed some promising biological responses against a variety of cancers and have emerged as a potential candidate that can show significant antitumor activity. Three ruthenium(II) polypyridyl complexes were biologically evaluated in vitro against the A549 cancer cell line. The complexes were selected based on initial DNA intercalation studies and MTT viability screening and were selected based on the most promising candidates, the [Ru(bpy)2o-CPIP].2PF6 (complex 1), [Ru(phen)2o-CPIP].2PF6 (complex 2) and [Ru(biq)2o-CPIP].2PF6 (complex 3). Confocal cellular uptake studies confirmed the intracellular transport of complexes into A549. Cytoplasmic and the nucleic accumulation of the complex 1 and 2 was seen while no fluorescent microscopy was performed for complex 3 due to instrumental limitations. Cellular cytotoxicity was investigated with the aid of the Alamar blue assay. The complexes displayed concentration and time dependent inhibitory effects yielding IC50 values from 5.00 to 32.75 µM. Complex 1 exhibit highest cytotoxicity with IC50 value of 5.00 ± 1.24 µM. All of the complexes have shown a significant effect in the reduction of intracellular reactive oxygen species (ROS) levels. Finally, the complexes have shown a transient effect on the cell cycle by arresting it at G0/G1 phase except for complex 2 [Ru(phen)2o-CPIP].2PF6 which has shown the significant G0/G1 arrest.

Synthesis, characterisation and DNA intercalation studies of regioisomers of ruthenium (II) polypyridyl complexes.

Regioisomers of the functional group of the main ligand (L) on a series of [Ru(phen)2L]2+and [Ru(bpy)2L]2+ complexes, where phen is 1,10 phenanthroline and bpy is 2,2'-bipyridine, were synthesised to investigate the interaction with deoxyribonucleic acid (DNA) as potential therapeutics. UV-Vis binding titrations, thermal denaturation and circular dichroism were used to evaluate their interaction with DNA. The conclusions indicated the significance of the auxiliary ligand; especially 1,10-phenanthroline has on the binding constants (Kb). The systematic variation of auxiliary ligand(phen or bpy), and polypyridyl ligand (4-(1H-Imidazo[4,5-f][1,10]phenanthrolin-2-yl)benzonitrile (CPIP), 2-(4-formylphenyl)imidazo[4,5-f] [1,10] phenanthroline (FPIP), 2-(4-bromophenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and 2-(4-nitrophenyl)imidazo[4,5-f] [1,10] phenanthroline (NPIP), split in terms of functional group change were investigated for DNA interaction. The CPIP analogues in particular were investigated for the regioisomerism (ortho, meta, para) effect of the nitrile group on the ligand. It was found that both the DNA interaction could be tailored through the systematic variation of the electronic nature of the individual auxiliary ligand and to a lesser extent the functional group and regioisomeric change. Preliminary cell line studies have been carried out to determine the selectivity of the complexes against cell lines such as A375 (Skin Cancer), HeLa (Cervical Cancer), A549 (Lung Cancer), Beas2B (Lung Normal Cell) and MCF-7 (Breast Cancer). Complexes which had strong DNA interactions in the binding studies have proven to be the most efficacious against certain cell lines. Establishing well-defined structure property relationships when looking at trends in spectroscopic properties and DNA binding will aid in the intelligent design of potential therapeutic complexes.

Influence of auxiliary ligands on the photophysical characteristics of a series of ruthenium(II)-polypyridyl complexes.

A series of ruthenium-polypyridyl complexes were studied using UV/vis absorption and luminescence spectroscopy as well as luminescence lifetime determination by time-correlated single photon counting (TCSPC). The complexes were characterized with regard to the variation in the electronic band gap as a result of the sequential variation of the auxiliary ligand 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), and 2,2'-biquinoline (biq) ligands while the main ligand remained constant for three different main ligand types. Luminescence yields were calculated and correlated with structural and electronic variation. It was found that both the absorption and emission characteristics could be tailored through the systematic variation of the reduction potential of the individual auxiliary ligand. This was shown to be the case regardless of the functional group at the end of the main ligand. Stokes shift and Raman spectroscopy were employed as a means to gauge the effect of ligand change on the conjugation and vibrational characteristics of the complexes. Luminescence yield and lifetimes were also shown to be well-defined with regards to systematic structure variations. The well-defined trends established elucidate the effect which variation of auxiliary ligands has on the electronic and excited state characteristics of the ruthenium-polypyridyl systems. These well-defined relationships can potentially be extended to optimize luminescence yield and lifetimes and therefore suitability of such compounds for the application in for example photodynamic therapy.