Correlation Between Molecular Modelling and Spectroscopic Techniques in Investigation With DNA Binding Interaction of Ruthenium(II) Complexes.

The DNA binding studies of rutheniumu(II) polypyridyl complexes {[Ru(phen)2Mipc]2+, [Ru(bpy)2Mipc]2+, [Ru(dmb)2Mipc]2+, [Ru(phen)2BrIPC]2+, [Ru(bpy)2BrIPC]2+, [Ru(dmb)2BrIPC]2+, [Ru(phen)2PIP-Cl]2+, [Ru(bpy)2PIP-Cl]2+, [Ru(dmb)2PIP-Cl]2+, [Ru(phen)2IPPBA]2+, [Ru(bpy)2IPPBA]2+, [Ru(dmb)2IPPBA]2+} with DNA investigated by electronic absorption titration, emission and molecular modelling studies to identify the binding interactions. All these complexes are showing good binding constant values ~104 to 105. The intercalative ligands makes the binding of the ruthenium(II) complex with DNA as intercalation mode. The ancillary ligands 1,10-phenanthroline (phen), 4,4'-Dimethyl-2,2'-dipyridyl (dmb) and 2,2'-dipyridine (bpy) having been discovered found to be involved in bond formation with the phosphate backbone of nucleotide base pairs in ruthenium(II) complex-DNA docked complex. The molecular docking results are good agreement with experimental results. The molecular modelling technic should help to extend knowledge about the nature (or) mode of binding of these ruthenium(II) complexes with (calf thymus) CT-DNA.

Studies on Photocleavage, DNA Binding, Cytotoxicity, and Docking Studies of Ruthenium(II) Mixed Ligand Complexes.

This article describes the synthesis and characterization of three new Ru(II) polypyridyl complexes including [Ru(phen)2(dpphz)]2+ (1), [Ru(bpy)2(dpphz)]2+ (2) and [Ru(dmb)2(dpphz)]2+ (3) where dpphz = dipyrido[3,2-a:2',3'-c] phenazine-11-hydrazide, phen =1,10-phenanthroline, bpy = 2,2'-bipyridine and dmb = 4,4'-dimethyl2,2'-bipyridine. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were explored by spectroscopic titrations, viscosity measurements. Results suggest that these complexes can bind to CT-DNA through intercalation. However, their binding strength differs from each other; this may be attributed to difference in the ancillary ligand. The cytotoxicity of 1-3 was evaluated by MTT assay; results indicated that all complexes have significant dose dependent cytotoxicity with HeLa tumor cell line. All complexes exhibited efficient photocleavage of pBR322 DNA upon irradiation. The DNA binding ability of 1-3 was also studied by docking the complexes into B-DNA using docking program.

Antiangiogenic activity of mononuclear copper(II) polypyridyl complexes for the treatment of cancers.

A series of four new mononuclear copper(II) polypyridyl complexes (1-4) have been designed, developed, and thoroughly characterized by several physicochemical techniques. The CT-DNA binding properties of 1-4 have been investigated by absorption, emission spectroscopy, and viscosity measurements. All the complexes especially 1 and 4 exhibit cytotoxicity toward several cancer cell lines, suggesting their anticancer properties as observed by several in vitro assays. Additionally, the complexes show inhibition of endothelial cell (HUVECs) proliferation, indicating their antiangiogenic nature. In vivo chick embryo angiogenesis assay again confirms the antiangiogenic properties of 1 and 4. The formation of excessive intracellular ROS (H2O2 and O2(•-)) and upregulation of BAX induced by copper(II) complexes may be the plausible mechanisms behind their anticancer activities. The present study may offer a basis for the development of new transition metal complexes through suitable choice of ligands for cancer therapeutics by controlling tumor angiogenesis.

Synthesis, characterization; DNA binding and antitumor activity of ruthenium(II) polypyridyl complexes.

Three new ruthenium(II) polypyridyl complexes [Ru(phen)2BrIPC](2+) (1), [Ru(bpy)2 BrIPC](2+) (2) and [Ru(dmb)2BrIPC](2+) (3) where, BrIPC = (6-bromo-3-(1H-imidazo[4,5-f] [1,10]-phenanthroline, phen = 1,10-phenanthroline, bpy = 2,2' bipyridine, dmb = 4,4'-dimethyl 2,2' bipyridine, were synthesised and characterised. DNA-binding nature was investigated by spectroscopic titrations and mode of binding was assessed by viscosity measurements. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be in the order of 10(5). Experimental results showed that these complexes interact with CT-DNA by intercalative mode. Photocleavage and antimicrobial activities were complex concentration dependent, at high concentration, high activity and vice versa. MTT assay was performed on HeLa cell lines, IC50 values of complexes in the order of 3 > 2 > 1 > cisplatin. From comet assay, cellular uptake studies, we observed that complexes could enter into the cell membrane and accumulate inside the nucleus. Molecular docking studies support the DNA binding affinity with hydrogen bonding and van der Waals attractions between base pairs and phosphate backbone of DNA with metal complexes.

Synthesis, characterization, DNA binding studies, photocleavage, cytotoxicity and docking studies of ruthenium(II) light switch complexes.

A new ligand 3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2yl)phenylboronic acid and its (IPPBA) three ruthenium(II) complexes [Ru(phen)2(IPPBA)](ClO4)2 (1), [Ru(bpy)2(IPPBA)](ClO4)2 (2) and [Ru(dmb)2(IPPBA)](ClO4)2 (3) have been synthesized and characterized by elemental analysis, UV/VIS, IR, (1)H-NMR,(13)C-NMR and mass spectra. The binding behaviors of the three complexes to calf thymus DNA were investigated by absorption spectra, emission spectroscopy, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1, 2 and 3 have been determined to be 7.9 × 10(5) M(-1), 6.7 × 10(5) M(-1) and 2.9 × 10(5) M(-1). The results suggest that these complexes bound to double-stranded DNA in an intercalation mode. Upon irradiation at 365 nm, three ruthenium complexes were found to promote the cleavage of plasmid pBR322 DNA from super coiled form І to nicked form ІІ. Further in the presence of Co(2+), the emission of DNA-Ru(ΙΙ) complexes can be quenched. And when EDTA was added, the emission was recovered. The experimental results show that all three complexes exhibited the "on-off-on" properties of molecular "light switch". The highest Cytotoxicity potential of the complex1 was observed on the Human alveolar adenocarcinoma (A549) cell line. Good agreement was generally found between the spectroscopic techniques and molecular docked model which provides further evidence of groove binding.