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.

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.

Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes.

Three new mononuclear [Ru (phen)2 ptip](2+) (1), [Ru (bpy)2 ptip](2+) (2) and [Ru (dmb)2 ptip](2+) (3) [ptip=(2-(5-phenylthiophen-2-yl)-1H-imidazo[4, 5-f][1,10 phenanthroline, phen=1, 10 phenanthroline, bpy=2, 2' bipyridine, dmb=4, 4'-dimethyl 2, 2' bipyridine] complexes were synthesized and characterised by elemental analysis, IR, NMR and Mass spectra. The DNA-binding behaviours were investigated by electronic absorption titration, luminescence spectra, viscosity measurements and photo-activated cleavage. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be 7.0 (± 0.06)× 10(5), 3.87 (± 0.04) × 10(5), 2.79 (±0.07) × 10(5) respectively. The results showed that these complexes interact with CT-DNA by intercalative mode. Cell viability experiments indicated that the Ru(II) complex showed significant dose-dependent cytotoxicity to HeLa tumour cell lines. Further flow cytometry experiments showed that the cytotoxic Ru(II) complex induced apoptosis of HeLa tumour cell lines. Our data demonstrated that the Ru(II) polypyridyl complex binds to DNA and thereby induces apoptosis in tumor cells, suggesting that anti-tumor activity of the Ru(II) complex could be related to its interaction with DNA. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of ruthenium complexes and with good visualisation images supporting with experimental results.

Synthesis, characterization, DNA binding, light switch "on and off", docking studies and cytotoxicity, of ruthenium(II) and cobalt(III) polypyridyl complexes.

The novel ligand (dmbip) 2-(4-N, N-dimethylbenzenamine)1H-imidazo[4, 5-f][1, 10]phenanthroline and its complexes [Ru(phen)2dmbip](2+) (1), [Ru(bpy)2dmbip](2+) (2), [Co(phen)2dmbip](3+) (3) and [Co(bpy)2dmbip](3+) (4) [where phen = 1, 10-phenanthroline, bpy = 2, 2'-bipyridine], have been synthesized and characterized by elemental analysis, IR, UV-Vis, (1)H NMR, (13)C NMR and Mass spectra. The DNA binding properties of the complexes were investigated by absorption, emission, quenching studies, light switch "on and off", salt dependent, sensor (cation and anion) studies, viscosity measurements, cyclic voltammetry, molecular modeling and docking studies. The four complexes were screened for Photo cleavage of pBR322 DNA, antimicrobial activity and cytotoxicity. The experimental results indicate that the four complexes can intercalate into DNA base pairs. The DNA-binding affinities of these complexes follow the order [Ru(phen)2dmbip](2+) > [Co(phen)2dmbip](3+) > [Ru(bpy)2dmbip](2+) > [Co(bpy)2dmbip](3+).

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.

Synthesis, characterization, and DNA binding, photocleavage, cytotoxicity, cellular uptake, apoptosis, and on-off light switching studies of Ru(II) mixed-ligand complexes containing 7-fluorodipyrido[3,2-a:2',3'-c]phenazine.

Four new ruthenium(II) polypyridyl complexes-[Ru(phen)2(7-F-dppz)](2+) (7-F-dppz is 7-fluorodipyrido[3,2-a:2',3'-c]phenazine, phen is 1,10-phenanthroline), [Ru(bpy)2(7-F-dppz)](2+)(2) (bpy is 2,2'-bipyridine), [Ru(dmb)2(7-F-dppz)](2+) (dmb is 4,4'-dimethyl-2,2'-bipyridine), and [Ru(hdpa)2(7-F-dppz)](2+) (hdpa is 2,2'-dipyridylamine)-have been synthesized and characterized. Their DNA binding behavior has been explored by various spectroscopic titrations and viscosity measurements, which indicated that all the complexes bind to calf thymus DNA by means of intercalation with different binding strengths. The light switching properties of these complexes have been evaluated, and their antimicrobial activities have been investigated. Photoinduced DNA cleavage studies have been performed. All the complexes exhibited efficient photocleavage of pBR322 DNA on irradiation. The cytotoxicity of these complexes has been evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay with various tumor cell lines. Cellular uptake was studied by flow cytometry and confocal microscopy. Flow cytometry experiments showed that these complexes induced apoptosis of HeLa cell lines.

Synthesis, DNA-binding, cytotoxicity, photo cleavage, antimicrobial and docking studies of Ru(II) polypyridyl complexes.

Three Ruthenium(II) polypyridine complexes, [Ru(phen)2(mipc)](2+)(1), [Ru(bpy)2(mipc)](2+) (2) and [Ru(dmb)2(mipc)](2+)(3) [mipc = 2-(6-methyl-3-(1H-imidazo[4, 5-f][1,10]-phenanthroline-2-yl)-4H-chromene-4-one, phen = 1,10-phenanthroline,bpy = 2, 2'bipyridine,dmb = 4, 4'-dimethyl-2, 2'-bipyridine] have been synthesized and characterized by elemental analysis, IR, UV-Vis, (1)H& (13)C NMR and mass spectra. The DNA-binding properties of the Ruthenium(II) complexes were investigated by spectrophotometric methods, viscosity measurements and light switch studies. These three complexes have been focused on photo activated cleavage studies with pBR-322 and antimicrobial studies. Experimental results indicate that the three complexes intercalate into DNA base pairs and follows the order of 1 > 2 > 3 respectively. Molecular docking studies also support the DNA interactions with complexes through hydrogen bonding and vander Waal's interactions. Cytotoxicity studies with Hela cell lines has been revealing about anti tumor activity of these complexes.

Synthesis, characterization, DNA binding properties, fluorescence studies and toxic activity of cobalt(III) and ruthenium(II) polypyridyl complexes.

The new ligand 4-(isopropylbenzaldehyde)imidazo[4,5-f ][1,10]phenanthroline (ippip) and its complexes [Ru(phen)(2)(ippip)](2+)(1),[Co(phen)(2)(ippip)](3+)(2),[Ru(bpy)(2)(ippip)](2+)(3),[Co(bpy)(2)(ippip)](3+)(4)(bpy=2,2-bipyridine) and (phen=1,10-phenanthroline) were synthesized and characterized by ES(+)-MS, (1)H and (13)C NMR. The DNA binding properties of the four complexes were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that complexes bind to calf thymus DNA (CT-DNA) through intercalation. When irradiated at 365 nm, the complexes promote the photocleavage of pBR322 DNA, and complex 1 cleaves DNA more effectively than 2, 3, 4 complexes under comparable experimental conditions. Furthermore, photocleavage studies reveal that singlet oxygen ((1)O(2)) plays a significant role in the photocleavage.