ABSTRACT
A novel polypyridyl ligand CNPFIP (CNPFIP=2-(5(4-chloro-2-nitrophenyl)furan-2-yl)-1H-imidazo[4,5f][1,10]phenanthroline) and its mononuclear Ru(II) polypyridyl complexes of [Ru(phen)2CNPFIP](2+)(1) (phen=1,10-phenanthroline), [Ru(bpy)2CNPFIP](2+)(2) (bpy=2,2'-bipyridine), and [Ru(dmb)2CNPFIP](2+)(3) (dmb=4,4'-dimethyl-2,2'-bipyridine) have been synthesized successfully and characterized thoroughly by elemental analysis, UV/Vis, IR, NMR, and ESI-MS. The interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence, viscosity measurements. The experimental results suggest that three complexes bind to CT-DNA through an intercalative mode and the DNA-binding affinity of complex 1 is greater than that of complexes 2 and 3. The photocleavage of plasmid pBR322 DNA by ruthenium complexes 1, 2, and 3 was investigated. We have also tested three complexes for their antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. The in vitro cytotoxicity of these complexes was evaluated by MTT assay, and complex 1 shows higher cytotoxicity than 2 and 3 on HeLa cells. The induced apoptosis and cell cycle arrest of HeLa cells were investigated by flow cytometry for 24h. The molecular docking of ruthenium complexes 1, 2, and 3 with the active site pocket residues of human DNA TOP1 was performed using LibDock.
Subject(s)
Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cytotoxins , Escherichia coli/growth & development , Pyridines , Ruthenium/chemistry , Staphylococcus aureus/growth & development , Cytotoxins/chemical synthesis , Cytotoxins/chemistry , Cytotoxins/pharmacology , HeLa Cells , Humans , Pyridines/chemical synthesis , Pyridines/chemistry , Pyridines/pharmacologyABSTRACT
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.
Subject(s)
Apoptosis/drug effects , DNA Cleavage/drug effects , DNA/metabolism , Light , Organometallic Compounds/chemical synthesis , Organometallic Compounds/pharmacology , Ruthenium/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Biological Transport , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , DNA/chemistry , DNA Cleavage/radiation effects , Escherichia coli/drug effects , Humans , Organometallic Compounds/chemistry , Organometallic Compounds/metabolism , Phenazines/chemistry , Staphylococcus aureus/drug effects , ViscosityABSTRACT
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.
Subject(s)
Cobalt/chemistry , DNA/metabolism , Organometallic Compounds/chemical synthesis , Organometallic Compounds/pharmacology , Pyridines/chemistry , Ruthenium/chemistry , Absorption , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cattle , Cell Line, Tumor , DNA/chemistry , Humans , Nucleic Acid Denaturation , Organometallic Compounds/chemistry , Organometallic Compounds/metabolism , Photochemical Processes , Spectrometry, Fluorescence , Stereoisomerism , Substrate Specificity , Temperature , ViscosityABSTRACT
Three symmetric ligands 7-methyl dipyrido-[3,2-a;2',3'-c]phenazine (dppz-CH(3)), 7-nitro dipyrido-[3,2-a;2',3'-c]phenazine (dppz-NO(2)) and benzo[i]dipyrido-[3,2-a;2',3'-c]phenazine (dppn) and their ruthenium(II) complexes [Ru(en)(2)(L)][ClO(4)](2) (en= ethylenediamine), L= dppz-CH(3), dppz-NO(2) and dppn have been synthesized and characterized by IR, (1)H, (13)C NMR and Mass spectra. The interactions of these complexes with calf thymus DNA have been investigated by spectrophotometric, spectrofluorimetric, circular dichroism, viscosity and thermal denaturation studies. As the planar extension of the intercalative ligand increases, the interaction of the complex with DNA increases, indicating that the size and shape of the intercalalative ligand has a marked effect on the strength of interaction. The plot of log K versus log [Na(+)] yield a slope of -1.26, -1.53, -1.60 for the complexes 1, 2 and 3 respectively. These three complexes have been found to promote the cleavage of plasmid pBR 322 DNA upon irradiation.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Luminescent Measurements , Organometallic Compounds/chemical synthesis , Organometallic Compounds/pharmacology , DNA/metabolism , DNA Damage/drug effects , Ethylenediamines/chemistry , Ligands , Phenazines/chemistry , Ruthenium/chemistryABSTRACT
A series of mixed-ligand ruthenium(II) complexes of the type [Ru(en)(2)bpy](2+) (bpy=2,2-bipyridine; 1), [Ru(en)(2)phen](2+) (phen=1,10-phenantroline; 2), [Ru(en)(2)IP](2+) (IP=imidazo[4,5-f][1,10]phenanthroline; 3), and [Ru(en)(2)PIP](2+) (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline; 4) have been isolated and characterized by UV/VIS, IR, and (1)H-NMR spectral methods. The binding of the complexes with calf thymus DNA has been investigated by absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA photo-cleavage. The spectroscopic studies together with viscosity measurements and DNA melting studies support that complexes 1 and 2 bind to CT DNA (=calf thymus DNA) by groove mode. Complex 2 binds more avidly to CT DNA than complex 1, complexes 3 and 4 bind to CT DNA by intercalation mode, 4 binds more avidly to CT DNA than 3. Noticeably, the four complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.
