The DNA-binding behavior and DFT calculation of ruthenium(II) complexes [Ru(phen)2L](ClO4)2 (L = HMOPIP and MOHPIP)

Two ruthenium(II) complexes, [Ru(phen)₂HMPIP]²⁺ (1) and [Ru(phen)₂MHPIP]²⁺ (2), have been synthesized and characterized by elemental analysis, ESI-MS, and ¹H NMR spectroscopy. The DNA-binding properties of 1 and 2 have been investigated by electronic and emission spectra and viscosity experiments. The results show that both 1 and 2 can bind to DNA in intercalating mode, with 1 exhibiting stronger binding affinity. These were confirmed by the strong hypochromism at IL and MLCT absorption bands in both complexes when DNA was added into solution, and the increase in relative viscosity of CT-DNA in the presence of both complexes. Moreover, the calculated intrinsic binding constant for 1 and 2 from the decay of electronic spectra is 3.82 × 10⁵ and 2.06 × 10⁵ M^?1, respectively. Finally, the effects of the substituent groups on the DNA-binding behavior of ruthenium(II) complexes have also been rationally discussed by computer calculation of density functional theory (DFT) methods.     

Synthesis and DNA interaction studies of ruthenium(II) complexes with isatino[1, 2-b]-1,4,8,9-tetraazatriphenylene as an intercalative ligand

The binding of the ruthenium(II) complexes [Ru(bpy)₂(ITAP)](ClO₄)₂ (bpy = 2,2’-bipyridine) and [Ru(phen)₂(ITAP)](ClO₄)₂ (phen = 1,10-phenanthroline, ITAP = isatino[1,2-b]-1,4,8,9-tetraazatriphenylene) to calf thymus DNA (CT-DNA) have been investigated with UV–visible and emission spectroscopy, viscosity measurements, thermal denaturation, and photoactivated cleavage. The experimental results indicate that the two complexes bind to CT-DNA through an intercalative mode. The two Ru(II) complexes in the presence of plasmid pBR322 DNA have been found to give rise to nicking of DNA upon irradiation.     

DNA-binding and cleavage activity of polypyridyl ruthenium(II) complexes

Polypyridyl ruthenium(II) complexes [Ru^II(3-bptpy)(dmphen)Cl]ClO₄ (1), [Ru^II(3-cptpy)(dmphen)Cl]ClO₄ (2), [Ru^II(2-tptpy)(dmphen)Cl]ClO₄ (3), and [Ru^II(9-atpy)(dmphen)Cl]ClO₄ (4) {where 3-bptpy?=?4′-(3-bromophenyl)-2,2′:6′,2″-terpyridine, 3-cptpy?=?4′-(3-chlorophenyl)-2,2′:6′,2″-terpyridine, 2-tptpy?=?4′-(2-thiophenyl)-2,2′:6′,2″-terpyridine, 9-atpy?=?4′-(9-anthryl)-2,2′:6′,2″-terpyridine, dmphen?=?2,9-dimethyl-1,10-phenanthroline} have been synthesized and characterized. The DNA-binding properties of the complexes with Herring Sperm DNA have been investigated by absorption titration and viscosity measurements. The ability of complexes to break the pUC19 DNA has been checked by gel electrophoresis. The experimental results suggest that all the complexes bind DNA via partial intercalation. The results also show that the order of DNA-binding affinities of the complexes is 4?<?3?<?2?<?1, confirming that planarity of the ligand in a complex is very important for DNA-binding.     

Effect of the ancillary ligands on the binding of ruthenium(II) complexes [Ru(dmp)2(MCMIP)]2+ and [Ru(dmb)2(MCMIP)]2+ with DNA

Two polypyridine ruthenium(II) complexes, [Ru(dmp)₂(MCMIP)]²⁺ (1) (MCMIP = 2-(6-methyl-3-chromonyl)imidazo[4,5-f][1,10]-phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline) and [Ru(dmb)₂(MCMIP)]²⁺ (2) (dmb = 4,4′-dimethyl-2,2′-bipyridine), have been synthesized and characterized by elemental analysis, ES-MS and ¹H NMR. The DNA-binding behaviors of these complexes were investigated by electronic absorption titration, fluorescence spectroscopy, viscosity measurements and thermal denaturation. The results show that 1 and 2 effectively bind to CT-DNA; the DNA-binding affinities are closely related to the ancillary ligand.     

Effect of substituents on DNA-binding behaviors of ruthenium(II) complexes: [Ru(dmb)2(dtmi)]2+ and [Ru(dmb)2(dtni)]2+

Two Ru(II) complexes [Ru(dmb)₂(dtmi)](ClO₄)₂ (1) (dmb = 4, 4′-dimethyl-2, 2′-bipyridine, dtmi = 3-(pyrazin-2-yl)-as-triazino[5, 6-f]-5-methoxylisatin) and [Ru(dmb)₂(dtni)](ClO₄)₂ (2) (dtni = 3-(pyrazin-2-yl)-as-triazino[5, 6-f]-5-nitroisatin) have been synthesized and characterized by elemental analysis, ES-MS, and ¹H NMR. DNA-binding behaviors of these complexes have been investigated by spectroscopic titration, viscosity measurements, and thermal denaturation. The results indicate that the two complexes interact with calf thymus DNA by intercalation.     

Synthesis,characterization, DNA-binding and DNA-photocleavage studies of [Ru(bpy)2(BPIP)] and [Ru(phen)2(BPIP)] (BPIP = 2-(4′-biphenyl)imidazo[4,5-f][1,10]phenanthroline)

New ligand 2-(4′-biphenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and its complexes [Ru(bpy)₂(BPIP)]²⁺ (1) (bpy = 2,2′-bipyridine) and [Ru(phen)₂(BPIP)]²⁺ (2) (phen = 1,10-phenanthroline) have been synthesized and characterized by mass spectroscopy, ¹H NMR and cyclic voltammetry. The interaction of two Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by spectroscopic and viscosity measurements. Results indicate that both complexes bind to DNA via an intercalative mode and the DNA-binding affinity of complex 2 is much greater than that of complex 1. Furthermore, when irradiated at 365 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA.     

Effects of the ancillary ligands of polypyridyl ruthenium(II) complexes on the DNA-binding and photocleavage behaviors

The new polypyridyl ligand MIP {MIP = 2-(2,3-methylenedioxyphenyl)imidazo[4,5-f]1,10-phenanthroline} and its ruthenium(II) complexes [Ru(phen)₂(MIP)]²⁺ (1) (phen = 1,10-phenanthroline) and [Ru(dmp)₂(MIP)]²⁺ (2) (dmp = 2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, MS and ¹H NMR spectroscopy. The DNA-binding properties of the two complexes to calf-thymus DNA (CT-DNA) were investigated by different spectrophotometric methods and viscosity measurements, as well as equilibrium dialysis and circular dichroism spectroscopy. The results suggest that complex 1 binds to CT-DNA through intercalation, and complex 2 binds to CT-DNA via a partial intercalative mode. This difference in binding mode probably is caused by the different ancillary ligands. Also, when irradiated at 400 nm, complex 1 was found to be a more-effective DNA-cleaving agent than complex 2.     

Synthesis, characterization and DNA-binding studies of ruthenium(II) mixed-ligand complexes containing dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline

A novel ligand dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline (dpoq) and its complexes [Ru(bpy)₂(dpoq)]²⁺ and [Ru(phen)₂(dpoq)]²⁺ (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline) have been synthesized and characterized by elemental analysis, electrospray mass spectra and ¹H NMR. The interaction of Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption spectroscopy, fluorescence spectroscopy, thermal denaturation and viscosity measurements. Results suggest that two Ru(II) complexes bind to DNA via an intercalative mode.     

Inducement and stabilization of G-quadruplex DNA by a thiophene-containing dinuclear ruthenium(II) complex

G-quadruplex structures are attractive targets for the development of anticancer drugs, as their formation in human telomere could impair telomerase activity, thus inducing apoptosis in cancer cells. In this work, a thiophene-containing dinuclear ruthenium(II) complex, [Ru₂(bpy)₄(H₂bipt)]⁴⁺ {bpy = 2,2′-bipyridine, H₂bipt = 2,5-bis[1,10]phenanthrolin[4,5-f]-(imidazol-2-yl)thiophene}, was prepared and the interaction between the complex and human telomeric DNA oligomers 5′-G₃(T₂AG₃)₃-3′ (HTG21) has been investigated by UV-Vis, fluorescence and circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, fluorescent intercalator displacement (FID) titrations, Job plot and color reaction studies. The results indicate that the complex can well induce and stabilize the formation of antiparallel G-quadruplex of telomeric DNA in the presence or absence of metal cations, and the ΔT_m value of the G-quadruplex DNA treated with the complex was obtained to be 12.8 °C even at levels of 50-fold molar of duplex DNA (calf-thymus DNA), suggesting that the complex exhibits higher G-quadruplex DNA selectivity over duplex DNA. The complex shows high interaction ability with G-quadruplex DNA at (1.17 ± 0.12) × 10⁷ M^?1 binding affinity using a 2:1 [complex]/[quadruplex] binding mode ratio. A novel visual method has been developed here for making a distinction between G-quadruplex DNA and duplex DNA by our ruthenium complex binding hemin to form the hemin-G-quadruplex DNAzyme.     

Cellular uptake, cytotoxicity, apoptosis, antioxidant activity and DNA binding of polypyridyl ruthenium(II) complexes

Ruthenium(II) polypyridyl complexes [Ru(phen)₂(APIP)](ClO₄)₂1 and [Ru(phen)₂(HAPIP)](ClO₄)₂2 have been synthesized and characterized. The DNA-binding behaviors were investigated by electronic absorption titration, luminescence spectra, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants K_b for complexes 1 and 2 were determined to be 3.38 (±0.42) × 10⁵ M⁻¹ (s = 1.48) and 3.93 (±0.60) × 10⁵ M⁻¹ (s = 3.14), respectively. The studies on the photocleavage demonstrated that the effects of cleavage are concentration-dependent. The results showed that complexes 1 and 2 interact with CT-DNA by intercalative mode. The cytotoxicity of complexes 1 and 2 has been evaluated by MTT method. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The cellular uptake showed that complexes can enter into the cytoplasm and accumulate in the nuclei. The antioxidant activity studies suggested that the ligands and complexes may be potential drugs to eliminate the radical.     

A copper(II) complex of 1,4,7-triazacyclononane featuring acetate pendant: an efficient DNA cleavage agent

A new water-soluble copper(II) complex, Cu(TACNA)Br?·?0.375H₂O (1) [TACNA?=?1,4,7-triazacyclononane-N-acetate], has been synthesized to serve as artificial nucleases. The X-ray crystal structure of 1 indicates that one bromide and an oxygen from acetate pendant coordinate to copper(II) in addition to the nitrogen atoms in the TACN macrocycle, resulting in a five-coordinate complex with square-pyramidal geometry. The interaction of 1 with calf thymus DNA (ct-DNA) has been investigated by UV absorption and fluorescence spectroscopies, and the mode of ct-DNA binding for 1 has been proposed. In the absence of external agents, supercoiled plasmid DNA cleavage by 1 was performed under aerobic condition; the influences on DNA cleavage of different complex concentrations and reaction times were also studied. The cleavage of plasmid DNA likely involves oxidative mechanism.     

Synthesis,DNA and Photocleavage Studies of Ru(II) Polypyridyl Complexes: [Ru(dppz)(pyz)4](ClO4)2 and [Ru(dppz)(dmpyz)4](ClO4)2 Complexes

In view of the growing interest for the synthesis of metal complexes and their interaction with DNA, we have synthesized and characterized two complexes containing ruthenium as metal center. The complexes are of the type [Ru(dppz)L₄](ClO₄)₂ where L are biologically important ligands such as pyrazole and dimethylpyrazole. The characterization of these complexes is done by ¹H NMR, ¹³C NMR, elemental analysis and mass spectroscopy. The interaction of these complexes with CT DNA was monitored and binding constants were determined using absorption and fluorescence spectroscopy. The mode of binding was found to be intercalative for both complexes and was determined using hydrodynamic viscosity studies. The complexes were further studied for photocleavage studies with supercoiled plasmid pBR322 DNA.     

Syntheses and photophysical properties of visible-light-absorbing Ru(II) polypyridyl complexes possessing (pyridylpyrazolyl)metal tethers

Novel Ru(II) polypyridyl complexes possessing pyridylpyrazolyl tethers were synthesized. Reactions with various organometallic precursors readily afforded multinuclear complexes which possess a light-harvesting Ru(II) core and (pyridylpyrazolyl)metal fragments in high yields. Analysis of the photophysical properties of the obtained multinuclear complexes revealed that the complexes had similar absorption and emission characteristics; however, their emission quantum yields decreased in proportion to the number of metal fragments. The di- and trinuclear complexes were stable under donating solvent such as CH₃CN.     

Binuclear ruthenium(II) pyridazine complex catalyzed transfer hydrogenation of ketones

A convenient and general method of synthesis of binuclear ruthenium(II) pyridazine complex was reported. The synthesized complex was characterized by analytical and spectral methods. The structure of the complex was confirmed by X-ray diffraction technique and was found to be an efficient catalyst for the transfer hydrogenation of ketones with excellent conversions in the presence of isopropanol/KOH at 82 °C. The effect of solvents, bases, and different catalyst/substrate ratio for the reaction was also investigated.     

Synthesis,crystal structure and DNA-binding properties of ruthenium(II) polypyridyl complexes with dicationic 2,2′-dipyridyl derivatives as ligands

New Ru(II) complexes with dicationic ligand, [Ru(phen)₂L¹]⁴⁺(1) and [Ru(phen)₂L²]⁴⁺(2) (phen = 1,10-phenanthroline; L: L¹ = 5,5′-di(1-(triethylammonio)methyl)-2,2′-dipyridyl cation; L² = 5,5′-di(1-(tributylammonio)methyl)-2,2′-dipyridyl cation) have been synthesized and structurally characterized. The interaction of these complexes with calf thymus DNA (CT-DNA) has been investigated. The intrinsic binding constants (K_b: 1, 7.73 × 10⁴ M⁻¹; 2, 2.50 × 10⁴ M⁻¹) determined by absorption spectral titrations of these complexes with CT-DNA indicate the DNA-binding affinity of 1 is stronger than that of 2. Both complexes can display luminescence either alone in aqueous solution or in the presence of DNA. Equilibrium dialysis experiments monitored by CD spectroscopy reveal the preferential binding of the Δ-enantiomer to the right-handed CT-DNA. DNA-viscosity studies suggest that the binding modes are different, 1 may partially intercalate between DNA base-pairs while 2 most likely interact with DNA in an electrostatic binding mode.     

Synthesis,characterization and DNA binding and photocleavage studies of [Ru(bpy)2BDPPZ]2+, [Ru(dmb)2BDPPZ]2+ and [Ru(phen)2BDPPZ]2+ complexes and their antimicrobial activity

Polypyridyl ligand 9a,13a‐dihydro‐4,5,9,14‐tetraaza‐benzo[b]triphenylene‐11‐yl)‐phenyl‐methanone (BDPPZ) and its complexes [Ru(bpy)₂BDPPZ]²⁺, [Ru(dmb)₂BDPPZ]²⁺ and [Ru(phen)₂BDPPZ]²⁺ (where bpy = 2,2′‐bipyridine, dmb = 4,4′‐dimethyl‐2,2′‐bipyridine, phen = 1,10‐phenanthroline) have been synthesized and characterized by elemental analysis, IR, UV–vis, ¹H‐NMR, ¹³C‐NMR and mass spectra. The DNA‐binding properties of the complexes were investigated by absorption, emission, melting temperature and viscosity measurements. Experimental results indicate that the three complexes can intercalate into DNA base pairs. Photo activated cleavage of pBR‐322 DNA by the three complexes was also studied. Further, all three Ru(II) complexes synthesized were screened for their antimicrobial activity. Copyright © 2009 John Wiley & Sons, Ltd.     

Redox,spectroscopic, photo-induced ligand exchange,and DNA interaction studies of a new Ru(II)Pt(II) bimetallic complex

A new bimetallic complex, [Ru(biq)₂(dpp)PtCl₂](PF₆)₂ (where biq = 2,2′-biquinoline and dpp = 2,3-bis(2-pyridyl)pyrazine), containing a cis-PtCl₂ moiety coupled to a sterically strained Ru(II)-based chromophore was designed, synthesized, and investigated with respect to its spectroscopic, redox, photo-induced ligand exchange, and DNA-interaction properties. The electrochemistry of the designed complex was found to be consistent with the bridging coordination of the dpp ligand and formation of the bimetallic complex. The complex displays intense ligand-based π → π* transitions in the UV region and metal-to-ligand charge-transfer transitions (MLCT) in the visible region. The loss of bridging coordination of the dpp ligand and formation of complexes, [Ru(biq)₂(CH₃CN)₂]²⁺ and [Pt(dpp)(CH₃CN)₂]²⁺ was observed when an acetonitrile solution of the metal complex was irradiated with visible light (λ_irr ≥ 550 nm). The designed complex displays covalent binding with DNA in dark through the cis-PtCl₂ moiety, as confirmed by agarose gel electrophoresis. Upon photoirradiation, the complex dissociates into two DNA-binding moieties and displays covalent binding through: (i) a cis-PtL₂ subunit of [Ptdpp(L)₂]²⁺ and (ii) open coordination sites of the ruthenium of [Ru(biq)₂(L)₂]²⁺ (L = solvent). The designed complex represents the first Ru(II)Pt(II) complex that undergoes photo-induced ligand exchange and displays multifunctional interactions with DNA upon photoirradiation.     

Synthesis,DFT analysis and DNA studies,cytotoxicity and luminescence properties of a dinuclear copper(II) complex with 1,10-phenanthroline and 4-aminobenzoate

The dinuclear copper(II) complex, [Cu₂(phen)₂(4-aminobenzoate)₂(H₂O)₂](NO₃)₂·2(4-aminobenzoic acid)·3H₂O (phen = 1,10-phenanthroline), has been synthesized and structurally characterized by elemental analyses, IR, EPR, UV-visible and single-crystal X-ray crystallography. The complex crystallized in a monoclinic system with space group C2/c, a?=?26.0022(10) Å, b?=?10.2524(4) Å, c?=?20.9983(7) Å, α?=?90°, β?=?106.9550(10)° and γ?=?90°. The Cu(II) ion adopts a distorted square-pyramidal geometry formed by two N atoms from the phen ligand and two O atoms of the two 4-aminobenzoic acid ligands and one water O atom. The Cu…Cu separation is 3.0570(5) Å. A twofold axis passes through the midpoint of the Cu-Cu vector. The complex has intraligand (π–π*) fluorescence properties. The binding of this dinuclear copper(II) complex with calf thymus DNA (CT-DNA) was investigated by UV-vis absorption, fluorescence spectroscopic, cyclic voltammetric and viscosity techniques. Also, the cleavage of pBR322 DNA with dinuclear copper(II) complex was studied using gel electrophoresis method. The exhibited potent cytotoxic effects against human cell line (HepG2) and it was found to have good antimicrobial activities. The primary coordination sphere of dinuclear copper(II) complex is optimized, structural parameters are calculated and energy gaps of frontier orbital (HOMO-LUMO) have been calculated with B3LYP/6-31G/LANL2DZ level of theory in the gaseous phase. The calculated geometric and spectral results reproduced the experimental data with well agreement. Theoretical calculated molecular orbitals (HOMO-LUMO) and their energies have been calculated that suggest charge transfer occurs within the complex.