Synthesis, characterization and DNA-binding characteristics of Ru(II) molecular light switch complexes

A series of four polypyridyl Ru(II) complexes such as [Ru(L)₄(PIP)]²⁺ and [Ru(L)₄PPIP]²⁺ where L is 4-amino pyridine and Pyridine (PIP?=?2-phenylimidazo[4,5-f] [1, 10] phenanthroline), (PPIP?=?2-(4??-phenoxy-phenyl) imidazo[4,5-][1, 10]phenanthroline) have been synthesized and characterized by elemental analysis, physicochemical methods such as UV?Cvis, IR and NMR spectroscopic techniques. The DNA-binding behavior of these complexes was investigated by electronic absorption titrations, fluorescence spectroscopy, viscosity measurements and salt-dependent studies. The experimental results indicate that all these complexes can bind to DNA through an intercalation mode, the DNA-binding affinities of these complexes follow the order [Ru(4-APy)₄(PPIP)]²⁺(1)?>?[Ru(Py)₄PPIP]²⁺(2)?>?[Ru(4-APy)₄(PIP)]²⁺(3)?>?[Ru(Py)₄PIP]²⁺(4). Noticeably, these complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA. Further, all four complexes screened for their antimicrobial activity indicate that the complexes show appreciable activity against Escherichia coli and Neurospora Crassa. In addition, in the presence of Co²⁺, the emission of DNA-[Ru(L₄)PPIP/PIP]²⁺ can be quenched and recovered by the addition of EDTA, which exhibited the DNA ??light switch?? properties.     

Synthesis,DNA-binding properties and cytotoxicity evaluation of two copper(II) complexes based on curcumin

Two Cu(II) complexes based on curcumin, namely CuL ₂ ¹ [HL¹ = 1,7-bis[4-(2-oxymethylenepyridine)-3-methoxyl]phenyl-1,6-heptadiene-3,5-diketone] and CuL ₂ ² [HL² = 1,7-bis[4-(3-oxymethylene-2-chlorothiophene)-3-methoxyl] phenyl-1,6-heptadiene-3,5-diketone], have been synthesized and characterized by physico-chemical and spectroscopic methods. The interactions of calf thymus DNA (CT-DNA) with both complexes have been investigated by UV–Vis absorption, fluorescence and viscosity titration methods. Both complexes are found to interact with CT-DNA by intercalative binding modes. Evaluation of the cytotoxicities of the complexes against three human tumor cells showed that they have potent cytotoxicities against all three cell lines.     

Synthesis,DNA-binding,and photocleavage properties of Ru(II) complexes containing dppz-based ligand

A ligand ipdp (ipdp?=?indeno[1′,2′?:?5,6]pyrazino[2,3-i]dipyrido[3,2-a?:?2′,3′-c]phenazine-8-one) and its ruthenium complexes, [Ru(L)₂(ipdp)]²⁺ (L?=?bpy (2,2′-bipyridine), phen (1,10-phenanthroline)), have been synthesized and characterized by elemental analysis, electrospray mass spectra, and ¹H NMR. The interaction between the complexes and calf thymus DNA (CT-DNA) has been investigated by spectroscopic methods and viscosity measurements. The results indicate that the complexes can bind to CT-DNA in an intercalative mode. In addition, both complexes promote the photocleavage of plasmid pBR322 DNA under irradiation. The mechanistic studies reveal that singlet oxygen ¹O₂ plays a significant role in DNA photocleavage.     

Synthesis,DNA-binding and photocleavage studies of cobalt(III) mixed-ligand complexes

Two novel complex ions [Co(bpy)₂IP]³⁺ and [Co(bpy)₂PIP]³⁺, have been prepared and characterized by EA, mass spectra, u.v.–vis., and cyclic voltammetry. The binding behavior of both complexes to calf thymus DNA (CT-DNA) has been investigated by spectroscopic methods, cyclic voltammetry, and viscosity measurements. The results suggest that both complexes bind to DNA by intercalation. Both promote cleavage of plasmid pBR 322 DNA from the supercoiled Form I to the open circular Form II upon irradiation. Mechanisms for photocleavage are proposed.     

Synthesis, characterization and DNA-binding and DNA-photocleavage studies of two Ru(II) complexes containing two main ligands and one ancillary ligand

DNA-binding and DNA-photocleavage properties of two Ru(II) complexes, [Ru(L¹)(dppz)₂](PF₆)₄ (1) and [Ru(L²)(dppz)₂](PF₆)₄ (2) (L¹ = 5,5′-di(1-(triethylammonio)methyl)-2,2′-dipyridyl cation; L² = 5,5′-di(1-(tributylammonio)methyl)-2,2′-dipyridyl cation; dppz = dipyrido[3,2-a:2′,3′-c]phenazine, have been investigated. Experimental results show that the DNA-binding affinity of complex 1 is greater than that of 2, both complexes emit luminescence in aqueous solution, either alone or in the presence of DNA, complex 1 can bind to DNA in an intercalative mode while 2 most likely interacts with DNA in a partial intercalation fashion, and complex 2 serves as a better candidate for enantioselective binding to CT-DNA compared with 1. Moreover, complex 1 reveals higher efficient DNA cleavage activity than 2, during which supercoiled DNA is converted to nicked DNA with both complexes. Theoretical calculations for the two complexes have been carried out applying the density functional theory (DFT) method at the level of the B3LYP/LanL2DZ basis set. The calculated results can reasonably explain the obtained experimental trends in the DNA-binding affinities and binding constants (K_b) of these complexes.     

DNA-binding and photocleavage, cytotoxicity, apoptosis and antioxidant activity studies of ruthenium(II) complexes

Two ruthenium(II) polypyridyl complexes, namely [Ru(phen)₂(DMDPPZ)](ClO₄)₂ 1 (phen = 1,10-phenanthroline, DMDPPZ = 3,6-dimethyldipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(dmp)₂(DMDPPZ)](ClO₄)₂ 2 (dmp = 2,9-dimethyl-1,10-phenanthroline), have been synthesized and characterized. The DNA-binding properties of the complexes were investigated by spectrophotometric methods, viscosity measurements, and photoactivated cleavage studies. The DNA-binding constants for complexes 1 and 2 have been determined as 8.78 (±0.94) × 10⁵ M⁻¹ (s = 3.02) and 1.26 (±0.35) × 10⁵ M⁻¹ (s = 1.69), respectively. The results suggest that these complexes bind to calf thymus DNA through intercalation. When irradiated at 365 nm, the complexes promote the photocleavage of pBR322 DNA, and complex 1 cleaves DNA more effectively than complex 2 under comparable experimental conditions. The cytotoxicities of complexes 1 and 2 have been evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method. Complex 2 shows higher anticancer potency than complex 1 against four tumor cell lines. The apoptosis-inducing activity was assessed by acridine orange/ethidium bromide staining assay, and the antioxidant activities of these complexes against hydroxyl radical were also explored.     

Synthesis,characterization, and cytotoxicity of mixed-ligand complexes of palladium(II) with 1,10-phenanthroline and N-carbonyl-L-isoleucine dianion

Three novel palladium(II) complexes [Pd(Phen)(Bzile)] (I), [Pd(Phen)(p-mBzile)] (II), and [Pd(Phen)(p-NBzile)] · H₂O (III), where Bzile = N-benzoyl-L-isolecine), p-MBzile = N-(p-methylbenzoyl)-L-isolecine), p-NBzile = N-(p-nitrobenzoyl)-L-isolecine), have been synthesized and characterized by elemental analysis, ES-MS, and IR. The crystal and molecular structure of the complex II has been determined by single crystal X-ray diffraction. The cytotoxicity was tested against carcinoma cell lines: KB, BGC-823, Bel-7402 and HL-60 by MTT assay. The results indicated that these complexes exerted cytotoxicity, but none of them showed higher cytotoxicity than cisplatin. The cytotoxicity against HL-60, BGC-823, Bel-7402 and KB cell lines decreases in the sequence: p-MBzile > Bzile > p-NBzile. It suggests that the acylated groups have important impact on the cytotoxicity of complexes.     

Cytotoxic and DNA-binding properties of two ruthenium(II) porphyrin complexes

Two ruthenium(II) porphyrin complexes [Ru(L)₂Cl(PTP)]⁺ (L = bpy, 1, phen; 2; PTP = 5-(3′-pyridyl)-10,15,20-trimethylphenylporphyrin) have been synthesized and their antitumor activities have been evaluated by MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) methods. Both complexes exhibit high inhibitory activity against the growth of human cervical carcinoma cell line HeLa, both with and without light treatment. However, when treated with light, the inhibitory activity for both complexes increases at low drug concentration. Spectroscopic studies show that both complexes can bind to HeLa DNA tightly with apparent binding constants of 1.54(±0.07) × 10⁵ and 1.01(±0.02) × 10⁵ M⁻¹ for 1 and 2, respectively.     

Non-covalent DNA binding and cytotoxicity of certain mixed-ligand ruthenium(II) complexes of 2,2'-dipyridylamine and diimines

A series of mixed ligand ruthenium(II) complexes [Ru(Hdpa)2(diimine)](ClO4)2, 1-5 where Hdpa is 2,2'-dipyridylamine and diimine is 1,10-phenanthroline (phen) and a modified/extended 1,10-phenanthroline such as, 5,6-dimethyl-1,10-phenanthroline (5,6-dmp), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), 5-methyldipyrido[3,2-d:2',3'-f]quinoxaline (mdpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been isolated and characterized by analytical and spectral methods. The complex [Ru(Hdpa)2(phen)](PF6)2 1 has been structurally characterized and the coordination geometry around Ru(II) in it is described as distorted octahedral. 1H NMR spectral data reveal that 1-5 should have a C2 symmetry lying on the diimine plane due to the rapid flapping of the coordinated Hdpa ligands. The interaction of the complexes with calf thymus (CT) DNA has been explored by using absorption and emission spectral and viscometry and electrochemical techniques and the mode of DNA binding of the complexes has been proposed. The DNA binding affinity of the complexes decreases with decrease in number of planar aromatic rings in the co-ligand supporting the intercalation of the diimine co-ligands in between the DNA base pairs. Circular dichroic spectral studies reveal that the complexes 3-5 exhibit induced circular dichroism upon binding to CT DNA. Interestingly, upon interaction with CT DNA all the complexes show an increase in anodic current in the cyclic voltammograms suggesting that they are involved in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 5 alters the DNA superhelicity upon binding with supercoiled pBR322 DNA, which is consistent with its higher DNA binding affinity. Further, the cytotoxicities of the complexes against human cervical epidermoid carcinoma cell line (ME180) have been examined. Interestingly, 5 exhibits a cytotoxicity against ME180 higher than other complexes with potency approximately 8 times more than cisplatin for 24 h incubation but 4 times lower than cisplatin for 48 h incubation.     

Synthesis,spectroscopy and electrochemistry of mixed-ligand complexes of platinum(II) and palladium(II)

Mixed-ligand complexes [MX₂(MBPY)] (M = Pd^II or Pt^II; X = Cl^–, I^–, N^– ₃ or NO₂ ^–; MBPY = 4,4-dimethyl-2,2-bipyridine) have been prepared and characterised by elemental analyses, conductivity measurements, i.r., electronic absorption and ¹H-n.m.r. spectroscopic techniques. The cyclic voltammograms of these complexes suggest the involvement of the metal d orbital in the one-electron oxidation process and the * orbital of the MBPY in the one-electron reduction process. [Pt(MBPY)(N₃)₂] shows solution-state luminescence at room temperature.     

Oligonuclear polypyridylruthenium(II) complexes incorporating flexible polar and non-polar bridges: synthesis, DNA-binding and cytotoxicity

The paper reports the synthesis and characterisation of a series of flexible di-bidentate bridging ligands in which two 4-methyl-2,2'-bipyridine groups are linked at the 4'-position by polymethylene (bb(n)), linear polyether (bbO(n)) or linear alkylamine (bbN(n)) chains of varying length (n). The enantiomers (ΔΔ/ΛΛ) of the rac forms of the ruthenium(ii) dinuclear complexes incorporating these ligands -i.e. [{Ru(phen)(2)}(2)(μ-BL)](4+) (phen = 1,10-phenanthroline; BL = bb(n), bbO(n) or bbN(n)) - have been isolated by reaction of Δ- or Λ-[Ru(phen)(2)(py)(2)](2+) (py = pyridine) with the respective bridging ligands. Mononuclear species - in which only one of the bidentate moieties of the bridging ligand is coordinated - have also been isolated, as well as trinuclear and tetranuclear species involving the bb(7) bridge. Fluorescence displacement studies of the DNA-binding of the dinuclear complexes containing the bbO(n) and bbN(n) bridges generally revealed a lower affinity than their bb(n) analogues for an oligonucleotide containing a single bulge site; the mononuclear complexes showed a lower affinity - and the trinuclear and tetranuclear complexes a higher affinity - than the dinuclear species, revealing an interesting interplay of lipophilicity, electrostatics and size in the complex/nucleic acid interaction. Cytotoxicity studies of these complexes against a murine leukaemia cell line revealed that the presence of the polyether or polyamine links in the chain lowered the cytotoxicity compared with their polymethylene analogues, and that the bb(7)-bridged trinuclear and tetranuclear complexes showed considerably enhanced cytotoxicity compared with the dinuclear Rubb(7) analogue.     

Synthesis,characterization and DNA-binding properties of Ru(II) complexes coordinated by ofloxacin as potential antitumor agents

Three Ru complexes coordinated by oxfloxacin, [Ru(L)₂(OFX)]Cl·2H₂O (L = bpy, 1; dmbpy, 2; phen, 3; and OFX = ofloxacin), were synthesized and characterized. These complexes can inhibit the growth of cervical cancer HeLa cells efficiently. Furthermore, these three complexes exhibited excellent binding affinities with DNA, as confirmed by spectroscopy methods and viscosity experiments. Therefore, the synthesized Ru(II) complexes have excellent DNA-binding abilities with potential applications in cancer chemotherapy.     

Structural and thermal decomposition characteristics of mixed-ligand complexes of Cu(II), Ni(II), Co(II) and Zn(II)

Mixed-ligand complexes of Cu(II), Ni(II), Co(II) and Zn(II) with 8-hydroxyquinoline and thiophene-2-carboxylic acid as two different ligands, have been isolated in pure state. The formation of these complexes has been inferred potentiometrically. The isolated complexes have been characterized by their elemental analyses, IR and electronic spectra, conductivity and magnetic measurements. Solid state dehydration of the hydrated complexes and subsequent decomposition of the anhydrous complexes have been studied by simultaneous DTA and TG techniques. The thermal stability order of the hydrated compounds is Cu>Co>Ni>Zn, but in the decomposition process the trend observed is Co>Zn>Ni>Cu. Some parameters like activation energy and order of reaction for each process have been computed.     

DNA-binding,antioxidant activity and in vitro cytotoxicity induced by ruthenium(II) complexes containing polypyridyl ligands

Two new ruthenium(II) polypyridyl complexes, [Ru(dmp)₂(maip)](ClO₄)₂ 1 (maip = 2-(3-aminophenyl)imizado[4,5-f][1,10]phenanthroline and [Ru(dmp)₂(paip)](ClO₄)₂ 2 (paip = 2-(4-aminophenyl)imidazo[4,5-f][1,10]phenanthroline, dmp = 2, 9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The DNA-binding behaviors of complexes 1 and 2 were studied by viscosity measurements, thermal denaturation, and absorption titration. The results show that the two complexes intercalate between the base pairs of DNA. The DNA-binding constants K _b for complexes 1 and 2 were determined to be 3.23 ± 0.16 × 10⁴ M⁻¹ (s = 0.97) and 4.34 ± 0.65 × 10⁴ M⁻¹ (s = 1.13). The cytotoxicity of these complexes has been evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The IC₅₀ values are 35.70, 41.04, 55.25 and 37.50 for complex 1 and 37.02, 103.08, 130.07 and 37.80 for complex 2 against BEL-7402, C-6, HepG-2 and MCF-7 cell lines, respectively. The antioxidant activity against hydroxyl radical (OH•) was also investigated.     

Synthesis, crystal structures and DNA-binding properties of two new mononuclear copper(II) complexes

Two mononuclear copper(II) complexes, [Cu(bpy)₂(CH₃OH)](pic)₂ (1) and [Cu(Me₂bpy)₂(H₂O)](pic)₂ (2) (bpy = 2,2′-bipyridine; Me₂bpy = 4,4′-dimethyl-2,2′-bipyridine; Hpic = 2,4,6-trinitrophenol), were synthesized and characterized by elemental analyses, conductivity measurements, IR, UV–Visible spectroscopy and single crystal X-ray analyses. Both complexes 1 and 2 are mononuclear compounds. The copper atom in complex 1 is in a distorted square pyramidal geometry with a CuN₄O chromophore as revealed from the τ value (0.25), while the Cu(II) ion in complex 2 displays a distorted trigonal bipyramidal stereochemistry with τ = 0.72. Hydrogen bonding interactions and π–π stacking interactions link the mononuclear copper complex 1 or 2 into a 1D infinite chain. The interactions of the two mononuclear complexes with herring sperm DNA (HS-DNA) have been studied by UV–visible absorption titration, fluorescence titration and ethidium bromide (EB) displacement experiments. The results suggest that both complexes might bind to DNA by intercalation.     

Spectroscopic studies on three mixed-ligand copper(II) complexes

The mixed-ligand complexes [Cu(den)en](ClO₄)₂, [Cu(den)Pn](ClO₄)₂ and [Cu(den)tn](ClO₄)₂ (where den = diethylenetriamine, en = ethylenediamine, Pn = 1,2-diaminopropane, and tn = 1,3-diaminopropane) have been synthesized, and their IR, electronic and ESR spectral properties have been studied to understand the stereochemistry of these complexes both in the solid state and in DMF (dimethylformamide) or pyridine solutions. The metal appears to be five-coordinate in the solid state, formed with five nitrogens of the mixed ligand, and is found to change in solution, probably due to the attachment of a solvent molecule in the sixth coordination position. The equatorial and axial bond strengths are estimated in the solutions.     

Preparation and characterization of mixed-ligand dihydrazone complexes of nickel(II)

Summary New complexes of Ni^II-containing dihydrazones derived from dehydroacetic acid as primary ligands and ammonia or pyridine as secondary ligand were prepared and characterized by elemental analysis, conductance, spectral and magnetic data. The dihydrazones react with NiCl₂ in their enolic forms as bis-tridentate complexing agents, forming dinuclear dihydrazido-diamine-dinickel complexes with ammino co-ligands. The ammino complexes were treated with pyridine to give the pyridino complexes. Squareplanar geometries are proposed for all the complexes and preliminary studies show that they possess antifungal activity.     

Syntheses of ruthenium(II) quinonediimine complexes of cyclam and characterization of their DNA-binding activities and cytotoxicity

The synthesis and characterization of ruthenium(II) complexes, [Ru(cyclam)(bqdi)] x ZnCl(4) (1 x ZnCl(4); cyclam = 1,4,8,11-tetraazacyclotetradecane, bqdi = o-benzoquinonediimine), [Ru(cyclam)(nqdi)] x (ClO(4))(2) (2 x (ClO(4))(2); nqdi = 2,3-naphthoquinonediimine), and [Ru(cyclam)(phi)] x (ClO(4))(2) (3 x (ClO(4))(2); phi = 9,10-phenanthroquinonediimine), are described. The DNA binding properties and biological activity of the Ru(II) complexes were studied by various biophysical and cytological techniques. As expected, only 3 showed significant binding with DNA. The thermodynamic profile of the binding of 3 and DNA was constructed by analyzing the experimental data of absorption titration and UV melting studies with the McGhee equation, van't Hoff's equation, and the Gibbs-Helmholtz equation. Compound 3 binds double-stranded DNA with a binding constant of 5.0 x 10(4) M(-1) at 20 degrees C, and the binding mode of the complex to DNA was proved to be intercalative. Cytotoxicity and induced type of cell death of 1-3 were also investigated. Basically, metal complexes with ligands of molecular shape closely related to the structure of DNA are more likely to bind DNA and possess higher toxicity.