DNA-binding and nuclease activity of1,10-phenanthroline-based thiocyanato, acetato, azido and benzoato bridged dinuclear copper(II) complexes

The mononuclear Cu(II) complex [Cu(phen)(H2O)(NO3)(2)] (1), obtained by the reaction of 1,10-phenanthroline with Cu(NO3)(2)center dot 3H(2)O in methanol solution, reacts with anionic ligands SCN-, AcO-, N-3(-) and PhCO2- in MeOH solution to form the stable binuclear complexes [Cu-2(H2O)(2)(phen)(2)(mu-X)(2)](2) (NO3)(2), where X = SCN- (2), AcO- (3), N-3(-) (4) or PhCO2- (5). The molecular structure of complex 3 was determined by single-crystal X-ray diffraction studies. These complexes were characterized by electronic, IR, ESR, magnetic moments and conductivity measurements. The electrochemical behaviour of the complexes was investigated by cyclic voltammetry. The interactions of these complexes with calf thymus DNA have been investigated using absorption spectrophotometry. Their DNA cleavage activity was studied on double-stranded pBR322 plasmid DNA using gel electrophoresis experiments in the absence and presence of H2O2 as oxidant.

DNA-binding and nuclease activity of 1,10-phenanthroline-based thiocyanato, acetato, azido and benzoato bridged dinuclear copper(II) complexes

The mononuclear Cu(II) complex [Cu(phen)(H2O)(NO3)(2)] (1), obtained by the reaction of 1,10-phenanthroline with Cu(NO3)(2)center dot 3H(2)O in methanol solution, reacts with anionic ligands SCN-, AcO-, N-3(-) and PhCO2- in MeOH solution to form the stable binuclear complexes [Cu-2(H2O)(2)(phen)(2)(mu-X)(2)](2) (NO3)(2), where X = SCN- (2), AcO- (3), N-3(-) (4) or PhCO2- (5). The molecular structure of complex 3 was determined by single-crystal X-ray diffraction studies. These complexes were characterized by electronic, IR, ESR, magnetic moments and conductivity measurements. The electrochemical behaviour of the complexes was investigated by cyclic voltammetry. The interactions of these complexes with calf thymus DNA have been investigated using absorption spectrophotometry. Their DNA cleavage activity was studied on double-stranded pBR322 plasmid DNA using gel electrophoresis experiments in the absence and presence of H2O2 as oxidant.

Air oxygenation chemistry of 4-TBC catalyzed by chloro bridged dinuclear copper(II) complexes of pyrazole based tridentate ligands: synthesis, structure, magnetic and computational studies

Four dinuclear bis(mu-Cl) bridged copper(II) complexes, Cu-2(mu-Cl)(2)(L-X)(2)](ClO4)(2) (L-X = N,N-bis(3,5-dimethylpyrazole-1-yl)-methyl]benzylamine with X = H(1), OMe(2), Me(3) and Cl(4)), have been synthesized and characterized by the single crystal X-ray diffraction method. In these complexes, each copper(II) center is penta-coordinated with square-pyramidal geometry. In addition to the tridentate L-X ligand, a chloride ion occupies the last position of the square plane. This chloride ion is also bonded to the neighboring Cu(II) site in its axial position forming an SP-I dinuclear Cu(II) unit that exhibits small intramolecular ferromagnetic interactions and supported by DFT calculations. The complexes 1-3 exhibit methylmonooxygenase (pMMO) behaviour and oxidise 4-tert-butylcatechol (4-TBCH2) with molecular oxygen in MeOH or MeCN to 4-tert-butyl-benzoquinone (4-TBQ), 5-methoxy-4-tert-butyl-benzoquinone (5-MeO-4-TBQ) as the major products along with 6,6'-Bu-t-biphenyl-3,4,3',4'-tetraol and others as minor products. These are further confirmed by ESI- and FAB-mass analyses. A tentative catalytic cycle has been framed based on the mass spectral analysis of the products and DFT calculations on individual intermediates that are energetically feasible.

Effect of anionic co-ligands on structure and magnetic coupling of bis(μ-phenoxo-bridged dinuclear copper(II) complexes

Two phenoxo bridged dinuclear Cu(II) complexes, [Cu2L2(NO2)(2)] (1) and [Cu2L2(NO3)(2)] (2) have been synthesized using the tridentate reduced Schiff-base ligand 2-[(2-dimethylamino-ethylamino)-methyl]-phenol (HL). The complexes have been characterized by X-ray structural analyses and variable-temperature magnetic susceptibility measurements. The structures of the two compounds are very similar having the same tridentate chelating ligand (L) and mono-dentate anionic ligand nitrite for 1 and nitrate for 2. In both complexes Cu(II) is penta-coordinated but the square pyramidal geometry of the copper ions is severely distorted (Addison parameter (tau) = 0.33) in 1 while the distortion is quite small (average tau = 0.11) in 2. These differences have marked effect on the magnetic properties of two compounds. Although both are antiferromagnetically coupled, the coupling constants (J = -140.8 and -614.7 cm (1) for 1 and 2, respectively) show that the coupling is much stronger in 2.

Preparation, characterization and electrochemical studies of dinuclear copper(II) complexes with pseudohalides and bidentate amines on platinum electrode in acetonitrile

The complexes: [Cu(N 3) 2(N,N-diEten)] 2, [Cu(N 3) 2(tmeen)] 2, [Cu(N 3)(NCO)(N,N-diEten)] 2, [Cu(N 3) 2(N,N′-diMeen)] 2 and [Cu(N 3)(NCO)(tmeen)] 2 were prepared, characterized and their electrochemical behavior was investigated by cyclic voltammetry and controlled potential electrolysis. Cyclic voltammograms for all complexes studied are similar and exhibit one pair of current peaks in the range of -0.65 to +0.0 V. The number of electrons obtained from controlled potential electrolysis at ca. -0.55 V for all compounds was 1.8 ≤ n ≤ 2.1, indicating that both copper(II) metallic centres in the molecule were reduced to copper (I). Comparing the peak potential values for these complexes one can observe that the redox process corresponding to copper(II)/copper(I) couple is slightly influenced by the σ-basicity of the ligands. © 1997 Soc. Bras. Química.

Dinuclear copper(II) complexes with valsartan. Synthesis, characterization and cytotoxicity

Two novel dinuclear complexes involving the antihypertensive drug valsartan and copper(II) ion have been prepared in water and DMSO. The complex compositions were determined as: [Cu(vals)(H(2)O)(3)](2)center dot 6H(2)O and [Cu(vals)(H(2)O)(2)DMSO](2)center dot 2H(2)O. They were thoroughly characterized by elemental and thermal analysis, spectrophotometric titrations and UV-visible, diffuse reflectance, FTIR, Raman and EPR spectroscopies. No effect of the ligand on two tested osteoblastic cell lines in culture (one normal MOT3E1 and one tumoral UMR106) was observed in concentrations up to 100 mu M. Higher concentrations of Valsartan are required to induce cytotoxicity in both cell lines. The antiproliferative effect of the tested complex ([Cu(vals) (H(2)O)(3)](2)center dot 6H(2)O) in a dose-response manner, was higher in the UMR106 osteoblastic cell line than that of the MC3T3E1 normal line at concentrations >= 100 mu M. Morphological alterations are in accordance with proliferative observations. (C) 2011 Elsevier Inc. All rights reserved.

Copper(II) complexes of tetradentate N2S2 donor sets: synthesis, crystal structure characterization and reactivity

Two mononuclear and one dinuclear copper(II) complexes, containing neutral tetradentate NSSN type ligands, of formulation [Cu-II(L-1)Cl]ClO4 (1), [Cu-II(L-2)Cl]ClO4 (2) and [Cu-2(II)(L-3)(2)Cl-2](ClO4)(2) (3) were synthesized and isolated in pure form [where L-1 = 1,2-bis(2-pyridylmethylthio)ethane, L-2 = 1,3-bis(2-pyridylmethylthio)propane and L-3 = 1,4-bis(2-pyridylmethylthio)butane]. All these green colored copper(II) complexes were characterized by physicochemical and spectroscopic methods. The dinuclear copper(II) complex 3 changed to a colorless dinuclear copper(I) species of formula [Cu-2(1)(L-3)(2)](ClO4)(2),0.5H(2)O (4) in dimethylformamide even in the presence of air at ambient temperature, while complexes I and 2 showed no change under similar conditions. The solid-state structures of complexes 1, 2 and 4 were established by X-ray crystallography. The geometry about the copper in complexes 1 and 2 is trigonal bipyramidal whereas the coordination environment about the copper(I) in dinuclear complex 4 is distorted tetrahedral. (C) 2008 Elsevier Ltd. All rights reserved.

Catecholase and DNase activities of copper(II) complexes containing phenolate-type ligands

Three new homodinuclear complexes containing substituted phenolate-type ligands based on the N(5)O(2) donor (2-(N,N-Bis(2-pyridylmethyl)aminomethyl)-6-(N`,N`-(2-hydroxybenzyl)(2-pyridylmethyl))aminomethyl)-4-methylphenol (H(2)L-H) were synthesized and characterized by X-ray crystallography. Potentiometric titration studies in 70% (v/v) aqueous ethanol show that all three complexes exhibit a common {Cu(II)(mu-phenoxo)(mu-OH)Cu(II)(OH)} core in solution. Kinetic studies on the oxidation reaction of 3,5-di-tert-butylcatechol revealed that the catalytic activity of the metal complexes increases toward the ligand containing an electron-donating group. In addition, these complexes also carried out DNA cleavage by hydrolytic and oxidative pathways. Copyright (C) 2010 John Wiley & Sons, Ltd.

Synthesis, spectroscopic characterization and radiosensitizing properties of acetato-bridged copper(II) complexes with 5-nitroimidazole drugs

Three novel acetato-bridged dinuclear copper(II) complexes with 5-nitroimidazoles (CuAcNtrim) and the known copper-acetato-metronidazole have been prepared by an environment-friendly route and spectroscopically characterized. The CuAcNtrim compounds of formula [Cu(2)(mu-O(2)CCH(3))(4)Ntrim(2)], where Ntrim = metronidazole (1), secnidazole (2), tinidazole (3) or nimorazole (4), exhibit dimeric copper-acetato paddle-wheel structures with Ntrim axial ligands coordinated to copper(II) ions through the N(3) atoms of the imidazole rings. EPR data indicate antiferromagnetic behavior for this novel series of copper complexes. The constant coupling has been found to decrease along with the increasing of basicity of the Ntrim axial ligand. The CuAcNtrim complexes and the correspondent Ntrim parent drugs have shown radiosensitizer properties for Hep2 (human larynx cancer) cell line in vitro. The best enhancement of radiosensitizer activity upon coordination of the Ntrim drug to copper(II) has been found for the nimorazole compound which has the strongest Cu-Ntrim bond and exhibits the highest lipophilicity within the series of CuAcNtrim complexes. (C) 2010 Elsevier B.V. All rights reserved.

Different supramolecular hydrogen bond structures and significant changes in magnetic properties in dinuclear mu(2)-1,1-N-3 copper(II) complexes with very similar tridentate Schiff base blocking ligands

Three new basal-apical, mu(2)-1,1-azide bridged complexes, [CuL1(N-3)](2) (1), [CuL2(N-3)](2) (2) and [CuL3(N-3)]2 (3) with very similar tridentate Schiff base blocking ligands [L-1=N-(3-aminopropyl) salicylaldimine, L-2=7-amino-4-methyl-5-azahept-3-en-2-one and L-3=8-amino-4-methyl-5-azaoct-3-en-2-one) have been synthesised and their molecular structures determined by X-ray crystallography. In complex 1, there is no inter-dimer H-bonding. However, complexes 2 and 3 form two different supramolecular structures in which the dinuclear entities are linked by strong H-bonds giving one-dimensional systems. Variable-temperature (300-2 K) magnetic susceptibility measurements and magnetization measurements at 2 K reveal that complexes 1 and 2 have antiferromagnetic coupling while 3 has ferromagnetic coupling which is also confirmed by EPR spectra at 4-300 K. Magnetostructural correlations have been made taking into consideration both the azido bridging ligands and the existence of intermolecular hydrogen bonds in complexes 2 and 3.

Supramolecular hydrogen-bond structures and magnetic interactions in basal-apical, dinuclear, azide-bridged copper(II) complexes

The synthesis, characterisation, X-ray single crystal structures and magnetic properties of three new basal-apical mu(2)-1,1-azide-bridged complexes [(CuLN3)-N-1](2) (1), [(CuLN3)-N-2](2) (2) and [(CuLN3)-N-3](2) (3) with very similar tridentate Schiff-base blocking ligands {HL1 = N-[2-(ethylamino) ethyl] salicylaldimine; HL2 = 7-(ethylamino)-4-methyl-5-azahept-3-en-2-one; HL3 = 7-amino-4-methyl-5-azaoct-3-en-2-one} have been reported [complex 1: monoclinic, P2(1)/c, a = 8.390(2), b = 7.512(2), c = 19.822(6) Angstrom, beta = 91.45(5)degrees; complex 2: monoclinic, P2(1)/c, a = 8.070(9), b = 9.787(12), c = 15.743(17) A, beta = 98.467(10)degrees; complex 3: monoclinic, P2(1)/n, a = 5.884(7), b = 16.147(18), c = 11.901(12) Angstrom, beta = 90.050(10)degrees]. The structures consist of neutral dinuclear entities resulting from the pairing of two mononuclear units through end-on azide bridges connecting an equatorial position of one copper centre to an axial position of the other, The copper ions adopt a (4+1) square-based geometry in all the complexes. In complex 2, there is no inter-dimer hydrogen-bonding. However, complexes 1 and 3 form two different supramolecular structures in which the dinuclear entities are linked by H-bonds giving one-dimensional systems. Variable temperature (300-2 K) magnetic-susceptibility measurements and magnetisation measurements at 2 K reveal that all three complexes have antiferromagnetic coupling. Magneto-structural correlations have been made taking into consideration both the azido bridging ligands and the existence of intermolecular hydrogen bonds. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

Metal-directed assembly of large dinuclear copper(II) dithiocarbamate macrocyclic complexes

The synthesis of a range of dinuclear Cu(II) dithiocarbamate (dtc)-based macrocycles and their characterisation are described. By carefully tuning the size of the aromatic spacer, cavities of different dimensions can be designed. The length and flexibility of the chosen spacer group dictates the intermetallic distance and hence the degree of communication between the two metal centres as evidenced by electrochemical and EPR experiments. This is illustrated by crystallographic evidence that show the macrocycles can host guests (such as CH2Cl2) or can fold and form unexpected Cu(I) dtc clusters.

Synthesis, crystal structure and hydrolysis of a dinuclear copper(II) complex constructed by N2O donor Schiff base and 4,4 '-bipyridine: discrete supra-molecular ensembles vs. oligomers

The tridentate Schiff base ligand, 7-amino-4-methyl-5-aza-3-hepten-2-one (HAMAH), prepared by the mono-condensation of 1,2diaminoethane and acetylacetone, reacts with Cu(BF4)(2) center dot 6H(2)O to produce initially a dinuclear Cu(II) complex, [{Cu(AMAH)}(2) (mu-4,4'-bipyJ](BF4)(2) (1) which undergoes hydrolysis in the reaction mixture and finally produces a linear polymeric chain compound, [Cu(acac)(2)(mu-4,4'-bipy)](n) (2). The geometry around the copper atom in compound 1 is distorted square planar while that in compound 2 is essentially an elongated octahedron. On the other hand, the ligand HAMAH reacts with Cu(ClO4)(2) center dot 6H(2)O to yield a polymeric zigzag chain, [{Cu(acac)(CH3OH)(mu-4,4'-bipy)}(ClO4)](n) (3). The geometry of the copper atom in 3 is square pyramidal with the two bipyridine molecules in the cis equatorial positions. All three complexes have been characterized by elemental analysis, IR and UV-Vis spectroscopy and single crystal X-ray diffraction studies. A probable explanation for the different size and shape of the reported polynuclear complexes formed by copper(II) and 4,4'-bipyridine has been put forward by taking into account the denticity and crystal field strength of the blocking ligand as well as the Jahn-Teller effect in copper(II). (c) 2007 Elsevier Ltd. All rights reserved.

Insertion of a hydroxido bridge into a diphenoxido dinuclear copper(II) complex: drastic change of the magnetic property from strong antiferromagnetic to ferromagnetic and enhancement in the catecholase activity

A diphenoxido-bridged dinuclear copper(II) complex, [Cu2L2(ClO4)(2)] (1), has been synthesized using a tridentate reduced Schiff base ligand, 2-[[2-(diethylamino)-ethylamino]methyl]phenol (HL). The addition of triethylamine to the methanolic solution of this complex produced a novel triple bridged (double phenoxido and single hydroxido) dinuclear copper(II) complex, [Cu2L2(OH)]ClO4 (2). Both complexes 1 and 2 were characterized by X-ray structural analyses, variable-temperature magnetic susceptibility measurements, and spectroscopic methods. In 1, the two phenoxido bridges are equatorial-equatorial and the species shows strong antiferromagnetic coupling with J = -615.6(6.1) cm(-1). The inclusion of the equatorial-equatorial hydroxido bridge in 2 changes the Cu center dot center dot center dot Cu distance from 3.018 angstrom (avg.) to 2.798 angstrom (avg.), the positions of the phenoxido bridges to axial-equatorial, and the magnetic coupling to ferromagnetic with J = 50.1(1.4) cm(-1). Using 3,5-di-tert-butylcatechol as the substrate, the catecholase activity of the complexes has been studied in a methanol solution; compound 2 shows higher catecholase activity (k(cat) = 233.4 h(-1)) than compound 1 (k(cat) = 93.6 h(-1)). Both complexes generate identical species in solution, and they are interconvertible simply by changing the pH of their solutions. The higher catecholase activity of 2 seems to be due to the presence of the OH group, which increases the pH of its solution.

Photoinduced DNA and Protein Cleavage Activity of Ferrocene-Conjugated Ternary Copper(II) Complexes

Ferrocene-conjugated ternary copper(II) complexes [Cu(L)(B)](ClO4)(2), where L is FcCH(2)N(CH2Py)(2) (Fc = (eta(5)-C5H4)Fe-II(eta(5)-C5H5)) and B is a phenanthroline base, viz., 2,2'-bipyridine (bpy, 1), 1, 10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4), have been synthesized and characterized by various spectroscopic and analytical techniques. The bpy complex 1, as its hexafluorophosphate salt, has been structurally characterized by X-ray crystallography. The molecular structure shows the copper(II) center having an essentially square-pyramidal coordination geometry in which L with a pendant ferrocenyl (Fc) moiety and bpy show respective tridentate and bidentate modes of binding to the metal center. The complexes are redox active, showing a reversible cyclic voltammetric response of the Fc(+)-Fc couple near 0.5 V vs SCE and a quasi-reversible Cu(II)-Cu(I) couple near 0.0 V. Complexes 2-4 show binding affinity to calf thymus (CT) DNA, giving binding constant (K-b) values in the range of 4.2 x 10(4) to 2.5 x 10(5) M-1. Thermal denaturation and viscometric titration data suggest groove binding and/or a partial intercalative mode of binding of the complexes to CT DNA. The complexes show good binding propensity to the bovine serum albumin (BSA) protein, giving K-BSA values of similar to 10(4) M-1 for the bpy and phen complexes and similar to 10(5) M-1 for the dpq and dppz complexes. Complexes 2-4 exhibit efficient chemical nuclease activity in the presence of 3-mercapto-propionic acid (MPA) as a reducing agent or hydrogen peroxide (H2O2) as an oxidizing agent. Mechanistic studies reveal formation of hydroxyl radicals as the reactive species. The dpq and dppz complexes are active in cleaving supercoiled (SC) pUC19 DNA on photoexposure to visible light of different wavelengths including red light using an argon-krypton mixed gas ion laser. Mechanistic investigations using various inhibitors reveal the fort-nation of hydroxyl radicals in the DNA photocleavage reactions. The dppz complex 4, which shows efficient photoioduced BSA cleavage activity, is a potent multifunctional model nuclease and protease in the chemistry of photodynamic therapy (PDT) of cancer.