DNA-binding and cleavage studies of novel binuclear copper(II) complex with 1,1'-dimethyl-2,2'-biimidazole ligand

DNA-binding properties of novel binulear copper(II) complex [Cu(2)(Dmbiim)(4)(H(2)O)(2)](ClO(4))(4).6H(2)O, where Dmbiim = 1,1'-Dimethyl-2,2'-biimidazole are investigated using electronic absorption spectroscopy, fluorescence spectroscopy, viscosity measurement and voltammetry. The results show that the copper(II) complex interacts with DNA through minor groove binding. The interaction between the complex and DNA has also been investigated by gel electrophoresis, interestingly, we found that the copper(II) complex can cleave circular plasmid pBR322 DNA efficiently in the presence of AH(2) (ascorbic acid) at pH 8.0 and 37 degrees C.     

A novel cytotoxic ternary copper(II) complex of 1,10-phenanthroline and L-threonine with DNA nuclease activity

A novel ternary copper(II) complex, [Cu(phen)(L-Thr)(H2O)](ClO4) (phen=1,10-phenanthroline, L-Thr=L-threonine), has been synthesized and structurally characterized. The complex crystallized in a triclinic system with space group P1 , a=7.526(15) A, b=11.651(2) A, c=12.127(2) A, alpha=115.41(3) degrees , beta=102.34(3) degrees and gamma=91.33(3) degrees . The copper(II) center is situated in a distorted square-pyramidal geometry. At a concentration of 10(-6) mol L(-1), the complex exhibited potent cytotoxic effects against human leukemia cell line HL-60 and human stomach cancer cell line SGC-7901 with inhibition rates of over 90%, however, less pronounced effects were observed for human liver carcinoma cell line BEL-7402 and human non-small-cell lung cancer cell line A-549. The complex was shown to bind DNA by intercalation and cleave pBR322 DNA in the presence of ascorbate.     

Synthesis, crystal structure and DNA binding studies of a binuclear copper(II) complex with phenanthroline

A new binuclear copper(II) complex, [Cu2Phen2Cl4] (Phen=1,10-phenanthroline), has been synthesized and characterized. Single crystal X-ray diffraction results suggest that this complex structure belongs to monoclinic crystal system, Cc (no. 9) with the cell dimensions: a=9.849(2)A, b=17.833(4)A, c=13.374(3)A, beta=106.61(3) degrees , V=2251.0(8)A(3), Dc=1.8569 Mgm(-3), F(000)=1256.0, Z=4. One Cu(II) central atom situated in a distorted square planar geometry is four-coordinated. The other situated in a distorted square pyramidal geometry is five-coordinated. Only one bridging Cl atom exists in the complex. Spectroscopic studies, including electronic absorption and fluorescence spectra, conductivity measurements and parallel factor analysis (PARAFAC) of fluorescence excitation-emission three-way data array, were carried out on the DNA binding behavior of the complex. All the results suggested that the breakage of DNA secondary structure took place at low molar ratio of complex to DNA (0.3 at most) and intercalation into the base pair of DNA took place at high molar ratio. Additionally, the equilibrium concentration of EB-DNA and EB (EB: ethidium bromide) could be directly obtained by PARAFAC algorithm, proved to be a convincing method for studying the interaction of complexes with DNA.     

Synthesis, crystal structure, cytotoxic activity and DNA-binding properties of the copper (II) and zinc (II) complexes with 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene

A new ligand L, 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene, and its two metal complexes, [Cu(L)3](ClO4)2 (1) and [Zn(L)3](ClO4)2(H2O)2 (2), have been synthesized and characterized. The crystal structure of complex 1 was determined by single crystal X-ray diffraction, which crystallized in monoclinic, space group P2(1)/n with unit cell parameters, a = 12.710(4) angstroms, b = 12.135(3) angstroms, c = 33.450(9) angstroms, beta = 93.281(5) degrees and Z = 4. The Cu atom was six-coordinated to N(1), N(2), N(4), N(5), N(7) and N(8) from three L ligands and formed a slightly distorted octahedral geometry. Complexes 1 and 2, and ligand L were subjected to biological tests in vitro using three different cancer cell lines (HL-60, BGC-823 and MDA-MB-435). Complex 1 showed significant cytotoxic activity against three cancer cell lines. The interactions of complexes 1 and 2, and ligand L with calf thymus DNA were then investigated by thermal denaturation, viscosity measurements and spectrophotometric methods. The experimental results indicated that complexes 1 and 2 bound to DNA by intercalative mode via the ligand L. The intrinsic binding constants of complexes 1 and 2, and ligand L with DNA were 1.8 x 10(4), 5.4 x 10(3) and 2.76 x 10(3) M(-1), respectively.     

Copper(II) complexes of tridentate pyridylmethylethylenediamines: role of ligand steric hindrance on DNA binding and cleavage

Copper(II) complexes of three linear unsymmetrical tridentate ligands viz. N-methyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L1), N,N-dimethyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L2) and N,N-dimethyl-N'-((6-methyl)pyrid-2-ylmethyl)ethylenediamine (L3) have been isolated and characterized by elemental analysis, electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes [Cu(L2)Cl2] and [Cu(L3)Cl2] have been structurally characterized by X-ray crystallography. The [Cu(L2)Cl2] complex crystallizes in the monoclinic space group P2(1)/n with a=11.566(2) A, b=7.369(1) A, c=15.703(3) A, alpha=90 degrees , beta=109.68(8) degrees , gamma=90 degrees and Z=4 while [Cu(L3)Cl2] crystallizes in the triclinic space group P1 with a=9.191(2) A, b=12.359(3) A, c=14.880(3) A, alpha=79.61(13) degrees , beta=86.64(13) degrees , gamma=87.28(8) degrees and Z=2. The coordination geometries around copper (II) in these two complexes are best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). The distorted CuN3Cl basal plane in them is comprised of three nitrogen atoms of the meridionally coordinated ligand and a chloride ion and the axial position is occupied by the other chloride ion. The interaction of these complexes with Calf Thymus DNA (CT DNA) has been studied by using absorption, emission and circular dichroic spectral methods, thermal denaturation studies, viscometry and cyclic and differential pulse voltammetry. A strong blueshift in the ligand field band and a redshift in the ligand based bands of the copper(II) complexes on binding to DNA imply a covalent mode of DNA binding of the complexes, which involves coordination of most possibly guanine N7 nitrogen of DNA to form a CuN4 chromophore. This is supported by studying the interaction of the complexes with N-methylimidazole (N-meim), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine (cytd) by ligand field and EPR spectral methods, which indicate the formation of a CuN4 chromophore only in the case of the more basic N-meim and GMP. The DNA melting curves obtained in the presence of copper(II) complexes reveal a monophasic and irreversible melting of the DNA strands and the high positive DeltaTm values (12-21 degrees C) also support the formation of strong Cu-N bonds by the complexes with DNA, leading to intra- and/or interstrand crosslinking of DNA. Competitive ethidium bromide (EthBr) binding studies show that the L2 and L3 complexes are less efficient than the L1 complex in quenching EthBr emission, which is consistent with their forming DNA crosslinking preventing the displacement of the DNA-bound EthBr. A very slight decrease in relative viscosity of DNA is observed on treating the L1 and L2 complexes with CT DNA; however, a relatively significant decrease is observed for the L3 complex suggesting that the length of the DNA fiber is shortened. DNA cleavage experiments show that all the complexes induce the cleavage of pBR322 plasmid DNA, the complex of L1 being more efficient than those of sterically hindered L2 and L3 ligands.     

Binding of nitrite and its reductive activation to nitric oxide at biomimetic copper centers

The reactivity of nitrite towards the copper(II) and copper(I) centers of a series of complexes with tridentate nitrogen donor ligands has been investigated. The ligands are bis[(1-methylbenzimidazol-2-yl)methyl]amine (1-bb), bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-bb), and bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (ddah) and carry two terminal benzimidazole (1-bb, 2-bb) or pyrazole (ddah) rings and a central amine donor residue. While 2-bb and ddah form two adjacent six-membered chelate rings on metal coordination, 1-bb forms two smaller rings of five members. The binding affinity of nitrite and azide to the Cu(II) complexes (ClO₄ ⁻ as counterion) has been determined in solution. The association constants for the two ligands are similar, but nitrite is a slightly stronger ligand than azide when it binds as a bidentate donor. The X-ray crystal structure of the nitrite complex [Cu(ddah)(NO₂)]ClO₄ (final R=0.056) has been determined: triclinic P1ˉspace group, a=8.200(2) ?, b=9.582(3) ?, c=15.541(4) ?. It may be described as a perchlorate salt of a “supramolecular” species resulting from the assembly of two complex cations and one sodium perchlorate unit. The copper stereochemistry in the complex is intermediate between SPY and TBP, and nitrite binds to Cu(II) asymmetrically, with Cu-O distances of 2.037(2) and 2.390(3) ? and a nearly planar CuO₂N cycle. On standing, solutions of [Cu(ddah)(NO₂)]ClO₄ in methanol produce the dinuclear complex [Cu(ddah)(OMe)]₂(ClO₄)₂, containing dibridging methoxy groups. In fact the crystal structure analysis (final R=0.083) showed that the crystals are built up by dinuclear cations, arranged on a crystallographic symmetry center, and perchlorate anions. Electrochemical analysis shows that binding of nitrite to the Cu(II) complexes of 2-bb and ddah shifts the reduction potential of the Cu(II)/Cu(I) couple towards negative values by about 0.3 V. The thermodynamic parameters of the Cu(II)/Cu(I) electron transfer have also been analyzed. The mechanism of reductive activation of nitrite to nitric oxide by the Cu(I) complexes of 1-bb, 2-bb, and ddah has been studied. The reaction requires two protons per molecule of nitrite and Cu(I). Kinetic experiments show that the reaction is first order in [Cu(I)] and [H⁺] and exhibits saturation behavior with respect to nitrite concentration. The kinetic data show that [Cu(2-bb)]⁺ is more efficient than [Cu(1-bb)]⁺ and [Cu(ddah)]⁺ in reducing nitrite. Received: 19 November 1999 / Accepted: 20 January 2000     

Interaction of flavins with electron-rich metals.

A complex of the electron-rich ion Cu(I) with the flavoquinone analogue 10-methylisoalloxazine has been synthesized and characterized by x-ray methods. The complex is unstable to oxygen. It is black-green in color, in contrast with the bright yellow, orange, or orange-brown crystalline complexes of 10-methylisoalloxazine or riboflavin with Cu(II), Ag(I), and Pb(II). These results are indicative of strong perturbation of the flavin electronic structure by the Cu(I) ion and suggest that this complex is a reasonable model for incipient transfer of an electron from a reduced metal to flavoquinone. the crystal structure is orthorhombic, Pna2-1, with unit cell constants a = 31.24(1) (figures in parentheses are estimated standard deviations), b = 12.862(4), c = 6.239(2) A, Pobs = 1.76 g per cm-3 and Pcalc = 1.77 g per cm-3 for Z = 4 and asymmetric formula CuClO4-2(C11H8N4O2). HCOOH. The final R factor based on 1250 counter-measured data is 8.8%. The 2 independent 10-methylisoalloxazine molecules, A and B, bind strongly to the cuprous ion throug N(5) of each flavin. The copper is approximately linearly coordinated with an N-Cu-N angle of 153(1) degrees, and Cu-N(5) distances of 1.94(2) A and 1.92(2) A. The next nearest atoms to Cu are the O(4) oxygens of each flavin, forming weak bonds with distances Cu-O(4) = 2.27(2) A and 2.21(2) A for molecules A and B. The dihedral angle between the 2 10-methylisoalloxazine molecules is 65.4 degrees.     

Low-temperature crystal structures of tetrakis-mu-3,5-diisopropylsalicylatobis-dimethylformamidodico pper(II) and tetrakis-mu-3,5-diisopropylsalicylatobis-diethyletheratodicopp er(II) and their role in modulating polymorphonuclear leukocyte activity in overcoming seizures

Two binuclear copper(II) complexes of 3,5-diisopropylsalicylic acid were characterized by single crystal X-ray diffraction methods and examined for anti-inflammatory activity using activated polymorphonuclear leukocytes and for anticonvulsant activities using electroshock and metrazol models of seizures. These complexes were crystallized from dimethylformamide (DMF) or diethylether. Tetrakis-mu-3,5-diisopropylsalicylatobis-dimethylformamidodicop per(II) [Cu(II)2(3,5-DIPS)4(DMF)2] I is in space group P 1; a = 10.393 (2), b = 11.258 (2), c = 12.734 (2) A, alpha = 96.64 (2), beta = 92.95 (2), gamma = 94.90 (2) degrees; V = 1471.7 (4) A3; Z = 1. Tetrakis-mu-3,5-diisopropylsalicylatobis-etheratodicopper(II ) [Cu(II)2(3,5-DIPS)4(ether)2] II is in space group P 1; a = 10.409 (3), b = 11.901 (4), c = 12.687 (6) A, alpha = 91.12 (5), beta = 90.84 (5), gamma = 100.90 (4) degrees; V = 1542 (1) A3; Z = 1. The structure of I was determined at 140 K from 4361 unique reflections (I > 2sigma(1)) and refined on F2 to R1 = 0.04 and wR2 = 0.09. The structure of II was determined at 180 K from 4605 unique reflections (I > 2sigma(I)) and refined on F2 to R1 = 0.05 and wR2 = 0.13. Each compound is a crystallographically centrosymmetric binuclear complex with Cu atoms bridged by four 3,5-diisopropylsalicylate ligands related by a symmetry center [Cu-Cu(i): 2.6139 (9) A in I and 2.613 (1) in II]. The four nearest O atoms around each Cu atom form a nearly rectangular planar arrangement with the square pyramidal coordination completed by the dimethylformamide (or diethylether) oxygen atom occupying an apical position, at a distance of 2.129 (2) A in I and 2.230 (3) A in II. Each Cu atom is displaced towards the DMF (or diethylether) ligand, by 0.189 A in I and 0.184 A in II, from the plane of the four O atoms. The crystal structures of I and II are essentially similar to each other, except for the DMF or diethylether accommodation. Many disorder phenomena were found in the crystal structure of I. Copper(II)2(3,5-DIPS)4(DMF)2 inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism in vitro. This effect was concentration related and significant for concentrations higher than 10 microg or 0.68 nmol/ml. Copper(II)2(3,5-DIPS)4(DMF)2 was more active than the parent ligand, 3,5-DIPS, as has been demonstrated with copper complexes of other non-steroidal anti-inflammatory drugs. The DMF and diethylether ternary complexes of Cu(II)2(3,5-DIPS)4 were found to have anticonvulsant activity in the maximal electroshock model of grand mal epilepsy in doses ranging from 26 to 258 micromol/kg of body mass following intraperitoneal, subcutaneous, or oral treatment. The DMF ternary complex was also found to be effective in the subcutaneous injection of metrazol model of petit mal epilepsy. We conclude that both ternary copper complexes are lipophilic and bioavailable, capable of facilitating the inflammatory response to brain injury and causing the subsidence of this response in bringing about remission of these disease states.     

Spectral, kinetic, and thermodynamic properties of Cu(I) and Cu(II) binding by methanobactin from Methylosinus trichosporium OB3b

To examine the potential role of methanobactin (mb) as the extracellular component of a copper acquisition system in Methylosinus trichosporium OB3b, the metal binding properties of mb were examined. Spectral (UV-visible, fluorescence, and circular dichroism), kinetic, and thermodynamic data suggested copper coordination changes at different Cu(II):mb ratios. Mb appeared to initially bind Cu(II) as a homodimer with a comparatively high copper affinity at Cu(II):mb ratios below 0.2, with a binding constant (K) greater than that of EDTA (log K = 18.8) and an approximate DeltaG degrees of -47 kcal/mol. At Cu(II):mb ratios between 0.2 and 0.45, the K dropped to (2.6 +/- 0.46) x 10(8) with a DeltaG degrees of -11.46 kcal/mol followed by another K of (1.40 +/- 0.21) x 10(6) and a DeltaG degrees of -8.38 kcal/mol at Cu(II):mb ratios of 0.45-0.85. The kinetic and spectral changes also suggested Cu(II) was initially coordinated to the 4-thiocarbonyl-5-hydroxy imidazolate (THI) and possibly Tyr, followed by reduction to Cu(I), and then coordination of Cu(I) to 4-hydroxy-5-thiocarbonyl imidazolate (HTI) resulting in the final coordination of Cu(I) by THI and HTI. The rate constant (k(obsI)) of binding of Cu(II) to THI exceeded that of the stopped flow apparatus that was used, i.e., >640 s(-)(1), whereas the coordination of copper to HTI showed a 6-8 ms lag time followed by a k(obsII) of 121 +/- 9 s(-)(1). Mb also solubilized and bound Cu(I) with a k(obsI) to THI of >640 s(-)(1), but with a slower rate constant to HTI (k(obsII) = 8.27 +/- 0.16 s(-)(1)), and appeared to initially bind Cu(I) as a monomer.     

Metal complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid and benzohydroxamic acid. Crystal and molecular structure of [Cu(phen)2(Cl)]Cl x H2Sha, a model for a peroxidase-inhibitor complex

Stability constants of iron(III), copper(II), nickel(II) and zinc(II) complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid (HAha) and benzohydroxamic acid (HBha) have been determined at 25.0 degrees C, I=0.2 mol dm(-3) KCl in aqueous solution. The complex stability order, iron(III) > copper(II) > nickel(II) approximately = zinc(II) was observed whilst complexes of H2Sha were found to be more stable than those of the other two ligands. In the preparation of ternary metal ion complexes of these ligands and 1,10-phenanthroline (phen) the crystalline complex [Cu(phen)2(Cl)]Cl x H2Sha was obtained and its crystal structure determined. This complex is a model for hydroxamate-peroxidase inhibitor interactions.     

Metal-N-saccharide chemistry: synthesis and structure determination of two Cu(II) complexes containing glycosylamines

Two new complexes [Cu(N,N',N"-(D-Glc)3-tren)Cl]Cl (1) and [Cu(N,N',N"-(maltose)-tren)]Cl2.H2O (2), have been synthesized and characterized by elementary analysis, and the IR and UV spectra suggest that complex 1 and complex 2 are arranged in trigonal bipyramidal configuration and square-pyramidal configuration, respectively. The crystal structure of complex 1 has been determined by X-ray diffraction as: a = 9.3476(8), b = 17.4236(13), c = 9.7836(8) angstroms, beta = 91.197 degrees, and V = 1593.1(2) Angstroms3, Z = 2, and R = 0.0325, which shows that three secondary amine groups (N-1, N-2, N-3) of the glycosylamine ligand forms the equatorial plane, and the tertiary amine (N-4) and one Cl- are located at the apical positions.     

Copper(II)-cis,cis-1,3,5-triaminocyclohexane complex-promoted hydrolysis of dipeptides: kinetic, speciation and structural studies

The hydrolysis of glycylglycine (GylGly), glycyl-L-leucine (GlyLeu), L-leucylglycine (LeuGly) and glycyl-DL-serine (GlySer) promoted by a copper(II)- cis, cis-1,3,5-triaminocyclohexane complex [Cu(II)TACH] was investigated at 70 degrees C and pH 7-10, using HPLC. The observed pseudo-first-order rate constants (k(obs)) and rate enhancing factors (REF) were as follows: 4.1x10(-3 )h(-1)(REF=23) for GylGly, 1.6x10(-3 )h(-1)(REF=21) for GlyLeu, 5.1x10(-3 )h(-1)(REF=64) for LeuGly and 9.2x10(-2 )h(-1)(REF=47) for GlySer [pH 8.1, dipeptide 2 mM, copper(II) 2 mM and TACH 2 mM]. Based on the pH dependence and dipeptide concentration dependence of the initial rates and speciation of the Cu(II)-TACH-dipeptide system at 25 degrees C and I=0.1, the reactions proceed via the formation of a ternary complex [Cu(TACH)(dipeptide)](+) as an intermediate followed by OH(-)-dependent and OH(-)-independent paths to give amino acid(s). GylGly, GlyLeu and LeuGly preferred the OH(-)-dependent path, while GlySer preferred the OH(-)-independent path. The latter can be explained by the intramolecular attack of the amide carbonyl group coordinated with its oxygen atom by the OH group in the serine residue. The X-ray crystal structure of [Cu(TACH)(GlyGly)]BPh(4).MeOH confirmed that GlyGly coordinates to copper(II) ion with its terminal amino N and amide O atoms. The crystal structures of [Cu(TACH)(Gly)]BPh(4) and [Cu(2)(TACH)(2)(OH)(2)](ClO(4))(2).NaClO(4).H(2)O are also reported.     

Oxidative cleavage of DNA by a dipyridoquinoxaline copper(II) complex in the presence of ascorbic acid

Complex [Cu(dpq)(2)(H(2)O)](ClO(4))(2).H(2)O (1), where dpq is dipyrido-[3,2-D:2',3'-f]-quinoxaline, has been prepared by reacting copper(II) perchlorate hexahydrate with dpq in methanol and structurally characterized. The complex crystallizes in the triclinic space group P-1 with the unit cell parameters a=8.646(2) A, b=12.290(5) A, c=14.283(4) A, alpha=94.01(2) degrees, beta=91.69(2) degrees,gamma=101.60 (3) degrees, V=1481.7(8) A(3) and Z=2. The structure, refined to R=0.0505 and R(w)=0.1441 for 5212 reflections with I>2sigma (I) using 440 parameters, shows the presence of a CuN(4)O chromophore in an axially compressed distorted trigonal-bipyramidal structure. The Cu-N distances lie in the range 1.969(3)-2.103(3) A. The Cu-OH(2) distance is 2.145(3) A. The complex is one-electron paramagnetic and exhibits a visible spectral d-d band at 718 nm in MeCN. It shows a quasi-reversible cyclic voltammetric response at 0.091 V (DeltaE(p)=229 mV) at 50 mV s(-1) in MeCN-0.1 M TBAP for the Cu(II)/Cu(I) couple. In 50 mM Tris-HCl/0.1 M KCl buffer-DMF mixture (1:4 v/v, pH 7.2), the couple appears at 0.089 V versus SCE. The complex undergoes facile reduction with sodium ascorbate in an aqueous DMF mixture (4:1 v/v) to form an unstable brown Cu(I) species (lambda(max)=440 nm, epsilon=7480 M(-1) cm(-1)) which converts to 1 on exposure to air giving a turnover frequency of ca. 400. Binding studies revealed that 1 is an efficient binder to calf thymus DNA. Complex 1 on reaction with supercoiled (SC) DNA in presence of ascorbic acid in a 50 mM Tris-HCl/50 mM NaCl buffer (pH 7.2) shows nuclease activity which is 4.5 times greater than that of the phen analogue.     

Oxidative DNA cleavage mediated by a new copper (II) terpyridine complex: crystal structure and DNA binding studies

The copper (II) complex [Cu(Itpy)(2)](ClO(4))(2) (1), (Itpy=imidazole terpyridine) has been synthesized and structurally characterized. Crystal structure of the complex shows the complex to be a monomeric copper (II) species with two Itpy ligands coordinated to the metal ion to give a six coordinate complex. The complex has a distorted octahedral geometry with axial elongation. Variable temperature crystal structure data shows dynamic nature of the Jahn-Teller distortion. The complex is an avid DNA binder with a binding constant of 4.26+/-0.20x10(3)M(-1). Observed changes in the viscosity and circular dichroic spectrum of calf thymus DNA solution in the presence of complex 1 suggests intercalative binding of complex 1 to DNA. The complex cleaves supercoiled pBR322 DNA oxidatively in the presence of hydrogen peroxide.     

Interactions of metal ions with a 2,4-diaminopyrimidine derivative (trimethoprim). Antibacterial studies

The interaction of copper (II), zinc(II) and cadmium(II) with Trimethoprim (2,4-diamino-5-(3',4',5'-trimethoxybenzyl) pyrimidine) has been studied. The crystal structures of [Zn(Trim)2Cl2] (2) and [Cd(Trim)Cl2(CH3OH)]n (4) are reported. Compound (2) exhibits a distorted tetrahedral environment around the metal center and crystallizes in the triclinic space group P1 with a=10.2397(6), b=10.4500(6), c=16.3336(16) A, alpha=96.141(8), beta=106.085(5), gamma=96.551(5) degrees and Z=2. In complex (4), the Cd(II) centers are bridged sequentially by two chlorine ions to form infinite chains and present a six-coordinated environment; the compound crystallizes in the monoclinic P2(1)/C space group with a=13.958(5), b=7.532(2), c=18.390(2) A, alpha=90, beta=97.32(5), gamma=90 degrees and Z=4. In both structures the Trimethoprim acts as a monodentate ligand through the pyrimidinic nitrogen N(1) atom. The characterization of the Cu(Trim)2(CH3O)(ClO4) complex through EPR and magnetic measurements suggests a binuclear or polinuclear nature, with bridging methoxo groups. The complexes were screened for their activity against several bacteria, showing activity similar to that of trimethoprim.     

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: the novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

The coordination geometry around copper(II) in [Cu(imda)(phen)(H2O)] (1) (H2imda = iminodiacetic acid, phen = 1,10-phenanthroline) is described as distorted octahedral while those in [Cu(imda)(5,6-dmp)] (2) (5,6-dmp = 5,6-dimethyl-1,10-phenanthroline) and [Cu(imda)(dpq)] (3) (dpq = dipyrido-[3,2-d:2',3'-f]-quinoxaline) as trigonal bipyramidal distorted square-based pyramidal with the imda anion facially coordinated to copper(II). Absorption spectral (Kb: 1, 0.60+/-0.04x10(3); 2, 3.9+/-0.3x10(3); 3, 1.7+/-0.5x10(4) M(-1)) and thermal denaturation studies (deltaTm: 1, 5.70+/-0.05; 2, 5.5+/-10; 3, 10.6+/-10 degrees C) and viscosity measurements indicate that 3 interacts with calf thymus DNA more strongly than 1 and 2. The relative viscosities of DNA bound to 1 and 3 increase while that of DNA bound to 2 decreases indicating formation of kinks or bends and/or conversion of B to A conformation as revealed by the decrease in intensity of the helicity band in the circular dichroism spectrum of DNA. While 1 and 3 are bound to DNA through partial intercalation, respectively, of phen ring and the extended planar ring of dpq with DNA base stack, the complex 2 is involved in groove binding. All the complexes show cleavage of pBR322 supercoiled DNA in the presence of ascorbic acid with the cleavage efficiency varying in the order 3 > 1 > 2. The highest oxidative DNA cleavage of dpq complex is ascribed to its highest Cu(II)/Cu(I) redox potential. Oxidative cleavage studies using distamycin reveal minor groove binding for the dpq complex but a major groove binding for the phen and 5,6-dmp complexes. Also, all the complexes show hydrolytic DNA cleavage activity in the absence of light or a reducing agent with cleavage efficiency varying in the order 1 > 3 > 2.     

Structural and functional models for the dinuclear copper active site in catechol oxidases. Synthesis,X-ray crystal structures,magnetic and spectroscopic properties of mu-methoxo-bridged dinuclear copper(II) complexes with N-substituted sulfonamide ligands

Two new mu-methoxo-bridged dinuclear copper(II) complexes with a N-substituted sulfonamide, [Cu(mu-OMe)(L)(NH(3))](2) (1) and [Cu(mu-OMe)(L)(DMSO)](2) (2) [HL, N-2-(4-methylbenzothiazole)benzenesulfonamide], have been prepared and characterized by single-crystal X-ray difraction analyses. Compound 1 crystallizes in the monoclinic space group C(2)/c with a=22.0678(18), b=7.9134(7), c=21.1186(18)A, beta=113.788(4) degrees and Z=8. Compound 2 crystallizes in the monoclinic space group C(2)/c with a=18.0900(10), b=9.5720(10), c=24.2620(10) A, beta=98.7120(10) degrees and Z=8. In both complexes the copper atoms have square-planar environments bridged by two oxygen atoms from methoxide groups. Magnetic susceptibility measurements indicate a very strong antiferromagnetic coupling between the copper(II) ions in both complexes (2J<-1000 cm(-1)). Electronic Paramagnetic Resonance (EPR) spectra of the two complexes both in solid and in solution are silent. 13C NMR spectra of the complexes in solid state have been studied. The complexes have been evaluated as model systems for the catechol oxidase enzyme using 3,5-di-tert-butylcatechol as the test substrate. Complex 2 is slightly more active than complex 1.     

Molecular structure, bioavailability and bioactivity of [Cu(o-phen)2(cnge)](NO3)2.2H2O and [Cu(o-phen)(cnge)(H2O)(NO3)2] complexes

Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals.     

Mixed-valence Cu(II)/Cu(I) complex of quinolone ciprofloxacin isolated by a hydrothermal reaction in the presence of L-histidine: comparison of biological activities of various copper-ciprofloxacin compounds

A new quinolone-metal complex was prepared by a hydrothermal reaction in the presence of L-histidine that served as a reducing agent for a metal. The title compound [Cu(II)(cfH)(2)(Cu(I)Cl(2))(2)] (1) is a mixed-valence Cu(II)-Cu(I) complex, which contains two ciprofloxacin (cfH) molecules bonded to the central copper(II) atom and two almost planar [Cu(I)Cl(2)](-) moieties. Both metal centers are connected through two bridging atoms (chloride and quinolone oxygen). The electrochemical methods (differential-pulse polarography and cyclovoltammetric measurements) confirmed the presence of various copper-ciprofloxacin complex species in aqueous solution at low concentrations used in biological activity tests and also indicated that the equilibria in this system are very complex. The biological properties of the title compound and some previously isolated copper-ciprofloxacin complexes ([Cu(cfH)(2)Cl(2)].6H(2)O (2) and [CuCl(cfH)(phen)]Cl.2H(2)O (3)) (phen=1, 10-phenantroline) were determined and compared. The DNA gyrase inhibition tests and antibacterial activity tests have shown that the effect of copper complexes is comparable to that of free quinolone. Additionally, an interesting DNA cleavage activity of the title compound was also discovered.     

Neutral and cationic mononuclear copper(II) complexes with enrofloxacin: structure and biological activity

The mononuclear copper complexes with the quinolone antibacterial drug enrofloxacin (=Herx) in the presence or not of a nitrogen donor heterocyclic ligand 1,10-phenanthroline (=phen) and 2,2'-bipyridine (=bipy) have been prepared and characterized. Interaction of copper(II) with deprotonated enrofloxacin leads to the formation of the neutral complex Cu(erx)2(H2O), 1, while the presence of phen or bipy leads to the formation of a neutral or a cationic mononuclear complex, respectively. The crystal structures of (chloro)(1,10-phenanthroline)(enrofloxacinato)copper(II), 2, and (aqua)(2,2'-bipyridine)(enrofloxacinato)copper(II) chloride, 3, have been determined with X-ray crystallography. The complexes have been studied with X-band electron paramagnetic resonance in aqueous solutions at liquid helium temperature. The study of the interaction of the complexes with calf-thymus DNA has been performed with diverse spectroscopic techniques and has showed that all complexes are bound to DNA by the intercalative mode. The antimicrobial efficiency of the complexes has been tested on three different microorganisms and the available evidence supports that the best inhibition is provided by Cu(erx)2(H2O) (minimum inhibitory concentration=0.125 microg mL(-1)) against Escherichia coli and Pseudomonas aeruginosa.