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.     

Synthesis,inhibitory activity and molecular docking studies of two Cu(II) complexes against Helicobacter pylori urease

Two mononuclear copper(II) complexes, [Cu(C₁₅H₁₆NO₂)₂] (1) and [Cu(C₆H₉N₂O₄)₂·3H₂O] (2·3H₂O), were synthesised and structurally characterised by single-crystal X-ray analysis. The copper(II) atom adopts a square-planar environment in complex 1, while the geometry in 2·3H₂O could be described as the distorted square pyramidal. Complexes 1 and 2·3H₂O were evaluated for their inhibitory activities against Helicobacter pylori (H. pylori) urease in vitro. They both were found to have strong inhibitory activities against H. pylori urease comparable to that of acetohydroxamic acid (AHA). A docking simulation was performed to position 2 into the H. pylori urease active site to determine the probable binding conformation.     

Three new Cu(II) and Cd(II) complexes with 3-(2-pyridyl)pyrazole-based ligand: syntheses, crystal structures, and evaluations for bioactivities

Three new complexes [Cu(L)(2)(NO(3))](NO(3))(H(2)O)(1/2)(CH(3)OH)(1/2) (1), [Cd(L)(2)(NO(3))(2)](H(2)O)(3) (2) and [Cd(L)(2)(ClO(4))(CH(3)OH)](ClO(4))(H(2)O)(1/4)(CH(3)OH) (3) (L=1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene) were synthesized and characterized by elemental analyses, IR and X-ray diffraction analysis. Among them, the Cu(II) and Cd(II) ions were both coordinated by four N donors from two distinct L ligands via N,N-bidentate chelating coordination mode. Additional weak interactions, such as the face-to-face pi-pi stacking and C-Hcdots, three dots, centeredO H-bonding interactions, linked the mononuclear unit into 1D chain and further into 2D network. Complexes 1-3 were subjected to biological assays in vitro against six different cancer cell lines. All of them exhibited cytotoxic specificity and notable cancer cell inhibitory rate. The interactions of 1-3 with calf thymus DNA were investigated by thermal denaturation, viscosity measurements, spectrophotometric and electrophoresis methods. The results indicate that these complexes bound to DNA by intercalation mode via the ligand L and had different nuclease activities, which were in good agreement with their DNA-binding strength. Moreover, the central metal ions of 1-3 played a vital role in DNA-binding behaviors, DNA-cleavage activities and cytotoxicities, whereas the contribution of the different counter anions to their bioactivities also should not be ignored.     

Synthesis, X-ray crystal structures and biomimetic and anticancer activities of novel copper(II)benzoate complexes incorporating 2-(4'-thiazolyl)benzimidazole (thiabendazole), 2-(2-pyridyl)benzimidazole and 1,10-phenanthroline as chelating nitrogen donor ligands

Cu(BZA)(2)(EtOH)(0.5) (1) was generated by the reaction of copper(II) hydroxide with benzoic acid (BZAH). [Cu(TBZH)(2)(BZA)](BZA).0.5TBZH.H(2)O (2) and [Cu(2-PyBZIMH)(2-PyBZIM)(BZA)].1.66EtOH (3) were obtained when 1 reacted with Thiabendazole (TBZH) and 2-(2-pyridyl)benzimidazole (2-PyBZIMH), respectively. [Cu(BZA)(2)(phen)(H(2)O)] (4) was isolated from the reaction of benzoic acid and 1,10-phenanthroline (phen) with copper(II)acetate dihydrate. Molecular structures of 2, 3 and 4 were determined crystallographically. 2 and 3 are hydrogen bonded dimers and trimers, respectively. The copper centres in complexes 2 and 3 are bis-chelate derivatives that have N(4)O ligation and their geometry is very similar being approximately square-pyramidal. However whereas in complex 2 both TBZH ligands are neutral in 3 one of the 2-PyBZIMH chelators is deprotonated on each copper. The structural results for 4 represent a re-examination of this crystallographically known compound for which no hydrogen atom coordinates have been previously reported. It crystallises as a hydrogen bonded dimmer and is a mono-chelate of phen with each copper centre possessing N(2)O(3) ligation and square pyramidal geometry. The catalase and superoxide dismutase (SOD) activities of the four complexes along with those of the known phenanthroline complexes [Cu(mal)(phen)(2)] and [Cu(phendione)(3)](ClO(4))(2) (malH(2)=malonic acid and phendione=1,10-phenanthroline-5,6-dione) were investigated. Complexes 1-4, the metal free ligands and a simple copper(II) salt were assessed for their cancer chemotherapeutic potential against the hepatocellular carcinoma (Hep-G(2)) and kidney adenocarcinoma (A-498) cell lines. TBZH, 2-PyBZIMH and benzoic acid when uncoordinated to a metal centre offer poor chemotherapeutic potential. copper(II) benzoate is significantly more active than the free acid. The bis-chelate derivatives [Cu(TBZH)(2)(BZA)](BZA).0.5TBZH.H(2)O (2) and [Cu(2-PyBZIMH)(2-PyBZIM)(BZA)].1.66EtOH (3) elicit a significant cytotoxic response to the cancer cell lines tested. Replacing TBZH and 2-PyBZIMH with phen to give [Cu(BZA)(2)(phen)(H(2)O)] (4) does not significantly increase the anti-cancer activity.     

Synthesis,structural characterization and antimicrobial activities of 12 zinc(II) complexes with four thiosemicarbazone and two semicarbazone ligands

Twelve zinc(II) complexes with thiosemicarbazone and semicarbazone ligands were prepared and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FT-IR and 1H and 13C NMR spectroscopy. Seven three-dimensional structures of zinc(II) complexes were determined by single-crystal X-ray analysis. Their antimicrobial activities were evaluated by MIC against four bacteria (B. subtilis, S. aureus, E. coli and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A. niger and P. citrinum). The 5- and 6-coordinate zinc(II) complexes with a tridentate thiosemicarbazone ligand (Hatsc), ([Zn(atsc)(OAc)](n) 1, [Zn(Hatsc)(2)](NO(3))(2).0.3H(2)O 2, [ZnCl(2)(Hatsc)] 3 and [Zn(SO(4))(Hatsc)(H(2)O)].H(2)O 4 [Hatsc=2-acetylpyridine(thiosemicarbazone)]), showed antimicrobial activities against test organisms, which were different from those of free ligands or the starting zinc(II) compounds. Especially, complex 2 showed effective activities against P. aeruginosa, C. albicans and moderate activities against S. cerevisiae and two molds. These facts are in contrast to the results that the 5- or 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridine-4N-morpholinethiosemicarbazone, ([Zn(mtsc)(2)].0.2EtOH 5, the previously reported catena-poly [Zn(mtsc)-mu-(OAc-O,O')](n) and [Zn(NO(3))(2)(Hmtsc)] [Hmtsc=2-acetylpyridine (4N-morpholyl thiosemicarbazone)]), showed no activities against the test microorganisms. The 5- and 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridinesemicarbazone, ([Zn(OAc)(2)(Hasc)] 6 and [Zn(Hasc)(2)](NO(3))(2) 7 [Hasc=2-acetylpyridine(semicarbazone)]), showed no antimicrobial activities against bacteria, yeasts and molds. Complex [ZnCl(2)(Hasc)] 8, which was isostructural to complex 3, showed modest activity against Gram-positive bacterium, B. subtilis. The 1:1 complexes of zinc(II) with pentadentate thiosemicarbazone ligands, ([Zn(dmtsc)](n) 9 and [Zn(datsc)](n) 10 [H(2)dmtsc=2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone) and H(2)datsc=2,6-diacetylpyridine bis(thiosemicarbazone)]), did not inhibit the growth of the test organisms. On the contrary, 7-coordinate zinc(II) complexes with one pentadentate semicarbazone ligand and two water molecules, ([Zn(H(2)dasc)(H(2)O)(2)](OAc)(2).5.3H(2)O 11 and [Zn(H(2)dasc)(H(2)O)(2)](NO(3))(2).H(2)O 12 [H(2)dasc=2,6-diacetylpyridine bis(semicarbazone)]), showed modest to moderate activities against bacteria. Based on the X-ray structures, the structure-activity correlation for the antimicrobial activities was elucidated. The zinc(II) complexes with 4N-substituted ligands showed no antimicrobial activities. In contrast to the previously reported nickel(II) complexes, properties of the ligands such as the ability to form hydrogen bonding with a counter anion or hydrated water molecules or the less bulkiness of the 4N moiety would be a more important factor for antimicrobial activities than the coordination number of the metal ion for the zinc(II) complexes.     

Synthesis,crystal structure,and nuclease activity of planar mono-heterocyclic base copper(II) complexes

A series of mononuclear copper(II) complexes having a 1:1 molar ratio of copper and the planar heterocyclic base like 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) are prepared from a reaction of copper(II) nitrate.trihydrate and the base (L) in ethanol or aqueous ethanol at different temperatures. The complexes [Cu(dpq)(NO(3))(2)] (2), [Cu(dpq)(NO(3))(H(2)O)(2)](NO(3)) (3), [Cu(dpq)(NO(3))(2)(H(2)O)(2)].2H(2)O (4.2H(2)O) and [Cu(dppz)(NO(3))(2)(H(2)O)].H(2)O (5.H(2)O) have been characterized by X-ray crystallography. The crystal structures show the presence of the heterocyclic base in the basal plane. The coordination geometries of the copper(II) centers are axially elongated square-pyramidal (4+1) in 2, 3 and 5, and octahedral (4+2) in 4. The nitrate anion in the coordination sphere displays unidentate and bidentate chelating bonding modes. The axial ligand is either H(2)O or NO(3) in these structures giving a Cu-L(ax) distance of approximately 2.4 A. The one-electron paramagnetic complexes (mu approximately 1.8 mu(B)) exhibit axial EPR spectra in DMF glass at 77 K giving g(parallel)>g( perpendicular ) with an A(parallel) value of approximately 170G indicating a [d(x)2(-y)2](1) ground state. The complexes are redox active and display a quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.0 V vs. SCE giving an order of the E(1/2) values as 5(dppz)>2-4 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). The complexes bind to calf thymus DNA giving an order 5 (dppz)>2 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). An effect of the extended planar ring in dpq and dppz is observed in the DNA binding. The complexes show nuclease activity with pUC19 supercoiled DNA in DMF/Tris-HCl buffer containing NaCl in presence of mercaptopropanoic acid as a reducing agent. The extent of cleavage follows the order: [Cu(phen)(2)(H(2)O)](ClO(4))(2)>5>2 approximately 3 approximately 4>1. The bis-phen complex is a better cleaver of SC DNA than 1-5 having mono-heterocyclic base. Mechanistic investigations using distamycin reveal minor groove biding for the phen, dpq complexes, and a major groove binding for the dppz complex 5. The cleavage reactions are found to be inhibited in the presence of hydroxyl radical scavenger DMSO and the reactions are proposed to proceed via sugar hydrogen abstraction pathway. The ancillary ligand is found to have less effect in DNA binding but are of importance in DNA cleavage reactions.     

Synthesis, biological evaluation, and molecular docking studies of 2,5-substituted-1,4-benzoquinone as novel urease inhibitors

A series of 2,5-substituted-1,4-benzoquinone (1-6) were prepared and structurally characterized by elemental analysis, IR spectra, (1)H and (13)C NMR spectra, and single crystal X-ray determination. The urease inhibitory activities of the compounds against H. pylori urease were studied. Among the compounds, 2,5-bis(2-morpholin-4-ylethylamino)-[1,4]benzoquinone (2) shows the most effective activity with IC(50) value of 27.30±2.17μM. Docking simulation was performed to insert compound 2 into the crystal structure of H. pylori urease at the active site to determine the probable binding mode. As a result, compound 2 may be used as a potential urease inhibitor.     

Dipeptides containing the alpha-aminoisobutyric residue (Aib) as ligands: preparation,spectroscopic studies and crystal structures of copper(II) complexes with H-Aib-X-OH (X=Gly,L-Leu,L-Phe)

Synthetic procedures are described that allow access to new copper(II) complexes with dipeptides containing the alpha-aminoisobutyric residue (Aib) as ligands. The solid complexes [Cu(H(-1)L(A))](n).nH(2)O (1) (L(A)H=H-Aib-Gly-OH), [Cu(H(-1)L(B))(MeOH)](n).nMeOH (2) (L(B)H=H-Aib-L-Leu-OH) and [Cu(H(-1)L(C))](n) (3) (L(C)H=H-Aib-L-Phe-OH) have been isolated and characterized by single-crystal X-ray crystallography, solid-state IR spectra and UV-Vis spectroscopy in solution (H(-1)L(2-) is the dianionic form of the corresponding dipeptide). Complexes 1 and 3 are three-dimensional coordination polymers with similar structures. The doubly deprotonated dipeptide behaves as a N(amino), N(peptide), O(carboxylate), O'(carboxylate), O(peptide) mu(3) ligand and binds to one Cu(II) atom at its amino and peptide nitrogens and at one carboxylate oxygen, to a second metal at the other carboxylate oxygen, while a third Cu(II) atom is attached to the peptide oxygen. The geometry around copper(II) is distorted square pyramidal with the peptide oxygen at the apex of the pyramid. The structure of 2 consists of zigzag polymeric chains, where the doubly deprotonated dipeptide behaves as a N(amino), N(peptide), O(carboxylate), O'(carboxylate) mu(2) ligand. The geometry at copper(II) is square pyramidal with the methanol oxygen at the apex. The IR data are discussed in terms of the nature of bonding and known structures. The UV-Vis spectra show that the solid-state structures of 1, 2 and 3 do not persist in H(2)O.     

Uracilato and 5-halouracilato complexes of Cu(II), Zn(II) and Ni(II). X-ray structures of [Cu(uracilato-N(1))(2)(NH(3))(2)].2(H(2)O), [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2), [Ni(5-chlorouracilato-N(1))(2)(en)(2)].2H(2)O and [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O)

Four new complexes of uracilato and 5-halouracilato with the divalent metal ions Cu(II), Zn(II) and Ni(II) were obtained and structurally characterized. [Cu(uracilato- N(1))(2)(NH(3))(2)].2(H(2)O) (1) and [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2) (2) complexes present distorted square planar co-ordination geometry around the metal ion. Although an additional axial water molecule is present [Cu(II)-OH(2)=2.89 A (for 1) and 2.52 A (for 2)] in both cases, only in the complex 2 would be considered in the limit of a bond distance. The Zn(II) in [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O) presents a tetrahedral co-ordination with three ammonia molecules and the N(1) of the corresponding uracilato moiety. A non-coordinated uracilato molecule is present as a counterion and a recognition between co-ordinated and free ligands, by means a tandem of H-bonds, should be mentioned. Finally, the complex [Ni(5-chlorouracilato-N(1))(2)(en)(2)] (H(2)O)(2) (where en is ethylenediamine) presents a typical octahedral trans co-ordination with additional hydrogen bonds between 5-chlorouracilato and the NH(2) groups of ethylenediamine units.     

Novel inhibition of some pathogenic fungal and bacterial species by new synthetic phytochemical coumarin derivatives

novel antifungal and antibacterial activities of new synthesized phytochemical coumarin compounds [H2L1, HL2 and H2L3] and their copper (II) complexes [L1Cu], [L2Cu(OAc)] and [(L3)Cu2(H2O)4(OAc)2] were evaluated against nine pathogenic fungal species (Alternaria alternata, Aspergillus flavus, Botrytis cinerea, Cladosporium herbarum, Fusarium moniliforme, Helminthosporium tetramera, Penicillium expansum, Rhizopus stolonifer andVerticillium albo-atrum) and eight pathogenic bacterial species, from which four Gram-positive bacteria (Bacillus subtilis, Micrococcus luteus, Staphylococcus citrus andStreptococcus pneumoniae) and four Gram-negative bacteria (Enterobacter aerogenes, Escherichia coli, Pseudomonas aeruginosa andSalmonella typhi). The phytochemical copper (II) complex [L2Cu(OAc)] was the most effective derivative, where it reaches to 90 and 100% inhibition in the most sensitive pathogens (B. subtilis and A. flavus), respectively accompanied with a significant reduction in pectinolytic and cellulytic enzyme activities in all tested pathogenic species. Addition of [L2Cu(OAc)] complex leading to leakage of sugars and electrolytes from the most sensitive microbial cells accompanied with collapsed hyphae ofA. Flavus and membrane blobbing ofB. Subtilis. The production of mycotoxins decreased with the extension exposure to [L2Cu(OAc)] complex reaching to a minimum values for the mycelium originating from the inoculum exposed to the minimum inhibitory concentration (2%). Both aflatoxin (AFB1) and citrinin were the most sensitive toxins.     

Synergistic anion-directed coordination of ferric and cupric ions to bovine serum transferrin--an inorganic perspective

A series of new iron(III) and copper(II) complexes of bovine serum transferrin (BTf), with carbonate and/or oxalate as the synergistic anion, are presented. The complexes [Fe(2)(CO(3))(2)BTf], [Fe(2)(C(2)O(4))(2)BTf], [Cu(2)(CO(3))(2)BTf] and [Cu(C(2)O(4))BTf] were prepared by standard titrimetric techniques. The oxalate derivatives were also obtained from the corresponding carbonate complexes by anion-displacement. The site-preference of the transition metal-oxalate synergism has facilitated the preparation and isolation of the mononuclear complex [Cu(C(2)O(4))BTf], the mixed-anion complexes [Cu(2)(CO(3))(C(2)O(4))BTf] and [Fe(2)(CO(3))(C(2)O(4))BTf] and the mixed-metal complex [FeCu(C(2)O(4))(2)BTf]. The sensitivity of electron paramagnetic resonance (EPR) spectroscopy to the nature of the synergistic anions at the specific-binding sites of the transferrins has made this physical technique particularly indispensable to this study. None of the other members of the transferrin family of proteins has ever been demonstrated to bind the ferric and cupric ions one after the other, each occupying a separate specific-binding site of the same transferrin molecule, as a response to the coordination restrictions imposed by the oxalate ion. The bathochromic shift of the visible p(pi)-d(pi*) CT band for iron(III)-BTf and the hypsochromic shift of the p(pi)-d(sigma*) CT band for copper(II)-BTf, on replacing carbonate by oxalate as the associated anion, are consistent with the relative positions of these anionic ligands in the spectrochemical series and the nature of the d-type acceptor orbitals involved in the CT transitions. The binding and spectroscopic properties of bovine serum transferrin--a serum transferrin--very nearly mirror those of human serum transferrin, but differ significantly from those of human lactoferrin.     

Oxidative strand scission of nucleic acids by a multinuclear copper(II) complex

The compound [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4).2H(2)O [D(1)=binucleating ligand with tris(2-pyridylmethyl)amine (TMPA) moieties linked in the 5-pyridyl position by a -CH(2)CH(2)- bridge] mediated efficient oxidative cleavage of pBR322 plasmid DNA under reducing conditions. A mononuclear analogue, [Cu(TMPA)(H(2)O)](ClO(4))(2), was less effective at linearizing supercoiled (Form I) plasmid DNA as compared to the binuclear complex. A new method for quenching the copper-dependent reactions has been developed to avoid plasmid scission by the binuclear complex and the standard gel loading buffer. EDTA was not sufficient for retarding copper reaction, but diethyldithiocarbamic acid was capable of inhibiting all reactivity. Investigation of oxidative cleavage of double-helical oligonucleotides by [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4) confirmed the enhanced reactivity of the binuclear over the mononuclear complex and provided mechanistic insights into the nature of the reaction. Cleavage of DNA required both the binuclear complex and a reductant and likely proceeded through an O(2)-derived intermediate that does not include a diffusible hydroxyl radical. The greater efficiency of the binuclear complex relative to the mononuclear analogue is consistent with their relative abilities to activate dioxygen.     

Synthesis, structural characterization, antiradical and antidiabetic activities of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and beta-alanine

A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O'-donor Schiff base derived from salicylaldehyde and beta-alanine {i.e. N-salicylidene-beta-alanine(2-), (L)}, having the composition [Cu(2)(L)(2)(H(2)O)].H(2)O (1), [Cu(L)(H(2)O)](n) (2), and [Zn(L)(H(2)O)](n) (3), have been prepared and characterized by elemental analyses, UV-visible (UV-VIS), FT-IR and ESI-MS spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single crystal X-ray analysis and also by temperature dependent magnetic susceptibility measurements (294-80K). All prepared complexes have been evaluated by the antiperoxynitrite activity assay and alloxan-induced diabetes model. The significant antioxidant and antidiabetic activities have been found in the case of both copper(II) complexes 1 and 2. In spite of first two complexes, the zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only insignificant protective effect against the tyrosine nitration in vitro.     

Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: synthesis, characterization and antitumour activity

The Pt(II) and Pd(II) complexes of the types cis-[Pt(L(1))(2)Cl(2)].H(2)O (1), cis-[Pt(L(2))(2)Cl(2)].3H(2)O (2), trans-[Pd(L(1))(2)Cl(2)].H(2)O (3), trans-[Pd(L(2))(2)Cl(2)].H(2)O (4), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) (L(1)-L(4)=cyclin-dependent kinase inhibitors derived from 6-benzylamino-9-isopropylpurine) have been prepared and characterized. The complexes have been studied by elemental analyses, conductivity measurements, ES+ MS, FT-IR, (1)H, (13)C and (195)Pt NMR spectra, differential scanning calorimetry and thermogravimetric analysis. The molecular structures of L(1), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) have been determined by single crystal X-ray analysis. The complexes have been tested in vitro due to their presumable anticancer activity against the following human cancer cell lines: K-562, MCF7, G-361 and HOS. Satisfying results were obtained for the complex 1 with IC(50) values of 6 microM acquired against G-361 as well as against HOS cell lines. The lowest values of IC(50) were achieved for the complexes 3 and 4 against MCF 7 cell line with IC(50) 3 microM(for 3) and also 3 microM (for 4).     

Low-temperature (180 K) crystal structures of tetrakis-mu-(niflumato)di(aqua)dicopper(II) N,N-dimethylformamide and N,N-dimethylacetamide solvates, their EPR properties, and anticonvulsant activities of these and other ternary binuclear copper(II)niflumate complexes

Two pseudopolymorphs, solvates, of [Cu(2)(II)(niflumate)(4)(H(2)O)(2)] of unknown structure were obtained following solution of [Cu(2)(II)(niflumate)(4)(H(2)O)(2)] in N,N-dimethylacetamide (DMA) or N,N-dimethylformamide (DMF). Low-temperature crystal structures obtained for these solvates revealed that they were ternary aqua DMA and DMF solvates: [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMA and [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMF. Intermolecular hydrogen bonding interactions account for the formation of these stable DMA and DMF solvates. These pseudopolymorphs contain a centrosymmetric binuclear center with Cu-Cu bond distances ranging from 2.6439(7) to 2.6452(9) A; the coordination sphere of Cu(II) is characterized by one long Cu-O (water) bond length of 2.128(3)-2.135(3) A and four short Cu-O (carboxylate) bonds of 1.949(3)-1.977(3) A. Crystal parameters for the DMA pseudopolymorph: a=10.372(1), b=19.625(2), c=17.967(2) A, beta=97.40(1) degrees , V=3626.8(6) A(3); monoclinic system; space group: P2(1)/a and for the DMF pseudopolymorph: a=10.125(2), b=18.647(3), c=19.616(4) A, alpha=74.38(2)(o), beta=88.18(2)(o), gamma=79.28(2)(o), V=3504(1) A(3); triclinic system; space group: P1. EPR spectra of these solids are identical and show strong antiferromagnetic coupling between the copper atoms, similar to the spectrum obtained for [Cu(2)(II)(niflumate)(4)(DMSO)(2)]. The [Cu(2)(II)(niflumate)(4)(H(2)O)(2)], [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMA, [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMF, [Cu(2)(II)(niflumate)(4)(DMF)(2)], and[Cu(2)(II)(niflumate)(4)(DMSO)(2)] evidenced protection against maximal electroshock-induced seizures and Psychomotor seizures at various times after treatment, consistent with the well known antiinflammatory activities of Cu chelates, but failed to protect against Metrazol-induced seizures while evidencing some Rotorod Toxicity consistent with a mechanism of action involving sedative activity.     

New copper(I) phosphane complexes of dihydridobis(3-nitro-1,2,4-triazolyl)borate ligand showing cytotoxic activity

New copper(I) complexes of the type [H(2)B(tz(NO2))(2)]Cu[PR(3)](2) (1-5), [H(2)B (tz(NO2))(2)]Cu[dppe] (6) and [H(2)B(tz(NO2))(2)]Cu[PR(3)] (7, 8) have been synthesized from the reaction of CuCl, potassium dihydrobis(3-nitro-1,2,4-triazol-1-yl)borate, K[H(2)B (tz(NO2))(2)], and mono- or bi-dentate tertiary phosphanes. The complexes obtained have been characterized by elemental analyses and FT-IR in the solid state, and by NMR ((1)H and (31)P{(1)H}) spectroscopy in solution. Selected complexes 1, 3 and 5 have also been tested against a panel of several human tumor cell lines in order to evaluate their cytotoxic activity. Complexes 1 and 5 showed IC(50) values appreciably lower than those exhibited by cisplatin, the most used metal-based antitumor drug. It is worth noting that all three tested Cu(I) complexes appear to be particularly effective against A549 carcinoma cells that are resistant to cisplatin treatment.     

Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II)

Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC(50) values in a microM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.     

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.     

Synthesis, crystal structure, magnetic property and oxidative DNA cleavage activity of an octanuclear copper(II) complex showing water-perchlorate helical network

A new octanuclear copper(II) complex has been synthesized and structurally characterized by X-ray crystallography: [Cu(8)(HL)(4)(OH)(4)(H(2)O)(2)(ClO(4))(2)].(ClO(4))(2).2H(2)O (1) (H(3)L=2,6-bis(hydroxyethyliminoethyl)-4-methyl phenol). The complex is formed by the linkage of two terminal bimetallic cationic units and a tetranuclear mu(3)-hydroxo bridged dicubane core by a very short intramolecular hydrogen bond (O-H...O, 1.48(3)A and the angle 175 degrees). The coordination sphere of the terminal copper atoms is square pyramidal, the apical positions being occupied by water and a perchlorate ion. Complex 1 self-assembles to form a new type of water-perchlorate helical network [(H(2)O)(2)(ClO(4))](infinity) involving oxygen atoms of coordinated perchlorate ion and the two lattice water molecules through hydrogen-bonding interaction. The variable temperature-dependent susceptibility measurement (2-300K) of 1 reveals a strong antiferromagnetic coupling, J(1)=-220cm(-1) and J(2)=-98cm(-1) (J(1) and J(2) representing the exchange constant within [Cu(2+)](4) and [Cu(2+)](2) units, respectively). The complex binds to double-stranded supercoiled plasmid DNA giving a K(app) value of 1.2x10(7)M(-1) and displays efficient oxidative cleavage of supercoiled DNA in the presence of H(2)O(2) following a hydroxyl radical pathway.     

Synthesis, characterization and biological activity of Ni, Cu and Zn complexes of isatin hydrazones

Nickel, copper, and zinc complexes of isatin (H(2)L(1)) and N-methylisatin 3-picolinoyl hydrazone (HL(2)), were synthesized and characterized by means of spectroscopic techniques. H(2)L(1) and a nickel complex [Ni(L(2))(2)].2C(6)H(14) were also characterized by X-ray diffractometry. Biological studies, carried out in vitro on human leukemic cell lines TOM 1 and NB4, have shown that both ligands and some copper and nickel complexes are active in inhibiting cell proliferation. Compounds H(2)L(1), Cu(HL(1))(2).2H(2)O, Zn(HL(1))(2).2H(2)O inhibit DNA synthesis and act constantly with time between 0 and 72 h. The cell cycle analysis has highlighted a reduction in the number of cells in phase S of about 40%. The same compounds present only a precocious action on cell line NB4 and therefore their activity is cell target specific.