Synthesis, characterization and antitumor studies of N-aroyl-N′-thioaroylhydrazines and their Co(II), Ni(II), Cu(II) and Zn(II) complexes

N-Salicyloyl-N-p-hydroxythiobenzohydrazide (H₂STPH) and N-benzoyl-N-thiobenzohydrazide (H₂BTBH) and their Co(II), Ni(II), Cu(II) and Zn(II) complexes were prepared and characterized by physicochemical studies. IR and NMR spectral studies imply dibasic tetradentate behaviour of the ligands bonding through `thiolato' sulfur, enolic oxygen and the two hydrazinic nitrogens in a polymeric fashion. The electronic spectra indicate [Ni(STPH)(H₂O)₂], [Co(STPH)(H₂O)₂] to be distorted octahedral while [Cu(BTBH)] has a square-planar geometry. In vitro antitumor results of the ligand and the complexes on P-815 (murine mastocytoma) and L-929 (murine fibroblast) indicate that these compounds show significant inhibition of ³H-thymidine and ³H-uridine incorporation in DNA and RNA, respectively, in these tumor cells at dose levels of 1, 2.5 and 5 g cm^–3. Antitumor studies suggest that [Cu(BTBH)] has significant dose dependent inhibitory effect on DNA synthesis. In vivo administration of [Cu(BTBH)] and [Ni(STPH)(H₂O)₂] resulted into prolongation of life span of Dalton's Lymphoma (DL) bearing mice.     

Synthesis and antimicrobial activity of copper(II) and manganese(II) α,ω-dicarboxylate complexes

Copper(II) ,-dicarboxylate complexes of general formulae, [Cu(O₂C(CH₂)_nCO₂)]·xH₂O, [Cu(O₂C(CH₂)_nCO₂) (phen)₂]·xH₂O and [Cu(O₂C(CH₂)_nCO₂)(bipy)_y]·xH₂O (n=1–8; y=1, 2; phen = 1,10-phenanthroline; bipy = 2,2-bipyridine) were synthesised. These copper complexes, some related manganese(II) complexes and the metal-free ligands were screened in vitro for their ability to inhibit the growth of Candida albicans. Metal-free 1,10-phenanthroline and all of the copper(II) and manganese(II) phenanthroline complexes were potent growth inhibitors, with only one bipyridine complex, [Cu(O₂C(CH₂)CO₂)(bipy)₂]·2H₂O, having moderate activity. The remaining substances were effectively inactive. Complexes which were active against C. albicans also proved effective against C. glabrata, C. tropicalis and C. kreusi with the manganese complexes retaining superior activity. For the phenanthroline complexes the active drug species is thought to be the dication [M(phen)₂(H₂O)_n]²⁺ (M = Cu, Mn). Escherichia coli and Staphylococcus aureus were resistant to all of the metal complexes and also to metal-free 1,10-phenanthroline. Only the copper phenanthroline complexes showed intermediate activity against Pseudomonas aeruginosa.     

Synthesis, Characterization and Antitumor Studies of Mn(II), Ni(II), Cu(II) and Zn(II) Complexes of N-Nicotinoyl-N′-o-Hydroxythiobenzhydrazide

A new ligand N-Nicotinoyl-N-o-hydroxythiobenzhydrazide (H₂Notbh) forms complexes [Mn(Notbh)(H₂O)], [M(Notbh)] [M=Ni(II) Cu(II) and Zn(II)] which were characterized by various physico-chemical techniques. All the metal complexes were observed to inhibit the growth of tumor in vitro, whereas, ligand did not. In vivo administration of these complexes resulted in prolongation of survival of tumor bearing mice. Tumor bearing mice administered with metal complexes showed reversal of tumor growth associated induction of apoptosis in lymphocytes. The paper discusses the possible mechanisms and therapeutic implication of the H₂Notbh and its metal complexes in tumor regression and tumor growth associated immunosuppression.     

Synthesis and characterization of β-diketiminate germanium(II) and tin(II) bromides

The equimolar reaction of a β-diketiminate lithium salt LLi(OEt₂) [L = HC(CMeNAr)₂; Ar = 2,6-iPr₂C₆H₃] with either GeBr₂ or SnBr₂ in diethyl ether affords the synthetically useful monomeric β-diketiminate-element halides LGeBr (1) and LSnBr (2), respectively. Both are soluble in hydrocarbon solvents, stable in inert atmosphere, and have been characterized by elemental analysis, NMR spectroscopy, and single-crystal X-ray diffraction analysis.     

Synthesis, structure and magnetic properties of two μ-oxo and thiocyanato-bridged manganese(II)-mercury(II) coordination polymers

Mixed-metal thiocyanate complexes [MnHg(SCN)₄(NOP)] (1) and [MnHg(SCN)₄(DMSO)] (2) (NOP = 3-methyl-4-nitropyridine-N-oxide, DMSO = dimethylsulfoxide) have been synthesized and structurally characterized by single crystal X-ray analysis. Complex 1 and 2 both contain a [Mn₂(μ₂-O)₂] lozenge, which is bridged to Hg(II) ions by end-to-end thiocyanate groups to form a 2-D and 3-D polymeric network, respectively. Magnetic studies indicate that both complexes are anti-ferromagnets, with 1 showing anti-ferrimagnetic ordering below 8.0 K.     

Biosorption of Cd(II) and Pb(II) onto brown seaweed, Lobophora variegata (Lamouroux): kinetic and equilibrium studies

The present work deals with the biosorption performance of raw and chemically modified biomass of the brown seaweed Lobophora variegata for removal of Cd(II) and Pb(II) from aqueous solution. The biosorption capacity was significantly altered by pH of the solution delineating that the higher the pH, the higher the Cd(II) and Pb(II) removal. Kinetic and isotherm experiments were carried out at the optimal pH 5.0. The metal removal rates were conspicuously rapid wherein 90% of the total sorption occurred within 90 min. Biomass treated with CaCl₂ demonstrated the highest potential for the sorption of the metal ions with the maximum uptake capacities i.e. 1.71 and 1.79 mmol g⁻¹ for Cd(II) and Pb(II), respectively. Kinetic data were satisfactorily manifested by a pseudo-second order chemical sorption process. The process mechanism consisting of both surface adsorption and pore diffusion was found to be complex. The sorption data have been analyzed and fitted to sorption isotherm of the Freundlich, Langmuir, and Redlich–Peterson models. The regression coefficient for both Langmuir and Redlich–Peterson isotherms were higher than those secured for Freundlich isotherm implying that the biosorption system is possibly monolayer coverage of the L. variegata surface by the cadmium and lead ions. FT-IR studies revealed that Cd(II) and Pb(II) binding to L. variegata occurred primarily through biomass carboxyl groups accompanied by momentous interactions of the biomass amino and amide groups. In this study, we have observed that L. variegata had maximum biosorption capacity for Cd(II) and Pb(II) reported so far for any marine algae. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synthesis, structure and magnetic property of μ-phenoxo-μ-acetato-bis(η-acetato)dicobalt(II, II) complexes

Dinuclear cobalt(II) complexes Co₂(bpmp)(OAc)₃ (1) and Co₂(bpcp)(OAc)₃ (2) have been synthesized by using acyclic ligands 2,6-bis((4-(pyridin-2-yl)pyrimidin-2-ylthio)methyl)-4-methylphenol [H(bpmp)] and 2,6-bis((4-(pyridin-2-yl)pyrimidin-2-ylthio)methyl)-4-chlorophenol [H(bpcp)] with versatile coordination sites. X-ray analysis uncovered that complex 1 · 3H₂O contains a μ-phenoxo-μ-acetato-bis(η²-acetato) dicobalt(II, II) core. Magnetic susceptibility was measured for 1 over the temperature range 1.8-300 K, and the best theoretical fitting parameters were g = 2.12(6), J = −3.63(9) cm⁻¹ and D = −12(4) cm⁻¹.     

Electronic coupling and photochemical stability of O,N bound mononuclear Ru(II) and Os(II) – Hydroquinone complexes

The synthesis, spectroscopic and electrochemical characterisation of a series of optically tuneable, ruthenium (II) and osmium (II) polypyridyl complexes, O,N coordinated to electroactive donor ligand, bis-2,5-(2-benzoxazolyl)-hydroquinone (bbhq) is described. The complexes exhibit a rich optical spectroscopy which can be controlled through the redox state of the metal and bbhq ligand. The influence of both the metal and counter-ligand identity on the optical properties of these hydroquinone-based complexes is addressed.Regardless of the identity of metal or counter-ligand, it is the bbhq which is the site of the most facile oxidation and hydroquinone, semiquinone (bbsq) and quinone (bbq) can be generated electrochemically. In each instance, the semiquinone is strongly stabilised with respect to disproportionation, reflected in large stability constants for this moiety. The levels of orbital mixing between metal and ligand are discussed on the basis of the optical properties of the complex and the nature of the metal and counter-ligand. In addition, we address, for the first time, the effect of metal and counter-ligand on the photostability, of Ru(II) and Os(II) hydroquinone bound complexes. We find that like other ruthenium (II) complexes containing strong σ-bonding ligands, the M(bpy)₂ containing complexes are photostable, but the [Ru(biq)₂(bbhq)]⁺ complex is relatively photolabile.     

Dicyanamido-metal(II) complexes. Part 4: Synthesis, structure and magnetic characterization of polynuclear Cu(II) and Ni(II) complexes bridged by μ-1,5-dicyanamide

The one pot aqueous reaction of M(ClO₄)₂ (M = Cu²⁺ or Ni²⁺) with N-methylbis[2-(2-pyridylethyl)]amine (MeDEPA) and N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)ethylenediamine (bpmen) and 1,4,7,10-tetraazacyclododecane (cyclen) in presence of sodium dicyanamide (Nadca) yielded dicyanamido-bridged polynuclear complex {[Cu(MeDEPA)(μ-1,5-dca)]ClO₄}_n (1), and two dinuclear complexes [Cu₂(bpmen)₂(μ-1,5-dca)]₂(ClO₄)₅dca (2) and [Ni(cyclen)(μ-1,5-dca)]₂(ClO₄)₂ (3). These complexes were characterized by IR and UV-Vis spectroscopy. Room temperature single-crystal X-ray studies have confirmed that the Cu(II) centers in 1 and 2 adopt geometries that are more close to trigonal bipyramidal (TBP) in 1 and close to square pyramidal (SP) in 2, whereas in 3, the Ni(II) centers are located in octahedral environment with doubly bridged μ-1,5-dca bonding mode. The intermolecular M···M distances in these complexes are in the range of 7.3-8.6 Å. Variable temperature magnetic susceptibility studies have confirmed that the dca-bridges mediate very weak antiferromagnetic interaction between the M(II) centers with J values of −0.35, −0.18 and −0.43 cm⁻¹ for 1, 2 and 3, respectively. The results are compared and discussed in the light of other related bridged μ-1,5-dca Cu(II) and Ni(II) complexes.     

Co (II), Ni(II) and Cu(II) complexes with a new pendant armed macrocyclic ligand showing several π,π-interactions

A new ligand, L, bearing four cyanoethyl pendant groups has been synthesized by reaction of the precursor ligand L¹ with acrylonitrile. The X-ray crystal structure of ligand L reveals the presence of a nanotubular structure in the solid state connected by intermolecular π,π-stacking interactions between adjacent pyridine rings. The coordination capability towards transition metal ions [Co(II), Ni(II) and Cu(II)] has been investigated starting from the hydrated nitrate and perchlorate salts of the metals. The new ligand L and the metal complexes obtained were characterized by elemental analysis, FAB MS, conductivity measurements, magnetic studies, IR and UV-vis spectroscopy. Furthermore, the crystal structure of ligand L and of the complexes [CoL][Co(NO₃)₄] · CH₃CN (1), [NiL](NO₃)₂ (3), [NiL](ClO₄)₂ · CH₃CN · 3H₂O (4), [CuL][Cu(NO₃)₃(H₂O)₂](NO₃) · H₂O (5) and [CuL](ClO₄)₂ · 2CH₃CN (6) were determined. The nitrate ions in the complexes are located near the pyridine rings and π,π-stacking interactions between pyridine rings, nitrate ions and nitrile groups have been found.     

Synthesis, characterization, and reactivity of (π-allyl)palladium(II) wrap-around complexes with 1,3-dienes

Synthesis of a series of cationic “wrap-around” complexes, η³-, η²- (CH₂-CH-CHR-CH₂-CH₂-CHCHX) Pd(II)L⁺ (R = H, CH₃; X = H, Cl, CO₂Me; L = PPh₃, P(C₄H₄N)₃), is described. These chelate complexes were prepared by exposure of π-allyl chloride dimers, (η³-(CH₂-CX-CH₂)PdCl)₂, to either 1,3-butadiene or isoprene to yield π-allyl chloride dimers of the type (η³-CH₂CHCRCH₂CH₂CH = CH(X)PdCl)₂ which result from insertion of the diene into each π-allyl unit. Abstraction of chloride with either AgSbF₆ or NaB(Ar_F)₄ in the presence of L gives the cationic wrap-around complexes in high yields. Single crystal X-ray diffraction studies of 8a (R = -CH₃, X = -Cl, L = PPh₃) and 9a (R = -H, X = -Cl, L = PPh₃) show that Pd(II) adopts essentially a square planar geometry and the chelate arm occupies a syn orientation with respect to the allyl unit. Exposure of these wrap-around complexes to nitriles of differing basicities displaces the chelated alkene to varying extents and allows assessment of the relative strengths of chelation as a function of substituents, X and R. Initial rapid displacement of the chelated alkene yields a syn-π-allyl isomer which equilibrates with the anti-π-allyl isomer which cannot close to form a chelate. Treatment of 8b with 1,3-butadiene gives not polybutadiene but 2-chloro-4-methyl-1,E-4,6-heptatriene and 2-chloro-4-methyl-1,Z-4,6-heptatriene. Formation of these trienes is first-order in butadiene. This reaction serves as a model for chain-transfer in the polymerization of butadiene.     

Synthesis and structures of three,four, and six-coordinate monomeric tin(II) and tin(IV) compounds containing η2-ketiminate ligands

A series of Sn(II) and Sn(IV) compounds containing ketiminate ligands were synthesized. Reactions of SnCl₂ with 1 or 2 equiv. Li[OCMeCHCMeNAr] (where Ar = 2,6-diisopropylphenyl) generate [OCMeCHCMeNAr]SnCl (1) and [OCMeCHCMeNAr]₂Sn (2) in moderate yield, respectively. Similarly, reacting SnCl₄ with 2 equiv. Li[OCMeCHCMeNAr] yields a six-coordinated [OCMeCHCMeNAr]₂SnCl₂ (3). Divalent tin compound 2 can be oxidized with I₂ in diethyl ether to generate tetravalent tin compound [OCMeCHCMeNAr]₂SnI₂ (4) in moderate yield. Compounds 1–4 have been characterized by ¹H and ¹³C NMR spectroscopy and have been analyzed by X-ray crystallography. Theoretical calculation found that the bonding of ketiminate ligands and tin atom in compound 2 has a strong ionic character.     

Synthesis and structural investigations of Ni(II)- and Pd(II)-coordinated α-diimines with chlorinated backbones

Novel square planar Pd(II) α-diimines [PdX₂{ArNC(Cl)}₂], where Ar = C₆H₅, (2,6-Me₂C₆H₃), (2,6-ⁱPr₂C₆H₃) and X = Cl or Br, and the octahedral Ni(II) complex [NiBr₂{(C₆H₅)NC(Cl)}₂(THF)₂] have been prepared and characterised by spectroscopic methods. For two of the Pd(II) complexes and the Ni(II) complex the crystal structures were determined by X-ray crystallography. A further insight into the geometry and electronic structure of [PdBr₂{(2,6-Me₂C₆H₃)NC(Cl)}₂] was gained using density functional theoretical calculations (DFT). This compound resembles structurally and electronically typical olefin polymerisation pre-catalysts supported by α-diimines incorporating methyl- and 1,8-naphtalenyl substituents at the ligand backbone. The chlorine-substituted backbone of the free ligand [2,6-Me₂C₆H₃NC(Cl)]₂ can be employed in further alkylation reactions to generate new multifunctional ligand prototypes with potential uses as ansa-metallocene/diimines building blocks for catalytic applications of heterobimetallic complexes.     

Antioxidant and Cytoprotective Activity of Oxydiacetate Complexes of Cobalt(II) and Nickel(II) with 1,10-Phenantroline and 2,2′-Bipyridine

Biological Trace Element Research - The antioxidant properties of oxydiacetate complexes of cobalt(II) and nickel(II) with 1,10-phenantroline and 2,2′-bipyridine have been investigated...     

Preparation and characterization of oxovanadium(IV), acetatomanganese(III), chloroiron(III), nickel(II), copper(II), zinc(II) and palladium(II) complexes of 3,3′-(1,2-phenylenediimino)diacrolein

The oxovanadium(IV), acetatomanganese(III), chloroiron(III), nickel(II), copper(II), zinc(II) and palladium(II) of 3,3′-(1,2-phenylenediimino)diacrolein were prepared and investigated by means of mass, electronic, vibrational, NMR and ESR spectroscopy as well as magnetic susceptibility measurements. The acetatomanganese(III) and chloroiron(III) complexes were confirmed to be of high spin type. The absorption bands appearing in the energy range greater than 23 000 cm⁻¹ were attributed to π→π^* transitions within a ligand molecule and charge- transfer transitions from metal to ligand. The metal complexes assume the square-planar configuration type since the ligand-field bands were detected in the 12 700–18 500 cm⁻¹ region. Strong bands appearing at 1601 and 1627 cm⁻¹ were assigned to the CC and CO stretching vibrational modes, respectively, and were shifted to lower frequency upon metal-coordination. A VO stretching band was observed at 982 cm⁻¹ for the oxovanadium(IV) complex and a CO stretching band was observed at 1547 cm⁻¹ for the acetatomanganese(III) complex. Upon complex formation the amine proton signal is found to vanish and the aldehydic methine proton signal in the lowest field is shifted upfield for the nickel(II), zinc(II) and palladium(II) complexes. ¹³C NMR spectra support the coordination structure of the complexes which is revealed by ¹H NMR spectra. As judged by the spin Hamiltonian parameters, the oxovanadium(IV) complex is of a square- planar type with an unpaired electron in the d_xy orbital and the copper(II) complex assumes a distorted square-planar coordination due to the presence of five- and six-membered chelate rings with an unpaired electron in the d_x2−y2 orbital.     

Synthesis,X-ray structures,and magnetic properties of heterometal dinuclear Cr(III)–M(II) complexes

New 3,5-bis(2-pyridyl)pyrazolato (bpypz) bridged heterometal dinuclear complexes [(nta)Cr(μ-bpypz)M^II(picen)]⁺ (M = Mn(II), Ni(II)) and [(acac)₂Cr(μ-bpypz)Ni^II(picen)]²⁺ (nta = nitrilotriacetate, picen = N,N′-bis(2-pyridylmethyl)ethylenediamine, acac = acetylacetate) were synthesized and characterized by the X-ray analysis, ESI-MS and the magnetic measurements, and/or ²H NMR spectra. The molecular structures were compared from a viewpoint of the conformation of the picen depending on M^II ionic radii or different modes of hydrogen bonds. The picen in [(nta)Cr(μ-bpypz)Mn^II(picen)]BF₄ takes an abnormal conformation with intramolecular bifurcated three-center hydrogen bonds between two carboxylate oxygens of nta and an amine proton of the picen as found for the previously reported corresponding Fe(II) complex [K. Ni-iya, A. Fuyuhiro, T. Yagi, S. Nasu, K. Kuzushita, S. Morimoto, S. Kaizaki, Bull. Chem. Soc. Jpn. 74 (2001) 1891]. On the other hand, for both Ni(II)-nta and Ni(II)-acac complexes, the picen takes a normal conformation with only a two-center hydrogen bond between non-bridging ligands. The magneto-structural relation is discussed for the Cr(III)–Ni(II) complexes in connection with the orthogonality or orbital overlap arising from the difference in distortion around Cr(III) moiety.     

IR and Raman study on the interactions of the 5′-GMP and 5′-CMP phosphate groups with Mg(II), Ca(II), Sr(II), Ba(II), Cr(III), Co(II), Cu(II), Zn(II), Cd(II), Al(III) and Ga(III)

The chief motive behind this research is the interest provoked by the presence of metal ions as necessary stabilizers of the negative charges of phosphate groups in nucleic acids. The effect that the presence of different metal ions produces on the band principally assigned to the nu(s) PO(3)(2-) mode has been studied using FT-IR and FT-Raman spectroscopy. The results obtained reveal the diagnostic capacity of these techniques in determining the type of metal ion interaction with respect to the mononucleotides that form DNA and RNA, providing a tool for improving the knowledge of the stabilizing or destabilizing effects of these ions on such macromolecules. The metal complexes of the ribonucleotides 5'-CMP and 5'-GMP with Mg(II), Ca(II), Sr(II), Ba(II), Cr(III), Co(II), Cu(II), Zn(II), Cd(II), Al(III) and Ga(III) were obtained in this study. After studying and analyzing the IR and Raman spectra of all these complexes and comparing them with the spectra of the corresponding disodium salts, it was verified that, independently of the type of nucleotide involved, the presence of the metal in the vicinity of the phosphate group produces an alteration in the aforementioned nu(s) PO(3)(2-) band. This effect is related to the type of interaction that the phosphate group has with the metal. Three components are observed: (1) one near 983-975 cm(-1) (detectable in IR and Raman), associated with phosphate groups in an electrostatic type of interaction with the metal ion, separated by two or more water molecules; (2) another near 989-985 cm(-1) (only in IR), associated with phosphate groups in indirect interaction through the water molecules of the coordination sphere of the metal ions; and (3) the IR and Raman bands near 1014-1001 cm(-1), which represent phosphate groups directly bonded to the metal ion. These results are supported by the behavior of 5'-CMP in aqueous solution in the presence of Mg(II) ions.     

Effects of Cold Atmospheric Plasma (CAP) on ?-Defensins,Inflammatory Cytokines,and Apoptosis-Related Molecules in Keratinocytes In Vitro and In Vivo

Cold atmospheric plasma (CAP) has been gaining increasing interest as a new approach for the treatment of skin diseases or wounds. Although this approach has demonstrated promising antibacterial activity, its exact mechanism of action remains unclear. This study explored in vitro and in vivo whether CAP influences gene expression and molecular mechanisms in keratinocytes. Our results revealed that a 2 min CAP treatment using the MicroPlaSter ß in analogy to the performed clinical studies for wound treatment induces expression of IL-8, TGF-ß1, and TGF-ß2. In vitro and in vivo assays indicated that keratinocyte proliferation, migration, and apoptotic mechanisms were not affected by the CAP treatment under the applied conditions. Further, we observed that antimicrobial peptides of the ß-defensin family are upregulated after CAP treatment. In summary, our results suggest that a 2 min application of CAP induces gene expression of key regulators important for inflammation and wound healing without causing proliferation, migration or cell death in keratinocytes. The induction of ß-defensins in keratinocytes describes an absolutely new plasma strategy. Activation of antimicrobial peptides supports the well-known antibacterial effect of CAP treatment, whereas the mechanism of ß-defensin activation by CAP is not investigated so far.