Synthesis, crystal structures, biological activities and fluorescence studies of transition metal complexes with 3-carbaldehyde chromone thiosemicarbazone

3-carbaldehyde chromone thiosemicarbazone (L) and its transition metal complexes were synthesized and characterized systematically. Crystal structures of Zn(II) and Ni(II) complexes were determined by single crystal X-ray diffraction analysis. Zn(II) complex exhibits blue fluorescence under UV light and its fluorescent property in solid state was investigated. Interactions of ligand and Cu(II), Zn(II) and Ni(II) complexes with DNA were investigated by spectral and viscosity studies, indicating the compounds bind to DNA via intercalation and Zn(II) complex binds to DNA most strongly. Antioxidant tests in vitro show the compounds possess significant antioxidant activity against superoxide and hydroxyl radicals, and the scavenging effects of Cu(II) complex are stronger than Zn(II), Ni(II) complexes and some standard antioxidants, such as mannitol and vitamin C.     

Synthesis, antibacterial, antifungal activity and interaction of CT-DNA with a new benzimidazole derived Cu(II) complex

The ligand [C(16)H(10)O(2)N(4)S(2)] L has been synthesized by the condensation reaction of 2-mercaptobenzimidazole and diethyloxalate. The ligand L was allowed to react with bis(ethylenediamine)Cu(II)/Ni(II) complexes to yield [C(20)H(22)N(8)S(2)Cu]Cl(2)1 and [C(20)H(22)N(8)S(2)Ni]Cl(2)2 complexes. The Ni(II) complex was synthesized only to elucidate the structure of the complex. The complexes 1 and 2 were characterized by elemental analyses, IR, NMR, EPR, UV-vis spectroscopy and molar conductance measurements. Both the complexes are ionic in nature and possess square-planar geometry. The binding of the complex 1 to calf thymus DNA was investigated spectrophotometrically. The absorption spectra of complex 1 exhibits a slight red shift with "hyperchromic effect" in presence of CTDNA. Electrochemical analysis and viscosity measurements were also carried out to ascertain the mode of binding. The complex 1 in the absence and in presence of CT DNA in aqueous solution exhibits one quasi-reversible redox wave corresponding to Cu(II)/Cu(I) redox couple at a scan rate of 0.2 V s(-1). The shift in DeltaE(p), E(1/2) and I(pa)/I(pc) values ascertain the interaction of calf thymus DNA with copper(II) complex. There is decrease in viscosity of CTDNA which indicates that the complex 1 binds to CTDNA through a partial intercalative mode. The antibacterial and antifungal studies of the [C(7)H(6)N(2)S], [C(4)H(16)N(4)Cu]Cl(2,) [C(16)H(10)N(4)S(2)O(2)] and [C(20)H(22)N(8)S(2)Cu]Cl(2) were carried out against S. aureus, E. coli and A. niger. All the results reveal that the complex 1 is highly active against the bacterial strains and also inhibits fungal growth.     

Synthesis, characterization, cytotoxicity, antibacterial and antifungal evaluation of some new platinum (IV) and palladium (II) complexes of thiodiamines

Some new platinum (IV) and palladium (II) thiodiamine complexes of type [Pt(L)2Cl2] and [Pd(L)Cl2], [where, L=(cyclohexyl-N-thio)-1,2-ethylenediamine (L(1)) and (cyclohexyl-N-thio)-1,3-propanediamine (L(2))] have been synthesized. The thiodiamines coordinate as a bidentate N-S ligand. The synthesized platinum (IV) and palladium (II) complexes of the thiodiamines were characterized by elemental analysis, IR, mass, electronic and (1)H NMR spectroscopic studies. These complexes were also screened for cytotoxicity, in vitro antifungal and in vitro antibacterial activities. Thermodynamic parameters such as activation energy (Ea), apparent activation entropy (S(#)) and enthalpy change (DeltaH) for the dehydration and decomposition reactions of one complex has also been evaluated.     

Synthesis and characterization of dinuclear macrocyclic cobalt(II), copper(II) and zinc(II) complexes derived from 2,2,2('),2(')-S,S[bis(bis-N,N-2-thiobenzimidazolyloxalato-1,2-ethane)]: DNA binding and cleavage studies

New homodinuclear macrocyclic complexes of cobalt(II), copper(II) and zinc(II) were isolated from the newly synthesized ligand 2,2,2',2'-S,S[bis(bis-N,N-2-thiobenzimidazolyloxalato-1,2-ethane)]. The structures of the complexes were elucidated by elemental analysis, molar conductance measurements, IR, 1H NMR, 13C NMR, electronic and ESI-MS spectroscopic techniques. In complex 1, Co(II) ions possess a tetrahedral coordination environment composed of O2S2 donor atoms while its Cu(II) and Zn(II) counterparts 2 and 3, respectively, reveal a six coordinate octahedral structure, defined by the O2S2 donors from the macrocyclic ring and two chloride ions. Molar conductance and spectroscopic data also support the proposed geometry of the complexes. DNA binding properties of complexes 1-3 were investigated using electronic absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and cyclic voltammetry. The absorption spectra of complexes 2 and 3 with calf thymus DNA showed hypochromism, while complex 1 showed hyperchromism attributed to a partial intercalation and electrostatic binding modes, respectively. The intrinsic binding constant K(b) of complexes 1-3 were determined as 16.6 x 10(4) M(-1), 4.25 x 10(4) M(-1) and 3.0 x 10(4) M(-1), respectively. The decrease in the relative specific viscosity of calf thymus DNA with increasing concentration of the complexes authenticates the partial intercalation binding mode. Gel electrophoresis of complex 2 with plasmid DNA demonstrated that complex exhibits excellent "artificial" nuclease activity.     

Some O,O',O',O'-di/tetra aryldithioimidophonate transition metal complexes derived from catechol and bisphenol-A as antibacterial and antifungal agents

Two new substituted-thioimidophonate derivatives H1L1 (O,O',O',O'-diaryldithioimidophonates) and H1L2 (O,O',O',O'-tetra aryldithioimidophonates) were synthesized. These thioimidophonates are potential ligands towards transition metal ions. The reaction of M(II) acetates (M(II)=Mn(II), Co(II), Ni(II), Cu(II), and Zn(II)) with H1L1 and H1L2 resulted in the formation of solid complexes with the composition (L1/L2)(2)M(II). These compounds were characterized through elemental analysis, electrical conductance, infrared, electronic spectra, nmr, magnetic susceptibilities etc. Vibrational mode assignments of nu(PN), nu(PS), nu(MS), phenyl and methyl group bands are made. Structural and bonding changes are correlated with these vibrational frequencies. All the compounds were screened for their antibacterial and antifungal properties and have exhibited potential activities with MIC (0.09-1.50 microg/ml).     

Solvatochromism, DNA binding, antitumor activity and molecular modeling study of mixed-ligand copper(II) complexes containing the bulky ligand: bis[N-(p-tolyl)imino]acenaphthene

Four mixed-ligand copper(II) complexes of the nitrogen ligand bis[N-(p-tolyl)imino]acenaphthene 1 (p-Tol-BIAN). These complexes, namely [Cu(p-Tol-BIAN)2](ClO4)2 2, [Cu(p-Tol-BIAN)(acac)](ClO4) 3, [Cu(p-Tol-BIAN)Cl2] 4 and [Cu(p-Tol-BIAN)(AcOH)(2)](ClO4)2 5, were prepared and characterized. Solvatochromism of the novel copper complexes in various solvents has been studied. Molecular mechanics (MM+) and molecular dynamic simulations have been performed to learn more about the solvatochromic behaviour and the DNA binding affinity of these complexes.     

Synthesis, characterization and biological studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with bidentate Schiff bases derived by heterocyclic ketone

A series of metal complexes of Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized with newly prepared biologically active ligands. These ligands were prepared by the condensation of 4-amino-5-mercapto-3-methyl-s-triazole (AMMT), 4-Amino-3-ethyl-5-mercapto-s-triazole (AEMT) with 2-acetylpyridine. The structure of the complexes have been proposed by elemental analyses, spectroscopic data i.e. IR, 1H NMR, electronic and magnetic measurements. Thermal studies of the complexes are also reported. Antibacterial activities of 10 complexes have been studied in vitro. Heterocyclic bidentate Schiff bases were associated with substantially higher antibacterial activities than some commercial antibiotics.     

Synthesis, characterization and antimicrobial activity of Fe(II), Zn(II), Cd(II) and Hg(II) complexes with 2,6-bis(benzimidazol-2-yl) pyridine ligand

2,6-Bis(benzimidazol-2-yl)pyridine (L) ligand and complexes [M(L)Cl(2)] and [Fe(L)(2)](ClO(4))(2) (M=Zn, Cd, Hg) have been synthesized. The geometries of the [M(L)Cl(2)] complexes were derived from theoretical calculation in DGauss/DFT level (DZVP basis set) on CACHE. The central M(II) ion is penta-coordinated and surrounded by N(3)Cl(2) environment, adopting a distorted trigonal bipyramidal geometry. The ligand is tridentate, via three nitrogen atoms to metal centre and two chloride ions lie on each side of the distorted benzimidazole ring. In the [Fe(L)(2)](ClO(4))(2) complex, the central Fe(II) ion is surrounded by two (3N) units, adopting a octahedral geometry. The elemental analysis, molecular conductivity, FT-Raman, FT-IR (mid-, far-IR), (1)H, and (13)C NMR were reported. The antimicrobial activities of the free ligand, its hydrochloride salt, and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against 10 bacteria and the results compared with that for gentamycin. Antifungal activities were reported for Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the results were referenced against nystatin, ketaconazole, and clotrimazole antifungal agents. In most cases, the compounds tested showed broad-spectrum (Gram positive and Gram negative bacteria) activities that were either more effective than or as potent as the references. The binding of two most biologically effective compounds of zinc and mercury to calf thymus DNA has also been investigated by absorption spectra.     

Metal(II) complexes of 2,2′-bipyridyl-6-carbothioamide as anti-tumor and anti-fungal agents

Complexes of Fe(II), Co(II), Ni(II), Cu(II), Cd(II), Pd(II), Pt(II) and Zn(II) with the anti-tumor agent 2,2′-bipyridyl-6-carbothioamide (bpyta, 1) were prepared and characterized. All these metal(II) complexes were screened for their cytostatic activities in vitro against murine P388 leukemia. The copper(II) complex 2f was found to be 12-fold more active than ligand 1. bpyta and its complexes were also evaluated for their anti-fungal activities. Some of the studied complexes displayed significant anti-fungal activity which, however, was lower than that of the parent ligand.     

Metal complexes of retinoid derivatives with antiproliferative activity: synthesis, characterization and DNA interaction studies

9-cis-Retinal thiosemicarbazone and its Co(III), Ni(II) and Cu(II) complexes are synthesized and characterized. Central Co(III) atom is in an octahedral environment while Ni(II) and Cu(II) atoms are in a square planar environment. DNA binding constants and spectroscopic data show an intercalative behavior for the nickel complex; an external binding mode is envisaged for the ligand and its copper complex. No DNA interaction can be hypothesized for the cobalt complex. The free ligand and its Ni(II) and Cu(II) complexes have a good lipophilic degree for an efficient uptake by the cells. The metal complexes exhibit a proliferation inhibition action against cell line U937 at micromolar concentration. Cu(II) complex also induces apoptosis, while Ni(II) complex has a strong interaction with CT-DNA.     

New transition metal ion complexes with benzimidazole-5-carboxylic acid hydrazides with antitumor activity

Metal complexes of 2-methyl-1H-benzimidazole-5-carboxylic acid hydrazide (4a; L(1)) and its Schiff base 2-methyl-N-(propan-2-ylidene)-1H-benzimidazole-5-carbohydrazide (5a; L(2)) with transition metal ions e.g., copper, silver, nickel, iron and manganese were prepared. The complexes formed were 1:1 or 1:2 M:L complexes and have the structural formulae [Cu(L(1))Cl(H(2)O)]Cl x 3 H(2)O (6), [Ag(L(1))NO(3)(H(2)O)] (7), [Ni(L(1))Cl(2)(H(2)O)(2)] x H(2)O (8), [Fe(L(1))Cl(3)(H(2)O)] x 3 H(2)O (9) and [Mn(L(1))(2)Cl(H(2)O)]Cl x 3 H(2)O (10) for ligand L(1), and [Cu(L(2))Cl(2)(H(2)O)(2)] x H(2)O (11), [Ag(L(2))(2)]NO(3) x H(2)O (12), [Ni(L(2))(2)Cl(2)] x 5 H(2)O (13), [Fe(L(2))(2)Cl(2)]Cl x 2 H(2)O (14) and [Mn(L(2))Cl(2)(H(2)O)(2)] x H(2)O (15) for ligand L(2). The antitumor activity of the synthesized compounds has been studied. The silver complex 7 was found to display cytotoxicity (IC(50)=2 microM) against both human lung cancer cell line A549 and human breast cancer cell line MCF-7.     

Synthesis,characterization and anti-bacterial studies of mixed-ligand complexes of dithiocarbamato—thiocyanato and iron(III), nickel(II), copper(II) and zinc(II)

Twelve mixed-ligand complexes of Fe(III), Ni(II), Cu(II) and Zn(II) with Schiff bases of N,N-diethylamino-dithiocarbamate and thiocyanate as ligands, have been synthesized and characterized on the basis of elemental analysis, infrared and electronic spectral studies, as well as magnetic measurements. Anti-bacterial action of these complexes has been evaluated against Staphylococcus aureus, Pasteurella multocida, Escherichia coli and Bacillus cereus. The activity has been estimated by the filter paper disc and the minimal inhibition concentration methods. A relationship between the anti-bacterial activity and the nature of the ligands and the central atoms of the complexes has been noted.     

Cytotoxic activity and chemical reactivity of cis-platinum(II) and trans-palladium(II) complexes with diethyl (pyridinylmethyl)phosphates

A series of square-planar platinum(II) and palladium(II) complexes of the formula cis-[PtCl2L2] and trans-[PdCl2L2] [L stands for diethyl (pyridin-2-ylmethyl)phosphate (2-pmOpe) or diethyl (pyridin-3-ylmethyl)phosphate (3-pmOpe) or diethyl (pyridin-4-ylmethyl)phosphate (4-pmOpe)] have been synthesized and tested in vitro for their cytotoxicity against mouse leukemia L1210 cells. The results indicated that the cis-platinum complexes showed superior activity than trans-palladium complexes, but lower in comparison to cisplatin. The chemical reactivity of the tested complexes has been determined in an in vitro NBP test. The platinum complexes exhibited very high chemical reactivity in NBP test, higher than cisplatin. The results showed no correlation between cytotoxicity and chemical reactivity for platinum complexes. Two platinum(II) complexes {cis-[PtCl2(2-pmOpe)2], cis-[PtCl2(3-pmOpe)2]} have been synthesized and characterized by IR, 1H NMR, 31P NMR, and elemental analysis.     

Comparative study of copper(II)-curcumin complexes as superoxide dismutase mimics and free radical scavengers

Two stoichiometrically different copper(II) complexes of curcumin (stoichiometry, 1:1 and 1:2 for copper:curcumin), were examined for their superoxide dismutase (SOD) activity, free radical-scavenging ability and antioxidant potential. Both the complexes are soluble in lipids and DMSO. The formation constants of the complexes were determined by voltammetry. EPR spectra of the complexes in DMSO at 77K showed that the 1:2 Cu(II)-curcumin complex is square planar and the 1:1 Cu(II)-curcumin complex is distorted orthorhombic. Cu(II)-curcumin complex (1:1) with larger distortion from square planar structure shows higher SOD activity. These complexes inhibit gamma-radiation induced lipid peroxidation in liposomes and react with DPPH acting as free radical scavengers. One-electron oxidation of the two complexes by radiolytically generated azide radicals in Tx-100 micellar solutions produced phenoxyl radicals, indicating that the phenolic moiety of curcumin in the complexes participates in free radical reactions. Depending on the structure, these two complexes possess different SOD activities, free radical neutralizing abilities and antioxidant potentials. In addition, quantum chemical calculations with density functional theory have been performed to support the experimental observations.     

Novel Cu(II) quinoxaline N1,N4-dioxide complexes as selective hypoxic cytotoxins

As an effort to develop novel selective hypoxia-cytotoxins and to improve bioavailability and pharmacological and toxicological properties of quinoxaline N1,N4-dioxide derivatives (L1 = 3-amino-6(7)-chloroquinoxaline-2-carbonitrile N1,N4-dioxide, L2 = 3-amino-6(7)-bromoquinoxaline-2-carbonitrile N1,N4-dioxide and L3 = 3-amino-6(7)-methylquinoxaline-2-carbonitrile N1,N4-dioxide) and to get a synergism among metals and these type of bioreductive agents, L2 and three novel Cu(II) complexes of general formulae [Cu(II)(H2O)x(L - H)2], where L = L1 (x = 1), L2 (x = 0) or L3 (x = 2) were developed. L2 and complexes were synthesized and structurally characterized by elemental and thermal analyses, and FTIR, electronic, MS, NMR, and EPR spectroscopies. The new compounds were subjected to cytotoxic evaluation in V79 cells in hypoxic and aerobic conditions. The complexes showed excellent selective cytotoxicity in hypoxia, being their cytotoxicity similar to or higher than that of the ligands L1-L3. Besides, the copper complexes were so poorly cytotoxic in oxia as the free ligands. In addition, for the first time Cu(II)-quinoxaline complexes are reported as a family of hypoxic cytotoxins.     

Synthesis, crystal structure and pharmacological evaluation of two new Cu(II) complexes of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (benzoyl) hydrazone: a comparative investigation

Two new copper(II) complexes have been synthesized by reacting 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (benzoyl) hydrazone (H(2)L) with CuCl(2)·2H(2)O or Cu(NO(3))(2)·3H(2)O. The structures of the complexes have been determined by single crystal X-ray diffraction studies. Results obtained using spectroscopic methods strongly suggested that the ligand and its Cu(II) complexes could interact with calf thymus DNA through intercalation. In the case of protein binding, the obtained results indicated that all the three compounds could quench the intrinsic fluorescence of bovine serum albumin through static quenching process. In addition, antioxidant activity tests showed that H(2)L and its copper(II) complexes possess significant scavenging effect against free radicals. Further, the two copper(II) complexes exhibited effective cytotoxic activity against a panel of human cancer cell lines.     

Bioactivity of novel transition metal complexes of N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide

Cu(II), Fe(III), and Mn(II) complexes of a novel ligand N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide (H(2)mtbh) have been synthesized and characterized by elemental analyses, IR, UV-vis, NMR, mass, EPR and M?ssbauer spectroscopy. The results suggest a square planar structure for [Cu(Hmtbh)Cl] and [Cu(mtbh)] whereas an octahedral structure for [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)]. Mn(II) and Fe(III) complexes were found to inhibit proliferation of HT29 cells. [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)] inhibited proliferation of HT29 cells with half maximal inhibition (IC(50)) of 8.15+/-0.87 and 68.1+/-4.8 microM, respectively, whereas H(2)mtbh showed growth inhibition with IC(50) of 90.9+/-7.8 microM and were able to inhibit NMT activity in vitro. Mn(II) and Fe(III) complexes inhibited NMT activity in a dose dependent manner with IC(50) values of 20+/-2.2 and 60+/-7.2 microM, respectively, whereas ligand (H(2)mtbh) displayed IC(50) of 3.2+/-0.5 mM.     

Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway

We previously published the synthesis, characterization and cytotoxic effect of the novel Zn(II), Ni(II), and Cd(II) complexes with 2-formylpyridine selenosemicarbazone. Here we further investigate the mechanism of their antiproliferative activity against several cancer and vascular endothelial cell lines and compared it to the activity of the ligand itself, corresponding salts and, as a referent compound, cisplatin. Investigated complexes induced apoptosis in a time- and dose-dependent manner as well as changes in a cell cycle distribution. Caspase-3 activation in HeLa cells, MDA-MB-361 and vascular endothelial cells EA.hy 926 cells by ligand alone, as well as Zn(II), Ni(II), and Cd(II) complexes was preceded by the activation of the p53 tumor-suppressor gene family protein p73. In addition to activation of p73, these compounds also trigger cytochrome C release by upregulation of Bax expression. The release of cytochrome C has been linked to loss of mitochondrial membrane potential. However, our data indicated that the increased phosphorylation of ERK could be also one of the mechanism involved in the Zn(II), and Cd(II) complexes- induction of apoptosis. Selenosemicarbazone complexes with Cd(II) and Ni(II), possess dual ability to induce apoptosis as well as necrosis, and might present an added advantage for inducing cell death in a diverse array of malignant cells. Taken together, our findings could indicate potential role of these complexes as activator of cross-talk between different signaling pathways that leads to cell death, and thus making the complex intriguing field for further scientific, and maybe clinical investigations.     

Synthesis, structure and biological activity of copper(II) complexes of 4-(2-pyridylmethyl)-1,7-dimethyl-1,4,7-triazonane-2,6-dione and 4-(2-pyridylethyl)-1,7-dimethyl-1,4,7-triazonane-2,6-dione

Four mononuclear copper(II) complexes 1-4 have been synthesized with two new N-functionalized macrocyclic ligands L(1) and L(2). All complexes are well characterized by various spectroscopic techniques, elemental analyses and conductivity measurements. Results suggest that Cu(II) ion has N(2)O coordination from ligand and S(2) from two coordinated solvent molecules (SCH(3)CN for 1 and 3 while CH(3)OH for 2 and 4). The crystal structure of a representative complex 3 strengthen the proposed formulations for other isostructural copper(II) complexes. The structure of 3 shows few interesting features including rare bent mode of the coordinated CH(3)CN molecules. All complexes were assayed for in vitro antimicrobial activity against clinically isolated resistant strains of Pseudomonas aeruginosa and Proteus vulgaris; and standard strains of Staphylococcus aureus, P. aeruginosa, Klebsiella planticola and Escherichia coli. Results indicate that the copper complexes possess notable antimicrobial properties with MIC values of 62.5-500 microg/ml. Studies on the U87 cancerous cell lines show potent cytotoxicity with IC(50) and IC(90) values of 2.9-93.5 and 30-250 microg/ml, respectively. In vitro toxicity tests demonstrate that all copper complexes are less cytotoxic than that of gentamycin on normal HEK cell lines. These copper complexes show the potential to act as antimicrobial and anticancer agent.     

Cytotoxic copper (II) mixed ligand complexes: crystal structure and DNA cleavage activity

Two new mixed ligand complexes of copper (II) containing an imidazolyl terpyridine ligand, [Cu(Itpy)(bpy)](ClO(4))(2)·(H(2)O), 1, and [Cu(Itpy)(phen) (ClO(4))](ClO(4))·(H(2)O), 2 have been synthesized and characterized. Complex 1 has been found to possess a distorted square pyramidal geometry whereas 2 exhibit a distorted octahedral geometry. Electronic spectral titrations suggest that 1 and 2 bind to DNA intercalatively with the binding constant, K(b) (4.12 ± 0.13) × 10(4) M(-1) (1) and (6.04 ± 0.15) × 10(4) M(-1) (2). Under physiological condition, in the absence of any external cofactor 2 has been found to bring about DNA cleavage via hydrolytic mechanism but 1 does not bring about any DNA cleavage. Both compounds show antitumor effects on the A549 lung adenocarcinoma cancer cell line.