Synthesis and characterization of new Pt(II) and Pd(II) complexes with 2-quinolinecarboxaldehyde selenosemicarbazone: cytotoxic activity evaluation of Cd(II), Zn(II), Ni(II), Pt(II) and Pd(II) complexes with heteroaromatic selenosemicarbazones

New complexes of Pt(II) and Pd(II) with 2-quinolinecarboxaldehyde selenosemicarbazone were synthesized and characterized by elemental analysis, NMR and IR spectroscopy and molar conductivity measurements. The assumed geometry of Pt(II) and Pd(II) complexes was square planar where the ligand was tridentately coordinated via the quinoline and imine nitrogen atoms and the selenium atom. The cytotoxic activity of the new Pt(II) and Pd(II) compounds, as well as of some previously synthesized Cd(II), Zn(II) and Ni(II) complexes with the same or analogous ligand, was tested against a panel of three human cancer cell lines: human cervix carcinoma cells (HeLa), human melanoma cells (FemX) and breast cancer cells (MDA-361). All investigated compounds, except Pt(II) complex, possess a strong dose-dependent cytotoxic activity of the same order of magnitude as cisplatin (CDDP). The investigation of potential of these compounds to induce HeLa cell cycle perturbations was also evaluated.     

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.     

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.     

Synthesis, antibacterial and antifungal activity of some new pyridazinone metal complexes

The new various metal complexes of 5-benzoyl-4-hydroxy-2-methyl-6-phenyl-2H-pyridazin-3-one were synthesized. All the complexes were evaluated for their antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi using microdilution procedure. The Cd(II) and Ni(II) complexes exhibited selective and effective activities against one Gram-positive bacterium (Staphylococcus aureus ATCC 6538), one Gram-negative bacterium (Pseudomonas putida ATCC 12633) and against two yeast (Candida albicans ATCC 27541 and Candida tropicalis 1828) in contrast to poor activity observed other microorganisms. The new synthesized complexes were characterized using IR, 1H-NMR and UV spectral data together with elemental analysis.     

Synthesis and antitumor studies on novel Co(II), Ni(II) and Cu(II) metal complexes of bis(3-acetylcoumarin)thiocarbohydrazone

The synthesis, structure, physico-chemical investigation and biological studies of some metal complexes of thiocarbohydrazone ligands are described. The ligand is obtained by condensation of N,N'-thiocarbohydrazide with 3-acetylcoumarin. The metal complexes of Co(II), Ni(II) and Cu(II) with bis(3-acetylcoumarin)thiocarbohydrazone were synthesized and isolated as solid products and characterized by analytical means as well as by spectral techniques such as FT-IR, (1)H NMR and EPR and UV spectrometry. The ligand acts as bidentate, through NO or NN, neutral in coordinating the M(II) ions. The bonding sites are the azomethine nitrogen, lactone carbonyl oxygen and respective anion counterparts. The metal complexes exhibit either octahedral or distorted octahedral structures. The complexes are found to be soluble in dimethylformamide and dimethylsulphoxide. Molar conductance values in dimethylsulphoxide indicate the non-electrolytic nature of the complexes. The compounds tested in present study have shown promising cytotoxic activity when screened using the in vitro method and at the same time were shown to have good activity when tested using the Ehrlich Ascites Carcinoma model. Preliminary antimicrobial screening shows the promising results against both bacterial and fungal strains.     

Co(III), Ni(II), Zn(II) and Cd(II) complexes with 2-acetyl-2-thiazoline thiosemicarbazone: Synthesis, characterization, X-ray structures and antibacterial activity

The new ligand 2-acetyl-2-thiazoline thiosemicarbazone (HATtsc) and the complexes [Co(ATtsc)₂]₂[CoCl₄]·2H₂O (1), [Co(ATtsc)₂]NO₃·H₂O (2), [Ni(HATtsc)₂](NO₃)₂ (3), [ZnCl₂(HATtsc)]·CH₃CN (4), [{CdCl(HATtsc)}₂(μ-Cl)₂]·2H₂O (5) and [{Cd(NO₃)(HATtsc)}₂(μ-NO₃)₂] (6) were isolated and characterized by a variety of physico-chemical techniques and X-ray diffraction. The structure of HATtsc in 1 and 2 presented a thiolate form while in 3-6 the thione form was present, as it was in free ligand. In addition, we studied the antibacterial activity of the ligand and complexes 2-6 against some representative bacteria. Cd(II) complexes were more active against Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Bacillus subtilis than organic ligand. Conversely, Cd(II) compounds seemed to interfere in the cell separation of B. subtilis.     

Synthesis, characterization of copper(II), cobalt(II), nickel(II), zinc(II) and cadmium(II) complexes of [7-hydroxy-4-methyl-8-coumarinyl]glycine and a comparitive study of their microbial activities

A new Mannich base, [7-hydroxy-4-methyl-8-coumarinyl]glycine [MCGH(2)], has been prepared by the condensation of 7-hydroxy-4-methyl-coumarin with glycine and formaldehyde. Its conformational changes on complexation with transition metal ions [copper(II), cobalt(II), nickel(II), zinc(II) and cadmium(II)] have been studied on the basis of elemental analysis, conductivity measurements, spectral (infrared, (1)H NMR, electronic, EPR), magnetic and thermogravimetric studies. The infrared spectral studies of all the complexes reveal that the ligand has coordinated through -NH and two hydroxyl groups. The conductance data of the complexes suggest them to be non-electrolytes. Fluorescence property of the ligand and its metal complexes was studied and concluded that the ligand MCGH(2) can be a potential candidate for the determination of zinc(II) and cadmium(II) at room temperature by fluorimetric method. The antimicrobial activity of all the compounds was studied against Gram negative (Escherichia coli) and Gram positive (Bacillus cirroflagellosus) bacteria and fungi, Aspergillus niger and Candida albicans. It was observed that the coordination of metal ion has a pronounced effect on the microbial activities of the ligand. All the metal complexes have shown higher antimicrobial effect than the free ligand.     

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.     

Synthesis and characterization of cobalt(II), nickel(II), copper(II) and zinc(II) complexes with Schiff base derived from 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine

A few (1:1) and (1:2) metal complexes of cobalt(II), nickel(II), copper(II) and zinc(II) have been isolated with ligand derived from the condensation of 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine with 2-acetylpyridine (L(1)) and characterized by elemental analysis, conductivity measurements, infrared, electronic, (1)H NMR spectral data, magnetic and thermogravimetric analyses. Due to insolubility in water and most of the common organic solvents and infusibility at higher temperatures, all the complexes are thought to be polymeric in nature. A square-planar geometry was suggested for copper(II) and octahedral proposed for cobalt(II), nickel(II) and zinc(II). Some of the chemically synthesized compounds have been screened in vitro against the three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Escherichia coli) organisms. It is observed that the coordination of metal ion has pronounced effect on the microbial activities of the ligand. The metal complexes have higher antimicrobial effect than the free ligands.     

Stereospecific ligands and their complexes. Part VII. Synthesis, characterization and in vitro antitumoral activity of platinum(II) complexes with O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid

Platinum(II) complexes (1-4) with bidentate N,N'-ligands, O,O'-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid were synthesized and characterized by IR, (1)H NMR and (13)C NMR spectroscopy and elemental analysis. DFT calculations were performed for the complexes and it was found that only one diastereoisomer could be formed. Cytotoxic activity of complexes 1-4 was determined against chronic lymphocytic leukemia cells (CLL) and compared to the activity of ligand precursors L1 · 2HCl-L4·2HCl and corresponding palladium(II) complexes, [PdCl(2)L] (L = L1-L4). The complexes were found to exhibit significantly higher antitumor activities than cisplatin on CLL cells. Cytotoxic effect of platinum(II) complexes on CLL cells was higher compared to corresponding palladium(II) complexes. In addition the mode of cell death induced by platinum(II) complexes was determined.     

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.     

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.     

The protective role of zinc and calcium in Vicia faba seedlings subjected to cadmium stress

The aim of the present study was to evidence the possible antagonistic effect of Zinc (Zn(2+)) and Calcium (Ca(2+)) against cadmium (Cd(2+))-induced DNA damage by using random amplification of polymorphic DNA (RAPD) and metabolic activities in Vicia faba. The results showed that all doses of Cd(2+) (10( -3) M, 10(-5) M) caused an increase in polymorphism value and a decrease in genomic template stability (GTS %). In addition, when 10( -4)-10(-6) M Ca(2+), 10(-6) M Zn(2+) were added together with 10(-3) M, 10(-4) M, 10(-5) M of Cd(2+), polymorphism value decreased besides GTS, total protein and chlorophyll content increased. Results suggested that Zn(2+) and Ca(2+) have an antagonistic effect against Cd(2+). The order of the antagonisms of Ca(2+), Zn(2+) against Cd(2+) toxicity was Ca(2+) > Zn(2+). Especially, the degree of antagonistic effect of Zn(2+) against Cd(2+) is probably related to its concentration ratio.     

Influence of essential elements on cadmium uptake and toxicity in a unicellular green alga: the protective effect of trace zinc and cobalt concentrations

Within the biotic ligand model (BLM) construct, major cations are considered to be simple competitors for metal binding to uptake sites and may offer some protection against metal-induced toxicity, but the influence of essential trace elements and cell preconditioning to different micronutrient concentrations on metal uptake and toxicity is considered negligible. To test these underlying assumptions, we monitored Cd uptake and toxicity in a green alga (Chlamydomonas reinhardtii) after long-term exposures (60 h) to a range of environmentally realistic free Zn(2+) , Co(2+) , Fe(3+) , Mn(2+) , Ca(2+) , and Cu(2+) concentrations buffered with nitrilotriacetic acid. A 200-fold increase in free [Mn(2+) ] as well as a 100-fold increase in free [Fe(3+) ] did not affect Cd uptake or toxicity, whereas a 50-fold increase in free [Ca(2+) ] effectively offered some protection, as predicted by the BLM. However, a 10-fold increase in free [Cu(2+) ] significantly enhanced Cd toxicity by a factor of approximately 2, whereas a 100-fold increase in free [Zn(2+) ] and [Co(2+) ] from 10(-11) to 10(-9) M significantly decreased Cd uptake and toxicity by more than twofold. These effects did not change with prior algal acclimation to different essential micronutrient concentrations. Low essential trace metal concentrations may strongly affect the uptake and toxicity of Cd in freshwater algae and should be taken into consideration in future developments of the BLM.     

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 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,cytotoxic activity on MCF-7 cell line and mutagenic activity of platinum(II) complexes with 2-substituted benzimidazole ligands

Four Pt(II) complexes with 2-H/or-methyl/or-aminomethylbenzimidazole or 1,2-dimethylbenzimidazole ligands as "non-leaving groups" were synthesized and their antiproliferative properties were tested against the human MCF-7 breast cancer cell line. The mutagenic potentials of the complexes were tested in Salmonella typhimurium strains TA 98 and TA 100 in the absence of S9 rat liver fraction. In general, Pt(II) complexes tested which were found to be less active than cisplatin, exhibited moderate in vitro cytotoxic activity on MCF-7 cell line. Among the complexes tested, Pt(II) complex with 2-aminomethylbenzimidazole ligand was found to be highly mutagenic in S. typhimurium TA 98 and low mutagenic in S. typhimurium TA 100. Pt(II) complex with 1,2-dimethylbenzimidazole was mutagenic only in S. typhimurium TA 98. The other two complexes were found to be non-mutagen in both strains.     

Synthesis, X-ray structure and cytotoxic effect of nickel(II) complexes with pyrazole ligands

Here we present the synthesis of the new Ni(II) complexes with chelating ligands 1-benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (a), 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (b) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (c). These ligands a–c create solid complexes with Ni(II). The crystal and molecular structures of two complexes were determined by X-ray diffraction method. Thermal stability of two complexes with ligand c by TG/DTG and DSC methods were also shown. Cytotoxic activity of all the complexes against three tumour cell lines and to normal endothelial cells (HUVEC) was also estimated. Complexes with ligand c exhibited relatively high cytotoxic activity towards HL-60 and NALM-6 leukaemia cells and WM-115 melanoma cells. Cytotoxic effectiveness of one of these complexes against melanoma WM-115 cells was two times higher than that of cisplatin. The protonation constant log K = 9.63 of ligand b corresponding to the phenol 2-hydroxy group has been determined in 10% (v/v) DMSO/water solution (25 °C). The coordination modes (formation of two monomeric species: NiL and NiL₂) in the complexes with Ni(II) are discussed for b on the basis of the potentiometric and UV/Vis data.     

In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents

Reactions of thiosemicarbazones of 2-formyl and 2-acetyl pyridine and containing an azepane ring (hexamethyleneiminyl ring) incorporated at N(4)-position, HL(1) (1) and HL(2) (2) with platinum(II) afforded the complexes, [Pt(L(1))Cl] (3) and [Pt(L(2))Cl] (4). Characterization of the compounds was accomplished by means of elemental analysis and spectroscopic techniques NMR, UV-vis and IR spectroscopy. The single-crystal X-ray structure of complex [Pt(L(2))Cl] (4) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N atom, the imine-N atom, and thiolato S-atom. Compounds 1-4 have been evaluated for antiproliferative activity in vitro against 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 L-929 (a fibroblast-like cell line cloned from strain L). Ligand 2 exhibited high activity as anticancer agent against all four cancer cell lines, while ligand 1 exhibited selectivity against MCF-7, L-929 cell lines and complex 4 against A-549, T-24 cancer cell lines. Also, the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. Complex 3 afforded five to six cures against leukemia P388. The in vivo results of the antitumor activity show the two platinum complexes as very effective chemotherapeutic antileukemic agents.     

Abiotic reduction of nitroaromatic contaminants by iron(II) complexes with organothiol ligands

Complexation of Fe(II) by dissolved and surface-bound ligands can significantly modify the metal's redox reactivity, and recent work reveals that Fe(II) complexes with selected classes of organic ligands are potent reductants that may contribute to the natural attenuation of subsurface contaminants. In the present study, we investigated the reactivity of Fe(II)-organothiol ligand complexes with nitroaromatic contaminants (NACs; ArNO(2)). Experimental results show that NACs are unreactive in Fe(2+)-only and ligand-only solutions but are reduced to the corresponding aniline compounds (ArNH(2)) in solutions containing both Fe(II) and a number of organothiol ligands. Observed reaction rates are highly dependent on the structure of the Fe(II)-complexing ligand, solution composition, Fe(II) speciation, and NAC structure. For two model ligands, cysteine and thioglycolic acid, observed pseudo-first order rate constants for 4-chloronitrobenzene reduction (k(obs); 1/s) are linearly correlated with the concentration of the respective 1:2 Fe(II)- organothiol complexes (FeL(2)(2-)), and k(obs) measurements are accurately predicted by k(obs) = k(FeL(2-)(2))[FeL(2-)(2)], where k(FeL(2-)(2)) = 1.70 (+/-0.59) 1/M/s and 26.0 (+/-4.8) 1/M/s for cysteine and thioglycolic acid, respectively. The high reactivity of these Fe(II) complexes is attributed to a lowering of the standard one-electron reduction potential of the Fe(III)/Fe(II) redox couple on complexation by organothiol ligands. The relative reactivity of a series of substituted NACs with individual Fe(II) complexes can be described by linear free-energy relationships with the apparent one-electron reduction potentials of the NACs. Tests also show that organothiol ligands can further promote NAC reduction indirectly by re-reducing the Fe(III) that forms when Fe(II) complexes are oxidized by reactions with the NACs.