Synthesis and antitumour activity of platinum(II) and platinum(IV) complexes containing ethylenediamine-derived ligands having alcohol, carboxylic acid and acetate substituents. Crystal and molecular structure of [PtL4CL2].H20 where L4 is ethylenediamine-N,N'-diacetate

Several cisplatin analogues of ethylenediamine-derived ligands containing alcohol, carboxylic acid and acetate substituents have been prepared and characterised. Oxidation of some of these square planar platinum(II) complexes using aqueous hydrogen peroxide gave octahedral platinum(IV) complexes, containing trans hydroxo ligands. Acetylation of the hydroxo ligands was achieved by reaction with acetic anhydride, giving complexes which are analogues of the antitumour drug, JM-216. Oxidation of the complex [Pt(H2L4)Cl2], where H2L4 is ethylenediamine-N,N'-diacetic acid, with H2O2 gave the platinum(IV) complex [PtL4Cl2].H2O in which L4 is tetradentate as shown by a crystal and molecular structure. This complex was previously reported to be [Pt(HL4)(OH)Cl2] in which HL4 is tridentate. Several of the complexes were tested for antitumour activity against five human ovarian carcinoma cell lines. IC50 values range from 4.0 microM for cis,trans-PtCl2(OH)2(NH2CH2CH2NHCH2CH2OH) against the CH1 cell line to >25 microM indicating moderate to low activity relative to other platinum complexes.     

Biological activity of complexes derived from pyridine-2-carbaldehyde thiosemicarbazone. Structure of

Biological studies on [Fe(L)2](NO3).0.5H2O (1), [Fe(L)2][PF6] (2), [Co(L)2](NCS) (3), [Ni(HL)2]Cl2.3H2O (4) and Cu(L)(NO3) (5), where HL=C7H8N4S, pyridine-2-carbaldehyde thiosemicarbazone, have been carried out. The crystal structure of compound 3 has been solved. It consists of discrete monomeric cationic entities containing cobalt(III) ions in a distorted octahedral environment. The metal ion is bonded to one sulfur and two nitrogen atoms of each thiosemicarbazone molecule. The thiocyanate molecules act as counterions. The copper(II) and iron(III) complexes react with reduced glutathione and 2-mercaptoethanol. The reaction of compound 1 with the above thiols causes the reduction of the metal ion and bis(thiosemicarbazonato)iron(II) species are obtained. The redox activity, and in particular the reaction with cell thiols, seems to be related to the cytotoxicity of these complexes against Friend erithroleukemia cells and melanoma B16F10 cells.     

Aluminium(III), chromium(III) and iron(III) complexes with 5-iodouracil and 5-iodouracil-histidine and their antitumour activity

Complexes of the type [Al(HL)(OH)Cl(2)], [M(HL)(OH)(2)Cl] and [M'(HL)(L')(OH)Cl], where HL = 5-iodouracil; HL' = histidine; M = Cr(III), Fe(III) and M' = Al(III), Cr(III), Fe(III), were synthesized and characterized. The complexes are polymeric showing high decomposition points and are insoluble in water and common organic solvents. The mu(eff) values, electronic spectral bands and ESR spectra suggest a polymeric 6-coordinate spin-free octahedral stereochemistry for the Cr(III) and Fe(III) complexes. 5-Iodouracil acts as a monodentate ligand coordinating to the metal ion through the O atom of C((4)) = O while histidine through the O atom of -COO(- ) and the N atom of -NH(2) group. In vivo antitumour effect of 5-iodouracil and its complexes was examined on C(3)H /He mice against P815 murine mastocytoma. As evident from their T/C values, Cr(III) and Fe(III) complexes display significant and higher antitumour activity compared to the 5-iodouracil ligand. The in vitro results of the complexes on the same cells indicate that Cr(III) and Fe(III) complexes show higher inhibition on (3)H-thymidine and (3)H-uridine incorporation in DNA and RNA replication, respectively, at a dose of 5 microg/mL.     

Herbicides interacting with lanthanide(III) and calcium(II) ions: structural and biological similarities of Gd and Ca polymers

In this paper we report the synthesis and characterization of Ca(II), Gd(III) and Ce(III) complexes with chlorophenoxyalkanoic acids, which are commonly used as herbicides. The Gd(III) and Ca(II) complexes were characterized by the typical formulas [Gd(III)(L)(3)(H(2)O)(2).2dmf](n) and [Ca(L)(2)(MeOH)(2)](n) [L=[2,4-D=2,4-dichlorophenoxyacetic acid, 2,4,5-T=2,4,5-trichlorophenoxyacetic acid, MCPA=2-methyl-4-chlorophenoxy acetic acid and 2,4-DP=2-(2,4-dichlorophenoxy)propanoic acid]]. The crystal structure of the Gd(III) complex with 2,4-D shows that the compound is a one-dimensional polymer with a [Gd(III)(2)(2,4-D)(6)(H(2)O)(4)] dimeric repeat unit and the gadolinium atoms are in a nine-coordination environment, while the crystal structure of the Ca analog shows that it also has a polymeric structure with a [Ca(2)(2,4-D)(4)(CH(3)OH)(4)] dimeric repeat unit and the calcium atoms are in an eight-coordination environment. The gadolinium compound displays three different coordination modes for the carboxylato moiety, bidentate chelate, bidentate double bound and bidentate triple bound, while the calcium compound displays only one, bidentate triple bound. Coordination spheres are completed with oxygens of H(2)O or MeOH molecules, respectively. The complexes were tested against a few common bacteria by minimum inhibitory concentration (MIC) experiments and did not exhibit any antimicrobial action at concentrations up to 1600 microg/ml.     

Syntheses, crystal structures and antimicrobial activities of monomeric 8-coordinate, and dimeric and monomeric 7-coordinate bismuth(III) complexes with tridentate and pentadentate thiosemicarbazones and pentadentate semicarbazone ligands

Novel bismuth(III) complexes 1-4 with the tridentate thiosemicarbazone ligand of 2N1S donor atoms [Hmtsc (L1); 2-acetylpyridine (4N-morpholyl thiosemicarbazone)], the pentadentate double-armed thiosemicarbazone ligand of 3N2S donor atoms [H2dmtsc (L3); 2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone)] and the pentadentate double-armed semicarbazone ligand of 3N2O donor atoms [H2dasc (L4b); 2,6-diacetylpyridine bis(semicarbazone)], were prepared by reactions of bismuth(III) nitrate or bismuth(III) chloride and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FTIR and NMR (1H and 13C) spectroscopy. The crystal and molecular structures of complexes 1, 2a, 2b and 4b, and the "free" ligand L1 were determined by single-crystal X-ray structure analysis. The dimeric 7-coordinate bismuth(III) complex [Bi(dmtsc)(NO3)]2, 1, and the monomeric 7-coordinate complexes [Bi(Hdasc)(H2O)](NO3)2.H2O (major product), 2a, and [Bi(dasc)(H2O)]NO3.H2O (minor product), 2b, all with pentagonal bipyramidal bismuth(III) centers, are depicted with one electron pair (6s2) of the bismuth(III) atom, deprotonated forms of multidentate thiosemicarbazone or semicarbazone ligands, and monodentate NO3 or H2O ligands, respectively. These complexes are related to the positional isomers of one electron pair of the bismuth(III) atom; 1 has an electron pair positioned in the pentagonal plane (basal position), while 2a and 2b have an electron pair in the apical position. The monomeric 8-coordinate complex [Bi(mtsc)2(NO3)], 4b, which was obtained by slow evaporation in MeOH of the 1.5 hydrates 4a, was depicted with one electron pair of the bismuth(III) atom, two deprotonated mtsc- ligand and one nitrate ion. On the other hand, crystals of the complex "[Bi(mtsc)Cl2]", 3, prepared by a reaction of BiCl3 with L1 showed several polymorphs (3a, 3b, 3c and 3d) due to coordination and/or solvation of dimethyl sulfoxide (DMSO) used in the crystallization. Bismuth(III) complexes 1 and 4a showed selective and effective antibacterial activities against Gram-positive bacteria. The structure-activity relationship was discussed.     

Synthesis,molecular structure,solution equilibrium,and antiproliferative activity of thioxotriazoline and thioxotriazole complexes of copper II and palladium II

Preparations of copper(II) and palladium(II) complexes of 4-amino-5-methylthio-3-(2-pyridyl)-1,2,4-triazole (L(1)) and the copper(II) complex of 1,4-dihydro-4-amino-3-(2-pyridyl)-5-thioxo-1,2,4-triazole (HL) are described. These complexes have been characterized by means of spectroscopy and microanalysis. Molecular structures of HL (1), [CuCl(2)(H(2)L)]Cl.2H(2)O (2a), cis-[CuCl(2)(L(1))] (3), and cis-[PdCl(2)(L(1))] (4) have been determined by single-crystal X-ray diffraction. The HL ligand acts as a N,S bidentate through the thioxo moiety and the exo-amino group whilst the ligand L(1) forms N,N coordination complexes through the pyridine and triazole nitrogen atoms. Speciation in solution of the systems Cu/HL and Cu/L(1) have been determined by means of potentiometry and spectrophotometry as well as for the Cu/L(1)/A (HA=glycine) system in order to determine species present at physiological pH. Antiproliferative activity of these complexes and their ligands was evaluated, using the AlamarBlue Assay, on normal human fibroblasts (HF) and human fibrosarcoma tumor (HT1080) cells. The copper compounds cis-[CuCl(2)(H(2)L)]Cl and cis-[CuCl(2)(L(1))] exerted significant antiproliferative activity of both normal and neoplastic cells; although dose-response experiments revealed that the HT1080 cell line was more sensitive to the tested drugs than normal fibroblasts.     

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, structural investigations on organotin(IV) chlorin-e6 complexes, their effect on sea urchin embryonic development and induced apoptosis

Four new organotin(IV) chlorin derivatives, [chlorin=chlorin-e(6)=21H,23H-porphine-2-propanoic acid, 18-carboxy-20-(carboxymethyl)-8-ethenyl-13-ethyl-2,3-di-hydro-3,7,12,17-tetramethyl-(2S-trans)-], with formula (R(2)Sn)(3)(chlorin)(2).2H(2)O (R=Me, n-Bu) and (R(3)Sn)(3)chlorin.2H(2)O (R=Me, Ph) have been synthesized. The solid state and solution phase structures have been investigated by FT-IR, (119)Sn M?ssbauer, (1)H and (13)C NMR spectroscopy. In the solid state, (R(2)Sn)(3)(chlorin)(2).2H(2)O complexes contain six coordinated Sn(IV), in a skew trapezoidal environment by forming trans-R(2)SnO(4) polymeric units. As far as (R(3)Sn)(3)chlorin.2H(2)O complexes are concerned, Sn(IV) is five coordinated in a polymeric (oligomeric) trigonal bipyramidal environment and eq-R(3)SnO(2) units, in the solid state. In saturated solutions, a polymeric structure comparable to the solid phase, with carboxylate groups of the ligand behaving in monoanionic bidentate fashion bridging Sn(IV) atoms, was detected for the (Me(3)Sn)(3)chlorin.2H(2)O complex, while in more diluted ones a tetrahedral configuration for the trimethyltin(IV) moieties was observed. Cytotoxic activity of the novel organotin(IV) chlorin was investigated in order to assay the effect on sea urchin embryonic development. The results obtained demonstrated that (n-Bu(2)Sn)(3)(chlorin)(2).2H(2)O and (Ph(3)Sn)(3)chlorin.2H(2)O exerted the antimitotic effect on the early stages of sea urchin development. In addition, the cytotoxic effect exerted by (n-Bu(2)Sn)(3)(chlorin)(2).2H(2)O appeared with necrosis of the blastomeres, which were clearly destroyed. After treatment with (Ph(3)Sn)(3)chlorin.2H(2)O, a programmed cell death was triggered, as shown by light microscope observations through morphological assays. The apoptotic events in 2-cell stage embryos revealed: (i) DNA fragmentation, with the TUNEL reaction (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling); (ii) phosphatidylserine translocation in the membrane, with Annexin-V assay and (iii) cytoplasm blebbing, with the TUNEL reaction. The results demonstrated that the novel compound (Ph(3)Sn)(3)chlorin.2H(2)O was the most toxic derivative, by exerting antimitotic effect very early and by triggering apoptosis in the 2-cell stage of sea urchin embryonic development.     

Carbohydrate-appended 3-hydroxy-4-pyridinone complexes of the [M(CO)3]+ core (M = Re, 99mTc, 186Re)

This work describes the use of 3-hydroxy-4-pyridinone ligands for binding the [M(CO)(3)](+) core (M = Re, Tc) in the context of preparing novel Tc(I) and Re(I) glucose conjugates. Five pyridinone ligands bearing pendent carbohydrate moieties, HL(1-5), were coordinated to the [M(CO)(3)](+) core on the macroscopic scale (M = Re) and on the tracer scale (M = (99m)Tc, (186)Re). On the macroscopic scale the complexes, ReL(1-5)(CO)(3)(H(2)O), were thoroughly characterized by mass spectrometry, IR spectroscopy, UV-visible spectroscopy, elemental analysis, and 1D/2D NMR spectroscopy. Characterization confirmed the bidentate coordination of the pyridinone and the pendent nature of the carbohydrate and suggests the presence of a water molecule in the sixth coordination site. In preliminary biological evaluation, both the ligands and complexes were assessed as potential substrates or inhibitors of hexokinase, but showed no activity. Labeling via the [(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor gave the tracer species (99m)TcL(1-5)(CO)(3)(H(2)O) in high radiochemical yields. Similar high radiochemical yields when labeling with (186)Re were facilitated by in situ preparation of the [(186)Re(CO)(3)(H(2)O)(3)](+) species in the presence of HL(1-5) to give (186)ReL(1-5)(CO)(3)(H(2)O). Stability challenges, incubating (99m)TcL(1-5)(CO)(3)(H(2)O) in the presence of excess cysteine and histidine, confirmed complex stability up to 24 h.     

Synthesis, crystal structures, in vitro biological evaluation of zinc(II) and bismuth(III) complexes of 2-acetylpyrazine N(4)-phenylthiosemicarbazone

Two metal complexes formulated as [Zn(L)(2)](2)·H(2)O (1) and [Bi(L)(NO(3))(2)(CH(3)OH)] (2), where HL=2-acetylpyrazine N(4)-phenylthiosemicarbazone, have been synthesized and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological studies, carried out in vitro against selected bacteria and the K562 leukemia cell lines, respectively, have shown that the free ligand and its two complexes may be endowed with important biological properties, especially HL with MIC=3.90 μg/mL against Pseudomonas aeruginosa, the zinc(II) complex 1 with IC(50)=1.0 μM against K562 leukemia cell lines, respectively. The compounds HL and 1 may exert their cytotoxicity activity via induced loss of mitochondria membrane potential (MMP).     

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, structure, and nuclease properties of several binary and ternary complexes of copper(II) with norfloxacin and 1,10 phenantroline

Three new binary Cu(II) complexes of norfloxacin have been synthesized and characterized. We also report the synthesis, characterization and X-ray crystallographic structures of a new binary compound, [Cu(HNor)(2)]Cl(2).2H(2)O (2) and two new ternary complexes norfloxacin-copper(II)-phen, [Cu(Nor)(phen)(H(2)O)](NO(3)).3H(2)O (4), and [Cu(HNor)(phen)(NO(3))](NO(3)).3H(2)O (5). The structure of 2 consists of two crystallographically independent cationic monomeric units of [Cu(HNor)(2)](2+), chloride anions, and uncoordinated water molecules. The Cu(II) ion is placed at a center of symmetry and is coordinated to two norfloxacin ligands which are related through the inversion center. The structures of 4 and 5 consist of cationic units ([Cu(Nor)(phen)(H(2)O)](+) for 4 and [Cu(HNor)(phen)(NO(3))](+) for 5), nitrate counteranions, and lattice water molecules that provide crystalline stability through a network of hydrogen-bond interactions. The complexes exhibit a five coordinated motif in a square pyramidal environment around the metal center. The ability of compounds 4 and 5 to cleave DNA has also been studied. Mechanistic studies with different inhibiting reagents reveal that hydroxyl radicals, singlet oxygen, and superoxide radicals are all involved in the DNA scission process mediated by these compounds.     

Ligand-exchangeability of 2-coordinate phosphinegold(I) complexes with AuSP and AuNP cores showing selective antimicrobial activities against Gram-positive bacteria. Crystal structures of [Au(2-Hmpa)(PPh(3))] and [Au(6-Hmna)(PPh(3))] (2-H(2)mpa=2-mercaptopropionic acid, 6-H(2)mna=6-mercaptonicotinic acid)

Selective and effective antimicrobial activities against Gram-positive bacteria (B. subtilis and/or S. aureus) were found in 2-coordinate gold(I)-PPh(3) complexes with AuSP and AuNP cores, i.e. [Au(L)(PPh(3))] (HL=2-H(2)mna [H(2)mna=mercaptonicotinic acid] 3, D-H(2)pen [H(2)pen=penicillamine] 4, D,L-H(2)pen 5, 4-H(2)mba [H(2)mba=mercaptobenzoic acid] 8, Hpz [Hpz=pyrazole] 9, Him [Him=imidazole] 10, 1,2,3-Htriz [Htriz=triazole] 11, 1,2,4-Htriz 12, Htetz [Htetz=tetrazole] 13), whereas no activity was observed in 2-coordinate AuSP core complexes [Au(2-Hmba)(PPh(3))] 6 and [Au(3-Hmba)(PPh(3))] 7. The two novel AuSP core complexes, [Au(2-Hmpa)(PPh(3))] [H(2)mpa=mercaptopropionic acid] 1 and [Au(6-Hmna)(PPh(3))] 2, were prepared and characterized by elemental analysis, FT-IR, TG/DTA, and ((31)P, 1H and 13C) NMR spectroscopy. The crystal structures of 1 and 2 were determined as a supramolecular arrangement of the 2-coordinate AuSP core. Both 1 and 2 significantly showed antibacterial activities. As a model reaction of phosphinegold (I) complexes with the cysteine residue in the biological ligands, we examined if the ligand exchange reactions of the aromatic anions L(1)(-) in [Au(L(1))(PPh(3))] (HL(1)=6-H(2)mna 2, 2-H(2)mna 3, 2-H(2)mba 6, Hpz 9, Him 10, 1,2,3-Htriz 11, 1,2,4-Htriz 12) with aliphatic thiols HL(2) (HL(2)=2-H(2)mpa, D-H(2)pen) occurred under the mild conditions and, also, if the 'reverse' reactions, namely, the ligand exchange reactions of the thiolate anions in [Au(2-Hmpa)(PPh(3))] 1, [Au(D-Hpen)(PPh(3))] 4 and [Au(2-Hmba)(PPh(3))] 6 with the free ligands HL(1) took place under similar conditions. In this work, a relationship of the ligand-exchangeability among 2-coordinate gold(I) complexes (1-4, 6, 9-12) was revealed. Complex 6 was substitution-inert, whereas complexes 1-4 and 9-12 were substitution-labile. The ligand-exchangeability of Au-S and Au-N bonds in the 2-coordinate phosphinegold(I) complexes with AuSP and AuNP cores to form new AuSP cores, with retention of the Au-P bond, was closely related to the observed activities against Gram-positive bacteria, and the ease of the ligand-exchange reaction was strongly related to the intensity of the activities.     

DNA cleavage studies of mononuclear and dinuclear copper(II) complexes with benzothiazolesulfonamide ligands

Copper-based transition metal complexes performing single- and double-strand scission of DNA have been studied. The dinuclear complexes [Cu(2)(L)(2)(OCH(3))(2)(NH(3))(2)] and [Cu(2)(L)(2)(OCH(3))(2)(DMSO)(2)] are more active than the corresponding mononuclear [Cu(L)(2)(py)(2)] (where HL= N-(4-methylbenzothiazol-2-yl)benzenesulfonamide), suggesting that the dinuclearity is an important factor in the oxidative cleavage of DNA. The cleavage efficiency of the complexes depends on the reducing agent used in the process, the tandem ascorbate/H(2)O(2) being the most efficient. PAGE analyses have shown that these complexes cleave DNA without sequence selectivity. The DNA degradation process takes place mainly by C1' oxidation, but C4' and C5' oxidations cannot be ruled out as minor pathways. These copper complexes preferably oxidize guanine under mild conditions, but under more drastic conditions the oxidation reactivity appears to be T>G>C>A, suggesting the intervention of hydroxyl radicals as active species.     

Preparation, physicochemical properties and biological activity of copper(II) complexes with 6-(2-chlorobenzylamino)purine (HL1) or 6-(3-chlorobenzylamino)purine (HL2). The single-crystal X-ray structure of

Copper(II) complexes of 6-(2-chlorobenzylamino)purine (HL1) and 6-(3-chlorobenzylamino)purine (HL2), respectively, were prepared. Depending on the pH of the medium and the molar ratio of reactants the following mononuclear (trigonal-bipyramidal) and dinuclear (octahedral, trigonal-bipyramidal or tetrahedral) complexes were isolated: [Cu2(mu-HL1)2(mu-Cl2)2(HL1)2Cl2] (1a,b), [Cu2(mu-Cl)2(mu-L1)2(H2O)2] (2a), [Cu2(mu-Cl)2(mu-L2)2(H2O)2] (2b), [Cu(H+L2)2Cl3]Cl.H2O (3a,b), [Cu2(mu-Cl)2(HL1)2Cl2] (4a), and [Cu2(mu-Cl)2(HL2)2Cl2] (4b). The compounds were characterized by elemental analyses, electronic, infrared and mass (FAB+, ES+) spectral data, magnetic susceptibility temperature dependence measurements and molar conductivity data. An X-ray single-crystal structural analysis of [Cu(H+L2)2Cl3]Cl.2H2O (3b) showed that the Cu2+ ion is penta-coordinated by three chloride ions and by two H+L2 ligands. Thus, the Cu2+ ion adopts a distorted trigonal bipyramidal coordination geometry with the protonated H+L2 ligands coordinated in trans apical positions, while the three chloride ions are situated in an equatorial plane. The cytotoxic activity of the complexes was determined by a calcein AM assay. Mouse melanoma cell line B16-FO, human malignant melanoma cell line G361, human osteogenic sarcoma cell line HOS and human breast adenocarcinoma cell line MCF7 were used. IC50 values, the drug concentrations lethal to 50% of the tumor cells, were estimated. One of the important mechanisms responsible for the cytotoxicity of cytokinin-derived compounds, the inhibition of cyclin-dependent kinases by the studied complexes, was also determined.     

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.     

The crystal structures of copper(II), manganese(II), and nickel(II) complexes of a (Z)-2-hydroxy-N'-(2-oxoindolin-3-ylidene) benzohydrazide--potential antitumor agents

Mononuclear complexes of Cu(II), Ni(II), and Mn(II) with a new Schiff base ligand derived from indoline-2,3-dione and 2-hydroxybenzohydrazide, [Cu(II)(L)(2)], [Ni(II)(L)(2)], and [Mn(II)L.(AcO).2C(2)H(5)OH] [HL=(Z)-2-hydroxy-N'-(2-oxoindolin-3-ylidene)benzohydrazide], have been prepared. The complexes have been structurally characterized by X-ray crystallography. Among the three complexes, the Cu(II) complex had the novel highest antitumor activity.     

Structural correlation of catecholase-like activities of oxy-bridged dinuclear copper(II) complexes

Eight oxy-bridged dinuclear copper(II) complexes with catecholase-like sites, [Cu(L1)X]2 (HL1 = 1-diethylaminopropan-2-ol, X=N3- 1, NCO- 2, and NO2- 3), [Cu(L2)X]2 (HL2=N-ethylsalicylaldimine, X=NO3- 4, Cl- 5, N3- 6, NCS- 7), and [Cu(L3)]2(ClO4)2, 8 (HL3=N-(salicylidene)-N'-(2-pyridylaldene)propanediamine) have been prepared and characterized. The single crystal X-ray analysis show that the structures of complexes 6 and 8 are dimeric with two adjacent copper(II) atoms bridged by pairs of micro-oxy atoms from the L2 and L3 ligands. Magnetic susceptibility measurements in the temperature range 4-300 K indicate significant antiferromagnetic coupling for 4, 5 and 7 and ferromagnetic coupling for 6 between the copper(II) atoms. The catecholase activity of complexes for the oxidation of 3,5-di-tert-butylcatechol by O2 was studied and it was found that the complexes with the bond distance of Cu(II)...Cu(II) located at 2.9-3.0 A show higher catecholase activity.     

Synthetic, spectral, magnetic and in vitro cytotoxic activity studies of cobalt(II) complexes with cytokinin derivatives: X-ray structure of 6-(3-methoxybenzylamino)purinium chloride monohydrate

Cobalt(II) complexes with 6-(2-hydroxybenzylamino)purine (HL1), 6-(2-methoxybenzylamino)purine (HL2), 6-(3-methoxybenzylamino)purine (HL3) and 6-(4-methoxybenzylamino)purine (HL4) of the composition [Co(L1)Cl(H2O)2].H2O (1), [Co(L2)Cl(H2O)2] (2), [Co(L3)2(H2O)2].2H2O (3), [Co(L4)2(H2O)2].2H2O (4) have been synthesized. The compounds have been characterized by elemental analysis, FT-IR, ES+ MS (electrospray mass spectra in the positive ion mode) and electronic spectroscopies, magnetic and conductivity data as tetrahedral high-spin cobalt(II) complexes. The thermal stability of the complexes has also been studied. The cytotoxicity of the complexes (1-4) was determined by a Calcein acetoxymethyl (AM) assay. Human malignant melanoma (G361), human chronic myelogenous erythroleukemia (K562), human osteogenic sarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines were used for the testing. The molecular structure of 6-(3-methoxybenzylamino)purinium chloride monohydrate, H2L3+.Cl.H2O, i.e. a protonated form of the free HL(3) ligand, has been determined by a single crystal X-ray analysis. The geometry optimisation and infrared frequencies calculations of HL1, HL2, and H2L3+ and H2L4+ were performed using density-functional theory (DFT) calculations at the B3LYP/6-31G* level of the theory. The geometry of complex (1) was optimised at the same level of the theory.     

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.