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.     

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.     

Synthesis, characterization and biological activity of copper complexes with pyridoxal thiosemicarbazone derivatives. X-ray crystal structure of three dimeric complexes

A dimeric copper complex of the unsubstituted pyridoxal thiosemicarbazone (H(2)L), [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O, previously tested on Friend murine cell lines has been recently resynthesized to evaluate its behavior on different murine and human leukemic cell lines and has been compared, in vitro and in vivo, with its monomeric counterpart [Cu(H(2)L)(OH(2))Cl]Cl. On TS/A murine adenocarcinoma cell line in vitro, both compounds significantly inhibit cell proliferation at micromolar concentrations, although the dimeric compound is more active. Despite this cytotoxicity they lack in vivo activity on TLX5 lymphoma. The unsubstituted dimeric [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O induces apoptosis on CEM and U937 human cell lines, with IC(50) concentrations of 1.2 x 10(-5) and 6.7 x 10(-6) M, respectively, but it is inactive on K562. Moreover, it alters significantly the cell cycle of U937 and CEM lines and decreases the telomerase activity of U937. To verify if other dimeric copper complexes show relevant biological activity new complexes with N-substituted pyridoxal thiosemicarbazones have been synthesized and characterized using spectroscopic techniques. Three of them, namely [Cu(Me(2)-HL)Cl](2).6H(2)O (Me(2)-H(2)L=pyridoxal N1,N1-dimethylthiosemicarbazone) (1), [Cu(MeMe-HL)Cl](2)Cl(2).4H(2)O (MeMe-HL=pyridoxal N1,N2-dimethylthiosemicarbazone) (2), [Cu(Et-H(2)L)Cl](2)Cl(2).2H(2)O (Et-H(2)L=pyridoxal N1-ethylthiosemicarbazone) (3), were also characterized by X-ray diffractometry. These complexes are dimeric and all three present a square pyramidal coordinative geometry with the ligand showing an SNO tridentate behavior. Their biological activities have been tested in vitro on U937, CEM and K562 cell lines to ascertain their effectiveness in comparison to the corresponding unsubstituted complex [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O. Compound 1 shows weak proliferation inhibition on all three cell lines, but it does not induce apoptosis and it does not inhibit telomerase activity, compound 2 is not effective at low concentration and is toxic at higher doses; compound 3 inhibits CEM cell growth better than complex 1 but it does not exert any other biological effect.     

Interaction between iron(II) and hydroxamic acids: oxidation of iron(II) to iron(III) by desferrioxamine B under anaerobic conditions

Interaction between iron(II) and acetohydroxamic acid (Aha), alpha-alaninehydroxamic acid (alpha-Alaha), beta-alaninehydroxamic acid (beta-Alaha), hexanedioic acid bis(3-hydroxycarbamoyl-methyl)amide (Dha) or desferrioxamine B (DFB) under anaerobic conditions was studied by pH-metric and UV-Visible spectrophotometric methods. The stability constants of complexes formed with Aha, alpha-Alaha, beta-Alaha and Dha were calculated and turned out to be much lower than those of the corresponding iron(II) complexes. Stability constants of the iron(II)-hydroxamate complexes are compared with those of other divalent 3d-block metal ions and the Irving-Williams series of stabilities was found to be observed. Above pH 4, in the reactions between iron(II) and desferrioxamine B, the oxidation of the metal ion to iron(III) by the ligand was found. The overall reaction that resulted in the formation of the tris-hydroxamato complex [Fe(HDFB)]+ and monoamide derivative of DFB at pH 6 is: 2Fe2+ + 3H4DFB+ = 2[Fe(HDFB)]+ + H3DFB-monoamide+ + H2O + 4H+. Based on these results, the conclusion is that desferrioxamine B can uptake iron in iron(III) form under anaerobic conditions.     

Design and synthesis of new models for diiron biosites

In order to mimic dinuclear active sites of some non-heme diiron proteins, ten new polydentate and potentially dinucleating ligands have been synthesized. Each ligand contains a carboxylate moiety designed to bridge two metal atoms. These central carboxylate moieties are derived from substituted benzoic acids that in turn are linked to terminal nitrogen or oxygen donors by spacers so that framework-type polydentate ligands similar to the polypeptide frames in diiron metallobiosites are formed. Reaction of these ligands with Fe(ClO4)3 x 9H2O leads to ferric mu-oxo-mu-carboxylato iron complexes of the general formulas [Fe2O(L)2(H2O)2](ClO4)2 and [Fe2O(L)(BzO)](ClO4)2 (L = ligand), containing one or two immobilized bridging carboxylates, respectively. While X-ray crystallography shows that some of these complexes are dimers or network polymers in the solid state, electrospray ionization mass spectrometry (ESMS) and spectroscopic data (UV-Vis, NMR, Móssbauer) indicate that they dissociate to monomeric Fe2O units in dilute CH3CN solutions.     

Synthesis, characterization, and antitumor activity of iron(II) and iron(III) complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones

Complexes of iron(II) and iron(III) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H), 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (4-Me-5-NH2-1-iqtsc-H) and 4-(m-aminophenyl)-2-formylpyridine thiosemicarbazone (4-m-NH2ph-2-pytsc-H) were synthesized and characterized by elemental analysis, conductance measurements, magnetic susceptibilities (from room temperature down to liquid N2 temperature), and M?ssbauer, electronic, and infrared spectral studies. On the basis of these studies, a highly distorted, high-spin, five-coordinate structure for Fe(HL)SO4 (HL = 1-iqtsc-H, 4-Me-5-NH2-1-iqtsc-H or 4-m-NH2ph-2-pytsc-H) and a distorted, low-spin, octahedral structure for Fe(HL)Cl2 are suggested. The EPR spectra of iron(III) complexes show that all have dxy low-spin ground state. All these complexes have been screened for their antitumor activity against the P 388 lymphocytic leukemia test system in mice and have been found to possess significant activity at the dosages employed.     

Differentiation activity of pyridoxal thiosemicarbazone and its copper and cobalt complexes on Friend erythroleukemia cells

Thiosemicarbazones are a wide group of organic derivatives whose biological activities are a function of the parent aldehyde or ketone and of the coordination metal type. Some thiosemicarbazones possess a broad spectrum of potentially useful chemotherapeutic properties (antitumor, antibacterial, antiviral, antimalarial). The present study reports the biological effects of pyridoxal thiosemicarbazone, H2L, and relative complexes with copper, [(Cu(HL)(OH2))2]++ and with cobalt, [Co(III)(L)(HL)] on the differentiation of Friend erythroleukemia cells (FLC). They are murine proerythroblasts chronically infected by a producing Friend leukemia virus complex; their exposure to dimethylsulfoxide (Me2SO) or other chemical agents induces these cells to terminal erythroid differentiation, therefore these cells represent a good model of differentiation in vitro. Here we describe induction differentiation experiment of pyridoxal thiosemicarbazone and relative complexes of copper and cobalt on FLC performed with concentrations of 50 ug/ml (ligand), 2 ug/ml (complexes). These have little effects on cell proliferation at doses used in these experiments. Higher doses have evident cytotoxic effects. The treatment with the copper complex induces a moderate differentiation of FLC and enhances effects on erythroid differentiation of Me2SO-induced FLC. On the contrary H2L and [Co(III)(L)(HL)] haven't inducing effects or enhancing effects on Me2SO-induced FLC hemopoietic differentiation. In conclusion, the present study shows that copper complexes of pyridoxal thiosemicarbazone exert action of inducing agent and are able to enhance Me2SO-induced FLC hemopoietic differentiation.     

Effect of metal ion complexation and chalcogen donor identity on the antiproliferative activity of 2-acetylpyridine N,N-dimethyl(chalcogen)semicarbazones

Three chalcogensemicarbazones, viz., 2-acetylpyridine N,N-dimethylsemicarbazone (HL(1)), 2-acetylpyridine N,N-dimethylthiosemicarbazone (HL(2)) and 2-acetylpyridine N,N-dimethylselenosemicarbazone (HL(3)), their corresponding gallium(III) complexes [Ga(L(1-3))(2)]PF(6) and the ruthenium(III) compound [Ru(L(2))(2)]PF(6) have been prepared and characterised by X-ray crystallography and spectroscopic techniques (IR, UV/vis, (1)H, (13)C, (15)N, (77)Se NMR) in order to elucidate the effect of metal ion complexation and chalcogen donor identity on the cytotoxicity of chalcogensemicarbazones in two human tumour cell lines 41M (ovarian carcinoma) and SK-BR-3 (mammary carcinoma).     

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.     

Reactions of sulfur-nitrosyl iron complexes of "g=2.03" family with hemoglobin (Hb): kinetics of Hb-NO formation in aqueous solutions.

NO-donating ability of nitrosyl [Fe-S] complexes, namely, mononuclear dinitrosyl complexes of anionic type [Fe(S2O3)2(NO)2]-(I) and neutral [Fe2(SL1)2(NO)2] with L1=1H-1,2,4-triazole-3-yl (II); tetranitrosyl binuclear neutral complexes [Fe2(SL2)2(NO)4] with L2=5-amino-1,2,4-triazole-3-yl (III); 1-methyl-1H-tetrazole-5-yl (IV); imidazole-2-yl (V) and 1-methyl-imidazole-2-yl (VI) has been studied. In addition, Roussin's "red salt" Na2[Fe2S2(NO)4] x 8H2O (VII) and Na2[Fe(CN)5NO] x H2O (VIII) have been investigated. The method for research has been based on the formation of Hb-NO adduct upon the interaction of hemoglobin with NO generated by complexes I-VIII in aqueous solutions. Kinetics of NO formation was studied by registration of absorption spectra of the reaction systems containing Hb and the complex under study. For determination of HbNO concentration, the experimental absorption spectra were processed during the reaction using standard program MATHCAD to determine the contribution of individual Hb and HbNO spectra in each spectrum. The reaction rate constants were obtained by analyzing kinetic dependence of Hb interaction with NO donors under study. All kinetic dependences for complexes I-VI were shown to be described well in the frame of formalism of pseudo first-order reactions. The effective first-order rate constants for the studied reactions have been determined. As follows from the values of rate constants, the rate of interaction of sulfur-nitrosyl iron complexes (I-VI) with Hb is limited by the stage of NO release in the solution.     

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.     

Polynuclear diorganotin(IV) complexes with arylhydroxamates: Syntheses, structures and in vitro cytotoxic activities

Series of polynuclear diorganotin(IV) complexes with di-halogenbenzohydroxamate ligands (substituents=2,4-Cl(2), 2,4-F(2), 3,4-F(2), 2,5-F(2), 2,6-F(2)), formulated as the polymeric [R(2)SnL](n)a (1:1) and the tetranuclear [R(4)Sn(2)(HL)(2)(L)](2)b (2:3) (HL=arylhydroxamate), were prepared and characterized by FT-IR, (1)H, (13)C, (119)Sn NMR spectroscopies, elemental analyses and melting point measurements. X-ray diffraction analyses were also carried out for the representative complexes [Me(2)Sn{2,4- F(2)C(6)H(3)C(O)NO}](n)2a and [n-Bu(4)Sn(2){2,4- F(2)C(6)H(3)C(O)NHO}(2) {2,4-F(2)C(6)H(3)C(O)NO}] (2)1b and show that the ligated mono- and di-basic forms, HL and L, of the arylhydroxamic acid (H(2)L) display the oxamic and oximic tautomeric forms, respectively. These compounds exhibit in vitro cytotoxicities toward human leukemic promyelocites HL-60, BGC-823, BEL-7402 and KB cell lines which, in some cases, are identical to, or even higher than, that of "cisplatin". The polymeric diorganotin/hydroxamato complexes a containing the long carbon chain butyl ligands are the most active ones, and the dependence of the antitumor activity of the complexes on various factors, namely the nuclearity, the organic ligand, the type, position and number of the X ring substituents, is also discussed.     

Study on synthesis, structure, and DNA-binding of lanthanide complexes with 2-carboxylbenzaldehyde thiosemicarbazone

2-Carboxylbenzaldehyde thiosemicarbazone (HL), and its three lanthanide (III) complexes, LnL(3) x 4H(2)O [Ln(III)=La, Sm, Eu], have been synthesized in water. The complexes were characterized by elemental analyses, molar conductivity and IR spectra. The crystal structure of [Sm(2)L(6)(CH(3)OH)(4)] x 7.5CH(3)OH x 0.5H(2)O obtained from methanol solution was determined by X-ray diffraction analysis, crystallized in the triclinic system, space group P-1, Z=1, a=12.217 (2)A, b=14.706 (2)A, c=15.035 (2)A, alpha=111.84(1) degrees , beta=103.47(1) degrees , gamma=104.24(1) degrees , R(1)=0.0290. It has symmetrical (mu-OCO)(2), (mu-O)(2) and disamarium(III) units. The coordination geometry of each Sm(III) ion is a distorted tetradecahedron with nine oxygen atoms. In addition, the DNA-binding properties of the ligand and its complexes have been investigated by absorption, fluorescence, and viscosity measurements. The experimental results indicate that the ligand and the Sm-complex can bind to DNA, but the other two complexes cannot; the binding affinity of the Sm-complex is higher than that of the ligand and the intrinsic binding constant K(b) of the complex is 3.22 x 10(5)M(-1).     

Antibacterial activity and spectral studies of trivalent chromium, manganese, iron macrocyclic complexes derived from oxalyldihydrazide and glyoxal

A new series of complexes is synthesized by template condensation of oxalyldihydrazide and glyoxal in methanolic medium in the presence of trivalent chromium, manganese and iron salts forming complexes of the type: [M(C(8)H(8)N(8)O(4))X]X(2) where M = Cr(III), Mn(III), Fe(III) and X = Cl(-1), NO(-1)(3), CH(3)COO(-1). The complexes have been characterized with the help of elemental analyses, conductance measurements, magnetic susceptibility measurements, electronic, NMR, infrared and far infrared spectral studies. On the basis of these studies, a five coordinate square pyramidal geometry for these complexes has been proposed. The biological activities of the metal complexes were tested in vitro against a number of pathogenic bacteria and some of the complexes exhibited remarkable antibacterial activities.     

Synthesis and characterization of bis(mu-hydroxo)diiron(III) complex of N-(4-nitro-2-hydroxy)phenylmethyl-N-(2-pyridylethyl)-N-(2-pyridylmethyl)amine and hydroxylation reaction of alkane

Bis(mu-hydroxo)diiron(III) complex, [Fe2III(mu-OH)2(NE)2](NO3)2 x 3H2O (3) (N-(4-nitro-2-hydroxy)phenylmethyl-N-(2-pyridylethyl)-N-(2-pyridylmethyl)amine = HNE, where H denotes a dissociable proton of the p-nitrophenol group), has been prepared and characterized by X-ray crystallography, electronic and magnetic spectroscopies.     

Crystal structure, solid state and solution characterisation of copper(II) coordination compounds of ethyl 5-methyl-4-imidazolecarboxylate (emizco)

The synthesis and characterisation of the following compounds derived from the biological relevant compound ethyl 5-methyl-4-imidazolecarboxylate (emizco) (1): [Cu(emizco)Cl2] (2), [Cu(emizco)2Cl2] (3), [Cu(emizco)2Br2] (4), [Cu(emizco)2(H2O)2](NO3)2 (5) and [Cu(emizco)4](NO3)2 (6), is presented. These compounds were characterised by IR and UV spectroscopic techniques, in addition the crystal structures of compounds 1-5 were determined. For complexes 2-5, emizco is coordinated as a bidentate ligand, through the oxygen atom of the carboxylate moiety and the nitrogen atom of the imidazolic ring. Different geometries are stabilised: compound 2 includes a pentacoordinated square pyramidal metal centre, while 3-5 are derived from octahedral geometry. Halide compounds 3 and 4 show a cis-octahedral arrangement, which is not very common on [CuN2O2X2] systems, while 5 stabilises the trans-octahedral isomer. Compound 6 displays a square planar geometry. Finally, hydrolysis of emizco to its corresponding carboxylic acid (mizco), allowed the preparation of another square planar complex 7, identified as [Cu(mizco)2] 0.5H2O. Solution studies of these compounds indicate that emizco is not substituted from the coordination sphere, remaining as a bidentate ligand. Halides are substituted by water molecules, changing from cis octahedral to the trans-[Cu(emizco)2(H2O)2]2+ isomer.     

Synthesis and spectroscopic properties of copper(II) complexes derived from thiophene-2-carbaldehyde thiosemicarbazone. Structure and biological activity of [Cu(C6H6N3S2)2].

The synthesis, structure and spectroscopic properties on complexes with the formula [Cu(Lm)2] (1) and Cu(NO3)2(HLm)2 (2), where HLm = thiophene-2-carbaldehyde thiosemicarbazone, have been developed. The molecular structure of compound 1 consists of monomeric entities. The copper(II) ions exhibit distorted square-planar geometry with both bidentate thiosemicarbazone ligands placed in a centrosymmetric way. Metal to ligand pi-backdonation is proposed to explain several structural and spectroscopic features in these complexes. The EPR spectra of compound 1 show an orthorhombic g tensor indicating the presence of weak magnetic exchange interactions. The reaction of compound 1 with glutathione causes the reduction of the metal ion and the substitution of the thiosemicarbazone ligand by the thiol ligand. This mechanism seems to be related to the cytotoxicity of this complex against Friend Erithroleukemia cells (FLC) and melanome B16F10 cells.     

Novel trihydroxamate-containing peptides: design, synthesis, and metal coordination

Novel trihydroxamate-containing peptides were designed to mimic desferrioxamine (Desferal(R), DFO, a naturally occurring siderophore) but possess distinct conformational restrictions and varied lipophilicity to probe structure vs. metal coordination. The synthesis was performed via fragment condensation of hydroxamate-containing oligopeptides such as Fmoc-Leu- Psi[CON(OBz)]-Phe-Ala-Pro-OH and H-Leu-Psi[CON(OBz)]-Phe-Ala-Pro-OBu(t) (Fmoc: 9-fluor enylmethoxycarbonyl; OBz: benzyl; OBu(t): tert-butyl) either in solution or on a solid support. The metal-binding properties were studied by electrospray ionization-mass spectroscopy (ESI-MS), ultraviolet (UV)-visible spectroscopy, and (1)H nuclear magnetic resonance (NMR). Similar to the dihydroxamate analogs previously explored [Biopolymers (Peptide Science), 2003, Vol. 71, pp. 489-515], the compounds with three hydroxamates arrayed at 10-atom intervals, i.e., H-[Leu-Psi[CON(OH)]-Phe-Ala-Pro](3)-OH (P1), cyclo[Leu-Psi[CON(OH)]-Phe-Ala-Pro](3) (P2), and H-[Leu-Psi(CONOH)-Phe-Ala-Pro](2)-Leu-NHOH (P7), exhibited high affinities for intramolecular coordination with Fe(III) and Ga(III). As expected, both P1 and P2 showed higher relative Fe(III)-binding affinities than the corresponding dihydroxamate-containing peptide analogs (P11 and P12). Even though both P1 and P2 did not compete with DFO in the relative metal-binding affinity in both solution and gas phases, P1, P2, and DFO exhibited similar relative binding selectivities to 11 different metal ions including Fe(III), Fe(II), Al(III), Ga(III), In(III), Zn(II), Cu(II), Co(II), Ni(II), Gd(III), and Mn(II). Compared to the other metal ions, they had higher relative binding affinities with Fe(III), Fe(II), Al(III), Ga(III), and In(III). The decreased metal-binding affinities of P1 and P2 in comparison with DFO suggested the conformational restrictions of their backbones perturb their three hydroxamate groups from optimal hexadentate orientations for metal coordination. As detected by ESI-MS, P2 was distinguished from both P1 and DFO by solvation of its Ga(III) and Fe(III) complexes (such as acetonitrile or water), thereby stabilizing the resulting complexes in the gas phase. Noteworthy, P2 led to 69% death rate in Hela cells at a concentration of 50 microM, exhibiting higher cytotoxicity than DFO in vitro despite its much lower affinity for iron. This enhanced toxicity may simply reflect the increased lipophilicity of the cyclic trihydroxamate (P2) together with the improvements in its cell penetration, and/or subsequent intracellular molecular recognition of both side chains and hydroxamate groups. The cytotoxicity was significantly suppressed by precoordination with Ga(III) or Fe(III), suggesting a mechanism of toxicity via sequestration of essential metal ions as well as the importance of curbing the metal coordination before targeting. The potential of such siderophore-mimicking peptides in oncology needs further exploration.     

Iron(III)- and copper(II) complexes of an asymmetric, pentadentate salen-like ligand bearing a pendant carboxylate group

The equilibrium and solution structural properties of the iron(III) and copper(II) complexes of an asymmetric salen-like ligand (N,N'-bis(2-hydroxybenzyl)-2,3-diamino-propionic acid, H(3)bhbdpa) bearing a pendant carboxylate group were characterized in aqueous solution by potentiometric, pH-dependent electron paramagnetic resonance (EPR) and UV-Vis (UV-Visible) measurements. In the equimolar systems the pentadentate ligand forms very stable, differently protonated mononuclear complexes with both metal ions. In the presence of iron(III) {NH, PhO(-), COO(-)}, {2NH, 2PhO(-), COO(-)} and {2NH, 2PhO(-), COO(-), OH(-)} coordinated complexes are dominant. The EPR titrations reflected the presence of microscopic complex formation pathways, leading to the formation of binding isomers in case of Cu(H(2)bhbdpa)(+), Cu(Hbhbdpa) and Cu(bhbdpa)(-). The {2NH, 2PhO(-)+COO(-)/H(2)O} coordinated Cu(bhbdpa) is the only species between pH 6-11. At twofold excess of metal ion dinuclear complexes were detected with both iron(III) and copper(II). In presence of iron(III) a mu-carboxylato-mu-hydroxo-bridged dinuclear complex (Fe(2)(bhbdpa)(OH)(3)) is formed from Fe(H(2)bhbdpa)(2+) through overlapping proton release processes, providing one of the rare examples for the stabilization of an endogenous carboxylate bridged diiron core in aqueous solution. The complex Cu(2)(bhbdpa)(+) detected in the presence of copper(II) is a paramagnetic (S=1) species with relatively weakly coupled metal ions.     

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.