Four novel mononuclear and polynuclear Cu(I) thiosaccharinates with triphenylphosphane and bis(diphenylposphino)methane. Synthesis and structural study of Cu(4)(tsac)(4)(PPh(3))(3), Cu(tsac)(PPh(3))(2), Cu(4)(tsac)(4)(dppm)(2), and Cu(2)(tsac)(2)(dppm)(2)

Four new ternary complexes of copper(I) with thiosaccharin and phosphanes were prepared. The reaction of [Cu(4)(tsac)(4)(CH(3)CN)(2)] (1) (tsac: thiosaccharinate anion) with PPh(3) in molar ratios Cu(I)/PPh(3) 1:075 and 1:2 gave the complexes [Cu(4)(tsac)(4)(PPh(3))(3)] center dot CH(3)CN (2) and Cu(tsac)(PPh(3))(2) (3), respectively. The reaction of 1 with Ph(2)PCH(2)PPh(2) (dppm) in molar ratios Cu(I)/dppm 2:1 and 1:1 gave the complexes [Cu(4) (tsac)(4)(dppm)(2)] center dot 2CH(2)Cl(2) (4) and [Cu(2)(tsac)(2)(dppm)(2)] center dot CH(2)Cl(2) (5), respectively. All the compounds have been characterized by spectroscopic and X-ray crystallographic methods. Complex 2 presents a tetra-nuclear arrangement with three metal centers in distorted tetrahedral S(2)NP environments, the fourth one with the Cu(I) ion in a distorted trigonal S(2)N coordination sphere, and the tsac anions acting as six electron donor ligands in mu(3)-S(2)N coordination forms. Complex 3 shows mononuclear molecular units with copper(I) in a distorted trigonal planar coordination sphere, built with the exocyclic S atom of a mono-coordinated thiosaccharinate anion and two P-atoms of triphenylphosphane molecules. With dppm as secondary ligand the structures of the complexes depends strongly on the stoicheometry of the preparation reaction. Complex 4 has a centrosymmetric structure. Two triply bridged Cu(2)(tsac)(2)(dppm) units are joined together by the exocyclic S-atoms of two tsac anions acting effectively as bridging tridentate ligands. Complex 5 is conformed by asymmetric dinuclear moieties where the two dppm and one tsac ligands bridge two Cu(I) atoms and the second tsac anion binds one of the metal centers through its exocyclic S-atom. (C) 2009 Elsevier B.V. All rights reserved.

Organotin Complexes of Alizarin and Purpurin

Five novel organotin complexes with the anthraquinone dyes alizarin (1,2-dihydroxyanthraquinone) and purpurin (1,2,4-trihydroxyanthraquinone) were synthesized and characterized by elemental analyses, FTIR and NMR spectroscopy ((1)H, (13)C and (119)Sn). The crystal and Molecular structures Of four complexes were determined by X-ray diffraction on single crystals: [Bu(2)Sn(aliz)(H(2)O)]center dot C(2)H(5)OH (A1 center dot EtO H), [Bu(2)Sn(aliz)(dmso)](2) (A3), [(Bu(2)Sn)(3)O(Hpurp)(2)] (P1) and [Bu(2)Sn(Hpurp)(dmso)](2) (P2), where H(2)aliz = alizarin and H(3)purp = purpurin. The coordination mode of the ligands is identical to that found in their Al/Ca complexes, where they act as dianionic tridentate ligands forming five and six-membered fused chelate rings. The coordination to the tin atoms occurs exclusively via the 1,2- phenolate oxygen and the adjacent quinoid oxygen atoms. The complexes A1, A3 and P1 are dimers with hepta-coordinated tin atoms in form of a slightly distorted pentagonal bipyramid. The trinuclear complex P2 contains two pentacoordinated and one heptacoordinated tin atoms.

Synthesis, Structural Characterization, and Biological Evaluation of Oxorhenium(V) Complexes with a Novel Type of Thiosemicarbazones Derived from N-[N `,N `-Dialkylamino(thiocarbonyl)]benzimidoyl Chlorides

Reactions of N-[N`,N`-diethylamino(thiocarbonyl)]benzimidoyl chloride with 4,4-dialkylthiosemicarbazides give a novel class of thiosemicarbazides/thiosemicarbazones, H(2)L, which causes a remarkable reduction of cell growth in in vitro experiments. These strong antiproliferative effects are also observed for oxorhenium(V) complexes of the general composition [ReOCl(L)], which are formed by reactions of the potentially tridentate ligands with (NBu(4))[ReOCl(4)]. A systematic substitution of the alkyl groups in the thiosemicarbazone building blocks of the ligands do not significantly influence the biological activity of the metal complexes, while the replacement of the chloro ligand by a PPh(3) ligand (by the replacement of the oxo unit by a nitrido ligand) completely terminated the cytotoxicity of the metal complexes.

Oxotechnetium(V) Complexes with a Novel Class of Tridentate Thiosemicarbazide Ligands

A novel tridentate thiosemicarbazide-type ligand class with an SNS donor set, H(2)L(1), was prepared by reactions of N-[N`,N`-dialkylamino(thiocarbonyl)]benzimidoyl chlorides with thiosemicarbazides. H(2)L(1) ligands readily react with (NBu(4))[TcOCl(4)] in MeOH under the formation of red oxotechnetium(V) complexes of composition [TcOCl(L(1))]. The monomeric, five-coordinate compounds are air-stable and bind (L(1))(2-) tridentate in the equatorial coordination sphere. The compounds represent the first examples of oxotechnetium(V) complexes with NS chelate-bonded thiosemicarbazones.

Synthesis, spectroscopic characterization and X-ray structures of five-coordinate diorganotin(IV) complexes containing 5-hydroxypyrazoline derivatives as ligands

Four new diorganotin(IV) complexes have been prepared from R(2)SnCl(2) (R = Me, Ph) with the ligands 5-hydroxy-3-metyl-5-phenyl-1-(S-benzildithiocarbazate)-pyrazoline (H(2)L(1)) and 5-hydroxy-3-methyl-5-phenyl-1-(2-thiophenecarboxylic)-pyrazoline (H(2)L(2)). The complexes were characterized by elemental analysis, IR. (1)H (13)C, (119)Sn NMR and Mossbauer spectroscopes The complexes [Me(2)SnL(1)], [Ph(2)SnL(1)] and [Me(2)SnL(2)] were also studied by single crystal X-ray diffraction and the results showed that the Sn(IV) central atom of the complexes adopts a distorted trigonal bipyramidal (TBP) geometry with the N atom of the ONX-tridentate (X = O and S) ligand and two organic groups occupying equatorial sites. The C-Sn-C angles for [Me(2)Sn(L(1))] and [Ph(2)Sn(L(1))] were calculated using a correlation between (119)Sn Mossbauer and X-ray crystallographic data based on the point-charge model Theoretical calculations were performed with the B3LYP density functional employing 3-21G(*) and DZVP all electron basis sets showing good agreement with experimental findings General and Sn(IV) specific IR harmonic frequency scale factors for both basis sets were obtained from comparison with selected experimental frequencies (C) 2010 Elsevier B V All rights reserved

Mixed-Ligand Complexes of Technetium and Rhenium with Tridentate Benzamidines and Bidentate Benzoylthioureas

Mixed-ligand complexes of technetium(V) or rhenium(V) containing tridentate N-[(dialkylamino)(thiocarbonyl)]benzamidine (H(2)L(1)) and bidentate N,N-dialkyl-N`-benzoylthiourea (HL(2)) ligands were formed in high yields when (NBu(4))[MOCl(4)] (M = Tc or Re) or [ReOCl(3)(PPh(3))(2)] was treated with mixtures of the proligands. Other approaches for the synthesis of the products are reactions of [MOCl(L(1))] complexes with HL(2) or compounds of the-composition [ReOCl(2)(PPh(3))(L(2))] with H(2)L(1). The resulting air-stable [MO(L(1))(L(2))] complexes possess potential for the development of metal-based radiopharmaceuticals. [TcO(L(1))(L(2))] complexes are readily reduced by PPh3 with formation of [Tc(L(1))(L(2))(PPh(3))]. The resulting Tc(III) complexes undergo two almost-reversible oxidation steps corresponding to one-electron transfer processes. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis, characterization and evaluation of antileishmanial activity of copper(II) with fluorinated alpha-hydroxycarboxylate ligands

In this study, Cu(II) complexes with fluorinated ligands were produced aiming at the development of new, less toxic antileishmanial metallodrugs. Complexes of the general formula CuL(2) (L = lactate, trifluorolactate, 2-hydroxyisobutyrate, trifluoro-2-hydroxyisobutyrate) were synthesized in methanolic medium, purified by crystallization and characterized by elemental analysis and electronic and infrared spectroscopies. In vitro experiments with Leishmania amazonensis promastigotes showed that the trifluorolactate derivative more active than its non-fluorinated counterpart. Our results indicate that fluorinated chelators may be interesting to increase metal toxicity and/or open new paths for metallodrug chemotherapy against leishmaniasis.

Differential effects of TR ligands on hormone dissociation rates: Evidence for multiple ligand entry/exit pathways

Some nuclear receptor (NR) ligands promote dissociation of radiolabeled bound hormone from the buried ligand binding cavity (LBC) more rapidly than excess unlabeled hormone itself This result was interpreted to mean that challenger ligands bind allosteric sites on the LBD to induce hormone dissociation, and recent findings indicate that ligands bind weakly to multiple sites on the LBD surface. Here we show, that a large fraction of thyroid hormone receptor (TR) ligands promote rapid dissociation (T(1/2) < 2 h) of , radiolabeled T(3) vs. T(3) (T(1/2), approximate to 5-7 h). We cannot discern relationships between this effect and ligand size, activity or affinity for TR beta. One ligand, GC-24, binds the TR LBC and (weakly) to the TR beta-LBD surface that mediates dimer/heterodimer interaction, but we cannot link this interaction to rapid T(3) dissociation. Instead, several lines of evidence suggest that the challenger ligand must interact with the buried LBC to promote rapid T(3) release. Since previous molecular dynamics simulations suggest that TR ligands leave the LBC by several routes, we propose that a subset of challenger ligands binds and stabilizes a partially unfolded intermediate state of TR that arises during T(3) release and that this effect enhances hormone dissociation. (C) 2009 Elsevier Ltd. All rights reserved.

Vanadium complexes with thiosemicarbazones: Synthesis, characterization, crystal structures and anti-Mycobacterium tuberculosis activity

The development of more efficient anti-tuberculosis drugs is of interest. Three oxovanadium(IV) and three cis-dioxovanadium(V) complexes with thiosemicarbazone derivatives bearing moieties with different lipophilicity have been prepared and had their inhibitory activity against Mycobacterium tuberculosis H(37)Rv ATCC 27294 evaluated. The analytical methods used by the complexes` characterization included IR, EPR, (1)H, (13)C and (51)V NMR spectroscopies, elemental analysis, cyclic voltammetry, magnetic susceptibility measurement and single crystal X-ray diffractometry. [VO(acac)(aptsc)], [VO(acac)(apmtsc)] and [VO(acac)(apptsc)] (acac = acetylacetonate; Haptsc = 2-acetylpyridinethiosemicarbazone; Hapmtsc = 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc = 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone) are paramagnetic and their EPR spectra are consistent with the monoanionic N,N,S-tridentate coordination of the thiosemicarbazone ligands, resulting in octahedral structures of rhombic symmetry and with the oxidation state +IV for the vanadium atom. As result of oxidation of the vanadium(IV) complexes above, the diamagnetic cis-dioxovanadium(V) complexes [VO(2)(aptsc)[, [VO(2)(apmtsc)[ and [VO(2)(apptsc)] are formed. Their (1)H, (13)C and (51)V NMR spectra were acquired and support a distorted square pyramidal geometry for them, in accord with the solid state X-ray structures determined for [VO(2)(aptsc)] and [VO(2)(apmtsc)]. In general, the vanadium compounds show comparable or larger anti-M. tuberculosis activities than the free thiosemicarbazone ligands, with MIC values within 62.5-1.56 (mu g/mL). (C) 2008 Elsevier Ltd. All rights reserved.

Syntheses, crystal structure and theoretical investigation of novel heteroleptic complexes of nickel(II) with N-R-sulfonyldithiocarbimate and phosphine ligands

Five new complexes of general formula: [Ni(RSO(2)N=CS(2))(dppe)], where R = C(6)H(5) (1), 4-ClC(6)H(4) (2), 4-BrC(6)H(4) (3), 4-IC(6)H(4) (4) and dppe = 1,2-bis(diphenylphosphino) ethane and [Ni(4-IC(6)H(4)SO(2)N=CS(2))(PPh(3))(2)] (5), where PPh3 = triphenylphosphine, were obtained in crystalline form by the reaction of the appropriate potassium N-R-sulfonyldithiocarbimate K(2)(RSO(2)N=CS(2)) and dppe or PPh(3) with nickel(II) chloride in ethanol/water. The elemental analyses and the IR, (1)H NMR, (13)C NMR and (31)P NMR spectra are consistent with the formation of the square planar nickel(II) complexes with mixed ligands. All complexes were also characterized by X-ray diffraction techniques and present a distorted cis-NiS(2)P(2) square-planar configuration around the Ni atom. Quantum chemical calculations reproduced the crystallographic structures and are in accord with the spectroscopic data. Rare C-H center dot center dot center dot Ni intramolecular short contact interactions were observed in the complexes 1-5. (C) 2011 Elsevier B. V. All rights reserved.

Two-dimensional QSAR studies on arylpiperazines as high-affinity 5-HT(1A) receptor ligands

5-HT(1A) receptor plays an important role in the delayed onset of antidepressant action of a class of selective serotonin reuptake inhibitors. Moreover, 5-HT(1A) receptor levels have been shown to be altered in patients suffering from major depression. In this work, hologram quantitative structure-activity relationship (HQSAR) studies were performed on a series of arylpiperazine compounds presenting affinity to the 5-HT(1A) receptor. The models were constructed with a training set of 70 compounds. The most significant HQSAR model (q(2) = 0.81, r(2) = 0.96) was generated using atoms, bonds, connections, chirality, and donor and acceptor as fragment distinction, with fragment size of 6-9. Predictions for an external test set containing 20 compounds are in good agreement with experimental results showing the robustness of the model. Additionally, useful information can be obtained from the 2D contribution maps.

Ruthenium(II) complexes containing N(4)-tolyl-2-acetylpyridine thiosemicarbazones and phosphine ligands: NMR and electrochemical studies of cis-trans isomerization

[Ru(HL)(PPh3)(2)Cl]Cl complexes have been obtained in which HL = N(4)-ortho (complex 1), N(4)-meta (complex 2) and N(4) pctratolyl 2-acetylpyridine thiosemicarbazone (complex 3). NMR and electrochemical studies indicate that both cis and trans isomers exist in solution, and that the cis isomers are converted into the trans isomers with time. Crystal structure determination of (1) reveals that the traps isomer is formed in the solid state. (c) 2007 Elsevier B.V. All rights reserved.

New insights on the Lewis acidity of diorganolead(IV) compounds: Diphenyllead(IV) complexes with N,O,S-chelating ligands

The reactions of PbPh2(OAC)(2) with alkylglyoxylate thiosemicarbazones (HRGTSC, R = Et, Bu) afforded complexes of the type [PbPh2(GTSC)] center dot H2O, [PbPh2(RGTSC)(2)] and [PbPh2Cl(BUGTSC)]. The structures of HRGTSC (R = Me, Et, Bu), [PbPh2(OAc)(RGTSC)](R = Me, Et, Bu), [PbPh2Cl(BuGTSC)] and [PbPh2(GTSC)] center dot H2O have been studied by X-ray diffraction. [PbPh2(OAc)(RGTSC)] and [PbPh2(GTSC)] center dot H2O have [PbC2NO3S] kernels and the coordination sphere of the metal is pentagonal bipyramidal. [PbPh2Cl(BuGTSC)] has a [PbC2NOSCI] kernel and the coordination geometry around lead is pentagonal bipyramidal with one vacant site. Analysis of the bond distances in [PbPh2(GTSC)] center dot H2O suggests a significant affinity between diphenyllead(IV) and carboxylate donor groups, supporting a borderline acidic character for this organometallic cation. H-1 and C-13 NMR spectra in DMSO-d(6) suggest the partial dissociation of the acetate in [PbPh2(OAc)(RGTSC)] solutions and indicate some differences in the coordination mode of the two RGTSC(-) ligands in [PbPh2(RGTSC)(2)] complexes. (C) 2007 Elsevier Ltd. All rights reserved.

New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: Molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity

New Pd(II) and Pt(II) complexes [ML2] (HL = a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M = Pd, Pt) or Pd(OAc)(2) with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cis-platinum-resistant cell line A2780cisR. (c) 2007 Elsevier Inc. All rights reserved.

Dithiocarbazate complexes with the [M(PPh(3))](2+) (M=Pd or Pt) moiety Synthesis, characterization and anti-Tripanosoma cruzi activity

New neutral Pd(II) and Pt(II) complexes of the type [M(L)(PPh(3))] (M Pd or Pt) were prepared in crystalline form in high-yield synthesis with the S-benzyldithiocarbazates and S-4-nitrobenzyldithiocarbazates derivatives from 2-hydroxyacetophenone, H(2)L(1a) and H(2)L(1b), and benzoylacetone, H(2)L(2a) and H(2)L(2b). The new complexes [Pt(L(1a))(PPh(3))] (1), [Pd(L(1a))(PPh(3))] (2), [Pt(L(1b))(PPh(3))] (3), [Pd(L(1b))(PPh(3))] (4), [Pt(L(2a))(PPh(3))] (5), [Pd(L(2a))(PPh(3))] (6), [Pt(L(2b))(PPh(3))] (7) and [Pd(L(2b))(PPh(3))] (8) were characterized on the basis of elemental analysis, conductivity measurements, UV-visible, IR, electrospray ionization mass spectrometry (ESI-MS), NMR ((1)H and (31)P) and by X-ray diffraction studies. The studies showed that differently from what was observed for the H(2)L(1a) and H(2)L(1b) ligands, H(2)L(2a) and H(2)L(2b) assume cyclic forms as 5-hydroxypyrazolinic. Upon coordination, H2L2a and H2L2b suffer ring-opening reaction, coordinating in the same manner as H(2)L(1a) and H(2)L(1b), deprotonated and in O,N,S-tridentate mode to the (MPPh(3))(2+) moiety. All complexes show a quite similar planar fourfold environment around the M(II) center. Furthermore, these complexes exhibited biological activity on extra and intracellular forms of Trypanosoma cruzi in a time- and concentration-dependent manner with IC(50) values ranging from 7.8 to 18.7 mu M, while the ligand H(2)L(2a) presented a trypanocidal activity on trypomastigote form better than the standard drug benznidazole. (C) 2010 Elsevier Inc. All rights reserved.