Copper(II) and zinc(II) complexes with 2-formylpyridine-derived hydrazones

In the present work 2-formylpyridine-para-chloro-phenyl hydrazone (H2FopCIPh) and 2-formylpyridine-para-nitro-phenyl hydrazone (H2FopNO(2)Ph) were obtained, as well as their copper(II) and zinc(II) complexes [Cu(H2FopClPh)Cl(2)] (1), [Cu(2FopNO(2)Ph)Cl] (2), [Zn(H2FopClPh)Cl(2)] (3) and [Zn(H2FopNO(2)Ph)Cl(2)] (4). Upon re-crystallization in DMSO:acetone conversion of 2 into [Cu(2FopNO(2)Ph)Cl(DMSO)] (2a) and of 4 into [Zn(2FopNO(2)Ph)Cl(DMSO)] (4a) occurred. The crystal structures of 1, 2a, 3 and 4a were determined. (C) 2009 Elsevier Ltd. All rights reserved.

Structural studies on zinc(II) complexes with 2-benzoylpyridine-derived hydrazones

2-Benzoylpyridine-phenylhydrazone (H2BzPh), 2-benzoylpyridine-para-chloro-phenylhydrazone (H2BzpClPh), and 2-benzoylpyridine-para-nitro-phenyl (H2BzpNO(2)Ph) hydrazone were obtained and fully characterized, as well as their zinc(II) complexes [Zn(H2BzPh)Cl(2)] (1), [Zn(H2BzClPh)Cl(2)] (2) and [Zn(H2BzpNO(2)Ph)Cl(2)] (3). During the syntheses of complex 1 a second product crystallized, which was characterized as [Zn(2BzPh)(2)] (1a). Upon re-crystallization in 1: 9 DMSO: acetone conversion of 2 into [Zn(H2BzpClPh)Cl2] center dot H(2)O (2a) and of 3 into [Zn(2BzpNO(2)Ph)Cl(DMSO)] (3a) occurred. The crystal structures of 1a, 2a and 3a were determined. In 1a the two nearly perpendicular H2BzPh ligands give rise to a distorted octahedral environment around the metal. The 5-fold coordination around the metal is completed with two chloride ions in 2a and with one chloride and one oxygen atom from DMSO in 3a. (c) 2008 Elsevier B.V. All rights reserved.

Diphenyllead(IV) thiosemicarbazonates and pyrazolonates: Synthesis and characterization

Cyclization of thiosemicarbazones derived from beta-keto esters and beta-keto amides (HTSC) in the presence of diphenyllead(IV) acetate was explored in methanol solution at room temperature and under reflux. All beta-keto ester TSCs underwent cyclization to give the corresponding pyrazolone (HL), which, except in one case, deprotonated and coordinated the PbPh(2)(2+) moiety to form homoleptic [PbPh(2)(L)(2)] or heteroleptic [PbPh(2)(OAc)(L)] derivatives. Cyclization did not occur with beta-keto amide TSCs and only [Pbph(2)(TSC)(2)] or [PbPh(2)(OAc)(TSC)] thiosernicarbazonates were isolated. The complexes were characterized by IR spectroscopy in the solid state and by (1)H, (13)C and (207)Pb NMR spectroscopy in DMSO-d(G) solution, in which they evolve and decompose with time. Additionally, crystals of p-acetoacetanisidide thiosemicarbazone (HTSC(10)), [PbPh(2)(OAc)(L(5))] center dot MeOH (HL(5) = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazolone-1-carbothioamide), [PbPh(2)Cl(L(2))] (HL(2) = 2,5-dihydro-5-oxo-3-phenyl-1H-pyrazolone-1-carbothioamide), [PbPh(2)(OAc)(TSC(8))]center dot 2MeOH (HTSC(8) = acetoacetanilide thiosemicarbazone), [PbPh(2)(OAc)(TSC(10))]center dot H(2)O and [PbPh(2)(OAc)(TSC(11))] center dot 0.75MeOH (HTSO(11) = o-acetoacetotoluidide) were studied by X-ray crystallography. The complexes, monomers or dimers with almost linear C-Pb-C moieties, are compared with the corresponding derivatives of Pb(II). (C) 2009 Elsevier Ltd. All rights reserved.

Copper(II) and zinc(II) complexes with 2-benzoylpyridine-methyl hydrazone

2-Benzoylpyridine-methyl hydrazone (HBzMe) has been obtained as well as its copper(II) [Cu(HBzMe)Cl(2)] (1) and zinc(II) [Zn(HBzMe)Cl(2)] (2) complexes. Upon re-crystallization in 1 - 9 DMSO:acetone conversion of I into dimeric [Cu(BzMe)Cl](2) (1a) occurred. The crystal structures of HBzMe, 1, 1a, and 2 were determined. HBzMe adopts the ZE conformation in the solid. In all complexes the hydrazone adopts the E configuration to attach to the metal through the N(py)-N2-O chelating system. In 1 and 2 a neutral hydrazone coordinates to the metal center while in 1a deprotonation occurs with coordination of an anionic ligand. la presents a dimeric structure. having two copper(II) ions per asymmetric unit. Two chlorides are also present in the copper coordination sphere, which act as bridging ligands and connect the copper centers to each other. (C) 2008 Elsevier B.V. All rights reserved.

Lead(II)-induced formation and coordination of 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one

Cyclization of (n)butyl glyoxylate thiosemicarbazone (HBuTSC) under reflux in the presence of Pb(OAc)(2) led to tile formation of the complex [Pb(HTz)(2)] (H(2)Tz = 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one), which after recrystallization from DMSO afforded the polymer [Pb(Tz)](n), the first example of a Tz(2-) metal complex. (C) 2008 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.

The mer-[RuCl(3)(dppb)(H(2)O)] complex: A versatile tool for synthesis of Ru(II) compounds

The complex mer-[RuCl(3)(dppb)(H(2)O)] [dppb = 1,4-bis(diphenylphosphino)butane] was used as a precursor in the synthesis of the complexes tc-[RuCl(2)(CO)(2)(dppb)], ct-[RuCl(2)(CO)(2)(dppb)]. cis-[RuCl(2)(dppb)(Cl-bipy)], [RuCl(2Ac4mT)(dppb)] (2Ac4mT = N(4)-meta-tolyl-2-acetylpyridine thiosemicarbazone ion) and trans-[RuCl(2)(dppb)(mang)] (mang = mangiferin or 1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside) complexes. For the synthesis of Run complexes, the Ru(III) atom in mer-[RuCl(3)(dppb)(H(2)O)] may be reduced by H(2)(g), forming the intermediate [Ru(2)Cl(4)(dppb)(2)], or by a ligand (such as H2Ac4mT or mangiferin). The X-ray structures of the cis-[RuCl(2)(dppb)(Cl-bipy)], tc-[RuCl(2)(CO)(2)(dppb)] and [RuCl(2Ac4mT)(dPpb)] complexes were determined. (C) 2010 Elsevier Ltd. All rights reserved.

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

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.

Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents

In previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400 nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones. (C) 2010 Elsevier Ltd. All rights reserved.

Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis

Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1.

Avaliação do potencial anticorrosivo de tiossemicarbazonas solubilizadas em sistemas microemulsionados

In this work thiosemicarbazones [4-N-cinnamoyl-thiosemicarbazone (CTSC), 4-N-(2'-methoxycinnamoyl)-thiosemicarbazone (MCTSC), and 4-N-(4'-hydroxy-3'-methoxybenzoyl)-thiosemicarbazone (HMBTSC)] were solubilized in an microemulsion system (ME_OCS) which is rich in aqueous phase (O/W system). The system ME_OCS was obtained with saponified coconut oil (OCS) as (surfactant), butanol (cosurfactant), and kerosene as oil phase (Fo), using 40% of C/T (cosurfactant/surfactant), 5% of Fo and 55% of aqueous phase. The microemulsions systems CTSC_ME_OCS, MCTSC_ME_OCS and HMBTSC_ME_OCS effectiveness on a AISI 1020 carbon steel corrosion inhibition process were evaluated in a saline solution (NaCl 0.5%), using a galavostatic method. The tested thiosemicarbazones (TSC) showed highest inhibitors effects (85.7% for CTSC_ME_OCS, 84.0% for MCTSC_ME_OCS, and 83.3% HMBTSC_ME_OCS) at lower concentrations [0.19% of CTSC, 0.07% (MCTSC), and 0.26% (HMBTSC)]. Comparatively, the surfactant OCS (solubilized in H2O) as well as the system ME_OCS showed lower efficacy [71% for OCS (at 0.20 - 0.25% of concentration) and 74% for ME_OCS (at 0.5% of concentration)]. Since the microemulsion systems ME_OCS showed satisfactory interfacial adsorption, the greatest inhibitory effect of those TSC_ME_OCS systems could be correlated to both chemical composition of each tested TSC (which is rich in heteroatoms and aromatic ring) and also the presence of the surfactant OCS

Free radical production by azomethine H: Effects on pancreatic and hepatic tissues

The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TEARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O-2(.-)), since Cu-Zn superoxide dismutase activities were increased by azomethine I-I treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O-2(.-)) maybe produced as a mediator of azomethine H action.