Montevideo, Uruguay
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Torres J.,Catedra de Quimica Inorganica | Morales P.,Catedra de Quimica Inorganica | Dominguez S.,University of La Laguna | Gonzalez-Platas J.,University of La Laguna | And 4 more authors.
Journal of Molecular Structure | Year: 2011

The stoichiometric reaction of copper(II) chloride with iminodiacetic acid (H2ida), and lanthanide(III) chloride in water yields the heteropolynuclear complexes [Ln2Cu3(ida) 6]·xH2O. In this work, the synthesis and full characterization of those complexes with Ln = Ce, Ho is presented. The structures are based on [Cu(ida)2] building blocks, linked by the Ln ions via carboxylate bridges. The formation of nanochannels along the crystallographic c axis is verified. The comparison with analogous complexes containing other Ln ions, shows that the channels are perfectly tuneable in size along the series. These chemical systems were also investigated in solution (25.0 °C, I = 0.5 M Me4NCl) by potentiometry. The same kind of polynuclear species have been found in aqueous solution. © 2011 Elsevier B.V. All rights reserved.


Benitez J.,Catedra de Quimica Inorganica | Becco L.,Laboratorio Of Interacciones Moleculares | Correia I.,University of Lisbon | Leal S.M.,Industrial University of Santander | And 8 more authors.
Journal of Inorganic Biochemistry | Year: 2011

In the search for new therapeutic tools against diseases produced by kinetoplastid parasites five vanadyl complexes, [VIVO(L-2H)(phen)], including 1,10-phenanthroline (phen) and tridentate salicylaldehyde semicarbazone derivatives as ligands have been synthesized and characterized in the solid state and in solution by using different techniques. EPR suggested a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and phen coordinated in an equatorial/axial mode. The compounds were evaluated in vitro on epimastigotes of Trypanosoma cruzi, causative agent of Chagas disease, Leishmania panamensis and Leishmania chagasi and on tumor cells. The complexes showed higher in vitro anti-trypanosomal activities than the reference drug Nifurtimox (IC50 values in the range 1.6-3.8 μM) and increased activities in respect to the free semicarbazone ligands. In vitro activity on promastigote and amastigote forms of Leishmania showed interesting results. The compounds [VO(L1-2H)(phen)] and [VO(L3-2H)(phen)], where L1 = 2-hydroxybenzaldehyde semicarbazone and L3 = 2-hydroxy-3-methoxybenzaldehyde semicarbazone, resulted active (IC50 2.74 and 2.75 μM, respectively, on promastigotes of L. panamensis; IC 50 19.52 and 20.75 μM, respectively, on intracellular amastigotes of L. panamensis) and showed low toxicity on THP-1 mammalian cells (IC 50 188.55 and 88.13 μM, respectively). In addition, the complexes showed cytotoxicity on human promyelocytic leukemia HL-60 cells with IC 50 values of the same order of magnitude as cisplatin. The interaction of the complexes with DNA was demonstrated by different techniques, suggesting that this biomolecule could be a potential target either in the parasites or in tumor cells. © 2010 Elsevier Inc.


Fernandez M.,Catedra de Quimica Inorganica | Varela J.,University of the Republic of Uruguay | Correia I.,University of Lisbon | Birriel E.,University of the Republic of Uruguay | And 6 more authors.
Dalton Transactions | Year: 2013

Searching for prospective metal-based drugs for the treatment of Chagas disease, a new series of ten mixed-ligand oxidovanadium(iv) complexes, [V IVO(L-2H)(NN)], where L is a tridentate salicylaldehyde semicarbazone derivative (L1-L5) and NN is either 5-amine-1,10-phenanthroline (aminophen) or 5,6-epoxy-5,6-dihydro-1,10-phenanthroline (epoxyphen), were synthesized. The compounds were characterized in the solid state and in solution. EPR spectroscopy suggests that the NN ligands act as bidentate through both nitrogen donor atoms in an axial-equatorial mode. The stability of the complexes in solution was investigated by EPR and 51V-nuclear magnetic resonance spectroscopies. The complexes were evaluated in vitro for their activities against Trypanosoma cruzi (T. cruzi), the parasite responsible for the disease, and their selectivity was analyzed using J-774 murine macrophages, as a mammalian model. All the complexes are more active than both the reference drug Nifurtimox and the previously reported [VIVO(L-2H)(NN)] complexes. In general they are more active than the corresponding free NN ligands. Complexation led to highly increased selectivities towards the parasite. In addition, the lipophilicity of the compounds was determined and correlated with the observed activity in order to perform a QSAR (quantitative structure-activity relationship) study. A clear quadratic correlation is found. This study also confirms the influence of the structure of the co-ligand on the anti-T. cruzi effect. To get insight into the mechanism of action of the compounds, the changes in biochemical pathways promoted by two of the most active and most selective complexes are studied by analyzing a few of the parasite excreted metabolites by 1H NMR spectroscopy. The combined information suggests that the mitochondrion could be a target for these complexes. Furthermore, DNA was preliminarily evaluated as a potential target by using atomic force microscopy (AFM), which showed that the complexes display an ability to interact with this biomolecule. This journal is © The Royal Society of Chemistry.


Benitez J.,Catedra de Quimica Inorganica | Cavalcanti De Queiroz A.,Federal University of Alagoas | Correia I.,University of Lisbon | Alves M.A.,Federal University of Rio de Janeiro | And 9 more authors.
European Journal of Medicinal Chemistry | Year: 2013

Searching for new promising metal-based hits against Trypanosoma cruzi and Leishmania parasites, two related oxidovanadium(IV) N-acylhydrazone complexes, [VIVO(LASSBio1064-2H)(H2O)], 1, and [V IVO(LASSBio1064-2H)(phen)]·(H2O), 2, where LASSBio1064 = (E)-N'-(2-hydroxybenzylidene-4-chlorobenzohydrazide and phen = 1,10-phenanthroline, were synthesized and characterized in the solid state and in solution by elemental analysis, conductimetric measurements and ESI-MS, FTIR, EPR and 51V NMR spectroscopies and were evaluated on T. cruzi and Leishmania major. In addition, their unspecific cytotoxicity was tested against murine macrophages. Furthermore, to provide insight into the possible mechanism of its antiparasitic action, [VO(LASSbio1064-2H)(phen)].(H2O) was tested for its DNA interaction ability on plasmid DNA by atomic force microscopy (AFM) and on CT DNA by using DNA viscosity measurements and fluorescence spectroscopy. Both complexes were active in vitro against the epimastigote form of T. cruzi (Tulahuen 2 strain) showing IC50 values of the same order or significantly lower than that of the reference trypanosomicidal drug Nifurtimox. However, only the mixed-ligand oxidovanadium(IV) complex 2, which includes phen in its coordination sphere, showed activity on L. major promastigotes with a IC50 value of 22.1 ± 0.6 μM. The compounds show low toxicity on mammalian cells (IC50 > 100 μM). DNA interaction studies showed that the mixed-ligand complex is able to interact with this biomolecule probably through an intercalative mode, pointing out at DNA as a potential target in the parasite. The results suggest that [VIVO(LASSBio1064-2H)(phen)]·(H2O) may be a promising compound for further drug development stages. © 2012 Elsevier Masson SAS. All rights reserved.


Arizaga L.,Catedra de Quimica Inorganica | Cerda M.F.,University of the Republic of Uruguay | Faccio R.,Laboratorio Of Cristalografia | Mombru A.W.,Laboratorio Of Cristalografia | And 4 more authors.
Inorganica Chimica Acta | Year: 2011

Reaction of sodium picolinate with FeIII oxo-centered carboxylate triangles in MeCN in the presence of PPh4Cl yields (PPh4)[Fe4O2(O2CR) 7(pic)2] (R = Ph (1), But (2)). Omitting the phosphonium cation produces [Fe8Na4O4(O 2CPh)16(pic)4(H2O)4] (3), which contains two Fe4Na2 units bridged by two picolinate ligands. X-ray crystal structures of 1 and 3 are reported. Voltammetric profiles in MeCN show four one-electron reduction steps for complexes 1 and 2. Variable-temperature magnetic susceptibility measurements in polycrystalline samples of 1 and 3 reveal strong antiferromagnetic couplings leading to S = 0 ground states. © 2011 Elsevier Ltd. All rights reserved.


Vieites M.,Catedra de Quimica Inorganica | Smircich P.,Laboratorio Of Interacciones Moleculares | Pagano M.,Catedra de Quimica Inorganica | Otero L.,Catedra de Quimica Inorganica | And 6 more authors.
Journal of Inorganic Biochemistry | Year: 2011

In the search for drugs with anti-trypanosome activity, we had previously synthesized two series of platinum and palladium analogous compounds of the formula [M IICl 2(HL)], where HL were bioactive 5-nitrofuryl or 5-nitroacroleine thiosemicarbazone derivatives. In this work, we thoroughly characterized [M IICl 2(HL)] complexes interaction with DNA by using different techniques: gel electrophoresis, DNA viscosity measurements, circular dichroism (CD) and atomic force microscopy (AFM). Electrophoresis results showed that all complexes induced a withdrawal of DNA superhelicity demonstrated by a decrease in electrophoretic mobility of supercoiled DNA form. This effect on migration was dependent on dose but also on the nature of both the metal and the ligand. In general, the effect produced by palladium complexes was significantly more intense than that observed for the corresponding platinum analogs. Differences between palladium and platinum complexes were also observed in CD experiments. While palladium complexes induce evident calf thymus (CT)-DNA profile changes compatible with B-DNA to Z-DNA conformational transition, no clear effect was observed for platinum ones. Additionally, AFM studies showed that changes in the shape of plasmid DNA, like supercoiling, kinks and thickness increase resulted more intense for the former. In addition, either Pd or Pt complexes increased the viscosity of CT DNA solutions in a concentration dependent manner. Although the nature of DNA interaction of both series of analogous palladium and platinum complexes seemed to be similar, an explanation for the observed differential intensity of the effect could be related to the known kinetic stability differences between palladium and platinum compounds. © 2011 Elsevier Inc. All rights reserved.


Becco L.,Laboratorio Of Interacciones Moleculares | Rodriguez A.,University of Barcelona | Bravo M.E.,National Autonomous University of Mexico | Prieto M.J.,University of Barcelona | And 4 more authors.
Journal of Inorganic Biochemistry | Year: 2012

The mixed-chelate copper(II) complexes Casiopeínas® have been tested in several models in vitro and in vivo, showing promising antitumoral results. However, their mechanism of action remains to be defined. Trying to get a deeper insight into their molecular mode of action, further analyses, including gel electrophoresis, atomic force microscopy and circular dichroism were carried out to study their interaction with DNA and some cytoskeleton proteins. Our results revealed that the interaction of Casiopeínas triggers DNA cleavage by a free radical mechanism. The tested complexes showed a differential response to reducing and scavenger agents. Differences on target preference were also evident using double stranded oligonucleotides as sequence competitors. Surprisingly, distamycin A, a minor groove binder, enhanced the Casiopeínas' action on DNA. On the other hand, the tested Casiopeínas produce strong changes in protein structure of tubulin, integrin and fibronectin. All together these results suggest a multiple mode of action for these metal-based drugs. In addition, since it has been proposed that antitumor drugs efficiently interacting with DNA could also show activity against Trypanosoma cruzi, etiologic agent of Chagas disease, we evaluated the activity of these compounds on this protozoan parasite. The tested complexes showed in vitro anti-T. cruzi activity similar to the anti-trypanosomal reference drug Nifurtimox. © 2012 Elsevier Inc. All rights reserved.


Gancheff J.S.,Catedra de Quimica Inorganica | Hahn F.E.,University of Munster
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy | Year: 2012

The reaction of K2ReCl6 with 1,2-bis(2,3- dimercaptobenzamido)ethane (H4-1), and 1,2-bis(2,3- dimercaptobenzamido)benzene (H4-2) in the presence of Na 2CO3 in methanol affords dinuclear complexes of Re V. Experimental evidence supports the presence of self-assembled complexes with two {Re(S2C6H3)3} units connected in a triple-stranded fashion. Density Functional Theory (DFT) studies on geometry and electronic properties were conducted employing the hybrid B3LYP and PBE1PBE functionals. The helical (ΔΔ and ΛΛ) and meso-helical (ΔΛ) isomers were considered. For the helicate complexes included in this study, differences in the stability of the isomers were observed originating in different steric and strain interactions between the three ligand strands. The geometries at the minimum exhibit a distorted trigonal-prismatic coordination environment at the metal centers. Natural bond orbitals (NBO) analysis indicates the presence of Re-S bonds which are strongly polarized toward the non-metal. Time-Dependent DFT (TD-DFT) calculations were performed for a further understanding of the optical spectra. The calculations show the occupied 5d orbitals of the rhenium lying beneath occupied sulfur-based MOs. The general features of the electronic spectra in the visible region are reasonably reproduced by the calculations. The analysis of molecular orbitals also allows the assignment of the origin for all experimentally detected absorption bands. In the high-energy region of the spectrum the absorptions are attributed to ligand-to-metal-ligand charge transfer (LMLCT), in which sulfur-based orbitals and unoccupied orbitals at the rhenium atom and the benzene-o-dithiolato groups are involved. Also in the blue region, shoulders originating from LMLCT are observed. © 2012 Elsevier B.V. All rights reserved.


Gancheff J.S.,Catedra de Quimica Inorganica
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy | Year: 2011

The electronic spectra of triple-stranded complexes of Ti(IV) with bis(benzene-o-dithiolato) ligands (H4-L1 = 1,2-bis(2,3-dimercaptobenzamido)ethane; H4-L2 = 1,2-bis(2,3-dimercaptobenzamido)benzene) were investigated at the TD-DFT level of theory employing B3LYP/LANL2DZ. The influence of the nature (aliphatic or aromatic) of the spacer bridging both {Ti(S2C6H 3)3} units on the absorptive features of the dinuclear complexes was also studied. B3LYP/LANL2DZ leads to spectra accounting for four absorption bands. At the lowest-energy region, the most important transitions are due to ligand-to-metal charge transfer (LMCT), in which out-of-plane ligand-centered orbitals and titanium-based MOs are involved. In going to the blue-region, a third band was detected with excitations showing an important contribution from ligand-to-ligand charge transfer (LLCT) and indeed, a combined LMCT + LLCT character has been considered. This observation seems to arise from a decrease in the metallic character of the LUMO-derivatives involved in the excitations. The origin of the absorption band at the highest-energy part of the spectrum is assigned to a LLCT. The influence of the nature of the spacer on the molar absorption coefficients (ε) for this band has been clearly observed. The complex bearing aliphatic spacer shows ε of about 5 E+4 M-1 cm-1, while the one containing an aromatic spacer present a value of ε of about 2 E+5 M-1 cm-1. © 2010 Elsevier B.V. All rights reserved.


PubMed | Catedra de Quimica Inorganica
Type: | Journal: European journal of medicinal chemistry | Year: 2013

Searching for new promising metal-based hits against Trypanosoma cruzi and Leishmania parasites, two related oxidovanadium(IV) N-acylhydrazone complexes, [V(IV)O(LASSBio1064-2H)(H2O)], 1, and [V(IV)O(LASSBio1064-2H)(phen)](H2O), 2, where LASSBio1064=(E)-N-(2-hydroxybenzylidene-4-chlorobenzohydrazide and phen = 1,10-phenanthroline, were synthesized and characterized in the solid state and in solution by elemental analysis, conductimetric measurements and ESI-MS, FTIR, EPR and (51)V NMR spectroscopies and were evaluated on T. cruzi and Leishmania major. In addition, their unspecific cytotoxicity was tested against murine macrophages. Furthermore, to provide insight into the possible mechanism of its antiparasitic action, [VO(LASSbio1064-2H)(phen)].(H2O) was tested for its DNA interaction ability on plasmid DNA by atomic force microscopy (AFM) and on CT DNA by using DNA viscosity measurements and fluorescence spectroscopy. Both complexes were active in vitro against the epimastigote form of T. cruzi (Tulahuen 2 strain) showing IC50 values of the same order or significantly lower than that of the reference trypanosomicidal drug Nifurtimox. However, only the mixed-ligand oxidovanadium(IV) complex 2, which includes phen in its coordination sphere, showed activity on L. major promastigotes with a IC50 value of 22.1 0.6 M. The compounds show low toxicity on mammalian cells (IC50 > 100 M). DNA interaction studies showed that the mixed-ligand complex is able to interact with this biomolecule probably through an intercalative mode, pointing out at DNA as a potential target in the parasite. The results suggest that [V(IV)O(LASSBio1064-2H)(phen)](H2O) may be a promising compound for further drug development stages.

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