Publications by authors named "Eduardo E Castellano"

69 Publications

New AlZn and AlCu dinuclear complexes: Phosphatase-like activity and cytotoxicity.

J Inorg Biochem 2021 Jun 13;219:111392. Epub 2021 Mar 13.

Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address:

Herein, we report the synthesis and characterization of the first two Al(μ-OH)M (M = Zn (1) and Cu (2)) complexes with the unsymmetrical ligand HL{2-[[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl]-6-bis(pyridylmethyl)aminomethyl}-4-methylphenol. The complexes were characterized through elemental analysis, X-ray crystallography, IR spectroscopy, mass spectrometry and potentiometric titration. In addition, complex 2 was characterized by electronic spectroscopy. Kinetics studies on the hydrolysis of the model substrate bis(2,4-dinitrophenyl)phosphate by 1 and 2 show Michaelis-Menten behavior, with 1 being slightly more active (8.31%) than 2 (at pH 7.0). The antimicrobial effect of the compounds was studied using four bacterial strains (Staphylococcus aureus, Pseudomonas aeuruginosa, Shigella sonnei and Shigella dysenteriae) and for both complexes the inhibition of bacterial growth was superior to that caused by sulfapyridine, but inferior to that of tetracycline. The dark cytotoxicity and photocytotoxicity (under UV-A light) of the complexes in a chronic myelogenous leukemia cell line were investigated. Complexes 1 and 2 exhibited significant cytotoxic activity against K562 cells, which undergoes a 2-fold increase on applying 5 min of irradiation with UV-A light. Complex 2 was more effective and a good correlation between cytotoxicity and intracellular concentration was observed, the intracellular copper concentration required to inhibit 50% of cell growth being 3.5 × 10 mol cell.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111392DOI Listing
June 2021

Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction.

Inorg Chem 2020 Oct 30;59(20):15004-15018. Epub 2020 Sep 30.

Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil.

In this paper, a series of new ruthenium complexes of the general formula [Ru(NS)(dpphpy)(dppb)]PF (-), where dpphpy = diphenyl-2-pyridylphosphine, NS ligands = 2-thiazoline-2-thiol (tzdt, ), 2-mercaptopyrimidine (pySm, ), and 4,6-diamino-2-mercaptopyrimidine (damp, ), and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by elemental analysis, spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and X-ray diffraction. In the characterization, the correlation between the phosphorus atoms and their respective aromatic hydrogen atoms of the compounds in the assignment stands outs, by H-P HMBC experiments. The compounds show anticancer activities against A549 (lung) and MDA-MB-231 (breast) cancer cell lines, higher than the clinical drug cisplatin. All of the complexes are more cytotoxic against the cancer cell lines than against the MRC-5 (lung) and MCF-10A (breast) nontumorigenic human cell lines. For A549 tumor cells, cell cycle analysis upon treatment with showed that it inhibits the mitotic phase because arrest was observed in the Sub-G1 phase. Additionally, the compound induces cell death by an apoptotic pathway in a dose-dependent manner, according to annexin V-PE assay. The multitargeted character of the compounds was investigated, and the biomolecules were DNA, topoisomerase IB, and proteasome, as well as the fundamental biomolecule in the pharmacokinetics of drugs, human serum albumin. The experimental results indicate that the complexes do not target DNA in the cells. At low concentrations, the compounds showed the ability to partially inhibit the catalytic activity of topoisomerase IB in the process of relaxation of the DNA plasmid. Among the complexes assayed in cultured cells, complex was able to diminish the proteasomal chymotrypsin-like activity to a greater extent.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01835DOI Listing
October 2020

Cytotoxicity of ruthenium-N,N-disubstituted-N'-acylthioureas complexes.

Mater Sci Eng C Mater Biol Appl 2020 Oct 20;115:111106. Epub 2020 May 20.

Departamento de Química, Universidade Federal de São Carlos - UFSCar, São Carlos, SP, Brazil. Electronic address:

Five new complexes with general formula [Ru(L)(PP)(bipy)]PF, where L = N,N'-dimethyl-N-Acyl thiourea, and P-P: 1,2-bis(diphenylphosphino)ethane (dppe) or 1,4-bis(diphenylphosphino)butane (dppb)) were synthesized and characterized by elemental analysis, molar conductivity, cyclic voltammetry, IR, NMR (H, C{H} and P{H}), and single crystal X-ray diffractometry. The cytotoxicity of compounds against lung and breast tumor cell lines was significant, where two complexes, [Ru(L)(bipy)(dppe)]PF (3) and [Ru(L)(bipy)(dppb)]PF (6), were selected to evaluate changes in morphology, inhibition of migration and cell death in the MDA-MB-231 lineage. The complexes caused alterations in the cell morphology and were able to inhibit cell migration at the concentrations evaluated, induce the cell cycle arrested in the Sub-G1 phase, and induced cell death by apoptosis. All the complexes presented interaction with HSA, and the interaction studies with DNA suggested weak interactions, probably by the minor groove.
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http://dx.doi.org/10.1016/j.msec.2020.111106DOI Listing
October 2020

Selective Coordination Mode of Acylthiourea Ligands in Half-Sandwich Ru(II) Complexes and Their Cytotoxic Evaluation.

Inorg Chem 2020 Apr 25;59(7):5072-5085. Epub 2020 Mar 25.

Departamento de Química, Universidade Federal de São Carlos-UFSCar, Rodovia Washington Luís KM 235, CP 676, 13561-901 São Carlos, SP, Brazil.

In this study, half-sandwich Ru(II) complexes containing acylthiourea ligands of the general type [Ru(η--cymene)(PPh)(S)Cl]PF (-) and [Ru(η--cymene)(PPh)(S-O)]PF (-) where S/S-O = -disubstituted acylthiourea were synthesized and characterized (via elemental analyses, IR spectroscopy, H NMR spectroscopy, C{H} NMR spectroscopy, and X-ray diffractometry), and their cytotoxic activity was evaluated. The different coordination modes of the acylthiourea ligands, monodentately via S (-) and bidentately via S,O (-), to ruthenium were modulated from different synthetic routes. The cytotoxicity of the complexes was evaluated in five human cell lines (DU-145, A549, MDA-MB-231, MRC-5, and MCF-10A) by MTT assay. The IC values for prostate cancer cells (2.89-7.47 μM) indicated that the complexes inhibited cell growth, but that they were less cytotoxic than cisplatin (2.00 μM). Unlike for breast cancer cells (IC = 0.28-0.74 μM) and lung cancer cells (IC = 0.51-1.83 μM), the complexes were notably more active than the reference drug, and a remarkable selectivity index (SI 4.66-19.34) was observed for breast cancer cells. Based on both the activity and selectivity, complexes and , as well as their respective analogous complexes in the monodentate coordination and , were chosen for further investigation in the MDA-MB-231 cell line. These complexes not only induced morphology changes but also were able to inhibit colony formation and migration. In addition, the complexes promoted cell cycle arrest at the sub-G phase inducing apoptosis. Interaction studies by viscosity measurements, gel electrophoresis, and fluorescence spectroscopy indicated that the complexes interact with the DNA minor groove and exhibit an HSA binding affinity.
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http://dx.doi.org/10.1021/acs.inorgchem.0c00319DOI Listing
April 2020

Non-mutagenic Ru(ii) complexes: cytotoxicity, topoisomerase IB inhibition, DNA and HSA binding.

Dalton Trans 2019 Oct;48(39):14885-14897

Dipartimentodi Biologia, UniversitàTorVergatadi Roma, 00133 Rome, Italy.

Herein we discuss five ruthenium(ii) complexes with good cytotoxicity against cancer cells. These complexes are named [Ru(tzdt)(bipy)(dppb)]PF6 (1), [Ru(mmi)(bipy)(dppb)]PF6 (2), [Ru(dmp)(bipy)(dppb)]PF6 (3), [Ru(mpca)(bipy)(dppb)]PF6 (4) and [Ru(2mq)(bipy)(dppb)]PF6 (5), where tzdt = 1,3-thiazolidine-2-thione, mmi = mercapto-1-methyl-imidazole, dmp = 4,6-diamino-2-mercaptopyrimidine, mpca = 6-mercaptopyridine-3-carboxylic acid, 2mq = 2-mercapto-4(3H)-quinazolinone, bipy = 2,2'-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane. In vitro cell culture experiments revealed significant cytotoxic activity for 1-5 against MDA-MB-231, MCF-7, A549, DU-145 and HepG2 tumor cells, higher than that for the standard anticancer drug cisplatin. Compound/DNA interaction studies were carried out showing that 1-5 interact with DNA by electrostatic force of attraction or by hydrogen bonding. Moreover, the complexes interact, moderately and spontaneously, with human serum albumin (HSA) through the hydrophobic region. The five complexes are able to inhibit the DNA supercoiled relaxation mediated by human topoisomerase IB (TopIB), and complex 1 is found to be the most efficient TopIB inhibitor among the five compounds. The inhibitory effect and analysis of different steps of the TopIB catalytic cycle indicate that complex 1 inhibits the cleavage reaction impeding the binding of the enzyme to DNA and has no effect on the religation step. Complexes 1, 2 and 3 did not show mutagenic activity when they were evaluated by the cytokinesis-block micronucleus cytome assay in HepG2 cells and the Ames test in the presence and absence of mouse liver S9 metabolic activation. Therefore, it is necessary to perform further in-depth analysis of the therapeutic potential of these promising ruthenium complexes as anticancer drugs.
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http://dx.doi.org/10.1039/c9dt01905gDOI Listing
October 2019

Light-activated generation of nitric oxide (NO) and sulfite anion radicals (SO˙) from a ruthenium(ii) nitrosylsulphito complex.

Dalton Trans 2019 Aug 8;48(29):10812-10823. Epub 2019 Jul 8.

São Carlos Institute of Chemistry, University of São Paulo, CEP 13560-970, São Carlos, SP, Brazil.

This manuscript describes the preparation of a new Ru(ii) nitrosylsulphito complex, trans-[Ru(NH)(isn)(N(O)SO)] (complex 1), its spectroscopic and structural characterization, photochemistry, and thermal reactivity. Complex 1 was obtained by the reaction of sulfite ions (SO) with the nitrosyl complex trans-[Ru(NH)(isn)(NO)] (complex 2) in aqueous solution resulting in the formation of the N-bonded nitrosylsulphito (N(O)SO) ligand. To the best of our knowledge, only four nitrosylsulphito metal complexes have been described so far (J. Chem. Soc., Dalton Trans., 1983, 2465-2472), and there is no information about the photochemistry of such complexes. Complex 1 was characterized by spectroscopic means (UV-Vis, EPR, FT-IR, H- and N-NMR), elemental analysis and single-crystal X-ray diffraction. The X-ray structure of the precursor complex 2 is also discussed in the manuscript and is used as a reference for comparisons with the structure of 1. Complex 1 is water-soluble and kinetically stable at pH 7.4, with a first-order rate constant of 3.1 × 10 s for isn labilization at 298 K (t∼ 373 min). Under acidic conditions (1.0 M trifluoroacetic acid), 1 is stoichiometrically converted into the precursor complex 2. The reaction of hydroxide ions (OH) with 1 and with 2 yields the Ru(ii) nitro complex trans-[Ru(NH)(isn)(NO)] with second-order rate constants of 2.1 and 10.5 M s (at 288 K), respectively, showing the nucleophilic attack of OH at the nitrosyl in 2 (Ru-NO) and at the nitrosylsulphito in 1 (Ru-N(O)SO). The pK value of the -SO moiety of the N(O)SO ligand in 1 was determined to be 5.08 ± 0.06 (at 298 K). The unprecedented photochemistry of a nitrosylsulphito complex is investigated in detail with 1. The proposed mechanism is based on experimental (UV-Vis, EPR, NMR and Transient Absorption Laser Flash Photolysis) and theoretical data (DFT) and involves photorelease of the N(O)SO ligand followed by formation of nitric oxide (NO˙) and sulfite radicals (SO˙, sulfur trioxide anion radical).
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http://dx.doi.org/10.1039/c9dt01432bDOI Listing
August 2019

Magnetic-field-tuned phase transition of a molecular material from the isolated-spin to the coupled-spin regime.

Phys Chem Chem Phys 2019 Feb;21(8):4394-4407

CEITEC - Central European Institute of Technology, Brno University of Technology, Purkyňova 123, 61200 Brno, Czech Republic.

We report the preparation, X-ray structure, chemical properties, and electron paramagnetic resonance (EPR) studies at Q and X-bands and temperature (mainly) T = 293 K of powder and oriented single crystal samples of the new compound [Cu(N',N'-dimethyl-N'-benzoylthiourea)(2,2'-bipyridine)Cl], called CuBMB. The EPR spectra of single crystal samples at the Q-band display abrupt merging and narrowing of the peaks corresponding to two rotated copper sites as a function of magnetic field (B0) orientation. This behaviour indicates a quantum transition from an array of quasi-isolated spins to a quantum-entangled spin array associated with exchange narrowing processes and produced by weak intermolecular exchange interactions Ji between neighbour copper spins. This transition occurs when the magnitudes of the anisotropic contributions to the Zeeman couplings, tuned with the direction of B0, approach these |Ji| and produce level crossings. The exchange couplings between neighbour spins are estimated from the angular variation of the single crystal EPR results at the Q-band. We analyse the quantum behaviour and phase transitions of the spin system and discuss the magnitudes of the exchange couplings in terms of the structure of the chemical paths connecting Cu neighbours. The single crystal data at the Q-band indicates an uncommon ground electronic state of CuII which is discussed and compared with the results of DFT calculations. The spectrum of polycrystalline (powder) samples at the Q-band is a sum of contributions of microcrystals in each phase, and the fraction F of the entangled phase depends on the microwave frequency. The X-band spectrum is compatible with the Q-band results, but does not display a transition, and the spin system is in the quantum-entangled phase for all field orientations. This behaviour is further studied with a simple geometric model giving basic predictions. The crystal structure of CuBMB is monoclinic, space group P21/n, with a = 11.9790(3) Å, b = 14.0236(5) Å, c = 12.1193(3) Å, β = 104.952(2)° and Z = 4, and the copper ions are equatorially bonded to the benzoylthiourea and bipyridine ligands in a heavily distorted square pyramidal structure.
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http://dx.doi.org/10.1039/c8cp06719hDOI Listing
February 2019

Hydrolysis reaction promotes changes in coordination mode of Ru(II)/acylthiourea organometallic complexes with cytotoxicity against human lung tumor cell lines.

J Inorg Biochem 2018 09 18;186:147-156. Epub 2018 Jun 18.

Departamento de Química, Universidade Federal de São Carlos - UFSCar, Rodovia Washington Luís KM 235, CP 676, 13565-905 São Carlos, SP, Brazil. Electronic address:

In this study, Ru(II)-arene complexes with acylthiourea ligands of the type [Ru(η‑p‑cymene)(PPh)(T)Cl]PF(1-5) and [Ru(η‑p‑cymene)(PPh)(T)]PF(1a, 4a), where PPh = triphenylphosphine and T = N‑acyl‑N'(monosubstituted)thiourea, were synthesized and characterized, and their cytotoxic properties were also evaluated. 1a and 4a were obtained from the hydrolysis reaction of 1 and 4. All complexes showed unusual coordination modes for acylthiourea ligands, which are coordinated in a monodentate fashion (S) in 1-5, while they found to be bidentate (S,N), in 1a and 4a. To the best of our knowledge, 1a and 4a are the first crystallographically reported ruthenium compounds with acylthiourea coordinated via S and N(amide) atoms. The cytotoxicity of the compounds was evaluated in human lung cells, A549 and MRC-5. The IC values ranging from 0.25 to 0.61 μM after 48 h incubation in lung cancer cells indicate that the compounds showed high cytotoxicity with values significantly lower than the reference drug, cisplatin (11.84 μM). Interaction studies were carried out using human serum albumin (HSA) and DNA. All complexes showed similar cytotoxic activity, however complex 1a, which is the hydrolysis product of 1, presented the highest activity and selectivity among all seven compounds synthesized here. Complexes 1 and 1a inhibited the colony formation decreasing the colony size and inducing morphology changes in A549 cells. These complexes induced apoptosis cell death and promoted cell cycle arrest in the Sub-G1 phase with a decrease in the cell number at the S phase.
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http://dx.doi.org/10.1016/j.jinorgbio.2018.06.007DOI Listing
September 2018

Half sandwich Ru(ii)-acylthiourea complexes: DNA/HSA-binding, anti-migration and cell death in a human breast tumor cell line.

Dalton Trans 2017 Oct;46(38):12865-12875

Departamento de Química, Universidade Federal de São Carlos, Brasil.

Organometallic ruthenium complexes as potential anticancer agents have been explored due to their suitable properties, such as stability in the solid state and in solution, water solubility and low toxicity. In this study, eight metal complexes of this class were synthesized, characterized and their important biological activities against a human breast tumor cell line (MDA-MB-231) were studied. Complexes 1-8 were obtained in good yields and have been characterized by satisfactory elemental analyses, IR, 1D and 2D H and C{H} NMR, UV-Vis spectroscopy, cyclic voltammetry, ESI-MS and X-ray diffractometry (1, 2, 3 and 6). All complexes exhibit growth inhibition on human breast and lung tumor cell lines, with IC values ranging from 6.0 to 45.0 μM in 48 h. Four compounds were selected to evaluate the changes in the morphology, clonogenic, migration, cell cycle arrest and cell death in MDA-MB-231 cells. The complexes are able to induce morphological changes and inhibit the size, number of colonies and cell migration, and induce cell cycle arrest in the sub-G1 phase and apoptosis cell death. The interaction of the complexes with DNA was determined by performing spectroscopic titration, a competitive assay with thiazole orange, circular dichroism, gel electrophoresis and interactions with guanosine or guanosine monophosphate by H NMR, indicating the non-covalent interaction. The HSA binding affinity measured by spectrophotometric titration, revealed the hydrophobic and spontaneous association with the human protein. Overall, the studies indicated that these metal complexes are potential agents against MDA-MB-231 cells, encouraging us to continue studies of these types of compounds.
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http://dx.doi.org/10.1039/c7dt01801kDOI Listing
October 2017

Understanding the conformational changes and molecular structure of furoyl thioureas upon substitution.

Spectrochim Acta A Mol Biomol Spectrosc 2017 Apr 28;176:8-17. Epub 2016 Dec 28.

CEQUINOR (UNLP-CONICET, CCT La Plata), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, C.C. 962 (1900), La Plata, Argentina. Electronic address:

1-Acyl thioureas [RC(O)NHC(S)NRR] are shown to display conformational flexibility depending on the degree of substitution at the nitrogen atom. The conformational landscape and structural features for two closely related thioureas having R=2-furoyl have been studied. The un-substituted 2-furoyl thiourea (I) and its dimethyl analogue, i.e. 1-(2-furoyl)-3,3-dimethyl thiourea (II), have been synthesized and fully characterized by spectroscopic (FT-IR, H and C NMR) and elemental analysis. According to single crystal X-ray diffraction analysis, compounds I and II crystallize in the monoclinic space group P21/c. In the compound I, the trans-cis geometry of the almost planar thiourea unit is stabilized by intramolecular NH⋯OC hydrogen bond between the H atom of the cis thioamide and the carbonyl O atom. In compound II, however, the acyl thiourea group is non-planar, in good agreement with the potential energy curve computed at the B3LYP/6-31+G(d,p) level of approximation. Centrosymmetric dimers generated by intermolecular NH⋯SC hydrogen bond forming R(8) motif are present in the crystals. Intermolecular interactions have been rationalized in terms of topological partitions of the electron distributions and Hirshfeld surface analysis, which showed the occurrence of S⋯H, O⋯H and H⋯H contacts that display an important role to crystal packing stabilization of both thiourea derivatives.
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http://dx.doi.org/10.1016/j.saa.2016.12.038DOI Listing
April 2017

Ruthenium(II) complexes of 1,3-thiazolidine-2-thione: Cytotoxicity against tumor cells and anti-Trypanosoma cruzi activity enhanced upon combination with benznidazole.

J Inorg Biochem 2016 Mar 2;156:153-63. Epub 2016 Jan 2.

Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil. Electronic address:

Three new mixed and mononuclear Ru(II) complexes containing 1,3-thiazolidine-2-thione (tzdtH) were synthesized and characterized by spectroscopic analysis, molar conductivity, cyclic voltammetry, high-resolution electrospray ionization mass spectra and X-ray diffraction. The complexes presented unique stereochemistry and the proposed formulae are: [Ru(tzdt)(bipy)(dppb)]PF6 (1), cis-[Ru(tzdt)2(PPh3)2] (2) and trans-[Ru(tzdt)(PPh3)2(bipy)]PF6 (3), where dppb=1,4-bis(diphenylphosphino)butane and bipy=2,2'-bipyridine. These complexes demonstrated strong cytotoxicity against cancer cell lines when compared to cisplatin. Specifically, complex 2 was the most potent cytotoxic agent against MCF-7 breast cells, while complexes 1 and 3 were more active in DU-145 prostate cells. Binding of complexes to ctDNA was determined by UV-vis titration and viscosity measurements and revealed binding constant (Kb) values in range of 1.0-4.9×10(3)M(-1), which are characteristic of compounds possessing weak affinity to ctDNA. In addition, these complexes presented antiparasitic activity against Trypanosoma cruzi. Specifically, complex 3 demonstrated strong potency, moderate selectivity index and acted in synergism with the approved antiparasitic drug, benznidazole. Additionally, complex 3 caused parasite cell death through a necrotic process. In conclusion, we demonstrated that Ru(II) complexes have powerful pharmacological activity, while the metal-free tzdtH does not provoke the same outcome.
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http://dx.doi.org/10.1016/j.jinorgbio.2015.12.024DOI Listing
March 2016

Ru(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells.

J Inorg Biochem 2015 Sep 22;150:63-71. Epub 2015 Apr 22.

Departamento de Química, Universidade Federal de São Carlos, UFSCar, Rodovia Washington Luís KM 235, CP 676, 13561-901, São Carlos, SP, Brazil. Electronic address:

Four ruthenium(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans-[Ru(PPh3)2(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA-binding constants, which were in the range of 3.3-6.5×10(4) M(-1), and the thermodynamic parameters (ΔG, ΔH and ΔS), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb = 0.8-1.8×10(4) M(-1)) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin.
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http://dx.doi.org/10.1016/j.jinorgbio.2015.04.008DOI Listing
September 2015

Synthesis, characterization, hydrolase and catecholase activity of a dinuclear iron(III) complex: Catalytic promiscuity.

J Inorg Biochem 2015 May 5;146:77-88. Epub 2015 Mar 5.

Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil. Electronic address:

Herein, we report the synthesis and characterization of the new di-iron(III) complex [(bbpmp)(H2O)(Cl)Fe(III)(μ-Ophenoxo)Fe(III)(H2O)Cl)]Cl (1), with the symmetrical ligand 2,6-bis{[(2-hydroxybenzyl)(pyridin-2-yl)methylamino]methyl}-4-methylphenol (H3bbpmp). Complexes 2 with the unsymmetrical ligand H2bpbpmp - {2-[[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl]-6-bis(pyridylmethyl) aminomethyl}-4-methylphenol and 3 with the ligand L(1)=4,11-dimethyl-1,8-bis{2-[N-(di-2-pyridylmethyl)amino]ethyl}cyclam were included for comparison purposes. Complex 1 was characterized through elemental analysis, X-ray crystallography, magnetochemistry, electronic spectroscopy, electrochemistry, mass spectrometry and potentiometric titration. The magnetic data show a very weak antiferromagnetic coupling between the two iron centers of the dinuclear complex 1 (J=-0.29cm(-1)). Due to the presence of labile coordination sites in both iron centers the hydrolysis of both the diester model substrate 2,4-BDNPP and DNA was studied in detail. Complex 1 was also able to catalyze the oxidation of the substrate 3,5-di-tert-butylcatechol (3,5-DTBC) to give the corresponding quinone, and thus it can be considered as a catalytically promiscuous system.
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http://dx.doi.org/10.1016/j.jinorgbio.2015.02.017DOI Listing
May 2015

Secondary coordination sphere effects in ruthenium(III) tetraammine complexes: role of the coordinated water molecule.

Inorg Chem 2015 Feb 5;54(4):2067-80. Epub 2015 Feb 5.

Instituto de Química and ‡Instituto de Física, Universidade de São Paulo , São Carlos, Brazil.

The complexes trans-[Ru(III)(NH3)4(4-pic)(H2O)](CF3SO3)3 (1) and [Ru(III)(NH3)5(4-pic)](CF3SO3)3 (2) were isolated and studied experimentally by electron paramagnetic resonance (EPR) and UV-vis spectroscopies, cyclic voltammetry, and X-ray crystallography and theoretically by ligand-field theory (LFT) and density functional theory (DFT) calculations. Complex 1 is reported in two different crystal forms, 1a (100 K) and 1b (room temperature). EPR and UV-vis spectroscopies suggest that aqua ligand interaction in this low-spin ruthenium(III) complex changes as a function of hydrogen bonding with solvent molecules. This explicit water solvent effect was explained theoretically by DFT calculations, which demonstrated the effect of rotation of the aqua ligand about the Npic-Ru-Oaq axis. The UV-vis spectrum of 1 shows in an aqueous acid solution a broad- and low-intensity absorption band around 28,500 cm(-1) (ε ≈ 500 M(-1) cm(-1)) that is assigned mainly to a charge-transfer (CT) transition from the equatorial ligands to the Ru β-4dxy orbital (β-LUMO) using DFT calculations. The electronic reflectance spectrum of 1 shows a broad and intense absorption band around 25,500 cm(-1) that is assigned to a CT transition from 4-picoline to the Ru β-4dxz orbital (β-LUMO) using DFT calculations. The t2g(5) set of orbitals had its energy splitting investigated by LFT. LFT analysis shows that a rhombic component arises from C2v symmetry by a simple π-bonding ligand (H2O in our case) twisting about the trans (C2) axis. This twist was manifested in the EPR spectra, which were recorded for 1 as a function of the solvent in comparison with [Ru(NH3)5(4-pic)](3+) and [Ru(NH3)5(H2O)](3+). Only 1 shows an evident change in the g-tensor values, wherein an increased rhombic component is correlated with a higher nucleophilicity (donor) solvent feature, as parametrized by the Abraham system.
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http://dx.doi.org/10.1021/ic5030857DOI Listing
February 2015

New La(III) complex immobilized on 3-aminopropyl-functionalized silica as an efficient and reusable catalyst for hydrolysis of phosphate ester bonds.

Inorg Chem 2014 Mar 3;53(6):2943-52. Epub 2014 Mar 3.

Departamento de Química, Laboratório de Bioinorgânica e Cristalografia (LABINC), Universidade Federal de Santa Catarina , SC, 88040-900 Florianópolis, Brazil.

Described herein is the synthesis, structure, and monoesterase and diesterase activities of a new mononuclear [La(III)(L(1))(NO3)2] (1) complex (H2L(1) = 2-bis[{(2-pyridylmethyl)-aminomethyl}-6-[N-(2-pyridylmethyl) aminomethyl)])-4-methyl-6-formylphenol) in the hydrolysis of 2,4-bis(dinitrophenyl)phosphate (2,4-BDNPP). When covalently linked to 3-aminopropyl-functionalized silica, 1 undergoes disproportionation to form a dinuclear species (APS-1), whose catalytic efficiency is increased when compared to the homogeneous reaction due to second coordination sphere effects which increase the substrate to complex association constant. The anchored catalyst APS-1 can be recovered and reused for subsequent hydrolysis reactions (five times) with only a slight loss in activity. In the presence of DNA, we suggest that 1 is also converted into the dinuclear active species as observed with APS-1, and both were shown to be efficient in DNA cleavage.
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http://dx.doi.org/10.1021/ic402705rDOI Listing
March 2014

On the cytotoxic activity of Pd(II) complexes of N,N-disubstituted-N'-acyl thioureas.

J Inorg Biochem 2014 May 8;134:76-82. Epub 2014 Feb 8.

Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil. Electronic address:

The rational design of anticancer drugs is one of the most promising strategies for increasing their cytotoxicity and for minimizing their toxicity. Manipulation of the structure of ligands or of complexes represents a strategy for which is possible to modify the potential mechanism of their action against the cancer cells. Here we present the cytotoxicity of some new palladium complexes and our intention is to show the importance of non-coordinated atoms of the ligands in the cytotoxicity of the complexes. New complexes of palladium (II), with general formulae [Pd(PPh3)2(L)]PF6 or [PdCl(PPh3)(L)], where L=N,N-disubstituted-N'-acyl thioureas, were synthesized and characterized by elemental analysis, molar conductivity, melting points, IR, NMR((1)H, (13)C and (31)P{(1)H}) spectroscopy. The spectroscopic data are consistent with the complexes containing an O, S chelated ligand. The structures of complexes with N,N-dimethyl-N'-benzoylthiourea, N,N-diphenyl-N'-benzoylthiourea, N,N-diethyl-N'-furoylthiourea, and N,N-diphenyl-N'-furoylthiourea were determined by X-ray crystallography, confirming the coordination of the ligands with the metal through sulfur and oxygen atoms, forming distorted square-planar structures. The N,N-disubstituted-N'-acyl thioureas and their complexes were screened with respect to their antitumor cytotoxicity against DU-145 (human prostate cancer cells), MDA-MB-231 (human breast cancer cells) and their toxicity against the L929 cell line (health cell line from mouse).
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http://dx.doi.org/10.1016/j.jinorgbio.2014.01.022DOI Listing
May 2014

Second-coordination-sphere effects increase the catalytic efficiency of an extended model for Fe(III)M(II) purple acid phosphatases.

Inorg Chem 2013 Apr 15;52(7):3594-6. Epub 2013 Mar 15.

Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil.

Herein we describe the synthesis of a new heterodinuclear Fe(III)Cu(II) model complex for the active site of purple acid phosphatases and its binding to a polyamine chain, a model for the amino acid residues around the active site. The properties of these systems and their catalytic activity in the hydrolysis of bis(2,4-dinitrophenyl)phosphate are compared, and conclusions regarding the effects of the second coordination sphere are drawn. The positive effect of the polymeric chain on DNA hydrolysis is also described and discussed.
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http://dx.doi.org/10.1021/ic400025jDOI Listing
April 2013

Design of a dinuclear nickel(II) bioinspired hydrolase to bind covalently to silica surfaces: synthesis, magnetism, and reactivity studies.

Inorg Chem 2012 Jun 15;51(11):6104-15. Epub 2012 May 15.

Departamento de Química, Laboratório de Química Bioinorgânica e Cristalografia (LABINC), Universidade Federal de Santa Catarina, SC, 88040-900 Florianópolis, Brazil.

Presented herein is the design of a dinuclear Ni(II) synthetic hydrolase [Ni(2)(HBPPAMFF)(μ-OAc)(2)(H(2)O)]BPh(4) (1) (H(2)BPPAMFF = 2-[(N-benzyl-N-2-pyridylmethylamine)]-4-methyl-6-[N-(2-pyridylmethyl)aminomethyl)])-4-methyl-6-formylphenol) to be covalently attached to silica surfaces, while maintaining its catalytic activity. An aldehyde-containing ligand (H(2)BPPAMFF) provides a reactive functional group that can serve as a cross-linking group to bind the complex to an organoalkoxysilane and later to the silica surfaces or directly to amino-modified surfaces. The dinuclear Ni(II) complex covalently attached to the silica surfaces was fully characterized by different techniques. The catalytic turnover number (k(cat)) of the immobilized Ni(II)Ni(II) catalyst in the hydrolysis of 2,4-bis(dinitrophenyl)phosphate is comparable to the homogeneous reaction; however, the catalyst interaction with the support enhanced the substrate to complex association constant, and consequently, the catalytic efficiency (E = k(cat)/K(M)) and the supported catalyst can be reused for subsequent diester hydrolysis reactions.
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http://dx.doi.org/10.1021/ic300018tDOI Listing
June 2012

2-Acetylpyridine- and 2-benzoylpyridine-derived hydrazones and their gallium(III) complexes are highly cytotoxic to glioma cells.

Eur J Med Chem 2012 Apr 2;50:163-72. Epub 2012 Feb 2.

Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.

2-Acetylpyridine-phenylhydrazone (H2AcPh), its para-chlorophenylhydrazone (H2AcpClPh) and para-nitrophenylhydrazone (H2AcpNO(2)Ph) analogues, the corresponding 2-benzoylpyridine-derived hydrazones (H2BzPh, H2BzpClPh and H2BzpNO(2)Ph) and their gallium(III) complexes were assayed for their cytotoxic activity against U87 (expressing wild-type p53 protein) and T98 (expressing mutant p53 protein) glioma cells. IC(50) values against both glioma cells and against the MRC5 (human fetal lung fibroblast) lineage were obtained for the hydrazones, but not for their gallium(III) complexes, due to their low solubility. Hydrazones were highly cytotoxic at nanomolar doses against U87 and T98 cells. The therapeutic indexes (TI = IC(50MRC5)/IC(50glioma)) were 2-660 for T98 cells and 28-5000 for U87 cells, indicating that the studied hydrazones could be good antitumor drug candidates to treat brain tumors.
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http://dx.doi.org/10.1016/j.ejmech.2012.01.051DOI Listing
April 2012

Bioinspired FeIIICdII and FeIIIHgII complexes: synthesis, characterization and promiscuous catalytic activity evaluation.

J Inorg Biochem 2011 Dec 28;105(12):1740-52. Epub 2011 Aug 28.

Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.

In this work we report on the synthesis, crystal structure, and physicochemical characterization of the novel dinuclear [Fe(III)Cd(II)(L)(μ-OAc)(2)]ClO(4)·0.5H(2)O (1) complex containing the unsymmetrical ligand H(2)L=2-bis[{(2-pyridyl-methyl)-aminomethyl}-6-{(2-hydroxy-benzyl)-(2-pyridyl-methyl)}-aminomethyl]-4-methylphenol. Also, with this ligand, the tetranuclear [Fe(2)(III)Hg(2)(II)(L)(2)(OH)(2)](ClO(4))(2)·2CH(3)OH (2) and [Fe(III)Hg(II)(L)(μ-CO(3))Fe(III)Hg(II)(L)](ClO(4))(2)·H(2)O (3) complexes were synthesized and fully characterized. It is demonstrated that the precursor [Fe(III)(2)Hg(II)(2)(L)(2)(OH)(2)](ClO(4))(2)·2CH(3)OH (2) can be converted to (3) by the fixation of atmospheric CO(2) since the crystal structure of the tetranuclear organometallic complex [Fe(III)Hg(II)(L)(μ-CO(3))Fe(III)Hg(II)(L)](ClO(4))(2)·H(2)O (3) with an unprecedented {Fe(III)(μ-O(phenoxo))(2)(μ-CO(3))Fe(III)} core was obtained through X-ray crystallography. In the reaction 2→3 a nucleophilic attack of a Fe(III)-bound hydroxo group on the CO(2) molecule is proposed. In addition, it is also demonstrated that complex (3) can regenerate complex (2) in aqueous/MeOH/NaOH solution. Magnetochemical studies reveal that the Fe(III) centers in 3 are antiferromagnetically coupled (J=-7.2cm(-1)) and that the Fe(III)-OR-Fe(III) angle has no noticeable influence in the exchange coupling. Phosphatase-like activity studies in the hydrolysis of the model substrate bis(2,4-dinitrophenyl) phosphate (2,4-bdnpp) by 1 and 2 show Michaelis-Menten behavior with 1 being ~2.5 times more active than 2. In combination with k(H)/k(D) isotope effects, the kinetic studies suggest a mechanism in which a terminal Fe(III)-bound hydroxide is the hydrolysis-initiating nucleophilic catalyst for 1 and 2. Based on the crystal structures of 1 and 3, it is assumed that the relatively long Fe(III···)Hg(II) distance could be responsible for the lower catalytic effectiveness of 2.
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http://dx.doi.org/10.1016/j.jinorgbio.2011.08.017DOI Listing
December 2011

Analgesic and anti-inflammatory activities of salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their zinc(II) complexes.

Molecules 2011 Aug 15;16(8):6902-15. Epub 2011 Aug 15.

LaFI Laboratório de Farmacologia e Imunidade, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, AL, Brazil.

Salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their complexes [Zn(LASSBio-466)H(2)O](2) (1) and [Zn(HLASSBio-1064)Cl](2) (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the anti-nociceptive activity was favored in the complex 1. H(2)LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H(2)LASSBio-466. H(2)LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.
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http://dx.doi.org/10.3390/molecules16086902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264688PMC
August 2011

A new nitrosyl ruthenium complex: synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action.

Eur J Med Chem 2011 Sep 19;46(9):3616-22. Epub 2011 May 19.

Departamento de Bioquímica e Imunologia, Faculdade de Medicine de Ribeirão Preto, Universidade de São Paulo, Av Bandeirantes, 3900-FMRP-USP, 14.049-900 Ribeirão Preto, SP, Brazil.

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl(2)NO(BPA)]is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis.
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http://dx.doi.org/10.1016/j.ejmech.2011.04.064DOI Listing
September 2011

Calixarene and resorcarene based receptors: from structural and thermodynamic studies to the synthesis of a new mercury(II) selective material.

J Phys Chem B 2011 Jun 5;115(21):6922-34. Epub 2011 May 5.

Thermochemistry Laboratory, Chemical Science Division, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kigdom.

Materials used in current technological approaches for the removal of mercury lack selectivity. Given that this is one of the main features of supramolecular chemistry, receptors based on calix[4]arene and calix[4]resorcarene containing functional groups able to interact selectively with polluting ions while discriminating against biologically essential ones were designed. Thus two receptors, a partially functionalized calix[4]arene derivative, namely, 5,11,17,23-tetra-tert-butyl [25-27-bis(diethyl thiophosphate amino)dihydroxy] calix[4]arene (1) and a fully functionalized calix[4]resorcarene, 4,6,10,12,16,18,22,24-diethyl thiophosphate calix[4]resorcarene (2) are introduced. Mercury(II) was the identified target due to the environmental and health problems associated with its presence in water Thus following the synthesis and characterization of 1 and 2 in solution ((1)HNMR) and in the solid state (X-ray crystallography) the sequence of experimental events leading to cation complexation studies in acetonitrile and methanol ((1)H NMR, conductance, potentiometric, and calorimetric measurements) with the aim of assessing their behavior as mercury selective receptors are described. The cation selectivity pattern observed in acetonitrile follows the sequence Hg(II) > Cu(II) > Ag(I). In methanol 1 is also selective for Hg(II) relative to Ag(I) but no interaction takes place between this receptor and Cu(II) in this solvent. Based on previous results and experimental facts shown in this paper, it is concluded that the complexation observed with Cu(II) in acetonitrile occurs through the acetonitrile-receptor adduct rather than through the free ligand. Receptor 2 has an enhanced capacity for uptaking Hg(II) but forms metalate complexes with Cu(II). These studies in solution guided the inmobilization of receptor 1 into a silica support to produce a new and recyclable material for the removal of Hg(II) from water. An assessment on its capacity to extract this cation from water relative to Cu(II) and Ag (I) shows that the cation selectivity pattern of the inmobilized receptor is the same as that observed for the free receptor in methanol. These findings demonstrate that fundamental studies play a critical role in the selection of the receptor to be attached to silicates as well as in the reaction medium used for the synthesis of the new decontaminating agent.
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http://dx.doi.org/10.1021/jp110195fDOI Listing
June 2011

Electronic structure and spectro-structural correlations of Fe(III)Zn(II) biomimetics for purple acid phosphatases: relevance to DNA cleavage and cytotoxic activity.

Inorg Chem 2010 Dec 16;49(24):11421-38. Epub 2010 Nov 16.

Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, South Carolina 88040-900, Brazil.

Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear Fe(III)M(II) center (M(II) = Fe, Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of phosphoric acid esters. The dinuclear complex [(H(2)O)Fe(III)(μ-OH)Zn(II)(L-H)](ClO(4))(2) (2) with the ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N'-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl]phenol (H(2)L-H) has recently been prepared and is found to closely mimic the coordination environment of the Fe(III)Zn(II) active site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a variety of structural, spectroscopic, and computational techniques the electronic structure of the Fe(III) center of this biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted Fe(III)N(2)O(4) octahedron with a dominant tetragonal compression aligned along the μ-OH-Fe-O(phenolate) direction. To probe the role of the Fe-O(phenolate) bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (-CH(3), -H, -Br, -NO(2)) in the 5-position. The effects of the substituents on the electronic properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This study establishes benchmarks against accurate crystallographic structural information using spectroscopic techniques that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase activity increases in the order -NO(2) ←Br ←H ←CH(3) when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear free energy relationship is found when log(k(cat)/k(0)) is plotted against the Hammett parameter σ. However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes containing the electron-withdrawing -NO(2) and electron-donating -CH(3) groups are the most active while the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups.
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http://dx.doi.org/10.1021/ic101433tDOI Listing
December 2010

Antimycobacterial and antitumor activities of palladium(II) complexes containing isonicotinamide (isn): X-ray structure of trans-[Pd(N3)2(isn)(2)].

Eur J Med Chem 2010 Nov 6;45(11):4863-8. Epub 2010 Aug 6.

Sao Paulo State Univ, Instituto de Química de Araraquara, Rua Prof. Francisco Degni s/n, C.P. 355, 14800-900 Araraquara, SP, Brazil.

Complexes of the type trans-[PdX(2)(isn)(2)] {X = Cl (1), N(3) (2), SCN (3), NCO (4); isn = isonicotinamide} were synthesized and evaluated for in vitro antimycobacterial and antitumor activities. The coordination mode of the isonicotinamide and the pseudohalide ligands was inferred by IR spectroscopy. Single crystal X-ray diffraction determination on 2 showed that coordination geometry around Pd(II) is nearly square planar, with the ligands in a trans configuration. All the compounds demonstrated better in vitro activity against Mycobacterium tuberculosis than isonicotinamide and pyrazinamide. Among the complexes, compound 2 was found to be the most active with MIC of 35.89 μM. Complexes 1-4 were also screened for their in vitro antitumor activity towards LM3 and LP07 murine cancer cell lines.
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http://dx.doi.org/10.1016/j.ejmech.2010.07.057DOI Listing
November 2010

Coordination of nitro-thiosemicarbazones to ruthenium(II) as a strategy for anti-trypanosomal activity improvement.

Eur J Med Chem 2010 Jul 11;45(7):2847-53. Epub 2010 Mar 11.

Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos (SP), Brazil.

Complexes [RuCl(H4NO(2)Fo4M)(bipy)(dppb)]PF(6) (1), [RuCl(H4NO(2)Fo4M)(Mebipy)(dppb)]PF(6) (2), [RuCl(H4NO(2)Fo4M)(phen)(dppb)]PF(6) (3), [RuCl(H4NO(2)Ac4M)(bipy)(dppb)]PF(6) (4), [RuCl(H4NO(2)Ac4M)(Mebipy)(dppb)]PF(6) (5) and [RuCl(H4NO(2)Ac4M)(phen)(dppb)]PF(6) (6) with N(4)-methyl-4-nitrobenzaldehyde thiosemicarbazone (H4NO(2)Fo4M) and N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M) were obtained from [RuCl(2)(bipy)(dppb)], [RuCl(2)(Mebipy)(dppb)], and [RuCl(2)(phen)(dppb)], (dppb = 1,4-bis(diphenylphospine)butane; bipy = 2,2'-bipyridine; Mebipy = 4,4'-dimethyl-2,2'-bipyridine; phen = 1,10-phenanthroline). In all cases the thiosemicarbazone is attached to the metal center through the sulfur atom. Complexes (1-6), together with the corresponding ligands and the Ru precursors were evaluated for their ability to in vitro suppress the growth of Trypanosoma cruzi. All complexes were more active than their corresponding ligands and precursors. Complexes (1-3) and (5) revealed to be the most active among all studied compounds with ID(50) = 0.6-0.8 microM. In all cases the association of the thiosemicarbazone with ruthenium, dppb and bipyridine or phenanthroline in one same complex proved to be an excellent strategy for activity improvement.
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http://dx.doi.org/10.1016/j.ejmech.2010.03.005DOI Listing
July 2010

Synthesis, structure, and phosphatase-like activity of a new trinuclear Gd complex with the unsymmetrical ligand H3L as a model for nucleases.

Inorg Chem 2010 Mar;49(6):3057-63

Laboratório de Bioinorgânica e Crystalografia, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, Santa Catarina, Brazil.

The new trinuclear gadolinium complex [Gd(3)L(2)(NO(3))(2)(H(2)O)(4)]NO(3).8H(2)O (1) with the unsymmetrical ligand 2-[N-bis-(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N-bis(2-hydroxy-2-oxoethyl)aminomethyl] phenol (H(3)L) was synthesized and characterized. The new ligand H(3)L was obtained in good yield. Complex 1 crystallizes in an orthorhombic cell, space group Pcab. Kinetic studies show that complex 1 is highly active in the hydrolysis of the substrate 2,4-bis(dinitrophenyl)phosphate (K(m) = 4.09 mM, V(max) = 2.68 x 10(-2) mM s(-1), and k(cat) = V(max)/[1] = 0.67 s(-1)). Through a potentiometric study and determination of the kinetic behavior of 1 in acetonitrile/water solution, the species present in solution could be identified, and a trinuclear monohydroxo species appears to be the most prominent catalyst under mild conditions. Complex 1 displays high efficiency in DNA hydrolytic cleavage, and complete kinetic studies were carried out (K(m) = 4.57 x 10(-4) M, k'(cat) = 3.42 h(-1), and k'(cat)/K(m) = 7.48 x 10(3) M(-1) h(-1)). Studies with a radical scavenger (dimethyl sulfoxide, DMSO) showed that it did not inhibit the activity, indicating the hydrolytic action of 1 in the cleavage of DNA, and studies on the incubation of distamycin with plasmid DNA suggest that 1 is regio-specific, interacting with the minor groove of DNA.
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http://dx.doi.org/10.1021/ic100276zDOI Listing
March 2010

Pt(II) and Ag(I) complexes with acesulfame: crystal structure and a study of their antitumoral, antimicrobial and antiviral activities.

J Inorg Biochem 2010 May 18;104(5):533-40. Epub 2010 Jan 18.

Instituto de Química, Universidade Estadual Paulista Júlio de Mesquita Filho - UNESP, Rua Prof. Francisco Degni s/n, CEP 14801-970, Araraquara, SP, Brazil.

Two new complexes of platinum(II) and silver(I) with acesulfame were synthesized. Acesulfame is in the anionic form acesulfamate (ace). The structures of both complexes were determined by X-ray crystallography. For K(2)[PtCl(2)(ace)(2)] the platinum atom is coordinated to two Cl(-) and two N-acesulfamate atoms forming a trans-square planar geometry. Each K(+) ion interacts with two oxygen atoms of the S(O)(2) group of each acesulfamate. For the polymeric complex [Ag(ace)](n) the water molecule bridges between two crystallographic equivalent Ag1 atoms which are related each other by a twofold symmetry axis. Two Ag1 atoms, related to each other by a symmetry centre, make bond contact with two equivalent oxygen atoms. These bonds give rise to infinite chains along the unit cell diagonal in the ac plane. The in vitro cytotoxic analyses for the platinum complex using HeLa (human cervix cancer) cells show its low activity when compared to the vehicle-treated cells. The Ag(I) complex submitted to in vitro antimycobacterial tests, using the Microplate Alamar Blue (MABA) method, showed a good activity against Mycobacterium tuberculosis, responsible for tuberculosis, with a minimal inhibitory concentration (MIC) value of 11.6microM. The Ag(I) complex also presented a promising activity against Gram negative (Escherichia coli and Pseudomonas aeruginosa) and Gram positive (Enterococcus faecalis) microorganisms. The complex K(2)[PtCl(2)(ace)(2)] was also evaluated for antiviral properties against dengue virus type 2 (New Guinea C strain) in Vero cells and showed a good inhibition of dengue virus type 2 (New Guinea C strain) replication at 200microM, when compared to vehicle-treated cells.
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http://dx.doi.org/10.1016/j.jinorgbio.2010.01.004DOI Listing
May 2010

Superoxidedismutase-mimetic copper(II) complexes containing saccharinate and 4-aminopyridine/4-cyanopyridine.

J Trace Elem Med Biol 2010 Jan 3;24(1):20-6. Epub 2009 Nov 3.

Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, C. Correo 962, 1900 La Plata, Argentina.

Two copper(II) complexes, [Cu(sac)(2)(4-cypy)(2)(H(2)O)], 1 and [Cu(sac)(2)(4-Ampy)(2)(H(2)O)], 2 (4-cypy: 4-cyanopyridine; 4-Ampy: 4-aminopyridine) were prepared. Physicochemical properties of the complexes were studied by spectroscopic (solution UV-vis, diffuse reflectance and IR) techniques. Structural X-ray diffraction data could be obtained only for [Cu(sac)(2)(4-cypy)(2)(H(2)O)] that it crystallized in the tetragonal space group P4cc with a=b=15.313(1), c=13.240(1)A, and Z=4 molecules per unit cell. The complex was cited on a crystallographic C(2)-axis with the Cu(II) ion in a square-pyramidal environment, coordinated at the pyramid basis to the nitrogen atom of two saccharine anions [d(Cu-N)=2.011(3)A] and the pyridine N-atom of two 4-cyanopyridine ligands [d(Cu-N)=2.038(4)A]. The coordination was completed by a water molecule at the pyramid apex [d(Cu-Ow)=2.189(5)A]. Elemental and spectroscopic analyses revealed an O-saccharinate coordination mode for complex 2 and a square-pyramidal structure. Only complex 2 retained its structure in methanolic solution. However, both complexes were able to catalyze the dismutation of superoxide anion (O(2)(-)) (pH 7.5) at micromolar concentrations. Therefore, these complexes behaved as useful SOD-mimetic compounds.
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http://dx.doi.org/10.1016/j.jtemb.2009.09.002DOI Listing
January 2010

Synthesis, characterization and cytotoxic activities of the [RuCl2(NO)(dppp)(L)]PF6 complexes.

J Inorg Biochem 2010 May 4;104(5):489-95. Epub 2010 Jan 4.

Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil.

The synthesis and characterization of ruthenium compounds of the type [RuCl(2)(NO)(dppp)(L)]PF(6) [dppp=1,3-bis(diphenylphosphino)propane; L=pyridine, 4-methylpyridine, 4-phenylpyridine and dimethyl sulfoxide] are described. The complexes were characterized by elemental analysis, UV/Vis and infrared spectroscopy, cyclic voltammetry, and X-ray crystallography for the complexes with the pyridine and 4-methylpyridine ligands. In vitro evaluation of these nitrosyl complexes revealed cytotoxic activity from 7.1 to 19.0 microM against the MDA-MB-231 breast tumor cells and showed that, in this case, they are more active than the reference metallodrug cisplatin. The 1,3-bis(diphenylphosphino)propane and the N-heterocyclic ligands alone failed to show cytotoxic activities at the concentrations tested (maximum concentration utilized=200 microM).
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http://dx.doi.org/10.1016/j.jinorgbio.2009.12.015DOI Listing
May 2010
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