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Item 2,2’,4-Trihydroxybenzophenone : crystal structure, and anti-inflammatory and antioxidant activities.(2007) Doriguetto, Antônio Carlos; Martins, Felipe Terra; Ellena, Javier Alcides; Salloum, Rogério; Santos, Marcelo Henrique dos; Moreira, Maria Eliza de Castro; Silva, Jose Mauricio Schneedorf Ferreira da; Nagem, Tanus JorgeThe crystal structure of C 2,2’,4-trihydroxybenzophenoneD (¼(2,4-dihydroxyphenyl)(2-hydroxyphenyl) methanone; 1) was determined, and its molecular structure, along with intra- and intermolecular Hbonds, was analyzed. The anti-inflammatory potential of 1, evaluated by means of the rat-paw-edema assay, with carrageenan as inflammation stimulus, was found to be similar high as that of indomethacin. In contrast, benzophenone proper (2) was hardly active in this assay. Our results indicate that these antiinflammatory effects are related to the action of kinins and prostaglandins. The radical-scavenging properties of 1 towards DPPH were found to be similar as those of typical phenolics, but somewhat lower than that of ascorbic acid. The structure–activity relationship (SAR) of 1 is discussed.Item Anti-mycobacterium tuberculosis and cytotoxicity activities of Ruthenium(II)/ bipyridine/diphosphine/pyrimidine-2-thiolate complexes : the role of the non- coordinated N-atom.(2016) Benedicto, Augusto Vieira Lima; Correa, Rodrigo de Souza; Graminha, Angelica Ellen; Kuznetsov, Aleksey Evgenyevich; Ellena, Javier Alcides; Pavan, Fernando Rogério; Leite, Clarice Queico Fujimura; Batista, Alzir AzevedoThe [Ru(Spym)(bipy)(P–P)]PF6, [Spym = pyrimidine-2-thiolate anion; P–P = 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane and 1,1’-bis(diphenylphosphino)ferrocene] complexes were synthesized and characterized by spectroscopic, electrochemical and elemental analysis, and by X-ray crystallography. The minimal inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis and the complex concentration causing 50% tumor cell growth inhibition (IC50) against breast cancer cells, MDA-MB-231, were determined. All three compounds gave promising values in both tests. It is interesting to mention that all three complexes display MICs against Mycobacterium tuberculosis showing higher activity than cycloserine, a second line drug used in the treatment of the illness. The complexes interact weakly with the DNA.Item Copper(I)−Phosphine polypyridyl complexes : synthesis, characterization, DNA/HSA binding study, and antiproliferative activity.(2017) Villarreal, Wilmer; Colina Vegas, Legna Andreina; Visbal, Gonzalo; Corona, Oscar; Correa, Rodrigo de Souza; Ellena, Javier Alcides; Cominetti, Márcia Regina; Batista, Alzir Azevedo; Navarro Acosta, Maribel CoromotoA series of copper(I)−phosphine polypyridyl complexes have been investigated as potential antitumor agents. The complexes [Cu(PPh3)2dpq]NO3 (2), [Cu(PPh3)2dppz]NO3 (3), [Cu(PPh3)2dppa]NO3 (4), and [Cu(PPh3)2dppme]NO3 (5) were synthesized by the reaction of [Cu(PPh3)2NO3] with the respective planar ligand under mild conditions. These copper complexes were fully characterized by elemental analysis, molar conductivity, FAB-MS, and NMR, UV−vis, and IR spectroscopies. Interactions between these copper(I)−phosphine polypyridyl complexes and DNA have been investigated using various spectroscopic techniques and analytical methods, such as UV−vis titrations, thermal denaturation, circular dichroism, viscosity measurements, gel electrophoresis, and competitive fluorescent intercalator displacement assays. The results of our studies suggest that these copper(I) complexes interact with DNA in an intercalative way. Furthermore, their high protein binding affinities toward human serum albumin were determined by fluorescence studies. Additionally, cytotoxicity analyses of all complexes against several tumor cell lines (human breast, MCF-7; human lung, A549; and human prostate, DU-145) and nontumor cell lines (Chinese hamster lung, V79-4; and human lung, MRC-5) were performed. The results revealed that copper(I)− phosphine polypyridyl complexes are more cytotoxic than the corresponding planar ligand and also showed to be more active than cisplatin. A good correlation was observed between the cytostatic activity and lipophilicity of the copper(I) complexes studied here.Item Cytotoxic activity and structural features of Ru(II)/phosphine/amino acid complexes.(2018) Santos, Edjane Rocha dos; Graminha, Angelica Ellen; Schultz, Mario Sergio; Correia, Isabel; Araujo, Heloisa Sobreiro Selistre de; Correa, Rodrigo de Souza; Ellena, Javier Alcides; Lacerda, Elisângela de Paula Silveira; Pessoa, João Costa; Batista, Alzir AzevedoThirteen new ruthenium amino acid complexes were synthesized and characterized. They were obtained by the reaction of α-amino acids (AA) with [RuCl2(P-P)(N-N)], where P-P = 1,4-bis(diphenylphosphino)butane (dppb) or 1,3-bis(diphenylphosphino)propane (dppp) and N-N = 4,4′-dimethyl-2,2′-bipyridine (4′-Mebipy), 5,5′-dimethyl-2,2′-bipyridine (5′-Mebipy) or 4,4′-Methoxy-2-2′-bipyridine (4′-MeObipy). This afforded a family of complexes formulated as [Ru(AA-H)(P-P)(N-N)]PF6, where AA = glycine (Gly), L-alanine (Ala), L-valine (Val), L-tyrosine (Tyr), L-tryptophan (Trp), L-histidine (His) and L-methionine (Met). All compounds were characterized by elemental analysis, spectroscopic and electrochemical techniques. The [Ru(AA-H)(P-P)(N-N)]PF6 complexes are octahedral (the AA-H ligand binding involves N-amine and O-carboxylate), diamagnetic (low-spin d6, S = 0) and present bands due to electronic transitions in the visible region. 1H, 13C{1H} and 31P{1H} NMR spectra of the complexes indicate the presence of C2 symmetry, and the identification of diastereoisomers. In vitro cytotoxicity assays of the compounds and cisplatin were carried out using MDA-MB-231 (human breast) tumor cell line and a non-tumor breast cell line (MCF-10A). Most complexes present promising results with IC50 values comparable with the reference drug cisplatin and high selectivity indexes were found for the complexes containing L-Trp. The binding of two Ru-precursors of the type [RuCl2(dppb)(NN)] (N-N = 4′-MeObipy or 4′-Mebipy) to the blood transporter protein human serum albumin (HSA) was evaluated by fluorescence and circular dichroism spectroscopy. Both complexes bind HSA, probably in the hydrophobic pocket near Trp214, and the Ru-complex containing 4′-MeObipy shows higher affinity for HSA than the 4′-Mebipy one.Item Esterification of the free carboxylic group from the lutidinic acid ligand as a tool to improve the cytotoxicity of Ru(II) complexes.(2019) Araujo Neto, João Honorato de; Colina Vegas, Legna Andreina; Correa, Rodrigo de Souza; Macedo, Adriana Pereira Mundim Guedes; Miyata, Marcelo; Pavan, Fernando Rogério; Ellena, Javier Alcides; Batista, Alzir AzevedoIn this study, we report on the selective esterification of the carboxyl group in a coordinated ligand based on the Fischer reaction. The new [Ru(N–O)(bipy)(dppb)]PF6 complex 1 was used as a precursor to obtain the ester derivative [Ru(N–Oet)(bipy)(dppb)]PF6 (2), and in order to establish the influence of either the free carboxyl group or the ethoxycarbonyl group on biological properties, the [Ru(pic)(bipy)(dppb)]PF6 complex (3) was synthesized for comparison (dppb = 1,4-bis(diphenylphosphino)butane, bipy = 2,2′-bipyridine, N–O = mono-deprotonated 2,4-pyridinedicarboxylic acid, N–Oet = 4-ethoxycarbonyl-2-pyridinecarboxylic acid). All three complexes interact weakly with human serum albumin (HSA) with Kb values ranging from 101–104 M−1, suggesting a spontaneous interaction with this protein by electrostatic (1–2) or van der Waals interactions (3). Moreover, complex/DNA-binding experiments indicate that complexes 2 and 3 interact weakly with DNA, while no interaction is observed between complex 1 and DNA, probably due to the repulsion involving the free carboxylate group/DNA-phosphate. Anti-Mycobacterium tuberculosis (MTB) activity and cytotoxicity assays against one normal cell line V79 (hamster fibroblast) and three human cancer cell lines A549 (lung), MCF7 and MDA-MB-231 (breast) revealed that complexes 2 and 3 exhibit good activity against MTB and tumor cells, presenting high cytotoxicity (low IC50). On the other hand, complex 1 is practically inactive. Therefore, the best biological results found for complex 2 can be attributed to its esterification, improving the lipophilicity and cellular uptake, in order to facilitate its passive permeation through the tumor cell membranes allowing for cell death, as well as DNA and HSA interactions, when compared with complex 1.Item Facile synthesis and characterization of symmetric N-[(Phenylcarbonyl) carbamothioyl]benzamide thiourea : experimental and theoretical investigations.(2018) Silveira, Rafael Gomes da; Catão, Anderson José Lopes; Cunha, Beatriz Nogueira da; Almeida, Fernando; Diniz, Luan Farinelli; Clavijo, Juan Carlos Tenorio; Ellena, Javier Alcides; Kuznetsov, Aleksey Evgenyevich; Batista, Alzir Azevedo; Alcântara, EdésioA thiourea derivative, N-[(phenylcarbonyl)carbamothioyl]benzamide, was synthesized and characterized by elemental analysis, thermal analysis, spectroscopic methods (Fourier transform infrared (FTIR), UV-Vis, Raman, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF), tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR)) and quantum-chemical calculations. The synthetic route was simple and efficient, conducted just by one-step and no purification step was needed. The compound crystallizes in a non-centrosymmetric orthorhombic crystal system with a P21 21 21 space group, with a= 5.06220(10) Å, b= 11.8623(3) Å, c= 21.9682(8) Å. The molecular conformation of the solid is stabilized by the N-H···O intramolecular hydrogen bond, which was present in the X-ray structure and was also found in the optimized geometry. The theoretical analysis showed that this strong interaction remains even when molecules are solvated, i.e., the rotation barrier and the hydrogen bond strength are greater than the solvent stabilization energy. In addition to this hydrogen bond effect, the relative position of phenyl groups has a certain influence on the chemical behavior of this thiourea and probably for other phenylthioureas.Item "Half-sandwich"/RuII anticancer complexes containing triphenylphosphine and p-substituted benzoic acids.(2020) Araujo Neto, João Honorato de; Oliveira, Katia Mara de; Leite, Celisnolia Morais; Colina Vegas, Legna Andreina; Nóbrega, Joaquim de Araújo; Castellano, Eduardo Ernesto; Ellena, Javier Alcides; Correa, Rodrigo de Souza; Batista, Alzir AzevedoMononuclear and binuclear RuII/arene/triphenylphosphine complexes with p-substituted benzoic acid derivatives were prepared and characterized. These monocationic complexes of type [Ru(η6 -p-cymene)(PPh3)L] (L = benzoic acid (1), p-hydroxybenzoic acid (2), p-nitrobenzoic acid (3) and terephthalic acid (4)) were characterized using various techniques, such as nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and the crystal structure of 1, 3 and 4 were determined by X-ray diffraction analysis. The cytotoxicity of the complexes was evaluated, in vitro, against tumorigenic [MDA-MB-231, MCF-7 (breast), A549 (lung) and DU-145 (prostate)] and non-tumorigenic [MCF-10A (breast), MRC-5 (lung) and PNT-2 (prostate)] cells. The binuclear complex (4) was inactive due to its low solubility. Complexes 1, 2 and 3 showed similar cytotoxicity, however, complex 1 presented better selectivity index against MDA-MB-231 than compounds 2 and 3. Cellular ruthenium absorption was explored by inductively coupled plasma mass spectrometry (ICP-MS) analyzing the whole cells and the culture medium. Complementary studies showed that complex 1 inhibited colony formation, induced morphology changes in cells and promoted cell cycle arrest in the Sub-G1 phase for the MDA-MB-231 cells.Item Influence of gold nanoparticles applied to catalytic hydrogenation of acetophenone with cationic complexes containing ruthenium.(2016) Souza, Lanarck Cristina Moro; Santos, Thiago A.; Prado, Cássio Roberto Arantes do; Lima, Benedicto Augusto Vieira; Correa, Rodrigo de Souza; Batista, Alzir Azevedo; Otubo, Larissa; Ellena, Javier Alcides; Ueno, Leonardo Tsuyoshi; Dinelli, Luís Rogério; Bogado, André LuizHerein the catalytic activity of cationic ruthenium(II) complexes [Ru]+ is described in the presence of gold nanoparticles (AuNPsn ) in the transfer hydrogenation of acetophenone, to produce phenylethanol. The catalytic activity of the complexes, with a general formula cis-[RuCl(CH3OH)(P–P)(N–N)]+ or cis- [RuCl(CH3OH)(P)2(N–N)]+ {where: P ¼ triphenylphosphine (PPh3); P–P ¼ 1,1-bis(diphenylphosphino) methane (dppm); 1,2-bis(diphenylphosphino)ethane (dppe); 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (dppb); N–N ¼ 2,20-bipyridine; 4,40-dimethyl-2,20-bipyridine} was investigated in the presence of AuNPsn . The interaction between [Ru]+ and AuNPsn citrate capped is an electrostatic interaction, by a self-assembly processes, to produce a supramolecular species, labeled as [Ru]+/AuNPsn . This non-covalent interaction has no effect over the chemical and physical chemical parameters of the complexes, which provides a good point of comparison in the presence and absence of AuNPsn . The AuNPsn alone have no catalytic activity in the transfer hydrogenation of acetophenone within 24 h of reaction. However, the AuNPsn have improved the catalytic activity of the complexes that have biphosphines with tensioned or large bite angle, while for the complexes that have biphosphines with a strong chelate effect a decrease in the catalytic activity was observed. The evidence is supported by experimental values of the yields of the hydrogenated product and DFT calculations of the “RuP–P” intermediates. Suitable crystals of cis-[RuCl2(dppe)(bipy)], cis-[RuCl2(dppp)(bipy)] and cis- [RuCl(CH3OH)(dppb)(bipy)](PF6) were obtained and the X-ray structures are presented here.Item Molecular structure of Ru(II)/diphosphine/4,6-dimethyl-2-pyrimidinethiol complexes : a combined experimental and density functional theory study.(2023) Lima, Benedicto Augusto Vieira; Varela Júnior, Jaldyr de Jesus Gomes; Ellena, Javier Alcides; Batista, Alzir Azevedo; Silva, Albérico Borges Ferreira da; Correa, Rodrigo de SouzaReactions of cis-[RuCl2(P-P)(bipy)] precursors with the SpymMe2 ligand (4,6-dimethyl-2- pyrimidinethiol) yielded complexes of the [Ru(SpymMe2)(P-P)(bipy)]PF6 type, where P-P = 1,2- bis(diphenylphosphino)ethane (dppe - for complex 1), 1,3-bis(diphenylphosphino)propane (dppp - for complex 2) and 1,1’-bis(diphenylphosphino)ferrocene (dppf - for complex 3) and bipy = 2,2’-bipyridine. The new compounds were obtained by displacing the chlorido ligands from the precursors and coordination of one monoanionic 4,6-dimethyl-2-pyrimidinethiol ligand. All complexes were characterized by spectroscopic, electrochemical and elemental analysis techniques, as well as single-crystal X-ray diffraction, where the structures of complexes 1, 2 and 3 showed that the SpymMe2 ligand coordinates to the ruthenium(II) center as bidentated, yielding complexes with the sulfur atom trans positioned to the nitrogen atom from the bipy ligand. A theoretical study of the structures of the complexes was performed using the DFT/B3LYP method. Distances and angles of optimized structures agree with X-ray experimental data. Furthermore, the calculated IR and UV-Vis spectra are compatible with experimental data. Charge decomposition analysis (CDA) and NBO (natural bond orbitals) charges showed that there was an overall charge transfer from bipy and P-P ligands to the ruthenium centers. Higher electrochemical stability and 1H and 31P{1H} NMR shifts of 1, 2 and 3 compared with precursors could be explained by the lower values of calculated molecular orbital energies, NBO charge on atoms and CDA data. Finally, the structure of the isomers of complexes 1, 2 and 3, considering the sulfur atom trans positioned to the phosphorus atom, were optimized, showing that they are slightly less stable, presenting total energy higher, 10.4, 31.5 and 60.5 kJ/mol than 1, 2 and 3, where nitrogen is trans to the phosphorus atom.Item New heteroleptic RuII/diphosphine complexes with cytotoxicity against human breast and murine ascitic sarcoma 180 tumor cells.(2020) Lima, Benedicto Augusto Vieira; Correa, Rodrigo de Souza; Graminha, Angelica Ellen; Varela Júnior, Jaldyr de Jesus Gomes; Silva, Albérico Borges Ferreira da; Ellena, Javier Alcides; Silva, Thales E. M.; Batista, Alzir AzevedoThe preparation, characterization, theoretical calculations and biological application of four RuII complexes with 2-picolinate (pic), 2,2’-bipyridine (bipy) and P-P as ligands [P-P = 1,1-bis(diphenylphosphino)methane (dppm-1), 1,2-bis(diphenylphosphino)ethane (dppe-2), 1,3-bis(diphenylphosphino)propane (dppp-3) or 1,1’-bis(diphenylphosphino)ferrocene (dppf-4)], is here presented. The complexes 1-4, with general formula [Ru(pic)(P-P)(bipy)]PF6, were characterized by elemental analysis and by infrared (IR), UV-Vis, nuclear magnetic resonance (NMR 1 H and 13P{1 H}) spectroscopies, cyclic voltammetry and X-ray crystallography technique. Additionally, preliminary in vitro tests against human breast (MDA-MB-231) and murine ascitic sarcoma 180 (S180) tumor cell lines were carried out, and compared with cisplatin, a reference drug. The drug concentration at which 50% of the cells are viable relative to the control (IC50) values found for complexes 1, 2, 3 and 4 against MDA-MB-231 tumor cells were around 14.6, 7.6, 3.3 and 0.4 μM, respectively, while against S180 tumor cells these complexes showed IC50 values of 71.9, 31.3, 11.2 and 3.5 μM, respectively. Therefore, the complexes were more active against MDA-MB-231 than S180.Item New ruthenium complexes containing salicylic acid and derivatives induce triple-negative tumor cell death via the intrinsic apoptotic pathway.(2022) Graminha, Angelica Ellen; Popolin, Cecília; Araujo Neto, João Honorato de; Correa, Rodrigo de Souza; Oliveira, Katia Mara de; Godoy, Luani Rezende; Colina Vegas, Legna Andreina; Ellena, Javier Alcides; Batista, Alzir Azevedo; Cominetti, Márcia ReginaIn this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF6 and [Ru(L)(dppe)2]PF6 where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis (diphenylphosphino)ethane and bipy = 2,2′ -bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV–vis and IR spectroscopies, and two by X-ray crystallography. The 31P{1 H} NMR spectra of the complexes with the general formula [Ru(L)(dppe)2]PF6 showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the complexes, inhibit the free rotation of the salicylic acid-based, modifying the diphosphine cone angles, leading to distortion of the phosphorus signals in the NMR spectra. The cytotoxicity of the complexes was evaluated in MCF7, MDA-MB-231, SKBR3 human breast tumor cells, and MCF-10 non-tumor cell lines. The complexes with the structural formula [Ru(L)(dppe)2]PF6 were the most cytotoxic, and the complex [Ru(AmSal)(dppe)2]PF6 with L = 4-aminosalicylic acid ligand was the most selective for the MDA-MB-231 cell line. This complex interacts with the transferrin and induces apoptosis through the intrinsic pathway, as demonstrated by increased levels of proteins involved in apoptotic cell death.Item Nitrosyl/Diphenylphosphine/Amino Acid–Ruthenium complexes as inhibitors of MDA-MB-231 breast cancer cells.(2023) Barbosa, Marília Imaculada Frazão; Correa, Rodrigo de Souza; Macedo, Adriana Pereira Mundim Guedes; Graça, Alex Marchezini; Andrade, Francyelli Mello; Leite, Celisnolia Morais; Lacerda, Elisângela de Paula Silveira; Ellena, Javier Alcides; Silva, Henrique Vieira Reis; Doriguetto, Antônio Carlos; Batista, Alzir AzevedoHerein, we report on the synthesis and characterization of ruthenium compounds with the general formula [RuCl(AA-H)(NO)(dppb]PF6 , where AA = glycine (1), L-alanine (2), L-phenylalanine (3) and L-valine (4), and dppb = 1,4-bis(diphenylphosphine)butane. The complexes were characterized using elemental analysis, UV/Vis and infrared spectroscopies, 1H, 13C, 31P NMR techniques, and cyclic voltammetry. Furthermore, the structures of the compounds (1) and (3) were determined using single-crystal X-ray diffraction. In vitro evaluation of the Ru(II)/nitrosyl/amino acid complexes revealed their cytotoxic activities against triple-negative MDA-MB-231 breast cancer cells, and against the non-tumor murine fibroblast cells. All the compounds decreased the percentage of viable cells, inducing cell death by apoptosis. Additionally, the Ru(II) complexes inhibited the migration of MDA-MB-231 cells at concentrations lower than 35 µM, after 48 h of exposure. Thus, these complexes may be promising agents for the treatment of triple-negative MDA-MB-231 breast cancer.Item On the conformation, molecular interactions and electron density of a natural flavonoid derivative.(2020) Niquini Junior, Fabiano Mafia; Clavijo, Juan Carlos Tenorio; Silva, Maria Fátima das Graças Fernandes da; Ribeiro, Alan Bezerra; Wanderley, Adilson Barros; Ellena, Javier Alcides; Correa, Rodrigo de SouzaThe molecular structure of limonianin (1), a natural compound isolated from the root of Citrus limonia, was determined by X-ray diffraction. The structure of 1 crystallizes in the monoclinic space group P21/c with one molecule per asymmetric unit. The compound has four six-membered rings: two benzenoid and one g-pyrone ring in a planar conformation, and one chromene ring presenting a half-boat conformation. Also, the molecule shows a pseudo-six-membered ring by resonance assisted hydrogen bond (RAHB). The molecular self-assembly of limonianin is stabilized by intra and intermolecular hydrogen bonding, which were assessed by Hirshfeld surfaces and two-dimensional fingerprint plots. Moreover, a detailed study of the molecular electron density and its corresponding topology and charge distribution based on the quantum theory of atom in molecules (QTAIM) was also one of the main aims of this work. Different methodologies were used to model the electron density distribution in limonianin molecule. The RAHB effect relating the crystal structure with its electron density analysis is discussed in detail. Therefore, this report contributes to the better understanding of the structural behavior of a flavonoid derivative, suggesting suitable methodologies to explore the electron density distribution, even in the absence of high-resolution experimental data.Item On the relationships between molecular conformations and intermolecular contacts toward crystal self-assembly of mono-, di-, tri-, and tetra-oxygenated xanthone derivatives.(2010) Correa, Rodrigo de Souza; Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Ellena, Javier AlcidesOxygenated xanthones have been extensively investigated over the years, but there are few reports concerning their crystal structure. Our chemical investigations of Brazilian plants resulted in the isolation of four natural products named 1-hydroxyxanthone (I), 1-hydroxy-7- methoxyxanthone (II), 1,5-dihydroxy-3-methoxyxanthone (III), and 1,7-dihydroxy-3,8-dimethoxyxanthone (IV). The structures of these compounds were established on the basis of single crystal X-ray diffraction. The xanthone nucleus conformation is essentially planar with the substituents adopting the orientations less sterically hindered. In addition, classical intermolecular hydrogen bonds (O–H O) present in III and IV give rise to infinite ribbons. However, the xanthone I does not present any intermolecular hydrogen bonds, meanwhile the xanthone II presents only a non-classical one (C–H O). The crystal packing of all xanthone structures is also stabilized by p–p interactions. The fingerprint plots, derived from the Hirshfeld surfaces, exhibited significant features of each crystal structures.Item Polypyridyl ruthenium complexes : novel DNA-intercalating agents against human breast tumor.(2017) Reis, João Paulo Barolli; Correa, Rodrigo de Souza; Miranda, Fabio da Silva; Ribeiro, Juliana Uema; Bloch Junior, Carlos; Ellena, Javier Alcides; Moreno, Virtudes; Cominetti, Márcia Regina; Batista, Alzir AzevedoThis paper describes a new series of four DNA-intercalating agents with promising anticancer activities, based on ruthenium(II) with the planar ligand dpqQX (dpqQX = dipyrido[3,2-a:2',3'-c]quinoxaline[2,3-b]quinoxaline). The complexes identified as trans-[RuCl2(dppb)(dpqQX)], cis-[RuCl2(dppb)(dpqQX)], ct-[RuCl(CO)(dppb)(dpqQX)]PF6 and ct-[RuCl2(PPh3)2(dpqQX)] (dppb = 1,4-bis(diphenylphosphine)butane and PPh3 = triphenylphosphine) were characterized by 31P{1H} nuclear magnetic resonance (NMR) and infrared spectroscopies, cyclic voltammetry, molar conductance measurements, elemental analysis, mass spectrometry and X-ray diffraction analysis for complex ct-[RuCl2(PPh3)2(dpqQX)]. Their in vitro cytotoxic activities against MDA-MB-213 and MCF-7 breast cancer cells were evaluated and compared with normal L-929 cells. Low drug concentration at which 50% of the cells are viable relative to the control (IC50) values were obtained for all four complexes compared with a reference metallodrug, cisplatin. In addition, DNA affinity studies from titrations, as well as the images obtained by atomic force microscopy (AFM) involving pBR322 plasmid DNA, suggest interactions between the metal complexes and the DNA macromolecule, in which they act as intercalating agents. The intercalation of the complexes with DNA was confirmed by viscosity measurements.Item Reactive nitrogen/oxygen species production by nitro/nitrosyl supramolecular ruthenium porphyrin complexes.(2017) Barbosa, Marília Imaculada Frazão; Gimenez Parra, Gustavo; Correa, Rodrigo de Souza; Sampaio, Renato Neiva; Magno, Lais Nogueira; Silva, Rodrigo Costa; Doriguetto, Antônio Carlos; Ellena, Javier Alcides; Barbosa Neto, Newton Martins; Batista, Alzir Azevedo; Gonçalves, Pablo JoséThis manuscript reports on new nitro/nitrosyl Ru-based complexes, which were synthesized with the purpose of using them as precursors to obtain supramolecular ruthenium porphyrin species ({TPyP[Ru (NO2)(5,50-Mebipy)2]4}(PF6)4) and ({TPyP[Ru(NO)(5,50-Mebipy)2]4}(PF6)12). The photochemical and photophysical properties of these porphyrin species were investigated. Results show that the complex containing nitrite is able to produce NO by homolytic O—NO cleavage (FPPh NO = 0.05) while the {TPyP[Ru (NO)(5,50-Mebipy)2]4}(PF6)12 does it by direct labilization (FPPh NO = 0.53) of the Ru NO bond. Furthermore, a triplet quantum yield of 0.09 and 0.27 was observed for complexes containing nitrite and nitric oxide, respectively. The reactive oxygen species quantum yield for the complex {TPyP[Ru(NO) (5,50-Mebipy)2]4}(PF6)12 (0.78) is consistent with the sum of quantum yields NO release (0.53) and triplet state (0.27), which suggests that both processes participate in the formation of the reactive species. Our results show that combining these characteristics, NO production and triplet states, on the same platform could induce a synergic effect, leading to a considerable improvement in the photodynamic action of these complexes.Item Ru(II) complexes containing uracil nucleobase analogs with cytotoxicity against tumor cells.(2019) Correa, Rodrigo de Souza; Bomfim, Larissa Mendes; Oliveira, Katia Mara de; Moreira, Diogo Rodrigo de Magalhães; Soares, Milena Botelho Pereira; Ellena, Javier Alcides; Bezerra, Daniel Pereira; Batista, Alzir AzevedoWe report on chemistry and cytotoxic studies of four new ruthenium (II) complexes containing uracil derivatives. All compounds are neutral, presenting the formula [Ru(PPh3)2(2TU)2] (1), [Ru(PPh3)2(6m2TU)2] (2), [Ru(dppb)(2TU)2] (3) and [Ru(dppb)(6m2TU)2] (4), where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane, 2TU = 2-thiouracil and 6m2TU = 6-methyl-2-thiouracil. They were characterized using NMR, UV–vis and IR spectroscopies, microanalytical analysis and mass spectrometry. Furthermore, the crystal structures of 1–4 were determined by single-crystal X-ray diffraction. The coordination of 2-thiouracil derivatives with ruthenium increases regions able to carry out hydrogen bonds with the biological targets, such as DNA. We evaluated the interaction of the complexes with DNA by UV/Vis spectrophotometric titration, and as a result, the values of DNA-binding constants are in the range of 0.8–1.8 × 104 M−1. Moreover, the interaction of the complexes with BSA was investigated. In vitro, activities against B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), HL-60 (human promyelocytic leukemia) and K562 (human chronic myelocytic leukemia) and non-tumor cells: PBMC (human peripheral blood mononuclear cells activated with concanavalin A – human lymphoblast) were carried out. Cytotoxicity assays revealed that complexes (2) and (4) present biological activity against tumor cells comparable with oxaliplatin, the reference platinum drug, revealing that they are promising molecules for developing new antitumor compounds.Item Ru(II)–thyminate complexes : new metallodrug candidates against tumor cells.(2018) Correa, Rodrigo de Souza; Freire, Vitória; Barbosa, Marília Imaculada Frazão; Bezerra, Daniel Pereira; Bomfim, Larissa Mendes; Moreira, Diogo Rodrigo de Magalhães; Soares, Milena Botelho Pereira; Ellena, Javier Alcides; Batista, Alzir AzevedoHerein, we used thymine (HThy) as a ligand to form two new ruthenium(II) complexes with formula [Ru(PPh3)2(Thy)(bipy)]PF6 (1) and [Ru(Thy)(bipy)(dppb)]PF6 (2). The complexes were characterized by spectroscopic, spectrometric and X-ray crystallography analyses. Complexes 1 and 2 can interact with ctDNA presenting binding constants, Kb, of 0.4 and 1.2 × 103 M−1, respectively. Their cytotoxic activities towards tumor cell lines (B16-F10, HepG2, K562 and HL-60) and non-tumor cells (PBMCs) were evaluated using the Alamar blue assay. Complex 1 exhibits high cytotoxicity against tumor cells, showing IC50 values of 0.01 and 1.81 μM against the HL-60 and HepG2 cell lines, respectively. Therefore, compound 1 can be considered as a promising antitumor metallodrug.Item Ruthenium(II) complexes with hydroxypyridinecarboxylates : screening potential metallodrugs against Mycobacterium tuberculosis.(2015) Barbosa, Marília Imaculada Frazão; Correa, Rodrigo de Souza; Pozzi, Lucas Vinícius dos Santos; Pavan, Fernando Rogério; Leite, Clarice Queico Fujimura; Ellena, Javier Alcides; Machado, Sérgio de Paula; Poelhsitz, Gustavo Von; Batista, Alzir AzevedoThree promising antimycobacterium tuberculosis ruthenium(II) complexes with the deprotonated ligands 2-hydroxynicotinic acid (2-OHnicH), 6-hydroxynicotinic acid (6-OHnicH) and 3-hydroxypicolinic acid (3-OHpicH) were synthesized and characterized. Structural analysis revealed three different coordination modes depending of the hydroxypyridinecarboxylate ligand. In the complex [Ru(2- OHnic)(dppb)(bipy)]PF6 (1), the 2-OHnic anion is coordinated by the O,O-chelating mode (via carboxylate group and phenolate oxygen), in the [Ru(6-OHnic)(dppb)(bipy)]PF6 (2) a O–O chelation by the carboxylate group is observed for the 6-OHnic ligand and for the complex [Ru(3-OHpic)(dppb)(bipy)]PF6 (3) a N,O-chelating mode (via carboxylate) occurs to the 3-OHpic anion. The compounds were evaluated for activity against Mycobacterium tuberculosis H37Rv ATCC 27294 using Resazurin Microtitre Assay (REMA) plate method and cytotoxicity in VERO CCL-81 cell line. All the synthesized compounds exhibited good antimycobacterial activity and a completely lack of cytotoxicity activity, indicating a good selectivity index.Item Ruthenium(II)/triphenylphosphine complexes : an effective way to improve the cytotoxicity of lapachol.(2017) Oliveira, Katia Mara de; Correa, Rodrigo de Souza; Barbosa, Marília Imaculada Frazão; Ellena, Javier Alcides; Cominetti, Márcia Regina; Batista, Alzir AzevedoThis study reports on the synthesis of a new ruthenium(II) complex, cis-[Ru(PPh3)2(lap)2] (1) with two molecules of the natural product known as lapachol [lap = (2-hydroxy-3-(3-methyl-2-buthenyl)-1,4- naphthoquinone)] coordinated as bidentated by oxygen atoms and two monodentate PPh3 (triphenylphosphine) in a cis configuration. This neutral complex was characterized by spectroscopic analysis, single-crystal X-ray diffraction, elemental analysis, molar conductivity and cyclic voltammetry. In this study, ruthenium complex trans-[Ru(lap)(PPh3)2(phen)]PF6 (2) was used for comparison purposes. The interaction of ruthenium complexes (1) and (2) with CT-DNA was evaluated by UV–Vis and circular dichroism and it was observed that the complexes interact weakly with the CT-DNA. The fluorescence measurements suggest that complex (1) shows stronger interaction with HSA and BSA proteins compared to complex (2). Cytotoxicity assays against A549 (lung cancer), MDA-MB-231 (breast cancer) and V79 (non-tumoral lung) revealed that complex (2) is more active (lower IC50 values) than complex (1) and the cisplatin, used as a reference.