Abnormal co-doping effect on the red persistent luminescence SrS:Eu2+,RE3+ materials

Persistent luminescence materials are a reality in several applications. However, there is still a lack of efficient red-emitting materials. SrS:Eu2+ phosphor is a potential candidate since its strong nephelauxetic effect shifts Eu(2+)4f(6)5d(1) -> 4f(7) to red, and its weak bond between strontium and sulphide, due to the soft base-hard acid character, generates a high number of intrinsic defects. SrS:Eu2+,RE3+ materials were efficiently prepared by two rounds of 22 min microwave-assisted solid-state synthesis. The highly crystalline purity and the material organization at the micro-scale were observed with X-ray powder diffraction and scanning electron microscopy, respectively. X-ray absorption spectroscopy revealed a low amount of Eu2+ compared to Eu3+ due to the efficient Eu2+ photo-oxidation by X-ray irradiation in the high storage capability SrS host matrix. Electron paramagnetic resonance spectra confirmed that at least 50% of Eu2+ ions in the material are photo-oxidized during excitation, reinforcing the previously established mechanisms. The RE2+ energy level positioned very close to or into the conduction band led to an abnormal co-doping effect, with similar effects independent of the co-dopant. The high concentration of intrinsic defects in SrS indicates that the soft-hard pair host is an excellent approach to develop efficient persistent luminescence materials

Imine copper complexes with antiparasitic activity against Chagas disease

Neste trabalho foram sintetizados e caracterizados três complexos de cobre com ligantes imínicos, com o objetivo de avaliar sua atividade tripanocida. Esses complexos foram caracterizados por diversas técnicas espectroscópicas, como UV-Vis, Infravermelho e EPR, além de análise elementar e espectrometria de massa. Juntamente com outros complexos similares previamente sintetizados pelo nosso grupo, tiveram suas atividades avaliadas frente à forma tripomastigota do parasita T. cruzi, responsável pela fase aguda da doença de Chagas, por ensaios de viabilidade celular, com determinação do valor de seus IC50, concentração em que observamos a morte de 50% da cultura celular, pela metodologia denominada MTT. Todos os complexos mostraram-se eficientes frente a tripomastigotas, apresentando valores de IC50 abaixo de 10 µM, com quatro deles obtendo índice de seletividade maior que 10, fator importante para definir agentes promissores antichagásicos. Complexos selecionados também tiveram sua atividade verificada frente à forma amastigota do parasita, responsável pela fase crônica da doença, utilizando método de imageamento por microscópio de fluorescência e contagem celular. Estudos de inibição da cruzaína, uma cisteíno-protease importante para o metabolismo do parasita foram conduzidos em colaboração com o laboratório do Prof. Wagner Alves de Souza Júdice, da Universidade de Mogi das Cruzes. Quatro dos compostos testados apresentaram atividade inibitória frente a cruzaína, sendo dois de cobre, um de zinco e um ligante livre. Os estudos também permitiram diferenciar os mecanismos de inibição dos compostos, com os complexos de cobre apresentando um mecanismo de inibição clássico e o composto de zinco e o ligante livre apresentando o mecanismo de inibição competitiva parabólica com cooperatividade.In this work, three copper complexes with iminic ligands were synthesized and characterized, with the objective of evaluating their trypanocidal activity. These complexes were characterized by several spectroscopic techniques, such as UV-Vis, Infrared and EPR, in addition to elementary analysis and mass spectrometry. Together with other similar complexes previously synthesized by our group, their activities were evaluated against the trypomastigote form of the parasite T. cruzi, responsible for the acute phase of Chagas disease, by cell viability tests, with determination of the value of their IC50, concentration in that we observed the death of 50% of the cell culture, by the methodology called MTT, all presenting IC50 values below 10 µM, with four of them obtaining a selectivity index greater than 10, important factor for defining promising antichagasic agents. Selected complexes also had their activity verified against the amastigote form of the parasite, responsible for the chronic phase of the disease, using a fluorescence microscope and cell counting imaging method. Inhibition studies of cruzain, a cysteine protease important for the metabolism of the parasite, were conducted in collaboration with the laboratory of Professor Wagner Alves de Souza Júdice at the University of Mogi das Cruzes. Four of the tested compounds showed inhibitory activity against cruzain, two of copper, one of zinc and a free ligand. The studies also allowed to differentiate the mechanisms of inhibition of the compounds, with the copper complexes presenting a classic inhibition mechanism and the zinc compound and the free ligand presenting the competitive parabolic inhibition mechanism with cooperativity

Antiparasitic Activity of Oxindolimine–Metal Complexes against Chagas Disease

Some copper(II) and zinc(II) complexes with oxindolimine ligands were tested regarding their trypanocidal properties. These complexes have already shown good biological activity in the inhibition of tumor cell proliferation, having DNA and mitochondria as main targets, through an oxidative mechanism, and inducing apoptosis. Herein, we demonstrate that they also have significant activity against the infective trypomastigote forms and the intracellular amastigote forms of T. cruzi, modulated by the metal ion as well as by the oxindolimine ligand. Selective indexes (LC50/IC50) determined for both zinc(II) and copper(II) complexes, are higher after 24 or 48 h incubation with trypomastigotes, in comparison to traditional drugs used in clinics, such as benznidazole, and other metal-based compounds previously reported in the literature. Additionally, tests against amastigotes indicated infection index <10% (% of infected macrophages/average number of amastigotes per macrophage), after 24 or 48 h in the presence of zinc(II) (60–80 µM) or analogous copper(II) complexes (10–25 µM). The copper complexes exhibit further oxidative properties, being able to damage DNA, proteins and carbohydrates, in the presence of hydrogen peroxide, with the generation of hydroxyl radicals. This redox reactivity could explain its better performance towards the parasites in relation to the zinc analogs. However, both copper and zinc complexes display good selective indexes, indicating that the influence of the ligand is also crucial, and is probably related to the inhibition of some crucial proteins

Copper(II) and Platinum(II) Naproxenates: Insights on Synthesis, Characterization and Evaluation of Their Antiproliferative Activities

The growth of antibiotic resistance is a matter of worldwide concern. In parallel, cancer remains one of the main causes of death. In the search for new and improved antiproliferative agents, one of the strategies is the combination of bioactive ligands and metals that are already consolidated in the synthesis of metallopharmaceutical agents. Thus, this work deals with the synthesis, characterization, and study of naproxen (Nap)-based complexes of copper(II) and platinum(II) as antiproliferative agents. The copper complex (Cu–Nap) presents a binuclear paddle-wheel structure in a 1 Cu:2 Nap:1 H2O molar composition, in which Cu(II) is bonded to the carboxylate oxygens from naproxenate in a bidentate bridging mode. The platinum complex (Pt–Nap) was identified as the square planar cis-[Pt(Nap)2(DMSO)2] isomer, in which Pt(II) is bonded to the carboxylate oxygen atom of Nap in a monodentate fashion. Both complexes were inactive against the Gram-positive and Gram-negative bacterial strains assessed. Pt–Nap presented low cytostatic behavior over a set of tumor cells, but good viability for normal cells, while Cu–Nap was cytotoxic against all cells, with a cytocidal activity against glioma tumor cells

Structural and spectroscopic characterization of epiisopiloturine-metal complexes, and anthelmintic activity <i>vs</i>. <i>S. mansoni</i>

<p>Epiisopiloturine (EPI), extracted from leaves of <i>Pilocarpus microphyllus</i>, a plant originally from the Amazon and Savanna regions in Brazil, was described as a potential drug against Schistosomiasis, a neglected severe disease. Herein, EPI was complexed with copper(II) or zinc(II) salts and the isolated species, [Cu(epi)₄](ClO₄)₂ (<b>1</b>) and [Zn(epi)₂Cl₂] (<b>2</b>), were structurally and spectroscopically characterized. By using X-ray diffraction, the crystal structures of both metal complexes were determined, indicating a square pyramidal geometry for copper for <b>1</b> and a tetrahedral environment around zinc for <b>2</b>. EPR spectra of <b>1</b> show a typical tetragonal environment around the central metal ion with some tetrahedral distortion, both in the solid state and in frozen acetonitrile solution, in accordance with crystallographic data. For <b>2</b>, NMR spectra have bands consistent with a tetrahedral species in solid state or in DMSO-d₆ solution. These spectroscopic characterization data were further supported by Density Functional Theory calculations, showing that these metal complexes are also stable in solution. Those metal complexes were tested against adult worms of <i>Schistosoma mansoni</i>, in comparison to the free alkaloid as anthelmintic agent. Coordination with copper(II) improved the alkaloid schistosomicidal properties, while binding to zinc(II) decreased its activity.</p