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In this work, we describe two novel 1-methylimidazole

La presente investigación analiza la epidemia de fiebre amarilla que arribó a Buenos Aires en el año 1871. A raíz de la pandemia de COVID-19, que puso en jaque al mundo globalizado, se pretende buscar en el pasado los problemas que enfrentaron las sociedades cuando las pestes arribaron a sus puertas. En este caso, se analizan las veloces conexiones transoceánicas de la segunda mitad del siglo XIX. A bordo de los buques no solo se transportaban personas, ideas y mercancías, sino también patógenos. A partir del enfoque trasnacional de la historia ambiental, se analizan las denuncias de la prensa porteña de la época, las memorias de la Junta Sanitaria del Puerto de Buenos Aires, las memorias de la Comisión Central de Inmigración, y artículos del periódico español Eco de Alicante, para establecer un vínculo entre la epidemia desatada hacia finales de 1870 en Barcelona, y la comenzada en Buenos Aires en 1871. Se concluye que, estando estos dos puertos conectados permanentemente entre sí, y ambos sujetos a las impericias a bordo de los buques, el hacinamiento de los pasajeros y el deficiente control de las autoridades sanitarias, la epidemia de fiebre amarilla de Buenos Aires puede haber arribado desde Barcelona y no solo desde Asunción, como se sostiene en la bibliografía consultada. Abstract This investigation analyses the yellow fever epidemic that arrived to Buenos Aires in the year 1871. Connected with the COVID-19 pandemic that defied the globalized world, it is intended to look in the past the problems that the societies faced when the plagues arrived at their front doors. In this case, the transoceanic connections that took place until the second half of the19th century will be analyzed. The ships not only transported people, ideas and cargo, but also pathogens inside them. From the transnational approach to environmental history, the newspapers’ reports, the memories of the Buenos Aires port health commission, those of the Central Immigration Commission, as well as articles from the Spanish newspaper Eco de Alicante will be analyzed, to stablish a connection between the epidemic developed in the end of 1870 in Barcelona the one that started in Buenos Aires in 1871. It is concluded that, being these two ports attached permanently and forced to face the shortcomings above the ships, such as the overcrowding of passengers and the deficient control of the sanitary authorities, the yellow fever epidemic of Buenos Aires could have arrived from Barcelona as well and not only from Asunción, as the consulted bibliography states.

El libro ¡Nunca más esclavos! Una historia comparada de los esclavos que se liberaron de las Américas, de Aline Hegl, es un repaso de largo plazo por todas las estrategias efectuadas por las esclavas y los esclavos americanos para conseguir su libertad. La obra se propone discutir con los diversos autores que abordaron el tema, realizando una historia comparada “desde abajo” sobre los distintos métodos emancipatorios que utilizaron quienes sufrieron del tráfico esclavista, relativizando la efectividad de unos y rescatando las ventajas de otros.

Alzheimer's disease (AD) is related to the presence of extracellular aggregated amyloid-β peptide (Aβ), which binds copper(II) with high affinity in its N-terminal region. In this sense, two new 1-methylimidazole-containing N-acylhydrazonic metallophores, namely, X1TMP and X1Benz, were synthesized as hydrochlorides and characterized. The compound X1TMP contains the 3,4,5-trimethoxybenzoyl moiety present in the structure of mescaline, a natural hallucinogenic protoalkaloid that occurs in some species of cacti. Single crystals of X1Benz, the unsubstituted derivative of X1TMP, were obtained. The experimental partition coefficients of both compounds were determined, as well as their apparent affinity for Cu

Based on a variety of evidence (photographs, feces, specimens), three previously unsuspected caviomorph rodents are reported from Argentina: (1) a spiny rat (Echimyidae) probably belonging to the genus Phyllomys, in northern Misiones Province near Iguazú National Park; (2) an undetermined octodontid (Octodontidae) in western Chacoan Córdoba Province; and (3) the octodontid Spalacopus (Octodontidae), in high-Andean ranges of San Juan Province. The latter constitutes the first record of the genus for Argentina, and all the three findings highlight the necessity to increase collecting efforts in the country.

International audience; Converging evidence indicates that neurotoxicity and memory impairment in Alzheimer's disease is induced by brain accumulation of soluble amyloid-β oligomers (AβOs). Physiological metals are poorly distributed and concentrated in the senile plaques typical of Alzheimer's disease, where they may be coordinated to the amyloid-β peptide (Aβ). Indeed, zinc and copper increase Aβ oligomerization and toxicity. Metal-protein attenuating compounds represent a class of agents proposed for Alzheimer's disease treatment, as they reduce abnormal interactions of metal ions with Aβ, inhibit Aβ oligomerization and prevent deleterious redox reactions in the brain. The present work investigates the protective action of an isoniazid-derived aroylhydrazone, INHHQ, on AβO-induced memory impairment. Systemic administration of a single dose of INHHQ (1 mg/kg) prevented both short-term and long-term memory impairment caused by AβOs in mice. In-vitro studies showed that INHHQ prevents Cu(Aβ)-catalyzed production of reactive oxygen species. Although the mechanism of protection by INHHQ is not yet fully understood at a molecular level, the results reported herein certainly point to the value of aroylhydrazones as promising neuroprotective agents in Alzheimer's disease and related disorders.

An analytical method for the determination of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ) is reported for the first time. The electrochemical method involving INHHQ was perf...

Reseña de Judkin Browning y Timothy Silver. An Environmental History of the Civil War. Chapel Hill: University of North Carolina Press, 2020, 272 pp.

Misfolded prion protein (PrPSc) is known for its role in fatal neurodegenerative conditions, such as Creutzfeldt-Jakob disease. PrP fragments and their mutants represent important tools in the investigation of the neurotoxic mechanisms and in the evaluation of new compounds that can interfere with the processes involved in neuronal death. Metal-catalyzed oxidation of PrP has been implicated as a trigger for the conformational changes in protein structure, which, in turn, lead to misfolding. Targeting redox-active biometals copper and iron is relevant in the context of protection against the oxidation of biomolecules and the generation of oxidative stress, observed in several conditions and considered an event that might promote sporadic prion diseases as well as other neurodegenerative disorders. In this context, ortho-pyridine aroylhydrazones are of interest, as they can act as moderate tridentate ligands towards divalent metal ions such as copper(II). In the present work, we explore the potentiality of this chemical class as peptide protecting agents against the deleterious metal-catalyzed oxidation in the M112A mutant fragment of human PrP, which mimics relevant structural features that may play an important role in the neurotoxicity observed in prion pathologies. The compounds inhere studied, especially HPCFur, showed an improved stability in aqueous solution compared to our patented lead hydrazone INHHQ, displaying a very interesting protective effect toward the oxidation of methionine and histidine, processes that are related to both physiological and pathological aging.

The present article discusses the relationship between Utria’s comic and marginalized sides. He is the main character in “Utria se destapa” by Jose Felix Fuenmayor. Utria is a parody that reproduces and disassembles a linguistic model. That is, an imitation and deformation (that verge on the satire) that become into the artificiality and automatism that shape the character, these are the features that later lead to laughter. This article aims to relate the parody-satirical aspects of Utria (from the diegesis to the extra-textual features of the story) to some aspects of the social and literary arena in Colombia in the early twentieth century. Finally, this study takes into account Bergson (The laughter, 1973) and Hutcheon’s (Ironie, satire, parodie: une approche pragmatique de l’ironie, 1981) discussions and theoretical proposals.

Resumen Este artículo presenta un diálogo entreRespiración artificial(1980), de Ricardo Piglia, y algunas ideas deMito y archivo(1990), desarrolladas por Roberto González Echevarría. La lectura conjunta apunta a poner bajo una nueva luz la discusión acerca de la problematización del discurso de la Historia en esta novela, para examinar específicamente la contigüidad y la multiplicidad de los documentos del Archivo que figuran en la novela. El artículo parte de las propuestas críticas que diferentes investigadores han hecho acerca deRespiración artificial,así como de notas periodísticas sobre Ricardo Piglia. Abstract This article presents a dialogue between Ricardo Piglia’sRespiración artificial(1980) and some ideas developed by Roberto González Echevarría inMyth and Archive(1990). This combined reading seeks to shed new light on the discussion concerning the problematization of the discourse of History in the novel, in order to specifically examine the proximity and multiplicity of documents of the Archive in the narrative. This article stems from the critical studies of various scholars regardingRespiración artificialas well as journalistic notes on Ricardo Piglia.

International audience; Two novel unsymmetrical binucleating aroylhydrazonic ligands and four dicopper(II) complexes carrying fluorescent benzopyranothiophene (BPT) or boron dipyrromethene (BODIPY) entities were synthesized and fully characterized. Complex 1, derived from the BPT-containing ligand H3L1, had its crystal structure elucidated through X-ray diffraction measurements. The absorption and fluorescence profiles of all the compounds obtained were discussed. Additionally, the stability of the ligands and complexes was monitored by UV–vis spectroscopy in DMSO and biologically relevant media. All the compounds showed moderate to high cytotoxicity towards the triple negative human breast cancer cell line MDA-MB-231. BPT derivatives were the most cytotoxic, specially H3L1, reaching an IC50 value up to the nanomolar range. Finally, fluorescence microscopy imaging studies employing mitochondria- and nucleus-staining dyes showed that the BODIPY-carrying ligand H3L2 was highly cell permeant and suggested that the compound preferentially accumulates in the mitochondria.

Reseña de la obra de Hora, Roy: ¿Cómo pensaron el campo los argentinos? Y cómo pensarlo hoy, cuando ese campo ya no existe. Buenos Aires, Siglo XXI, 2018. 240 pp.

Although normal aging presents an accumulation of copper and iron in the brain, this becomes more relevant in neurodegeneration. α-Synuclein (α-Syn) misfolding has long been linked with the development of Parkinson's disease (PD). Copper binding promotes aggregation of α-Syn, as well as generalized oxidative stress. In this sense, the use of therapies that target metal dyshomeostasis has been in focus in the past years. Metal-Protein Attenuating Compounds (MPACs) are moderate chelators that aim at disrupting specific, abnormal metal-protein interactions. Our research group has now established that N-acylhydrazones compose a set of truly encouraging MPACs for the bioinorganic management of metal-enhanced aggregopathies. In the present work, a novel ligand, namely 1-methyl-1H-imidazole-2-carboxaldehyde isonicotinoyl hydrazone (X1INH), is reported. We describe solution studies on the interaction and affinity of this compound for copper(ii) ions showing that a fine tuning of metal-affinity was achieved. A series of in vitro biophysical NMR experiments were performed in order to assess the X1INH ability to compete with α-Syn monomers for the binding of both copper(i) and copper(ii) ions, which are central in PD pathology. A preference for copper(i) has been observed. X1INH is less toxic to human neuroglioma (H4) cells in comparison to structure-related compounds. Finally, we show that treatment with X1INH results in a higher number of smaller, less compact inclusions in a well-established model of α-Syn aggregation. Thus, X1INH constitutes a promising MPAC for the treatment of Parkinson's disease.

The interaction of oxidovanadium(V) with INHOVA (the condensation product of isoniazid and o-vanillin) lead to the formation of the ester-like complex [VO(INHOVA)EtO(OH2)]Cl·H2O (1). Crystals suitable for X-ray diffraction methods were obtained. The complex crystallizes as a dimer in the space group P21/c of the monoclinic system. A detailed analysis, including solid-state vibrational spectroscopy and electronic spectroscopy in DMSO solution, was performed for both INHOVA and complex (1). A complete theoretical study based on DFT was also carried out. The calculations were of valuable assistance in the spectra assignments and interpretation. The electrochemical characterization allows determining the redox behavior of INHOVA and complex (1). Cytotoxicity was assayed against the chronic myelogenous leukemia K562 cell line. The IC50 values obtained denote that both the ligand and complex (1) are good candidates for further studies., Centro de Química Inorgánica

Quality of vegetable oils is affected by the presence of metals, even at low concentrations. A study was conducted to advance evaluate the degradation of canola induced by the presence of copper CuO (expected to be less reactive than Cu 2+ ). Samples were heated at 90 °C for fourteen days and the results suggested that contamination does influence not only the oxidation rate but also the extension of the degradation processes. FT-IR and Raman spectra showed the decreasing of the carbonyl absorption belonging to triglycerides during the oxidation process, which was most pronounced in the CuO contaminated oil, indicating the increasing of the hydrolysis process. Furthermore, the oxidation of the olefinic bonds also appears to be copper-mediated, since the cis C H vibration band decreases to a larger extent in the metal-containing samples. CuO exerted a greater degradation as it caused a more pronounced decrease of both the number of unsaturations and carbonyl groups of esters, besides the more effective decrease in the induction time and the higher production of secondary oxidation products.

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential ‘Metal-Protein Attenuating Compound’ for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200 mg kg− 1. INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24 h after intraperitoneal administration. After 48 h, brain clearance is complete. INHHQ is able to disrupt, in vitro, anomalous copper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compound is non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization. INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well. Fil: Cukierman, Daphne Schneider. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Pinheiro, Ana Beatriz. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Castiñeiras-Filho, Sergio L.P.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: da Silva, Anastácia Sá P.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Miotto, Marco César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: De Falco, Anna. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: de P. Ribeiro, Thales. Universidade Federal do Rio de Janeiro; Brasil Fil: Maisonette, Silvia. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: da Cunha, Alessandra L.M.C.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Hauser-Davis, Rachel A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Fernandez, Claudio Oscar. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Aucélio, Ricardo Q.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Outeiro, Tiago F.. Universität Göttingen; Alemania Fil: Pereira, Marcos D.. Universidade Federal do Rio de Janeiro; Brasil Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: Rey, Nicolás A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil

Very few inorganic antineoplastic drugs have entered the clinic in the last decades, mainly because of toxicity issues. Because copper is an essential trace element of ubiquitous occurrence, decreased side effects could be expected in comparison with the widely used platinum anticancer compounds. In the present work, two novel hydrazonic binucleating ligands and their μ-hydroxo dicopper(II) complexes were prepared and fully characterized. They differ by the nature of the aromatic group present in their aroylhydrazone moieties: while H3L1 and its complex, 1, possess a thiophene ring, H3L2 and 2 contain the more polar furan heterocycle. X-ray diffraction indicates that both coordination compounds are very similar in structural terms and generate dimeric arrangements in the solid state. Positive-ion electrospray ionization mass spectrometry analyses confirmed that the main species present in a 10% dimethyl sulfoxide (DMSO)/water solution should be [Cu2(HL)(OH)]+ and the DMSO-substituted derivative [Cu2(L)(DMSO)]+. Scattering techniques [dynamic light scattering (DLS) and small-angle X-ray scattering] suggest that the complexes and their free ligands interact with bovine serum albumin (BSA) in a reversible manner. The binding constants to BSA were determined for the complexes through fluorescence spectroscopy. Moreover, to gain insight into the mechanism of action of the compounds, calf thymus DNA binding studies by UV-visible and DLS measurements using plasmid pBR322 DNA were also performed. For the complexes, DLS data seem to point to the occurrence of DNA cleavage to Form III (linear). Both ligands and their dicopper(II) complexes display potent antiproliferative activity in a panel of four cancer cell lines, occasionally even in the submicromolar range, with the complexes being more potent than the free ligands. Our data on cellular models correlate quite well with the DNA interaction experiments. The results presented herein show that aroylhydrazone-derived binucleating ligands, as well as their dinuclear μ-hydroxodicopper(II) complexes, may represent a promising structural starting point for the development of a new generation of highly active potential antitumor agents.

Misfolded prion protein (PrP

Aroylhydrazones are versatile compounds with a series of applications, from biological to technological spheres. The simplicity of their preparation allows for a great chemical variability and synthetic manageability. However, the process can be not as straightforward as one would imagine. Some parameters such as specific reactants, the amount of acid employed as catalyst and reaction temperature can have a direct impact on the obtained product. In the present work, we describe two series of novel isoniazid-derived compounds prepared from a pair of different aldehyde precursors, as well as the solvolysis, under harsh synthetic conditions, of the initially formed aroylhydrazones, leading to unexpected dihydrazones. All compounds were unequivocally characterized in solution using 1D and 2D NMR experiments in DMSO‑d6 and, in the solid-state, by other classic techniques. System I is composed by 2-(1H-pyrazol-1-yl)benzaldehyde and its hydrazone derivatives, while system II comprises 2-(4-metoxyphenoxy)benzaldehyde and its related Schiff-base products. The first aldehyde was obtained for the first time via the copper-catalyzed Ullmann C–N coupling between 2-bromobenzaldehyde and pyrazole. Single crystals of its aroylhydrazone and dihydrazone derivatives were isolated and thoroughly characterized, including Hirshfeld surfaces and energy frameworks studies. Finally, we describe an NMR and theoretically-based proposed reaction pathway for the unexpected formation of the dihydrazones involving the solvolysis of the initially formed isonicotinoyl hydrazone followed by attack to a second free aldehyde molecule.

A series of physicochemical studies performed on Brazilian commercial Bx (0%, 7%, 20%, and 100% soybean/tallow biodiesel) mixtures in S10 and S500 oil diesel, as well as the performance of two rapid and still underexplored techniques, namely, FTIR-HATR and Raman spectroscopies, to evaluate the hydrolysis and oxidative stability of these blends are reported. The addition of biodiesel to diesel affects negatively the aging resistance of the resulting blends. S500 blends are more acidic than S10 blends, in accordance with the higher water content of the former. Rancimat accelerated oxidative stability tests showed that, as expected, the induction times of B7 and B20 samples are greater than that of B100, independent of the sulfur content of the diesel. The practical use of FTIR-HATR to characterize the mixtures’ degradation stage is conditioned by the fact that there are two chemical contributions for the studied band. On the other hand, Raman spectroscopy represents a very suitable spectroscopic probe for u...

Hydrazones and several substituted hydrazones are associated with a broad spectrum of biological activities, as well as compounds containing the thiophene ring. In this context, a novel di-hydrazone derived from 2-thiophenecarboxylic acid hydrazide was synthesized and completely characterized by elemental analysis, XRD, FT-IR, Raman and UV–Vis spectroscopies, thermogravimetry, 1H NMR, 1H–1H COSY and 1H–1H ROESY. A preliminary in silico pharmacological evaluation was also performed in order to assess the performance of the new compound regarding some molecular properties relevant for a drug's pharmacokinetics in the human body.

Hydrazones constitute a class of compounds presenting azomethine R′R″N N CH R hydrogens, which show diverse properties and a wide range of applications. A hydrazone derived from the antituberculosis drug isoniazid, namely, N,N′-diisonicotinoyl-2-hydroxy-5-methylisophthalaldehyde hydrazone (DMD) was synthesized and chemically characterized. Its luminescent properties were also investigated, as well as the possibility of using this compound as a constituent of the emitting layer for the fabrication of OLEDs. Co-deposited devices were fabricated using the organic molecule BSBF as matrix and DMD as dopant. All the devices presented a broad electroluminescence band, in which it was possible to recognize the DMD emission along with emissions of some of the other organic layers. The best results were obtained with 35% DMD doping, achieving a luminance of about 35 cd/m2.

Tuberculosis (TB) is a significant cause of morbidity and mortality worldwide. The patient compliance with the long treatment regimens is essential for successful eradication. Pyrazinamide (PZA) shortens these regimens from 9 to 6 months, and therefore, improves treatment completion rates. Although PZA is a first-line medication for the treatment of TB, no simple or reliable assay to determine PZA resistance is yet available. In the presence of PZA, only susceptible Mycobacterium tuberculosis strains release pyrazinoic acid (POA). Therefore, the measurement and quantification of released POA is an indicator of PZA resistance.Two electrochemical sensors were constructed and tested with alternative working electrodes in conjunction with a portable potentiostat to measure the current produced when a potential difference of 2 V is applied to varying concentrations of POA in controlled solutions.The large (13.2 mm) electrochemical sensor was able to detect POA at a minimum concentration of 40 μM to a statistically significant level (P = 0.0190). Similar graphical trends were obtained when testing the electrochemical sensor in the supernatant of a negative microscopic observation drug susceptibility assay culture, irrespective of the presence of PZA.Inexpensive and reusable electrochemical sensors with a portable potentiostat are a promising tool for the detection of POA, a biomarker of PZA susceptible M. Tuberculosis.

With the increasing life expectancy of the world’s population, neurodegenerative diseases, such as Alzheimer’s disease (AD), will become a much more relevant public health issue. This fact, coupled with the lack of efficacy of the available treatments, has been driving research directed to the development of new drugs for this pathology. Metal-protein attenuating compounds (MPACs) constitute a promising class of agents with potential application on the treatment of neurodegenerative diseases, such as AD. Currently, most MPACs are based on 8-hydroxyquinoline. Recently, our research group has described the hybrid aroylhydrazone containing the 8-hydroxyquinoline group INHHQ as a promising MPAC. By studying the known structure-related ligand HPCIH, which does not contain the phenol moiety, as a simplified chemical model for INHHQ, we aimed to clarify the real impact of the aroylhydrazone group for the MPAC activity of a compound with potential anti-Alzheimer’s activity. The present work describes a detailed solution and solid-state study of the coordination of HPCIH with Zn2+ ions, as well as its in vitro binding-ability towards this metal in the presence of the Aβ(1–40) peptide. Similar to INHHQ, HPCIH is able to efficiently compete with Aβ(1–40) for Zn2+ ions, performing as expected for an MPAC. The similarity between the behaviors of both ligands is remarkable. Taken together, the data presented herein point to aroylhydrazones, such as the compounds HPCIH and the previously published INHHQ, as encouraging MPACs for the treatment of AD. Fil: Cukierman, Daphne S.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Accardo, Elio. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Gomes, Rosana Garrido. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: De Falco, Anna. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Miotto, Marco César. Universidad Nacional de Rosario; Argentina Fil: Freitas, Maria Clara Ramalho. Universidade Federal do Rio de Janeiro; Brasil Fil: Lanznaster, Mauricio. Universidade Federal Fluminense; Brasil Fil: Fernández, Claudio O.. Universidad Nacional de Rosario; Argentina Fil: Rey, Nicolás A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil

Nanocrystalline MgO was synthesized via the sol–gel combustion method using polyvinyl alcohol (PVA) and metal nitrate as precursor. The obtained powders were characterized using infrared absorption spectroscopy (IR), X-ray diffraction (XRD), BET (Brunauer–Emmett–Teller), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The effects of the thermal treatment parameters on the crystallite growth kinetics, crystalline size and specific surface area were investigated. The crystallite size of MgO increases with increasing temperature, whereas the specific surface area decreases with increasing temperature. The activation energy for the crystallite growth was estimated to be approximately 223.7 kJ/mol. MgO with crystallite size in range of 13.6 nm to 98.7 nm and a specific surface area up to 81.54 m 2 g - 1 can be produced by controlling the processing parameters. The crystallite size growth during combustion is consistent with grain rotation coalescence, which seems to be related to the loss of external hydroxyl groups, derived from chemisorbed water, in the samples treated at higher combustion temperatures.

Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2 and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.

The catalytic mechanism that involves the cleavage of the phosphate diester model BDNPP (bis(2,4-dinitrophenyl) phosphate) catalyzed through a dinuclear copper complex is investigated in the current study. The metal complex was originally designed to catalyze catechol oxidation, and it showed an interesting catalytic promiscuity case in biomimetic systems. The current study investigates two different reaction mechanisms through quantum mechanics calculations in the gas phase, and it also includes the solvent effect through PCM (polarizable continuum model) single-point calculations using water as solvent. Two mechanisms are presented in order to fully describe the phosphate diester hydrolysis. Mechanism 1 is of the S(N)2 type, which involves the direct attack of the μ-OH bridge between the two copper(II) ions toward the phosphorus center, whereas mechanism 2 is the process in which hydrolysis takes place through proton transfer between the oxygen atom in the bridging hydroxo ligand and the other oxygen atom in the phosphate model. Actually, the present theoretical study shows two possible reaction paths in mechanism 1. Its first reaction path (p1) involves a proton transfer that occurs immediately after the hydrolytic cleavage, so that the proton transfer is the rate-determining step, which is followed by the entry of two water molecules. Its second reaction path (p2) consists of the entry of two water molecules right after the hydrolytic cleavage, but with no proton transfer; thus, hydrolytic cleavage is the rate-limiting step. The most likely catalytic path occurs in mechanism 1, following the second reaction path (p2), since it involves the lowest free energy activation barrier (ΔG(⧧) = 23.7 kcal mol(-1), in aqueous solution). A kinetic analysis showed that the experimental k(obs) value of 1.7 × 10(-5) s(-1) agrees with the calculated value k1 = 2.6 × 10(-5) s(-1); the concerted mechanism is kinetically favorable. The KIE (kinetic isotope effect) analysis applied to the second reaction path (p2) in mechanism 1 was also taken into account to assess the changes that take place in TS1-i (transition state of mechanism 1) and to perfectly characterize the mechanism described herein.

Alzheimer’s disease is characterized by the loss of synapses and by the presence of extra-cellular amyloid β-peptide (Aβ) plaques, and it has been associated to copper metabolism. The plasma of patients with Alzheimer’s disease presents higher levels of the amino acid homocysteine (hCys). In this study, three new ternary complexes of copper(II) with homocysteine and three amino acids of Aβ (aspartate, glutamate or methionine) were studied both in solution (pH-potentiometry and UV–Vis) and in the solid state (CHNS, AAS, TGA, EPR, and FT-IR). Molar conductance and electrochemical (CV) measurements were carried out as well. The binary complex [Cu(hCys)2] was also synthesized and characterized. For the ternary complexes, the values of the stability constants (log β equal to 25.62 for CuAsphCys, 23.53 for CuGluhCys, and 18.61 for CuMethCys) are similar to those of the cysteine-containing ternary complexes CuAspCys and CuGluCys, recently reported by us, indicating a related N2OS coordination. The results found in the solid state are in agreement with the data found in solution studies whereby methionine, aspartic, and glutamic acids coordinate to copper(II) ion through the nitrogen atom of the amino group and one oxygen atom of the α-carboxylate group, and homocysteine coordinates through nitrogen and sulfur atoms. EPR data suggest that, in solution, the complexes are in a distorted tetrahedral geometry.

A new zinc(II) complex of the mycobactericidal drug isoniazid (complex 1) was synthesized and characterized by XRD, vibrational spectroscopy (IR, Raman) and thermogravimetric analysis. The complex is constituted by two isoniazid (INH) molecules, six hydration water molecules and two perchlorate counter-ions for each metal center (C12H26N6Cl2O16Zn). Zinc(II) adopts a distorted octahedral geometry, where two INH molecules coordinate in a bidentate manner through the hydrazide group (N, O) and the other two isoniazid residues complete the coordination sphere of zinc(II) through their aromatic nitrogen atoms. This coordination pattern gives rise to a 2-D coordination polymer. Complex 1 belongs to the monoclinic system [a = 8.1190(2) A, b = 17.977(4) A, c = 9.1051(2) A and β = 100.87(3)°], space group P21. A biological assay with Artemia salina was also performed. Complex 1 is almost 8.5 times more active than the free ligand. Its toxicity against A. salina correlates well with the cytotoxic activity for some human solid tumors. Therefore, antitumoral properties could be expected from complex 1.

This paper describes a stripping method for the determination of zidovudine at the submicromolar concentration levels. This method is based on the controlled adsorptive accumulation of zidovudine at the thin-film mercury electrode, followed by a linear-sweep stripping voltammetry measurement of the surface species. Optimal experimental conditions include a NaOH solution of 2.0 × 10–3 mol●L–1 (sup-porting electrolyte), an accumulation potential of –0.30 V and a scan rate of 100 mV?s–1. The response of zidovudine is linear over the concentration range 0.01 - 0.08 ppm. After an accumulation time of 5 minutes, the detection limit was found to be 0.67 ppb (2.5 × 10–9 mol●L–1). More convenient methods to measure zidovudine concentration in the presence of the didanosine, acyclovir, nevirapine, lamivudine, and efavirenz, were also investigated. The presence of zidovudine together with ATP or ssDNA demonstrates the utility of this method.

Four new ternary complexes of Cu(II) containing aspartic or glutamic acids and methionine or cysteine as ligands were studied both in solution and in solid state. The solution study was performed using potentiometry, UV–Vis spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, and electrochemistry. The stability constants of the ternary complexes were determined by potentiometry. The order of the values for the stability constants was CuGluMet (complex 4 ) 2 ) 3 ) 1 ), with complex 1 ≈ complex 3 ≫ complex 2 ≈ complex 4 . This behavior was confirmed by the electronic spectra, EPR parameters and cyclic voltammetry. The compounds were synthesized in the solid state and characterized by thermogravimetry as well as vibrational and EPR spectroscopy. The results found in solid state are in agreement with the data found in solution studies where methionine, aspartic and glutamic acids coordinate to the copper(II) ion using the nitrogen atom of the amino group and one oxygen atom of the carboxylate group and cysteine coordinates through the nitrogen and sulfur atoms. The EPR data suggest that the complexes are square planar and that the complexes with cysteine as one of the ligands have some distortion.

Disruptions of biometal-Aβ(1-40) interactions by an isoniazid-derived hydrazone, INHHQ, were demonstrated via in vitro NMR titrations. The compound has adequate theoretical BBB absorption properties, assessed by in silico studies. In vivo acute toxicity assays indicate that INHHQ is innocuous up to 300 mg kg(-1), showing potential as an anti-Alzheimer's drug.

With the increase in life expectancy registered in the past few decades, the prevalence of various medical conditions related to aging has been observed, such as dementia and related neurodegenerative conditions. The number of patients afflicted with these conditions is expected to significantly increase in the coming years. The growing social impact of dementia underlines the need for research aimed at identifying and better understanding this type of condition. Among neurodegenerative diseases, amyloidogenic diseases, in particular Alzheimer's disease (AD), are currently the most common form of dementia. Over the years, several hypotheses have been raised regarding the etiology of AD, such as the cholinergic, glutamatergic, amyloid cascade, oligomeric, metallic and diabetes type 3 hypotheses. Unfortunately, no cure is yet available for this disease, only drugs that aid in controlling the symptoms. This review article conducts a comprehensive approach of the main etiological hypotheses of AD, as well as the treatment prospects associated with each hypothesis.

The crystal structures of the new complexes [Cu(HL1)(OH2)(ClO4)]ClO4·2H2O (1) and [Zn2(HL2)(L2)]ClO4 (2), derived from two related, phenol-based compartmental ligands, are described. Compound 2 constitutes the first report of a complex obtained from H2L2. The metal compounds are structurally different; 2 is a dimer in which all the heteroatoms of the ligand take part in coordination, while 1 is mononuclear containing a pair of cis-oriented ligands that complete an “open” coordination sphere, in which the aldehyde group of HL1 is not involved. The protonation status of the central phenol groups of HL1 and H2L2 are also dissimilar between the complexes. Infrared vibrational analyses of both complexes, as well as their respective ligands, were performed to connect the observed spectral features with the structural properties of the solids. While some distinctive bands shifted upon complexation, it was not possible to confirm involvement of the aromatic aldehyde group in coordination by this technique. 1H NMR experiments involving 2 suggest that its particular protonation status is maintained upon dissolution in d6-DMSO.

The title compound (H2L), C27H28N4O2, is an asymmetric binucleating ligand with well defined soft (N3O-donor) and hard (NO2-donor) sides. H2L was designed as a ligand for the preparation of heterodinuclear mixed-valence MIII/M′II complexes which are models for heterobimetallic active sites of enzymes, principally calcineurin. The mol­ecular structure of H2L shows a spatial pre-organization of the donor groups for coordination. This conformation is stabilized by bifurcated intra- and inter­molecular O—H⋯N hydrogen bonds involving both phenol groups. The inter­molecular hydrogen bonds link mol­ecules of H2L into chains running parallel to the crystallographic c axis.

Research in Medicinal Chemistry has involved numerous aspects focusing on the treatment of several kinds of diseases, such as cancer, especially by the combination of therapeutic potentials by using different molecules. With this aim, a computational study combining pyrazinamide (PZA), an indispensable tuberculostatic drug, and cisplatin, an important antitumoral agent, was conducted to combine the best features of both compounds. A search for the most stable structure of the platinum(II)-PZA complex at a 2:1 stoichiometry: diclorodi(pyrazinamido)platinum(II), or cis-[PtCl2(PZA)2], was performed, using functional theory (DFT) associated to a mixed-level factorial design of two factors type 5 × 3, totaling 15 experiments. After evaluating the response surface and following the performance of seven experiments to validate the area identified as optimal, the most stable structure is that in which the dihedral 2Cl/1Pt/5O/7C is at an 18.9° angle.

Ternary systems of Cu(II) with phosphocreatine (PCr) and the polyamines (PAs), ethylenediamine (en), 1,3-diaminopropane (tn), putrescine (Put), spermidine (Spd), and spermine (Spm), were investigated in aqueous solution through potentiometry, ultraviolet–visible, EPR and Raman spectroscopy. The binary complex CuPCr was also studied by Raman spectroscopy, and the calculation of the minimum stabilization energy was done assuming this molecule in aqueous solution. The stability constants of the CuPCrPA ternary complexes were determined by potentiometry (T = 25 °C, I = 0.1 mol L − 1 , KNO 3 ). The stability order determined was CuPCrSpm > CuPCrSpd > CuPCren > CuPCrtn > CuPCrPut, the same order of the corresponding binary complexes of Cu(II) with these polyamines. The evaluation of intramolecular PA–PCr interactions in protonated and deprotonated species of ternary complexes was carried out using the equation Δlog K = log β CuPCrPAHq + p − (log β CuPAHq + log β CuPCrHp ). All of the CuPCrPA ternary complexes have a square planar structure and are bonded to PCr through the nitrogen atom of the guanidine group and the oxygen atom of the phosphate group, and to the PAs through two nitrogen atoms of the amine groups. The structure of the complex CuPCrSpm is planar with distortion towards tetrahedral. Calculation of the minimum stabilization energy for the CuPCr and CuPCrenH complexes confirmed the proposed coordination mode.

A stripping method for the determination of the antiretroviral drug efavirenz at the submicromolar concentration levels in diluted alkaline electrolyte is described. Optimum experimental conditions were: 2.0 × 10-3 mol L-1 NaOH, accumulation potential of -0.10 V, pulse amplitude of 50 mV and scan rate of 50 mV s-1. The response is linear over the concentration range of 0.01-0.25 ppm. For an accumulation time of 10 min, the limit of detection was 1.0 ppb (3.0 × 10-9 mol L-1). The most convenient conditions to measure the efavirenz concentration in the presence of ATP, DNA, several metals, and other antiviral drugs was also investigated. The utility of the method is demonstrated by the determination of efavirenz in a synthetic mixture containing both lamivudine and zidovudine, which are frequently used in the clinic in association with efavirenz as part of highly active antiretroviral therapy (HAART).

This paper describes a stripping method for the determination of nevirapine at the submicromolar concentration levels. The method is based on controlled adsorptive accumulation of nevirapine at thin-film mercury electrode, followed by a linear cyclic scan voltammetry measurement of the surface species. Optimal experimental conditions include a 2.0 x 10(-3) mol L(-1) NaOH solution (supporting electrolyte), an accumulation potential of -0.20 V, and a scan rate of 100 mV s(-1). The response of nevirapine is linear over the concentration range 0.01-0.14 ppm. For an accumulation time of 6 minutes, the detection limit was found to be 0.87 ppb (3.0 x 10(-9) mol L(-1)). More convenient methods to measure the nevirapine in presence of the efavirenz, acyclovir, didanosine, indinavir, nelfinavir, saquinavir, lamivudine, zidovudine and metals ions were also investigated. The utility of this method is demonstrated by the presence of nevirapine together with ATP or DNA.

Catechol oxidases (COs) are plant enzymes that belong to the oxidoreductases class. They contain a dinuclear copper center in their active site. In this article, we have investigated the dicopper(II) model complex [Cu2(μ-OH)(C21H33ON6)]2+ (Complex-A) under a computational perspective, using the DFT method, since this approach has been very useful in the treatment of bimetallic copper systems. The structural and spectroscopic study of Complex-A as well as the structural analysis of the BDNPP/Complex-A (Complex-B) adduct have been carried out. The calculated parameters for Complex-A are in good accordance with the experimental X-ray data. Some remarkable points can be observed from the calculated UV–vis relative excitations. The Complex-B computed structure verifies its identity as a key intermediate species in the BDNPP hydrolysis mechanism. The CuII···CuII calculated distance in Complex-B (3.026 A) is shorter than the calculated for Complex-A (3.080 A); one copper atom is bonded to the oxygen of phosphate [Cu (2)···O64–P] at 2.511 A. These arguments clearly suggest a monodentate interaction and lead to a new mechanism involving terminal substrate coordination and subsequent intramolecular nucleophilic attack by a bridging hydroxide. Such a hypothesis is completely new in terms of homobimetallic copper systems, and may have important implications regarding the chemistry of several biological dinuclear catalytic sites. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

We have studied the protonation equilibria of a dicopper(II) complex [Cu(2)(micro-OH)(C(21)H(33)ON(6))](ClO(4))(2).H(2)O, (1), in aqueous solution, its interactions with DNA, its cytotoxic activity, and its uptake in tumoral cells. C(21)H(33)ON(6) corresponds to the ligand 4-methyl-2,6-bis[(6-methyl-1,4-diazepan-6-yl)iminomethyl]phenol. From spectrophotometric data the following pKa values were calculated 3.27, 4.80 and 6.10. Complex 1 effectively promotes the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions. The following kinetic parameters were calculated k(cat) of 2.73 x 10(-4)s(-1), K(M) of 1.36 x 10(-4)M and catalytic efficiency of 2.01 s(-1)M(-1), a 2.73 x 10(7) fold increase in the rate of the reaction compared to the uncatalyzed hydrolysis rate of DNA. Competition assays with distamycin reveal minor groove binding. Complex 1 inhibited the growth of two tumoral cell lines, GLC4 and K562, with the IC(50) values of 14.83 microM and 34.21 microM, respectively. There is a good correlation between cell growth inhibition and intracellular copper content. When treated with 1, cells accumulate approximately twice as much copper as with CuCl(2). Copper-DNA adducts are formed inside cells when they are exposed to the complex. In addition, at concentrations that compound 1 inhibits tumoral cell growth it does not affect macrophage viability. These results show that complex 1 has a good therapeutic prospect.

Presented in this Communication are the structure, physicochemical properties, and catalytic promiscuity of a new dinuclear CuII(mu-OH)CuII complex containing a novel N,O-donor symmetric dinucleating ligand.

A tetracycline–platinum(II) complex, [PtCl2(C22H24N2O8)], was synthesized and characterized by elemental analysis, conductivity and thermogravimetric analyses, and infrared spectroscopy. The interaction of tetracycline (Tc) with platinum(II) ions was also studied in aqueous solution by 1H NMR and circular dichroism spectroscopies. Tetracycline forms a 1:1 complex with platinum via the oxygen of the hydroxyl group at the A ring and that of the amide group. The complex is as efficient as tetracycline in inhibiting the growth of two Escherichia coli sensitive bacterial strains and six times more potent against E. coli HB101/pBR322, a bacterial strain resistant to tetracycline. This finding is very important because the use of tetracycline to treat bacterial infections has declined due to the emergence of resistant organisms.

This paper describes the synthesis, structure and spectroscopic and magnetic properties of two (μ-phenoxo)(μ-hydroxo)dicopper(II) complexes (1 and 2) which contain similar N,O-donor atoms but with distinct coordination arrangements around the Cu(II) centers. Structural and magnetic studies of 1 and 2 allowed us to evaluate, for the first time, the individual contributions of the {Cu(μ-phenoxo)Cu} and {Cu(μ-hydroxo)Cu} structural units to the antiferromagnetic coupling between the Cu(II) centers in these complexes.