Síntese, caracterização, imobilização e estudo da ação catalítica de compostos de coordenação de ferro

Resumo: Compostos modelo para metaloproteínas do tipo não-heme, imobilizados em matrizes inorgânicas ou não, têm sido objeto de muitòs estudos nos últimos anos. Foram sintetizados e caracterizados 4 novos compostos binucleares de ferro com o ligante (2- hydroxibenzyl)(2-methylpyridyl)amine, Hbpa, as models of iron metallobiomolecules: [Fe2(bpa)2(µ-OCH3)2Cl2] (1), [Fe2(bpa)2(µ-CH3OH)(H2O)](CIO4)3.2H2O (2), [Fe2(bpa)2(µ -O2CCH3)( µ -CH3O)2](CI04).2H2O (3), [Fe2(bpa)2(µ -02CCH3)( µ -0H)2] (CI04).H20 (4). Esses compostos foram obtidos pela reação do ligante Hbpa com cloreto férrico ou perclorato de Fe(ll) ou Fe(lll) na presença de base. Foi efetuada a imobilização de compostos em zeólita NaY utilizando duas metodologias diferentes: misturando-se o ligante com a zeólita já metalada (Fe e Cu) em refluxo de metanol ou tolueno; e misturando-se o complexo previamente sintetizado com a zeólita pura em refluxo de metanol. Os compostos de coordenação puros e imobilizados em zeólita foram caracterizados por RPE, espectroscopia eletrônica, infravermelho, análise elementar de C, H e N, absorção atômica, voltametria cíclica, condutividade termogravimetria (TG) e calorimetria diferencial de varreduras simultâneas (DSC). O composto 1 teve sua estrutura resolvida através de difração de raios X, o que confirmou a proposta feita baseada nas análise elementares. O composto é um binuclear de ferro, no qual os átomos de ferro possuem sua esfera de coordenação preenchida por um ligante (Fe1-Oph = 1,9042 Á), cloreto e pontes metóxido (Fe1-Ometóxidoi = 1,9635 A, Fe1- Ometóxido2 = 2,0354 A, Ometóxidoi-Fe1-Ometóxido2 = 76,18° e Fe1-0-Fe2 = 103,82°). O composto 2, além das técnicas já citadas, foi caracterizado por espectrometria de massa, a qual deu suporte à proposta feita através das análises elementares. A observação do aparecimento de uma banda em 672 nm no espectro eletrônico do composto 1 com a adição de H202, a qual poderia se tratar de uma espécie n-peroxo cataliticamente ativa na oxidação de substratos orgânicos, nos levou à testar este composto como modelo das metano monooxigenases (MMO) na oxidação de cicloexano e cicloexeno. O composto 2 não apresenta o mesmo comportamento espectroscópico de 1 mas também foi testado como modelo das MMO. Os dois compostos não apresentaram rendimentos comparáveis aos observados para outros compostos-modelo não-hêmicos. Foram testados também alguns compostos imobilizados em zeólita na oxidação de cicloexano, entretanto apresentaram rendimentos inferiores aos obtidos para a zeólita metalada e sem o ligante. Os compostos 1 e 2 foram testados frente à hidrólise do bis-(2,4-dinitrofenil)fosfato para investigá-los como modelos das fosfatases ácidas púrpuras (PAP's). Os valores de kobs para as reações efetuadas chegaram à ordem de 103 s-1, enquanto que os valores para a enzima testada in vitro são da ordem de 102 s-1. Os compostos de ferro reportados na literatura como modelos para as PAP's, normalmente apresentam valores de k0bs na faixa de 104s-1. O composto 2 é mais eficiente na hidrólise, provavelmente devido à sua esfera de coordenação possuir moléculas de água e uma ponte µ acetato

Brown adipose tissue: is it affected by intermittent hypoxia?

<p>Abstract</p> <p>Background</p> <p>Intermittent hypoxia (IH), a model of sleep apnea, produces weight loss in animals. We hypothesized that changes in brown adipose tissue (BAT) function are involved in such phenomenon. We investigated the effect of IH, during 35 days, on body weight, brown adipose tissue wet weight (BATww) and total protein concentration (TPC) of BAT.</p> <p>Methods</p> <p>We exposed Balb/c mice to 35 days of IH (n = 12) or sham intermittent hypoxia (SIH; n = 12), alternating 30 seconds of progressive hypoxia to a nadir of 6%, followed by 30 seconds of normoxia. During 8 hours, the rodents underwent a total of 480 cycles of hypoxia/reoxygenation, equivalent to an apnea index of 60/hour. BAT was dissected and weighed while wet. Protein was measured using the Lowry protein assay.</p> <p>Results</p> <p>Body weight was significantly reduced in animals exposed to IH, at day 35, from 24.4 ± 3.3 to 20.2 ± 2.2 g (p = 0.0004), while in the SIH group it increased from 23.3 ± 3.81 to 24.1 ± 2.96 g (p = 0.23). BATww was also lower in IH than in SIH group (p = 0.00003). TPC of BAT, however, was similar in IH (204.4 ± 44.3 μg/100 μL) and SIH groups (213.2 ± 78.7 μg/100 μL; p = 0.74) and correlated neither with body weight nor with BATww. TPC appeared to be unaffected by exposure to IH also in multivariate analysis, adjusting for body weight and BATww. The correlation between body weight and BATww is significant (rho= 0.63) for the whole sample. When IH and SIH groups are tested separately, the correlations are no longer significant (rho= 0.48 and 0.05, respectively).</p> <p>Conclusion</p> <p>IH during 35 days in a mice model of sleep apnea causes weight loss, BATww reduction, and no change in TPC of BATww. The mechanisms of weight loss under IH demands further investigation.</p

VOLTAMETRIA DE VARREDURA LINEAR ANÓDICA EM EFLUENTES CONTAMINADOS COM SULFETO DE HIDROGÊNIO (H2S)

In view of the highly toxic characteristic presented by hydrogen sulfide, a by-product of several industrial processes, its removal from an effluent becomes indispensable. Therefore, the electrochemical effect of H2S oxidation was evaluated, seeking to obtain the potential range and peak potential at which the oxidation reactions of the contaminant occur. For that, we used the anodic linear sweep voltammetry technique with the use of a reticulated vitreous carbon rotary working electrode. Using a synthetic solution in three concentrations, the scanning speeds for different rotations of the working electrode were varied between the potentials of -0.5 V (vs. ECS) and 1.0 V (vs. ECS), for using a potentiotate/galvanostat coupled to a computer. The results obtained indicate that the potentials, in which the reactions of interest occur, are close to 0.3 V (vs. ECS), which suggests the presence of the same reactions for all analyzed cases. It was observed in the voltamograms a proportional increase of the peak current with the sweep rate and concentration, indicating the control of the system by mass transport. Thus, the present study reveals that elemental sulfur does not passivate the electrode surface and that there is the possibility of using cross-linked glassy carbon electrodes to electrochemically oxidize sulfide ions in aqueous solutions.Dada la característica altamente tóxica que presenta el sulfuro de hidrógeno, un subproducto de varios procesos industriales, su eliminación de un efluente se vuelve indispensable. Por lo tanto, se evaluó el efecto electroquímico de la oxidación del H2S, buscando obtener el rango de potencial y el pico de potencial en el que ocurren las reacciones de oxidación del contaminante. Para eso, utilizamos la técnica de voltamperometría de barrido lineal anódico con el uso de un electrodo de trabajo rotativo de carbono vítreo reticulado. Usando una solución sintética en tres concentraciones, las velocidades de escaneo para diferentes rotaciones del electrodo de trabajo se variaron entre los potenciales de -0.5 V (frente a ECS) y 1.0 V (frente a ECS), para usar un potenciómetro/galvanostato acoplado a un ordenador. Los resultados obtenidos indican que los potenciales, en los que ocurren las reacciones de interés, son cercanos a 0.3 V (frente a ECS), lo que sugiere la presencia de las mismas reacciones para todos los casos analizados. Se observó en los voltamogramas un aumento proporcional del pico de corriente con la tasa de barrido y concentración, indicando el control del sistema por transporte de masa. Así, el presente estudio revela que el azufre elemental no pasiva la superficie del electrodo y que existe la posibilidad de utilizar electrodos de carbono vítreo reticulado para oxidar electroquímicamente iones sulfuro en soluciones acuosas.Diante da característica altamente tóxica apresentada pelo sulfeto de hidrogênio, subproduto de diversos processos industriais, a sua remoção de um efluente torna-se indispensável. Assim sendo, avaliou-se o efeito eletroquímico da oxidação de H2S, buscando-se obter a faixa de potencial e o potencial de pico em que ocorrem as reações de oxidação do contaminante. Para tanto, utilizou-se a técnica de voltametria de varredura linear anódica com o emprego de eletrodo de trabalho rotatório de carbono vítreo reticulado. Utilizando-se de uma solução sintética em três concentrações, foram variadas as velocidades de varredura para rotações distintas do eletrodo de trabalho entre os potenciais de -0,5 V (vs. ECS) e 1,0 V (vs. ECS), por meio de um potenciotato/galvanostato acoplado à um computador. Os resultados obtidos indicam que os potenciais, nos quais ocorrem as reações de interesse, ficam próximos a 0,3 V (vs. ECS), o que sugere a presença das mesmas reações para todos os casos analisados. Observou-se nos voltamogramas um aumento proporcional da corrente de pico com a taxa de varredura e concentração, indicando o controle do sistema por transporte de massa. Assim, o presente estudo revela que o enxofre elementar não passiva a superfície do eletrodo e que há a possibilidade de utilização de eletrodos de carbono vítreo reticulado para oxidar eletroquimicamente íons sulfeto em soluções aquosas

Stearic acid, beeswax and carnauba wax as green raw materials for the loading of carvacrol into nanostructured lipid carriers

The use of lipid nanoparticles as drug delivery systems has been growing over recent decades. Their biodegradable and biocompatible profile, capacity to prevent chemical degradation of loaded drugs/actives and controlled release for several administration routes are some of their advantages. Lipid nanoparticles are of particular interest for the loading of lipophilic compounds, as happens with essential oils. Several interesting properties, e.g., anti-microbial, antitumoral and antioxidant activities, are attributed to carvacrol, a monoterpenoid phenol present in the composition of essential oils of several species, including Origanum vulgare, Thymus vulgaris, Nigellasativa and Origanum majorana. As these essential oils have been proposed as the liquid lipid in the composition of nanostructured lipid carriers (NLCs), we aimed at evaluating the influence of carvacrol on the crystallinity profile of solid lipids commonly in use in the production of NLCs. Different ratios of solid lipid (stearic acid, beeswax or carnauba wax) and carvacrol were prepared, which were then subjected to thermal treatment to mimic the production of NLCs. The obtained binary mixtures were then characterized by thermogravimetry (TG), differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS) and polarized light microscopy (PLM). The increased concentration of monoterpenoid in the mixtures resulted in an increase in the mass loss recorded by TG, together with a shift of the melting point recorded by DSC to lower temperatures, and the decrease in the enthalpy in comparison to the bulk solid lipids. The miscibility of carvacrol with the melted solid lipids was also confirmed by DSC in the tested concentration range. The increase in carvacrol content in the mixtures resulted in a decrease in the crystallinity of the solid bulks, as shown by SAXS and PLM. The decrease in the crystallinity of lipid matrices is postulated as an advantage to increase the loading capacity of these carriers. Carvacrol may thus be further exploited as liquid lipid in the composition of green NLCs for a range of pharmaceutical applications.This work was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil, FinanceCode 001), by the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE) under the projects M-ERA-NET/0004/2015 and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

The effect of caffeine supplementation on exercise performance evaluated by a novel animal model

Introduction: Caffeinated drinks are used for improve performance. Animal models represent investigational strategy that circumvents most of the drawbacks of research in humans, including motivational factors and the placebo effect. No animal model that could test whether different forms of administering caffeine affect exercise propensity was found in the literature. Methods: An animal model of grouped voluntary exercise was tested. Two-month-old male C57/bl mice were housed in a cage fitted with one running wheel and a monitoring system. Six animals per cage were introduced individually. To assess the sensitivity of the model, the effect of different caffeinated drinks was observed in mice exercising ad libitum. During 2 days, the mice received: 1) pure anhydrous caffeine 0.125 mg/mL (PC), 2) cola drink (CC), and 3) caffeine-taurine-glucuronolactone drink (CTG), intercalating wash-out periods of 2 days, receiving pure water. Results: The distance run during the periods of water ingestion was significantly lower than during the periods of stimulant drinks ingestion: PC (5.6 ± 1.3 km; p = 0.02), of CC ingestion (7.6 ± 0.6 km; p = 0.001), and of CTG ingestion (8.3 ± 1.6 km; p = 0.009). The performances when ingesting the three caffeinated drinks do not follow a dose-response curve. Conclusions: The model described here was able to measure the effect of caffeine intake on voluntary exercise of mice. The sensitivity of the model to the effect of caffeine needs to be further validated. The action of each component of the drinks on exercise performance needs to be clarified in future research. The present model is adequate for such investigation

The effect of caffeine supplementation on exercise performance evaluated by a novel animal model

Introduction: Caffeinated drinks are used for improve performance. Animal models represent investigational strategy that circumvents most of the drawbacks of research in humans, including motivational factors and the placebo effect. No animal model that could test whether different forms of administering caffeine affect exercise propensity was found in the literature. Methods: An animal model of grouped voluntary exercise was tested. Two-month-old male C57/bl mice were housed in a cage fitted with one running wheel and a monitoring system. Six animals per cage were introduced individually. To assess the sensitivity of the model, the effect of different caffeinated drinks was observed in mice exercising ad libitum. During 2 days, the mice received: 1) pure anhydrous caffeine 0.125 mg/mL (PC), 2) cola drink (CC), and 3) caffeine-taurine-glucuronolactone drink (CTG), intercalating wash-out periods of 2 days, receiving pure water. Results: The distance run during the periods of water ingestion was significantly lower than during the periods of stimulant drinks ingestion: PC (5.6±1.3 km; p = 0.02), of CC ingestion (7.6±0.6 km; p = 0.001), and of CTG ingestion (8.3±1.6 km; p = 0.009). The performances when ingesting the three caffeinated drinks do not follow a dose-response curve. Conclusions: The model described here was able to measure the effect of caffeine intake on voluntary exercise of mice. The sensitivity of the model to the effect of caffeine needs to be further validated. The action of each component of the drinks on exercise performance needs to be clarified in future research. The present model is adequate for such investigation. Key words: Exercise; caffeine; energy drinks; runnin

ABCA3, a key player in neonatal respiratory transition and genetic disorders of the surfactant system

Genetic disorders of the surfactant system are rare diseases with a broad range of clinical manifestations, from fatal respiratory distress syndrome (RDS) in neonates to chronic interstitial lung disease (ILD) in children and adults. ABCA3 [ATP-binding cassette (ABC), subfamily A, member 3] is a lung-specific phospholipid transporter critical for intracellular surfactant synthesis and storage in lamellar bodies (LBs). Its expression is developmentally regulated, peaking prior to birth under the influence of steroids and transcription factors. Bi-allelic mutations of the ABCA3 gene represent the most frequent cause of congenital surfactant deficiency, indicating its critical role in lung function. Mutations affect surfactant lipid and protein processing and LBs' morphology, leading to partial or total surfactant deficiency. Approximately 200 mutations have been reported, most of which are unique to individuals and families, which makes diagnosis and prognosis challenging. Various types of mutations, affecting different domains of the protein, account in part for phenotype diversity. Disease-causing mutations have been reported in most coding and some non-coding regions of the gene, but tend to cluster in the first extracellular loop and the second nucleotide-binding domain (NBD), leading to defective glycosylation and trafficking defects and interfering with ATP binding and hydrolysis respectively. Mono-allelic damaging and benign variants are often subclinical but may act as disease modifiers in lung diseases such as RDS of prematurity or associate with mutations in other surfactant-related genes. Diagnosis is complex but essential and should combine pathology and ultrastructure studies on lung biopsy with broad-spectrum genetic testing of surfactant-related genes, made possible by recent technology advances in the massive parallel sequencing technology

Inorganic UV filters

Nowadays, concern over skin cancer has been growing more and more, especially in tropical countries where the incidence of UVA/B radiation is higher. The correct use of sunscreen is the most efficient way to prevent the development of this disease. The ingredients of sunscreen can be organic and/or inorganic sun filters. Inorganic filters present some advantages over organic filters, such as photostability, non-irritability and broad spectrum protection. Nevertheless, inorganic filters have a whitening effect in sunscreen formulations owing to the high refractive index, decreasing their esthetic appeal. Many techniques have been developed to overcome this problem and among them, the use of nanotechnology stands out. The estimated amount of nanomaterial in use must increase from 2000 tons in 2004 to a projected 58000 tons in 2020. In this context, this article aims to analyze critically both the different features of the production of inorganic filters (synthesis routes proposed in recent years) and the permeability, the safety and other characteristics of the new generation of inorganic filters