Geração de carbenos n-heterocíclicos (nhcs) em soluções aquosas com micelas constituídas por surfactantes zwiteriônicos que contêm anel imidazólio

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Programa de Pós-Graduação em Química, Florianópolis, 2023.Carbenos N-heterocíclicos (NHCs) mostraram-se importantes nucleófilos estáveis em síntese orgânicas, sendo amplamente aplicado no campo dos organometálicos. No entanto, estudos relacionados a geração de NHCs livres (sem metais) com propriedades surfactantes, bem como a sua aplicação como organocatalisadores, são bastantes escassos. Nesta tese investigou-se a formação de NHCs em micelas do tipo ImS3-n (n = 10, 12, 14, 16) em meio aquoso. Esses são surfactantes zwitteriônicos que contêm na porção hidrofóbica uma cadeia alquílica linear e na porção hidrofílica um grupo sulfonato, aniônico, e um grupo imidazólio, capaz de formar NHCs transientes. Os experimentos foram conduzidos pela avaliação da cinética de incorporação de deutério (D) no carbono C(2) do núcleo imidazólio dos referidos surfactantes por meio do desaparecimento do sinal C(2)?H na região de 8,75 - 9,10 ppm em D2O via RMN de 1H. Essa reação ocorre por meio da desprotonação do C(2)?H, com formação do respectivo NHC que é então rapidamente protonado pelo D2O. A velocidade de incorporação é dependente do tipo de ânion do sal de sódio (NaX) presente no meio: X = Cl-, Br-, NO3-, BF4-, SCN- e ClO4-. Para o ImS3-12 na presença do ânion Cl-, o coeficiente de incorporação é cerca de 12 e 14 vezes maior do que aqueles observados na presença de ClO4- e SCN-, respectivamente. Já para o análogo não surfactante ImS3-1, nenhum efeito salino foi observado. Esses resultados podem ser compreendidos por meio do fenômeno da pequena atração de íons hidróxido à superfície micelar (efeito que comparativamente acelera a formação de NHC) e a ligação preferencial de íons grandes, como ClO4- e SCN-, na superfície micelar, reduzindo a concentração da base específica responsável pela desprotonação do C(2)?H. O fenômeno da incorporação de D no carbono C(2) também foi avaliado em condições acima e abaixo da CMC para o surfactante ImS3-10, sendo constatado que acima da CMC a incorporação é acelerada. Ainda, foi observado a influência do número de carbonos da cadeia alquílica dos surfactantes da série ImS3-n e os resultados foram comparados ao análogo ImS3-1. Constatou-se que quanto maior número carbono da cadeia alquílica maior é a influência no deslocamento químico de RMN de 1H no próton C(2)?H. De maneira importante, constatou-se que na forma micelizada, os núcleos imidazólicos são cerca de 1 a 2 unidades de pKa menores (pKa 21,3 ? 21,9) do que o esperado. Esses NHCs, apesar de exibirem tempos de vida muito curtos, atuam como organocatalisadores na reação de oxidação seletiva do 4-nitrobenzaldeído (4NB) a ácido 4-nitrocarboxílico (4NBAc). Já na ausência de micelas de ImS3-n ou na presença de outros surfactantes (CTAB, SDS e SB3-12) ocorre apenas a reação de Cannizzaro. Assim, pela primeira vez demonstrou-se que os efeitos micelares levam a formação mais rápida de NHCs reativos, abrindo a possibilidade para diversos outros trabalhos envolvendo catálise por esse tipo de molécula.Abstract: N-heterocyclic carbenes (NHCs) have proven to be important stable nucleophiles in organic synthesis, being widely applied in organometallics. However, studies related to the generation of free NHCs (without metals) with surfactant properties, as well as their application as organocatalysts, are quite scarce. In this work, the formation of NHCs in ImS3-n (n = 10, 12, 14, 16) micelles in aqueous medium was investigated. These are zwitterionic surfactants that contain a linear alkyl chain in the hydrophobic portion and a sulfonate group, anionic, and an imidazolium group hydrophilic portion, capable of forming transient NHCs. The experiments were conducted by evaluating the kinetics of deuterium (D) incorporation at the C(2) carbon of the imidazolium core of the surfactants through the disappearance of the C(2)?H signal in the 8.75 - 9.10 ppm region in D2O via 1H NMR. This reaction occurs through the deprotonation of C(2)?H, with the formation of the respective NHC, which is then rapidly protonated by D2O. The incorporation rate depends on the type of sodium salt anion (NaX) present in the medium: X = Cl-, Br-, NO3-, BF4-, SCN-, and ClO4-. For ImS3-12 in the presence of the Cl- anion, the incorporation coefficient is about 12 to 14 times greater than that observed in the presence of ClO4- and SCN-, respectively. No saline effect was observed for the non-surfactant analog ImS3-1. These results can be understood through the phenomenon of weak hydroxide attraction to the micellar surface (which comparatively accelerates NHC formation) and the preferential binding of large ions, such as ClO4- and SCN-, to the micellar surface, reducing the concentration of the specific base responsible for the deprotonation of C(2)?H. The phenomenon of D incorporation at the C(2) carbon was also evaluated under conditions above and below the CMC for the ImS3-10 surfactant, and it was found that above the CMC, incorporation is accelerated. Furthermore, the influence of the number of carbon atoms in the alkyl chain of the ImS3-n surfactant series was observed, and the results were compared to the ImS3-1 analog. It was found that the greater the number of carbon atoms in the alkyl chain, the greater the influence of the anion on the chemical shift of 1H NMR in the C(2)?H proton. Importantly, it was found that in the micellar form, the imidazolium cores are approximately 1 to 2 pKa units more acidic (pKa 21.3 - 21.9) than expected. These NHCs, despite exhibiting very short lifetimes, act as organocatalysts in the selective oxidation reaction of 4-nitrobenzaldehyde (4NB) to 4-nitrocarboxylic acid (4NBAc). However, In the absence of ImS3-n micelles or in the presence of other surfactants (CTAB, SDS, and SB3-12), only the Cannizzaro reaction occurs. Thus, for the first time, it was demonstrated that micellar effects lead to the faster formation of reactive NHCs, opening possibilities for various other studies involving catalysis by this type of molecule

Femoral anteversion and the neck-shaft angle: relationship with hip osteoarthritis

OBJECTIVE: To compare the existence of agreement between measurements of anteversion of the femoral neck and the degrees of osteoarthritis and abnormality of the neck-shaft angle in patients with unilateral idiopathic hip osteoarthritis, among three evaluators. METHODS: Forty- two patients with unilateral hip osteoarthritis were evaluated by means of simple radiography and computed tomography. RESULTS: It was observed that there was no significant variation in femoral anteversion between the diseased and healthy hips. There was strongest agreement between observers 1 and 2 in relation to both the diseased hips (cases) and the healthy hips (controls). Moreover, no significant agreement was found between observers 1 and 3 (p = 0.13) and between observers 2 and 3 (p = 0.12), in relation to the neck-shaft angle of the control hips. CONCLUSION: Although there was no relationship between femoral anteversion and the neck-shaft angle in the patients with unilateral hip osteoarthritis, the present study showed that there was also no relationship with these angular deviations.OBJETIVO: Comparar, entre três avaliadores, a existência de concordância das medidas da anteversão do colo femoral com o grau da osteoartrite e a alteração do ângulo cervicodiafisário em pacientes com osteoartrite idiopática unilateral do quadril. MÉTODOS: Foram avaliados 42 pacientes com osteoartrite unilateral do quadril por meio de radiografia simples e tomografia computadorizada. RESULTADOS: Observou-se que não ocorreu variação significativa na anteversão femoral entre o quadril doente e o sadio. Houve uma concordância mais forte entre os observadores 1 e 2, tanto em relação ao quadril doente (caso) quanto ao sadio (controle). Além disso, não foi verificada concordância significativa entre os observadores 1 e 3 (p = 0,13) e entre 2 e 3 (p = 0,12) em relação ao ângulo cervicodiafisário do quadril controle. CONCLUSÃO: Apesar de não ter ocorrido relação entre a anteversão femoral e o ângulo cervicodiafisário nos pacientes com osteoartrite unilateral do quadril, este estudo demonstrou não haver relação com estes desvios angulares.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaHospital Santa Teresa Serviço de Ortopedia e TraumatologiaHospital Santa Teresa Serviço de Ortopedia e Traumatologia Grupo de QuadrilUFRJ Faculdade de MedicinaINTOINTO Grupo de Pelve e AcetábuloUNIFESP, EPMSciEL

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Análise da eficácia da Tirzepatida como agente terapêutico para perda de peso em pacientes com Obesidade

A obesidade e o diabetes são doenças crônicas que afetam milhões de pessoas em todo o mundo, sendo consideradas epidemias crescentes. O tratamento da obesidade envolve uma abordagem multifacetada, incluindo mudanças no estilo de vida e intervenções farmacológicas. Nesse contexto, a tirzepatida, uma terapia combinada de dois medicamentos que atuam em diferentes vias metabólicas para reduzir o apetite e promover a perda de peso em pacientes com obesidade, tem se destacado como uma opção terapêutica promissora. O objetivo deste estudo foi avaliar a eficácia e segurança da tirzepatida como agente terapêutico para perda de peso em pacientes com obesidade. Para isso, foram selecionados quatro artigos que avaliaram o uso da tirzepatida em pacientes com obesidade, publicados entre 2018 e 2023, nas bases de dados PubMed (Medline), Scientific Electronic Library Online (SciELO) e Cochrane Library. Os resultados indicam que a tirzepatida é uma terapia promissora e segura para perda de peso em pacientes com obesidade. Todos os estudos relataram perda de peso significativa em pacientes tratados com essa terapia, variando de 8,6% a 16,0% do peso corporal inicial. Além disso, a tirzepatida também apresentou efeitos benéficos em outros parâmetros metabólicos, como redução da glicemia e melhora da função hepática. Efeitos adversos foram relatados em menor frequência e gravidade em comparação com outras terapias para perda de peso. Em resumo, a tirzepatida é uma terapia combinada de dois medicamentos que tem demonstrado eficácia e segurança para a perda de peso em pacientes com obesidade, de acordo com os resultados de quatro estudos avaliados nesta pesquisa. Essa terapia pode ser uma opção terapêutica válida para pacientes com obesidade. No entanto, é importante destacar a necessidade de mais pesquisas para avaliar sua eficácia e segurança a longo prazo e sua aplicabilidade em diferentes populações. Portanto, é fundamental que o tratamento seja realizado com acompanhamento médico e que cada caso seja avaliado individualmente

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

A vision on biomass-to-liquids (BTL) thermochemical routes in integrated sugarcane biorefineries for biojet fuel production

Crude oil price volatility directly affects the worldwide fuels and chemicals markets, impacts food production costs, as well as it influences investments in alternative energy sources. Global warming is a consequence of greenhouse gases emissions, among which CO2 plays a crucial role. A circular economy appears to be a global consensus to limit the negative impacts on the environment caused by fossil-based emissions. Transportation of goods and people are responsible for a large fraction of manmade CO2 vented to the atmosphere. Although alternatives have already been developed and are already in use for Otto and Diesel cycle engines in the form of bioethanol and biodiesel, respectively, the aviation sector is still short of a consolidated solution for biojet fuel procurement. Among the possible pathways, Biomass-to-Liquids (BTL) thermochemical routes are candidates to produce green hydrocarbons in the near future, including biojet fuel. For the deployment of a BTL thermochemical route, a true biorefinery concept can be employed, through which a flexibility in the product portfolio may increase business competitiveness and reduce production costs through heat and mass integration. Bearing this context in mind, the present work presents a vision on BTL thermochemical routes focusing on biojet fuel production through fast pyrolysis, gasification, and Fischer-Tropsch (FT) synthesis in integrated sugarcane biorefineries119COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESsem informaçã

Hepatocarcinoma fibrolamelar (HFL): relato de caso Fibrolamellar hepatocarcinoma (FLH): report case

INTRODUÇÃO: O hepatocarcinoma fibrolamelar, variante do hepatocarcinoma, é neoplasia rara, responsável por 2% das de origem hepatocelular. RELATO DO CASO: Homem de 24 anos iniciou sintoma doloroso abdominal quatro meses antes da primeira consulta com hiporexia, emagrecimento, vômitos, aumento hepático e nodulação em hipocôndrio direito. Ressonância magnética abdominal mostrou lesão hepática heterogênea, hipervascular, com cicatriz central (provável calcificação), sugestivo de hepatocarcinoma fibrolamelar e presença de hepatomegalia moderada. Realizou-se trissegmentectomia hepática (segmentos VI, VII, VIII), com margem de segurança, sendo a via de acesso a por incisão subcostal direita. Houve confirmação de carcinoma hepatocelular (variante fibrolamelar) moderadamente diferenciado. Na evolução em seis meses encontrava-se bem com exame ultrassonográfico de controle normal, exceto sinais da ressecção efetuada. CONCLUSÃO: Apesar de prognóstico sombrio, o tratamento cirúrgico do hepatocarcinoma fibrolamelar é boa opção quando ampla hepatectomia pode ser realizada.BACKGROUND: Fibrolamellar hepatocarcinoma is rare and responsible for 2% of the hepatocarcinomas. CASE REPORT: Man with 24 years old was attended by medical institution with abdominal pain, abdominal tumor mass, vomiting and bad general conditions. MRI showed hepatic tumor suggesting hepatocarcinoma. An hepatectomy (segments VI, VII, VIII) was done. It was confirmed malignancy with fibrolamellar hepatocarcinoma. In six months follow-up ultrasonography showed normal aspect of the remained liver. CONCLUSION: Although the bad prognosis of the tumor, hepatectomy should always be tried, if technical resection is feasible

Inhibition of <i>Paracoccidioides lutzii Pb</i>01 Isocitrate Lyase by the Natural Compound Argentilactone and Its Semi-Synthetic Derivatives

<div><p>The dimorphic fungus <i>Paracoccidioides</i> spp. is responsible for paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America, causing serious public health problems. Adequate treatment of mycotic infections is difficult, since fungi are eukaryotic organisms with a structure and metabolism similar to those of eukaryotic hosts. In this way, specific fungus targets have become important to search of new antifungal compound. The role of the glyoxylate cycle and its enzymes in microbial virulence has been reported in many fungal pathogens, including <i>Paracoccidioides</i> spp. Here, we show the action of argentilactone and its semi-synthetic derivative reduced argentilactone on recombinant and native isocitrate lyase from <i>Paracoccidioides lutzii Pb</i>01 (<i>Pb</i>ICL) in the presence of different carbon sources, acetate and glucose. Additionally, argentilactone and its semi-synthetic derivative reduced argentilactone exhibited relevant inhibitory activity against <i>P. lutzii Pb</i>01 yeast cells and dose-dependently influenced the transition from the mycelium to yeast phase. The other oxygenated derivatives tested, epoxy argentilactone and diol argentilactone<b>-</b>, did not show inhibitory action on the fungus. The results were supported by <i>in silico</i> experiments.</p></div

Molecular surface representation of PbICL and the three-dimensional structures of A) 1, B) 3, C) 4, and D) isocitrate (native ligand) in the PbICL binding pocket and key interactions of PbICL with the best conformation (mode 1) of each compound (orange).

<p>Ligplots of the compounds in binding pocket of PbICL. Pink circles indicate residues involved in hydrogen-bond polar or charged interactions; green circles indicate residues involved in van der Waals interactions. Dashed lines represent stronger interactions. The PbICL residues that interact with the compounds are shown, and the dashed lines represent stronger interactions. Oxygen is colored red. The structures of the compounds shown refer to the lowest Fscore obtained in mode 1 from the docking simulations with AutoDock Vina. The grid was defined considering only the region of the PbICL site using sizex = sizey = sizez = 20 Å, centerx = 21.37 Å, centerx = 1.14 Å, and centerz = 10.83 Å.</p