Development of novel ionic liquids based on ampicillin

Novel ionic liquids containing ampicillin as an active pharmaceutical ingredient anion were prepared with good yields by using a new, efficient synthetic procedure based on the neutralization of a moderately basic ammonia solution of ampicillin with different organic cation hydroxides. The relevant physical and thermal properties of these novel ionic liquids based on ampicillin were also evaluated.

Crime fiscal: "Abuso de confiança fiscal - artigo 105º RGIT"

Mestrado em Fiscalidade

Fraude Carrossel: Métodos de Combate

Mestrado em Fiscalidade

Acompanhamento da construção de obras de arte

No âmbito do Trabalho Final de Mestrado (TFM), propus a realização do presente relatório de estágio para obtenção do grau de Mestre em Engenharia Civil, inserido no perfil de estruturas do mestrado de engenharia civil, do Instituto Superior de Engenharia de Lisboa. Para realização deste relatório, realizei um estágio com o período de quatro meses, na Mota-Engil, Engenharia e Construção, SA, onde estive integrado na obra de construção do sublanço da estrada denominada “EN238 – Sertã/ Oleiros” integrado na subconcessão do Pinhal Interior (Lote 10). A obra localiza-se na província da Beira Baixa, no distrito de Castelo Branco e abrange os concelhos de Sertã e Oleiros. Neste trabalho desenvolveram-se essencialmente duas vertentes da área da Engenharia: “Coordenação” e “Construção”.

New ionic liquids and salts derived from β-Lactam antibiotics

In recent years ionic liquids (ILs) have been increasing the popularity and the number of applications. Ionic liquids were used mainly as solvent in organic synthesis, but in recent years they are also used in analytical chemistry, separation chemistry and material science. Additional to significant developments in their chemical properties and applications, ionic liquids are now bringing unexpected opportunities at the interface of chemistry with the life sciences. Ionic liquids (ILs) are currently defined as salts that are composed solely of cations and anions which melt below 100ºC. Our goal in this work is to explore the dual activity of the ionic liquids, due to the presence of two different ions, an anion with bacterial activity as β-lactam antibiotics and different kinds of cations. In this work the anions of ILs and salts were derived from three different antibiotics: ampicillin, penicillin and amoxicillin. The cations were derived from substituted ammonium, phosphonium pyridinium and methylimidazolium salts, such as: tetraethyl ammonium, trihexiltetradecilphosphonium, cetylpyridinium, choline (an essential nutrient), 1-ethyl-3-methylimidazolium, and 1-ethanol-3-methyl imidazolium structures. Commercial ammonium and phosponium halogen salts were first transformed into hydroxides on ionic exchange column (Amberlite IRA-400) in methanol. The prepared hydroxides were then neutralized with β-lactam antibiotics. After crystallization we obtained pure ILs and salts containing β-lactam antibiotics. This work presents a novel method for preparation of new salts of antibiotics with low melting point and their chemistry and microbiological characterization.

Development of novel ionic liquids based on valproate anion

Valproic acid (2-propyl pentanoic acid) is a pharmaceutical drug used for treatment of epileptic seizures absence, tonic-clonic (grand mal), complex partial seizures, and mania in bipolar disorder [1]. Valproic acid is a slightly soluble in water and therefore as active pharmaceutical ingredient it is most commonly applied in form of sodium or magnesium valproate salt [1].However the list of adverse effects of these compounds is large and includes among others: tiredness, tremor, sedation and gastrointestinal disturbances [2]. Ionic liquids (ILs) are promising compounds as Active Pharmaceutical Ingredients (APIs)[3]. In this context, the combinations of the valproate anion with appropriate cation when ILs and salts are formed can significantly alter valproate physical, chemical and thermal properties.[4] This methodology can be used for drug modification (alteration of drug solubility in water, lipids, bioavailability, etc)[2] and therefore can eliminate some adverse effect of the drugs related to drug toxicity due for example to its solubility in water and lipids (interaction with intestines). Herein, we will discuss the development of ILs based on valproate anion (Figure 1) prepared according a recent optimized and sustainable acid-base neutralization method [4]. The organic cations such as cetylpyridinium, choline and imidazolium structures were selected based on their biocompatibility and recent applications in pharmacy [3]. All novel API-ILs based on valproate have been studied in terms of their physical, chemical (viscosity, density, solubility) and thermal (calorimetric studies) properties as well as their biological activity.

Synthesis, characterization and antiproliferative activity on cancer cell lines of new ionic liquids from ampicillin

Ionic Liquids (ILs) are ionic compounds that possess melting temperature below 100ºC and they have been a topic of great interest since the mid-1990s due to their unique properties. The range of IL uses has been broadened, due to a significant increase in the variety of physical, chemical and biological ILs properties. They are now used as Active Pharmaceutical Ingredients (APIs) and recent interests are focused on their application as innovative solutions in new medical treatment and delivery options.1 In this work, our principal objective was the synthesis and investigation of physicochemical and medical properties of ionic liquids (ILs) and organic salts from ampicillin. This approach is of huge interest in pharmaceutical industry as cation and anion composition of ILs and organic salts can greatly alter their desired properties, namely the melting temperature and even synergistic effects can be obtained.2,3 For the synthesis of these compounds we used a recently developed method proposed by Ohno et al.4 for the preparation of quaternary ammonium and phosphonium hydroxides, that were neutralized by ampicillin. After purification we obtained pure ILs and salts in good yields. These ILs shows good antimicrobial and antifungal activities. As it is well known that some ionic liquids containing phosphonium and ammonium cation also shows anti-cancer activity1,5 we also decided to study these compounds against some cancer cell lines.

Preparation and characterization of beta-lactam antibiotic as Ionic liquids and salts

With the increase of bacterial resistance a large number of therapeutic strategies have been used to fight different kind of infections. In recent years ionic liquids (ILs) have been increasing the popularity and the number of applications. First ionic liquids were used mainly as solvent in organic synthesis, but now they are used in analytical chemistry, separation chemistry and material science among others. Additional to significant developments in their chemical properties and applications, ionic liquids are now bringing unexpected opportunities at the interface of chemistry with the life sciences Ionic liquids (ILs) are currently defined as salts that are composed solely of cations and anions which melt below 100ºC. Our goal in this work is to explore the dual activity of the ionic liquids, due to the presence of two different ions, an ion with bacterial activity as a beta-lactam antibiotic and different kinds of cations. In this work the anions of ILs and salts were derived from three different antibiotics: ampicillin, penicillin and amoxicillin. The cations were derived from substituted ammonium, phosphonium pyridinium and methylimidazolium salts, such as: tetraethyl ammonium, trihexiltetradecilphosphonium, cetylpyridinium, choline (an essential nutrient), 1-ethyl-3-methylimidazolium, and 1-ethanol-3-methyl imidazolium structures. Commercial ammonium and phosponium halogen salts were first transformed into hydroxides. on ionic exchange column (Amberlite IRA-400) in methanol. The prepared hydroxides were then neutralized with beta-lactam antibiotics. After crystallization we obtained pure ILs and salts containing beta-lactam antibiotics. This work presents a novel method for preparation of new salts of antibiotics with low melting point and their characterization.

Development and biological evaluation of API-ILs based on anti-bacterial and anti-fungal drugs

In recent years Ionic Liquids (ILs) are being applied in life sciences. ILs are being produce with active pharmaceutical drugs (API) as they can reduce polymorphism and drug solubility problems [1] Also ILs are being applied as a drug delivery device in innovative therapies What is appealing in ILs is the ILs building up platform, the counter-ion can be carefully chosen in order to avoid undesirable side effects or to give innovative therapies in which two active ions are paired. This work shows ILs based on ampicillin (an anti-bacterial agent) and ILs based on Amphotericin B. Also we show studies that indicate that ILs based on Ampicillin could reverse resistance in some bacteria. The ILs produced in this work were synthetized by the neutralization method described in Ferraz et. al. [2] Ampicillin anion was combined with the following organic cations 1-ethyl-3-methylimidazolium, [EMIM]; 1-hydroxy-ethyl-3-methylimidazolium, [C2OHMIM]; choline, [cholin]; tetraethylammonium, [TEA]; cetylpyridinium, [C16pyr] and trihexyltetradecylphosphonium, [P6,6,6,14]. Amphotericin B was combined with [C16pyr], [cholin] and 1-metohyethyl-3-methylimidazolium, [C3OMIM]. The ILs-APIs based on ampicillin[2] were tested against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumonia (clinical isolated), as well as on Gram positive Staphylococcus Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis. The arising resistance developed by bacteria to antibiotics is a serious public health threat and needs new and urgent measures. We study the bacterial activity of these compounds against a panel of resistant bacteria (clinical isolated strains): E. coli CTX M9, E. coli TEM CTX M9, E. coli TEM1, E. coli CTX M2, E. coli AmpC Mox2. In this work we demonstrate that is possible to produce ILs from anti-bacterial and anti-fungal compounds. We show here that the new ILs can reverse the bacteria resistance. With the careful choice of the organic cation, it is possible to create important biological and physic-chemical properties. This work also shows that the ion-pair is fundamental in ampicillin mechanism of action.

Organizações e lideranças positivas: estudo empírico

Dissertação de Mestrado, Ciências Económicas e Empresariais, 9 de Janeiro de 2014, Universidade dos Açores.

Apanha-me se puderes! tradução comentada do capítulo “White-collar and Corporate Crime”, The Oxford Handbook of Criminology

Dissertação de Mestrado Apresentada ao Instituto Superior de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Tradução e Interpretação Especializadas, sob orientação da Mestre Suzana Noronha Cunha

Acidentes de trabalho: custos previdenciários e dias de trabalho perdidos

OBJETIVO: Estimar a contribuição de benefícios concedidos por acidentes de trabalho dentre o total de benefícios relacionados com a saúde da Previdência Social, focalizando os custos conforme o tipo de benefício, e o impacto sobre a produtividade relativa a dias perdidos de trabalho. MÉTODOS: Utilizam-se registros dos despachos de benefícios do Sistema Único de Benefícios do Instituto Nacional de Seguridade Social da Bahia, em 2000. Acidentes de trabalho foram definidos com o diagnóstico clínico para Causas Externas, Lesões e Envenenamentos (SS-00 a T99) da Classificação Internacional de Doenças 10ª Revisão, e o tipo de benefício que distingue problemas de saúde ocupacionais e não ocupacionais. RESULTADOS: Foram estudados 31.096 benefícios concedidos por doenças ou agravos à saúde, dos quais 2.857 (7,3%) eram devidos a acidentes de trabalho. Maiores proporções foram estimadas entre os trabalhadores da indústria da transformação e construção/eletricidade/gás, 18% do total dos benefícios. Os custos com os benefícios para acidentes de trabalho foram estimados em R$8,5 milhões, com aproximadamente meio milhão de dias perdidos de trabalho no ano. CONCLUSÕES: Apesar do conhecimento de que esses dados são sub-enumerados, e restritos aos trabalhadores que conseguiram receber benefícios relacionados com a saúde, os achados revelam o grande impacto sobre a produtividade e o orçamento do Instituto Nacional de Previdência Social de agravos reconhecidos como evitáveis, reforçando a necessidade de sua prevenção.

Floresta natural dos Açores

O efeito da insularidade reflecte-se no número limitado de espécies arbóreas naturais dos Açores. As mais comuns são a Morella faya (Faia-da-terra), Picconia azorica (Pau-branco), Laurus azorica (Louro), Juniperus brevifolia (Cedro-do-mato), Ilex perado subsp. azorica (Azevinho), Erica azorica (Urze) e Frangula azorica (Sanguinho). Pelo contrário, Prunus azorica (Ginjeira-brava) é actualmente muito rara e Taxus bacatta (Teixo) encontra-se à beira da extinção. Dependendo das condições ambientais, particularmente de temperatura, pluviosidade e exposição ao vento, encontramos diferentes espécies a dominar a copa da floresta. […].

Mas que rica toalha!

O termo padrão quando empregue no dia a dia pode assumir diferentes significados. Em geral, está associado à identificação de algum tipo de regularidade. A Matemática, enquanto ciência dos padrões, fornece ferramentas que permitem classificar de forma rigorosa e exaustiva os padrões que encontramos, sejam eles numéricos, geométricos ou de outra natureza qualquer. Esta é a missão de um matemático: identificar regularidades para que, no meio da desordem e de um volume considerável de informação, se possa extrair algum tipo de invariância que conduza à caracterização das propriedades comuns aos diferentes casos analisados. (...) Dedicamos este artigo à caracterização de outro padrão bidimensional, desta vez proveniente do artesanato: analisamos as simetrias de uma toalha feita em renda tradicional ou croché de arte, com diferentes tipos de pontos (laça, amora, escadinha, ponto de serrilha, entre outros). A foto analisada foi enviada pela Dona Maria Freitas, da freguesia de Castelo Branco, que agradeço pela disponibilidade e simpatia. A peça foi executada pela sua mãe, Filomena Correia, há 8 anos quando tinha 80 anos! (...) Verificamos, de seguida, que a toalha apresenta os quatro tipos possíveis de simetria. (...) Destaca-se outro aspeto relevante que pode facilmente ser comprovado com recurso a um espelho: por cada centro de ordem 4 passam quatro eixos de simetria (representados por linhas contínuas em C) e por cada centro de ordem 2 passam dois eixos de simetria. Ficam, assim, caracterizadas as simetrias de reflexão. Resta identificar as simetrias de reflexão deslizante. Ora, estas estão associadas aos eixos de deslocamento representados a tracejado em C: por cada centro de rotação de ordem 2 passam dois eixos de deslocamento. Identifica-se em D um desses eixos de deslocamento: há uma reflexão seguida de uma translação de vetor paralelo ao eixo. Ao fixar o olhar ao longo do eixo de deslocamento, é possível verificar que os losangos alternam sucessivamente de posição, algo semelhante às marcas das nossas pegadas quando caminhamos descalços na areia. (...)

Reproductive dynamics of Sterna hirundinacea Lesson, 1831 in Ilha dos Cardos, Santa Catarina, Brazil

In this work, we intend to describe the reproductive dynamics of Sterna hirundinacea in an island fromSouth Brazil.We studied the reproductive biology of this species in its natural environment and provide data on their growth, survival, and reproductive success in Ilha dosCardos, SantaCatarina, South Brazil. Samplingswere carried out daily on the island throughout the reproductive seasons of 2003, 2005, and 2006 and the different stages of development of the chicks were characterized according to age, length of the beak, and plumage characteristics.We provide a basic equation Lm = 167.91 (1 – e −0.062t−(−0.23)) to determine the approximate age of individuals using their body mass. The main cause of chick mortality on the island was natural (63.17% in 2003, 81.41% in 2005, and 79.96% in 2006), whereas predation contributed to mortality in a proportion of 38.83% in 2003, 18.59% in 2005, and 20.04% in 2006.The absence in the area of the chicks’ main predator, Kelp gull (Larus dominicanus), the large number of chicks that reached the final stages of development, and their reproductive success demonstrate that Ilha dos Cardos is an important breeding site for the species in southern Brazil.