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.

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.

Determinação preliminar de parâmetros construtivos de barreiras reactivas permeáveis com recurso a colunas para remediação de crómio com ferro zerovalente

Um dos principais problemas com que se deparam as sociedades actuais, e que é consequência da sua forma de se organizar prende-se com a mudança das características originais dos locais onde habitam e dos seus componentes como resultado das actividades humanas que transformam solos e águas em depósitos de resíduos. Entre as substâncias que são depositadas no meio físico, que requerem especial atenção, encontra-se o grupo dos metais pesados, uma vez que são considerados como perigosos pela sua toxicidade e potencial cancerígeno quando em contacto com populações ou ecossistemas. Destes metais, o crómio é um dos metais que requer especial atenção devido a sua relativa abundância como contaminante, e à periculosidade dos seus iões, em especial o Cr6+. Este trabalho pretende contribuir para o conhecimento dos fenómenos geoambientais associados à remediação de águas contaminadas com Cr6+ recorrendo ao ferro monovalente de forma a estabelecer parâmetros de aplicabilidade através de estudos laboratoriais baseados em ensaios em colunas.

Evaluation of solubility and partition properties of ampicillin-based ionic liquids

In order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), herein we explore a modular ionic liquid synthetic strategy for improved APIs. Ionic liquids containing l-ampicillin as active pharmaceutical ingredient anion were prepared using the methodology developed in our previous work, using organic cations selected from substituted ammonium, phosphonium, pyridinium and methylimidazolium salts, with the intent of enhancing the solubility and bioavailability of l-ampicillin forms. In order to evaluate important properties of the synthesized API-ILs, the water solubility at 25 °C and 37 °C (body temperature) as well as octanol–water partition coefficients (Kow's) and HDPC micelles partition at 25 °C were measured. Critical micelle concentrations (CMC's) in water at 25 °C and 37 °C of the pharmaceutical ionic liquids bearing cations with surfactant properties were also determined from ionic conductivity measurements.

Sistema de busca e salvamento baseado em múltiplos veículos terrestres

Esta dissertação visa o desenvolvimento de um sistema de busca e salvamento baseado em múltiplos veículos terrestres, utilizando para tal os veículos LINCE do Laboratório de Sistemas Autónomos. Tendo como principal propósito conferir autonomia aos veículos, foram estudados possíveis cenários de actuação, para determinar as principais funcionalidades requeridas do sistema. Foram também estudadas metodologias de análise e caracterização de sistemas multirobóticos, baseadas no estado da arte existente, e foi elaborada a arquitectura conceptual do sistema e dos veículos a desenvolver. A preparação dos veículos abordou o estudo das possíveis soluções sensoriais e de actuação, e o desenvolvimento de uma arquitectura de hardware capaz de interligar todos os periféricos dos mesmos. Foram adaptados novos sensores e actuadores, e desenvolvidos alguns desses sensores. Para a interligação e manutenção dos mesmos foram ainda desenvolvidos novos periféricos de interface e controlo, e periféricos de gestão de energia. Por fim, foi ainda adaptado um gestor de missões nos veículos, capaz de receber a especificação das mesmas.

Copper, nickel and zinc removal by peanut hulls: batch and column studies in mono, tri-component systems and with real effluent

The main goal of this research study was the removal of Cu(II), Ni(II) and Zn(II) from aqueous solutions using peanut hulls. This work was mainly focused on the following aspects: chemical characterization of the biosorbent, kinetic studies, study of the pH influence in mono-component systems, equilibrium isotherms and column studies, both in mono and tri-component systems, and with a real industrial effluent from the electroplating industry. The chemical characterization of peanut hulls showed a high cellulose (44.8%) and lignin (36.1%) content, which favours biosorption of metal cations. The kinetic studies performed indicate that most of the sorption occurs in the first 30 min for all systems. In general, a pseudo-second order kinetics was followed, both in mono and tri-component systems. The equilibrium isotherms were better described by Freundlich model in all systems. Peanut hulls showed higher affinity for copper than for nickel and zinc when they are both present. The pH value between 5 and 6 was the most favourable for all systems. The sorbent capacity in column was 0.028 and 0.025 mmol g-1 for copper, respectively in mono and tri-component systems. A decrease of capacity for copper (50%) was observed when dealing with the real effluent. The Yoon-Nelson, Thomas and Yan’s models were fitted to the experimental data, being the latter the best fit.

Novel potentiometric sensors of molecular imprinted polymers for specific binding of chlormequat

Molecularly imprinted polymers (MIP) were used as potentiometric sensors for the selective recognition and determination of chlormequat (CMQ). They were produced after radical polymerization of 4-vinyl pyridine (4-VP) or methacrylic acid (MAA) monomers in the presence of a cross-linker. CMQwas used as template. Similar nonimprinted (NI) polymers (NIP) were produced by removing the template from reaction media. The effect of kind and amount of MIP or NIP sensors on the potentiometric behavior was investigated. Main analytical features were evaluated in steady and flow modes of operation. The sensor MIP/4-VP exhibited the best performance, presenting fast near-Nernstian response for CMQover the concentration range 6.2×10-6 – 1.0×10-2 mol L-1 with detection limits of 4.1×10-6 mol L-1. The sensor was independent from the pH of test solutions in the range 5 – 10. Potentiometric selectivity coefficients of the proposed sensors were evaluated over several inorganic and organic cations. Results pointed out a good selectivity to CMQ. The sensor was applied to the potentiometric determination of CMQin commercial phytopharmaceuticals and spiked water samples. Recoveries ranged 96 to 108.5%.

Characterizations of power indices based on null player free winning coalitions

In this paper, we characterize two power indices introduced in [1] using two different modifications of the monotonicity property first stated by [2]. The sets of properties are easily comparable among them and with previous characterizations of other power indices.

Membrane design and characterisation by incorporation of ionic liquids

Dissertação apresentada para obtenção do Grau de Doutor em Engenharia Química, especialidade de Operações Unitárias e Fenómenos de Transferência, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Seqins: a sequencing tool for educational resources

The teaching-learning process is increasingly focused on the combination of the paradigms “learning by viewing” and “learning by doing.” In this context, educational resources, either expository or evaluative, play a pivotal role. Both types of resources are interdependent and their sequencing would create a richer educational experience to the end user. However, there is a lack of tools that support sequencing essentially due to the fact that existing specifications are complex. The Seqins is a sequencing tool of digital resources that has a fairly simple sequencing model. The tool communicates through the IMS LTI specification with a plethora of e-learning systems such as learning management systems, repositories, authoring and evaluation systems. In order to validate Seqins we integrate it in an e-learning Ensemble framework instance for the computer programming learning.

Alteration and alterability of the anorthosite from Angola

Siliceous rocks are widely used as dimension stone but the last decades have registered an increase rate of their alteration when exposed to polluted environments. Anorthosites were treated by acidified solutions of HCl, HN03 and H2S04 simulating acid rain and the response was recorded through different experiments such as on the surface of the polished rock and on the surface of uncovered thin sections. The main components, plagioclase and olivine, both responded in similar ways to each acid solution, although following different trends; while plagioclase develops a thin layer which acts as protection to the mineral, olivine at first undergoes alteration due to leaching of magnesium and iron and in a following stage, is mechanically removed from the rock. The action of warm water on the rock was tested through the use of the Soxhlet extractor which caused changes on the rock colour and leaching of several cations from its components.

Silver coordination polymers with tri- and hexacyanoethyl-functionalized macrocyclic ligands

Tri-and hexa-cyanoethyl functionalized 17-(L-1) and 42-membered (L-2) macrocyclic compounds were obtained by [1 + 1] (for L-1) or [2 + 2] (for L-2) cyclocondensation of the corresponding dialdehyde and diethylenetriamine, followed by hydrogenation by KBH4 and subsequent cyano-functionalization with acrylonitrile. They react with silver nitrate, leading to the formation of [AgL1](NO3) (1) and of the metalorganic coordination polymers [Ag-2(NO3)(2)L-1](n) (2) and {[Ag2L2](NO3)(2)}(n) (3). The complexes were characterized by elemental analysis, H-1 NMR, C-13 NMR, IR spectroscopies, and ESI-MS; moreover, L-2, 1, 2 and 3 were also characterized by single crystal X-ray diffraction. The metal cation in 1 is pentacoordinated with a N3O2 coordination environment; in 2, the metal cations display N4O2 octahedral and N2O3 square-pyramid coordination and in 3 they are in square-planar N-4 sites. In 1, the ligand acts as a pentadentate chelator, and in the other two cases, the ligands behave as octadentate chelators in a 1 kappa N-3:kappa O-2,2 kappa N,3 kappa N,4 kappa N (in 2) or 1 kappa N-3,2 kappa N-3,3 kappa N,4 kappa N fashion (in 3). The cyanoethyl strands of the ligands are directly involved in the formation of the 2D frameworks of 2 and 3, which in the former polymer can be viewed as a net composed of hexametallic 36-membered macrocyclic rings and in the latter generates extra hexametallic 58-membered cyclic sets that form zig-zag layers. The thermal analytical and electrochemical properties of these silver complexes were also studied.

Phase behaviour of alternative solvents

Dissertation presented to obtain the Ph.D. degree in Chemistry (Physical Chemistry) at the Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa

Electron driven reactions in complexes embedded in superfluid helium droplets

A thesis submitted to the University of Innsbruck for the doctor degree in Natural Sciences, Physics and New University of Lisbon for the doctor degree in Physics, Atomic and Molecular Physics