Development of novel active pharmaceutical ionic liquids and salts based on antibiotics and anti-fungal drugs

Ionic Liquids (ILs) are class of compounds, which have become popular since the mid-1990s. Despite the fact that ILs are defined by one physical property (melting point), many of the potential applications are now related to their biological properties. The use of a drug as a liquid can avoid some problems related to polymorphism which can influence a drug´s solubility and thus its dosages. Also, the arrangement of the anion or cation with a specific drug might be relevant in order to: a) change the correspondent biopharmaceutical drug classification system; b) for the drug formulation process and c) the change the Active Pharmaceutical Ingredients’ (APIs). The main goal of this Thesis is the synthesis and study of physicochemical and biological properties of ILs as APIs from beta-lactam antibiotics (ampicillin, penicillin G and amoxicillin) and from the anti-fungal Amphotericin B. All the APIs used here were neutralized in a buffer appropriate hydroxide cations. The cation hydroxide was obtained on Amberlite resin (in the OH form) in order to exchange halides. The biological studies of these new compounds were made using techniques like the micro dilution and colorimetric methods. Overall a total of 19 new ILs were synthesised (6 ILs based on ampicillin, 4 ILs, based on amoxicillin, 6 ILs based on penicillin G and 4 ILs based on amphotericin B) and characterized by spectroscopic and analytical methods in order to confirm their structure and purity. The study of the biological properties of the synthesised ILs showed that some have antimicrobial activity against bacteria and yeast cells, even in resistant bacteria. Also this work allowed to show that ILs based on ampicillin could be used as anti-tumour agents. This proves that with a careful selection of the organic cation, it is possible to provoke important physico-chemical and biological alteration in the properties of ILs-APIs with great impact, having in mind their applications.

Context-based identification of energy consumption in industrial plants

Nowadays, reducing energy consumption is one of the highest priorities and biggest challenges faced worldwide and in particular in the industrial sector. Given the increasing trend of consumption and the current economical crisis, identifying cost reductions on the most energy-intensive sectors has become one of the main concerns among companies and researchers. Particularly in industrial environments, energy consumption is affected by several factors, namely production factors(e.g. equipments), human (e.g. operators experience), environmental (e.g. temperature), among others, which influence the way of how energy is used across the plant. Therefore, several approaches for identifying consumption causes have been suggested and discussed. However, the existing methods only provide guidelines for energy consumption and have shown difficulties in explaining certain energy consumption patterns due to the lack of structure to incorporate context influence, hence are not able to track down the causes of consumption to a process level, where optimization measures can actually take place. This dissertation proposes a new approach to tackle this issue, by on-line estimation of context-based energy consumption models, which are able to map operating context to consumption patterns. Context identification is performed by regression tree algorithms. Energy consumption estimation is achieved by means of a multi-model architecture using multiple RLS algorithms, locally estimated for each operating context. Lastly, the proposed approach is applied to a real cement plant grinding circuit. Experimental results prove the viability of the overall system, regarding both automatic context identification and energy consumption estimation.

Quadrature generators based on ring oscillators and shift registers

Quadrature oscillators are key elements in modern radio frequency (RF) transceivers and very useful nowadays in wireless communications, since they can provide: low quadrature error, low phase-noise, and wide tuning range (useful to cover several bands). RC oscillators can be fully integrated without the need of external components (external high Q-inductors), optimizing area, cost, and power consumption. The conventional structure of ring oscillator offers poor frequency stability and phasenoise, low quality factor (Q), and besides being vulnerable to process, voltage and temperature (PVT) variations, its performance degrades as the frequency of operation increases. This thesis is devoted to quadrature oscillators and presents a detailed comparative study of ring oscillator and shift register (SR) approaches. It is shown that in SRs both phase-noise and phase error are reduced, while ring oscillators have the advantage of occupying less area and less consumption due to the reduced number of components in the circuit. Thus, although ring oscillators are more suitable for biomedical applications, SRs are more appropriate for wireless applications, especially when specification requirements are more stringent and demanding. The first architecture studied consists in a simple CMOS ring oscillator employing an odd number of static single-ended inverters as delay cells. Subsequently, the quadrature 4-stage ring oscillator concept is shown and post-layout simulations are presented. The 3 and 4-phase single-frequency local oscillator (LO) generators employing SRs are presented, the latter with 50% and 25% duty-cycles. The circuits operate at 600 MHz and 900 MHz, and were designed in a 130 nm standard CMOS technology with a voltage supply of 1.2 V.

Field-effect transistors based on Zinc oxide nanoparticles

This work reports the development of field-effect transistors (FETs), whose channel is based on zinc oxide (ZnO) nanoparticles (NPs). Using screen-printing as the primary deposition technique, different inks were developed, where the semiconducting ink is based on a ZnO NPs dispersion in ethyl cellulose (EC). These inks were used to print electrolyte-gated transistors (EGTs) in a staggered-top gate structure on glass substrates, using a lithium-based polymeric electrolyte. In another approach, FETs with a staggered-bottom gate structure on paper were developed using a sol-gel method to functionalize the paper’s surface with ZnO NPs, using zinc acetate dihydrate (ZnC4H6O4·2H2O) and sodium hydroxide (NaOH) as precursors. In this case, the paper itself was used as dielectric. The various layers of the two devices were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR), thermogravimetric and differential scanning calorimetric analyses (TG-DSC). Electrochemical impedance spectroscopy (EIS) was used in order to evaluate the electric double-layer (EDL) formation, in the case of the EGTs. The ZnO NPs EGTs present electrical modulation for annealing temperatures equal or superior to 300 ºC and in terms of electrical properties they showed On/Off ratios in the order of 103, saturation mobilities (μSat) of 1.49x10-1 cm2(Vs)-1 and transconductance (gm) of 10-5 S. On the other hand, the ZnO NPs FETs on paper exhibited On/Off ratios in the order of 102, μSat of 4.83x10- 3 cm2(Vs)-1and gm around 10-8 S.

Engineering bio-based polymers using alternative solvents and processes

The work presented in this thesis explores novel routes for the processing of bio-based polymers, developing a sustainable approach based on the use of alternative solvents such as supercritical carbon dioxide (scCO2), ionic liquids (ILs) and deep eutectic solvents (DES). The feasibility to produce polymeric foams via supercritical fluid (SCF) foaming, combined with these solvents was assessed, in order to replace conventional foaming techniques that use toxic and harmful solvents. A polymer processing methodology is presented, based on SCF foaming and using scCO2 as a foaming agent. The SCF foaming of different starch based polymeric blends was performed, namely starch/poly(lactic acid) (SPLA) and starch/poly(ε-caprolactone) (SPCL). The foaming process is based on the fact that CO2 molecules can dissolve in the polymer, changing their mechanical properties and after suitable depressurization, are able to create a foamed (porous) material. In these polymer blends, CO2 presents limited solubility and in order to enhance the foaming effect, two different imidazolium based ILs (IBILs) were combined with this process, by doping the blends with IL. The use of ILs proved useful and improved the foaming effect in these starch-based polymer blends. Infrared spectroscopy (FTIR-ATR) proved the existence of interactions between the polymer blend SPLA and ILs, which in turn diminish the forces that hold the polymeric structure. This is directly related with the ability of ILs to dissolve more CO2. This is also clear from the sorption experiments results, where the obtained apparent sorption coefficients in presence of IL are higher compared to the ones of the blend SPLA without IL. The doping of SPCL with ILs was also performed. The foaming of the blend was achieved and resulted in porous materials with conductivity values close to the ones of pure ILs. This can open doors to applications as self-supported conductive materials. A different type of solvents were also used in the previously presented processing method. If different applications of the bio-based polymers are envisaged, replacing ILs must be considered, especially due to the poor sustainability of some ILs and the fact that there is not a well-established toxicity profile. In this work natural DES – NADES – were the solvents of choice. They present some advantages relatively to ILs since they are easy to produce, cheaper, biodegradable and often biocompatible, mainly due to the fact that they are composed of primary metabolites such as sugars, carboxylic acids and amino-acids. NADES were prepared and their physicochemical properties were assessed, namely the thermal behavior, conductivity, density, viscosity and polarity. With this study, it became clear that these properties can vary with the composition of NADES, as well as with their initial water content. The use of NADES in the SCF foaming of SPCL, acting as foaming agent, was also performed and proved successful. The SPCL structure obtained after SCF foaming presented enhanced characteristics (such as porosity) when compared with the ones obtained using ILs as foaming enhancers. DES constituted by therapeutic compounds (THEDES) were also prepared. The combination of choline chloride-mandelic acid, and menthol-ibuprofen, resulted in THEDES with thermal behavior very distinct from the one of their components. The foaming of SPCL with THEDES was successful, and the impregnation of THEDES in SPCL matrices via SCF foaming was successful, and a controlled release system was obtained in the case of menthol-ibuprofen THEDES.

Garland, since 1776- a unique ownership structure

The case is based on Garland, a 240 years old Portuguese family business, now owned by the Dawson family. It focuses on a decision made 50 years ago, aligned with what had been the company’s history, about the ownership rules for family members, which influences the ownership structure of the firm. It addresses the main issues about ownership in family businesses, and tackles the problem of succession planning and fair process. It contains a teaching note to support the utilization of the case in a classroom context, with learning objectives, target audience, a teaching plan, questions and proposed answers, and theory that relates to the case. It is also complemented with an epilogue and an overview of the case.