LAQV Requimte Projects

PhD Projects for Research Scholarships Application LAQV Requimte

Supervisors: Joana Alexandra da Silva Oliveira Pinto da Silva (Laboratório Associado para Química Verde - REQUIMTE, Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto) and Nuno Miguel Jesuíno Basílio (Laboratório Associado para a Química verde – REQUIMTE, Departamento de Química da Universidade Nova de Lisboa).

Project Title: DEEPER – DEveloping new photosensitizers for highly Effective Photodynamic thERapy: from synthesis to target delivery.

Summary:

Squamous cell carcinoma (SCC) is the second most common type of non-melanoma skin cancer, with an incidence that has been rising 3-10% per year. The treatment at early stages, such as of pre-cancer lesions as actinic keratosis (AK), is required once SCC has the ability to spread and form metastases in deeper layers of skin and spread to distant organs. Photodynamic therapy (PDT) has being extensively studied due to its efficiency in destroying cancer cells with several advantages that are not observed in the current therapies, including low side effects and invasiveness. In PDT, a photosensitizer (PS) is activated with red light (600-800 nm) to produce singlet oxygen that locally destroys cancer cells. The major research problem is to find compounds that can be qualified as an ideal PS for PDT, which would ensure a highly successful therapy. Nevertheless, this remains unsolved since there are no current compounds with such photochemical features. DEEPER proposes to obtain new porphyrins conjugates using a class of anthocyanin-derived compounds, with a high absorption band of the red light and, consequently, with improved photoactivation features for PDT. This project also aims to manage the delivery of the PS conjugates to pre-cancer (AK) and cancer skin cells (SCC) using two different strategies: their chemical lipophilization using fatty acids and their encapsulation by functionalized nanoparticles, so we can specifically deliver PSs to the target cells, with increased efficacy and safety. DEEPER will impact the chemistry field, contributing to custom made new PSs with a high photo-toxicity and selectivity to SCC, and the biological field, with insights of the behaviour of PSs in biological environments. Given that cutaneous SCC is one of the most aggressive and metastatic kind of non-melanoma skin cancer, DEEPER will ultimately and significantly contribute to improve the treatment of SCC by increasing the exploitation of PDT as a first-line treatment.

Supervisors: Leandro Miguel de Oliveira Lourenço (University of Aveiro) and José Enrique Rodríguez-Borges (University of Porto).

Project Title: Versatile porphyrin- and phthalocyanine-cyclodextrin derivatives for photodynamic therapy against cancer cells.

Summary:

This Ph.D. project aims to find different approaches to combat diseases that are being worldwide studied, such as cancer caused by changes (mutations) to the DNA within cells. The goal is to develop an effective treatment with no adverse effects for healthy cells and tissues. Photodynamic Therapy (PDT), through the combination of a photosensitizer (PS), light and reactive oxygen species (ROS), has shown very promising results in cancer, macular degeneration and infections caused by microorganisms through the biodistribution of targets located in real time and in situ. In addition to being used as a treatment, PDT can be used as a means of diagnosis because it is possible to track the actual location of the PS drug activated by light irradiation. Currently, porphyrin (Por) and phthalocyanine (Pc) compounds have been described in the treatment of cancer through PDT. However, selectivity and interaction with carcinogenic cells are the biggest challenge, so we propose a new generation of photosensitizers of derivatives of these compounds, hoping to combat some gaps. To achieve this goal, the candidate will design, prepare and structurally characterize new molecules of Por / Pc with cyclodextrin (CD) units and subsequently apply them against cancer cells with high selectivity/affinity to kill them.

Supervisors: João Sotomayor (NOVA FCT) and Elisabete da Palma Carreiro (Universidade de Évora).

Project Title: Digital Optical Memories based on printed PDLC films.

Summary:

The main objective of this project is the production of dispersed polymer / liquid crystal (LC) systems as inclusion, by printing on substrates by microlithography. With LC molecules impregnated into the polymer, the system exhibits high hysteresis properties, known as permanent memory (PME) effect. Heretofore our results show examples in which a PME value of about 100% is observed. In these devices, digital information (opaque / transparent state) can be electrically written into pixels formed by these chemical systems, read through the transmittance difference of the pixels and erase the written information by thermally promoting the initial random reorientation of the LC molecules with no energy expenditure during the whole memory state. The project will begin with the synthesis of new monomers, (Task 1), followed by the polymerization in composites with LC (Task 2), by spectroscopic characterization to identify phase changes, microscopic characterization to monitor the LC domain and matrix morphology, and electro-optical characterization (Task 3). The films will be tested in an electro-optical and heating system (Task 4), which will allow to optimize the memory effect. At the same time, ITO and indium oxide deposition processes will be developed on glass and plastic substrates, with and without alignment layer for the LC, either planar alignment or homeotropic alignment, to form out-of-plane and in-plane electrodes, (Task 5), processes that will be optimized against the electro-optical response obtained (Task 6).
The present proposal brings together different research teams with experience in organic synthesis, liquid crystals, spectroscopy and calorimetry, electro-optical properties and deposition techniques of fine films of oxides and materials by microlithography. These studies represent a new strategy for producing films, printed on several possible substrates, to be used as digital optical information storage systems.

Supervisors: Cristina Maria Cordas (LAQV, REQUIMTE, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa) and Susana Maria Santos Rocha (LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto).

Project title: Green energy and added-value chemical production via enzymatic fuel cells working with biomass degradation.

Summary:

Two groups from LAQV, with common interests, join their expertise to purpose the construction of a novel EFC for the production of energy from biomass waste, using LPMO (and associated peroxidases and laccases) and modified electrodes (enzyme immobilization). The proposed “macro” and “micro” approaches will enable to study the viability of the enzymes modified electrodes and EFC efficiency in a normal (“macro”) size biofuel cell (FCT-NOVA) and in microfluidic EFC (FF, UP). Different industrial interests are envisaged namely the producing of in-situ energy in micro devices (“micro”) to the bioproduction of added-value compounds using similar technology (“macro”). Also, different low-cost materials as supports for bio-cathodes and bio-anodes will be used to be embedded in the “micro” approach through the microfluidic platforms. Amongst these is the use of impermeabilized paper coated with carbon nanoparticles. The immobilization procedures will be modelled and characterized by microscopy, ellipsometry and impedance spectroscopy, amongst others. The proposal is aligned with the Sustainable Chemistry research of LAQV, REQUIMTE and in particular with the Research Centre thematic lines of Clean Energy, Functional Materials and Resource Efficiency.

Supervisors: Susana Isabel Fonseca de Almeida Santos Braga (LAQV-REQUIMTE & Departamento de Química da Universidade de Aveiro) and Cláudia Daniela Oliveira de Lacerda Nunes Pinho (LAQV-REQUIMTE & Departamento de Ciências da Vida, Faculdade de Farmácia da Universidade do Porto).

Project title: Ruthenium-based leishmanicidals with improved medicinal activity.

Summary:

Leishmaniasis is a vector-borne parasitosis endemic to most tropical countries and classified as a neglected tropical disease. It affects a large number of people, not only in endemic but also in other countries, accounting for roughly one and a half billion new cases each year worldwide. Leishmaniasis poses growing concern due to the limited number and aggressiveness of available therapeutics and to the increase in the area of distribution of the vector due to global warming. The present work aims at developing therapeutic solutions for leishmaniasis with higher specificity of action than the current ones. A two-step strategy will be followed, with the first step comprising in the preparation and selection of Ru(II) complexes drug candidates. The complexes will feature active ligands from two different classes: 3,5-disubstituted pyrazoles, based on known leishmanicidal pharmacophores, and steroids, to damage the steroid metabolism and functionality by targeting lipid rafts and/or steroid biosynthesis. The preparation will employ, preferably, environmentally friendly methods and non-toxic solvents. The leishmanicidal activity of the molecules will be tested to select the most active ones. The second step will comprise the loading of selected Ru(II) complexes into rationally designed targeted lipid based nanocarriers, to selectively enable their entry into parasite-infected immune cells and thus increase their activity and decrease off-target effects.
At the end of the work, we expect to have a library of molecules with well-known activity and to demonstrate their medicinal value through adequate result dissemination, thus contributing to their translation into the clinics.

Supervisors: Diana Cláudia Pinto (Departamento de Química da Universidade de Aveiro) and Célia Gomes Amorim (Faculdade de Farmácia da Universidade do Porto).

Project Title: New non-toxic siderophore complexes for filtration and monitorization of iron in the water.

Summary:

Iron is a very abundant element in the Earth's crust, especially iron(III). Iron is essential for many known living organisms though its availability is limited by the very low solubility of the surficial iron(III) compounds. Although iron is essential to human and vertebrate health, its excess results in several diseases, being necessary to find mechanisms to its depletion. The average lethal dose of iron is 200–250 mg/kg of body weight, but death has occurred following the ingestion of lower doses. Concentrations of iron in drinking-water typically are less than 0.3 mg/L. They may be higher in countries where various iron salts are used as coagulating agents in water-treatment plants and cast iron, steel, and galvanized iron pipes for water distribution. Considering the main daily iron intakes by food and by drinking-water, iron must be controlled, namely in geographical regions where drinkable water is scarce due to its high levels. Hence, this project aims to synthesize new non-toxic compounds to chelate iron ions (II and III) selectively and to immobilizing them in polymeric filtration membranes for water treatment. Earlier works show that pyridoxal isonicotinoyl hydrazone (PIH), salicylaldehyde isonicotinoyl hydrazone (SIH), and acetohydroxamic acid (AHA) are siderophores from the hydroxamate type that have formation constants much higher for iron(III) than for iron(II), calcium, and magnesium. For that, changes in the siderophore's chemical structure will be done to improve the formation constant for iron(II). After siderophores characterization, concerning mainly the determination of the formation constants with iron ions, the solubility in aqueous solutions, and the determination of log P, the compounds will be used to prepare polymeric filtration membranes for water treatment. The ones that have lower formation constants will be evaluated as ionophores for iron(III) selective electrodes to monitor the water treatment process.

Supervisors: Susana Soares (REQUIMTE/LAQV - Faculdade de Ciências Universidade do Porto), Elisabete Coelho (REQUIMTE/LAQV - Universidade de Aveiro) and Victor de Freitas (Faculdade de Ciências da Universidade do Porto).

Project Title: Astringency modulation to make heathy foods tasty: the match between phenolic compounds and polysaccharides.

Summary:

Phenolic compounds are one of the most important plant compounds contributing both to the health properties as well as to the undesirable taste properties, in particular astringency and bitter taste. The unpleasant taste properties create a challenge to the food industry since marketing studies show that taste, no matter the health benefits, is the key to food choices by consumers. The big challenge is to develop strategies to turn healthy food taste better. Within this challenge, polysaccharides are a promising tool. Polysaccharides are known to interact with phenolic compounds and also to affect their interaction with salivary proteins. Therefore, polysaccharides can impact astringency and bitter taste. Polysaccharides can act by two mechanisms: can form ternary complex protein/phenolic compounds/polysaccharides which enhances solubility in an aqueous medium; or by a competition mechanism in which salivary proteins and polysaccharides compete by phenolic compounds binding. While it is known that polysaccharides can modulate these interactions, this knowledge is so far empiric. The aim of this PhD proposal is to understand the modulation of unpleasant taste (e.g. astringency and bitter taste) by the structure-activity relationship on polysaccharides effect toward salivary proteins and phenolic compounds.

Supervisores: Nuno Candeias (Universidade de Aveiro) e David Pereira (Universidade do Porto)

Título do Projecto: Novas moléculas quiméricas fenol-alcaloide com atividade anti-inflamatória: síntese e avaliação biológica.

Sumário:

Os compostos fenólicos apresentam elevada atividade biológica e conseguem, por vezes, apresentar características estruturais compatíveis com uma farmacocinética favorável. Por outro lado, os alcaloides são produtos naturais que apresentam azoto e que estão entre a classe de moléculas com maior incidência de atividade farmacológica. A reação multicomponente de Petasis boro-Mannich (rPbM) apresenta-se como uma ferramenta versátil na preparação de compostos alquilfenólicos e na sua diversificação estrutural. A possibilidade de usar solventes não voláteis ou água como meio reacional, aliada à elevada economia de átomos, ou até a utilização de métodos reacionais alternativos, fazem da rPbM uma excelente ferramenta para o desenvolvimento sustentável de princípios ativos. Este projeto pretende avaliar a atividade anti-inflamatória de compostos derivados da rPbM, identificar/otimizar os requisitos estruturais do composto-protótipo, e identificar o(s) alvo(s) biológico(s) envolvido(s). Utilizar-se-á uma biblioteca de compostos previamente construída e que engloba moléculas contendo aminas terciárias em posição benzílica, maioritariamente derivadas de heterociclos. Considerando a prevalência de unidades fenólicas e heterocíclicas de azoto em produtos naturais biologicamente ativos (i.e. polifenóis e alcaloides, respetivamente), antecipa-se com este projeto a criação de uma nova família de compostos quiméricos de inspiração em produtos naturais. Tais compostos combinarão as propriedades farmacocinéticas e farmacodinâmicas dos fenóis com a potência farmacológica dos alcaloides. O projeto irá ser desenvolvido entre o grupo NatPro (LAQV@FF-UPorto) e o MolSyn (LAQV@UAveiro), combinando expertises de ambas as instituições e grupos de investigação. Será promovida a movimentação do(a) candidato(a) entre ambas as instituições com vista ao desenvolvimento e obtenção de competências na área da síntese química e, simultaneamente, na bioquímica, biologia celular e farmacologia.

Supervisors: Elisabete Oliveira Marques (LAQV-REQUIMTE, FCT NOVA) and Maria Amparo Faustino (LAQV-REQUIMTE, Department of Chemistry, University of Aveiro).

Project Title: Porphyrin-conjugated Mesoporous Nanoparticles as dual-function carriers for drug delivery in Cancer cells And Associated Bacterial Infections.

Summary:

In the last years, nanomaterials have become one of the most promising and innovative disciplines in research, alongside chemistry and biomedicine. The search and design of complex nanostructures where are considered the combination of several types of materials, like metals, metal oxides, inorganic (i.e. silica) and organic polymers, has been a hot topic in the construction of specific target-nanocarriers for drug delivery. In particular, mesoporous silica nanoparticles are one of the appealing materials for biomedical applications due to their porosity, biocompatibility and easy functionalization. These drug nanocarriers are being explored in different types of medical applications like imaging [e.g. magnetic resonance imaging (MRI)] and therapies like Chemotherapy and Photodynamic Therapy (PDT). For instance, studies involving mesoporous silica nanoparticles conjugated to hematoporphyrin and loaded with doxorubicin demonstrated much lower cell viability compared to doxorubicin and nanocages alone. These results indicate this dual-functional nanoparticles (PDT and chemotherapy) can provide enhanced anticancer therapeutic ability and complementary imaging capacity. In chemotherapy besides the well-known side effects, the chance of patients to develop bacterial infections associated with antibiotic resistance is a real threat. Thus, the combination of antibiotics with chemotherapy could lead to serious reductions on tumor and tumor-associated bacterial activities, as well as, increasing survival rates over those of conventional therapies.
This project envisages the design and preparation of novel biocompatible Nanocarriers for healthcare applications, i.e. cancer and antibiotics resistance infections. The main aim is the development of groundbreaking precise-targeted nanoformulations, containing the most effective drug combinations (i.e. anticancer and antibiotics) to avoid resistance, and increase specific tissue distribution, in colon cancer treatment.

Supervisors: Paula Branco (FCT NOVA) and Marisa Freitas (REQUIMTE LAQV, UP).

Project Title: Phosphoglycoglycerol from Nature as model to new putative therapeutic agents .

Summary:

Phosphoglycoglycerols (PGG) have a relevant role in nature being the constituents of the cell walls and cell membranes. These compounds are formed from the condensation of ubiquitous subunits common to all living beings and are the goals on the demand for targets for therapeutic interventions. Herein, we aim to synthesize new families of PGG (unreported until the moment) and evaluate their biological activity, through the assessment of their antioxidant and anti-inflammatory activities, using in vitro microanalysis systems. The new structures come from three natural structural motives: a glycerol unit, a carbohydrate unit and a phosphate or phosphoamidate group. Initially drawn to have the α-D-galactose building block in its constitution, it can later be expanded to other saccharides as, glucose and ribose. Furthermore, several derivatives can be synthesized in order to exploit the biological activity of PGG: ethanolamine can be replaced by ethanodiol, ethanodiamine or mercaptoethanol, aminoethanethiol, choline or long fatty acid chains. Synthesis of a library of compounds that combines these three units is key of this work, which will allow SAR studies to better define their antioxidant and anti-inflammatory activities. Therefore, the main goals of this project involve: i) synthesis of phosphates or phosphoramidates compounds, ii) coupling reaction to glycerol and to the galactose moieties will endeavour a set of glycosyl phosphates and phosphoglycerols, iii) evaluation of antioxidant and anti-inflammatory activities of the synthesized phosphoglycoglycerols. The methodologies developed will allow enlarging the synthesized PGG families to glycoglycerophospholipids with all the advantages that may outcome. This work accounts for Goal 3 (Good health and well-being) of Sustainable Development Goals from UN.

Supervisors: Luísa Maia (FCT NOVA), Paula Andrade (Faculdade de Farmácia da Universidade do Porto) and Romeu Videira (Faculdade de Farmácia da Universidade do Porto).

Project Title: Salvage nitric oxide generation pathways in humans - Paving the way for innovative therapeutic approaches to cardiovascular and related diseases.

Summary:
Nitric oxide radical (NO) is a signaling molecule that controls numerous functions in humans, being a well-known key mediator in the vascular and nervous systems. The NO formation is known for long to be catalysed by specific NO synthases (NOS) and the NO lifetime is controlled by its rapid oxidation to nitrite and nitrate (Fig). More recently, a new, alternative NO source was identified that relies on the reductive nitrate-nitrite-NO pathway. Even though the enzymes responsible for these 2 reductions remain a matter of intense debate, it is widely accepted that cells can use nitrite to sustain the crucial NO generation (avoid NO deficiency) under hypoxic conditions, when the O₂-dependent NOS activity is compromised.
The identification of this salvage NO source is opening the possibility of using nitrate/nitrite as innovative drugs to target conditions associated with a decreased NO bioavailability, such as hypertension, endothelial dysfunction, ischaemia-reperfusion injury, myocardial infarction, pulmonary hypertension, asthma, chronic kidney disease or dementia. These cardiovascular and related diseases are major concerns of our western society and the identification of safer and cheaper therapeutics will have a huge beneficial impact, both in economic and health terms. However, the design of successful nitrate/nitrite-based therapeutics is being delayed by the lack of knowledge about the enzymes that catalyze the reductive NO generation and the metabolic conditions under which these salvage pathways operate in different tissues. Hence, this project aims to: (a) identify the conditions that trigger the nitrate/nitrite-dependent NO generation in human endothelial and heart cells, focusing on O₂ availability and cellular redox status; (b) identify and characterize the enzymes responsible for the conversion of nitrate/nitrite into NO in those cells; (c) evaluate the capacity of the nitrate/nitrite-dependent NO to induce vessel relaxation.

Supervisors: Anthony J. Burke (LAQV, Universidade de Évora), Andreia Filipa Ribeiro de Oliveira Peixoto (LAQV-REQUIMTE, FCUP) and João Paulo Serejo Goulão Crespo (LAQV-REQUIMTE, FCT NOVA).

Project Title: Novel Chiral Immobilized Organocatalysts for applications in Batch -, Flow- and Membrane Reactors.

Summary:

Catalysis plays a major role in the manufacture of many APIs, Agrochemicals, Fragrances and many other important products, in many cases these chemicals need to be obtained in enantiomerically pure form which requires the use of chiral chemocatalysts. Moreover, industry constantly strives to achieve this goal in the most sustainable and efficient and continuous manner possible [1]. Therefore, there is clearly the need to further improve research and development towards eco-friendly, sustainable and economically advantageous processes. One way, to achieve this objective is through catalysis involving catalysis recycling [1]. The catalyst is linked to an appropriate support (generally a solid), employed in the reaction in question and then separated from the product via simple filtration and utilized in further reactions (these supported catalysts can be used in continuous flow processes or membrane reactor systems).
We have developed a family of organocatalysts 1 (Figure 1, with a US patent for certain analogues) that have shown good application in the synthesis of chiral amines, some of which can be used to access Alzheimer’s disease drugs [2]. In this project, the goal will be the immobilization of these catalysts and others 2, via a novel immobilization strategy, followed by their application in two reactions; a) imine hydrosilylation [2] and b) Michael reactions [3]. The synthesis of these catalysts and their eventual application in the immobilized form, will be conducted in the Burke lab. These catalysts will then be immobilized to (a) suitably functionalized cellulose (organic) supports prepared in the Peixoto lab and b) to appropriate silicone carbide (inorganic) membranes that will be developed in the Crespo lab. The immobilized catalysts will be highly tuneable. The immobilized catalysts will be carefully and completely characterized, and then evaluated in the above benchmark reactions.

Supervisors: Eduarda das Graças Rodrigues Fernandes (LAQV-REQUIMTE, Faculdade de Farmácia da Universidade do Porto), Vera Lúcia Marques da Silva (LAQV-REQUIMTE, Departamento de Química, Universidade de Aveiro) and Daniela Sofia Almeida Ribeiro (LAQV-REQUIMTE, Faculdade de Farmácia da Universidade do Porto).

Project Title: Synthesis of new chalcone and styrylchromone scaffolds as an alternative research pipeline for rheumatoid arthritis treatment.

Summary:

Rheumatoid arthritis (RA) is a systemic autoimmune chronic inflammatory disease characterized by a highly coordinated inflammation of the synovial tissue in joints, joint destruction, pain and incapacity. RA represents a heavy burden in people’s life and health economy. The current therapeutics have low efficacy, hazardous side effects and are extremely expensive. Furthermore, none of them is effective enough to provide complete and life-long relief for the patients. In this sense, research pipelines for new, alternative, safer, and more affordable molecules with the ability to modulate the inflammatory process, are deemed of special interest in RA treatment. Flavonoids have long been demonstrating their anti-inflammatory potential. However, these compounds and their derivatives have been poorly studied as treatment alternatives for chronic inflammatory diseases. Thus, this project aims to synthesize new flavonoids’ derivatives, 2-styrylchromones, and flavonoids’ precursors, chalcones, with the evaluation of their anti-inflammatory activity and their potential as anti-RA drugs, in in vitro and in vivo models. This project foresees the finding of a more effective and affordable anti-RA therapy.

Supervisors: Mafalda Sofia Coelho da Cruz Sarraguça (Faculdade de Farmácia da Universidade do Porto) and Ana Rita Cruz Duarte (FCT NOVA).

Project Title: Improving paediatric formulations for the treatment of tuberculosis by a crystal engineering approach and green chemistry.

Summary:

This project aims at producing pharmaceutical cocrystals of drugs used to treat tuberculosis (TB) and develop child-friendly oral formulations with improved palatability and acceptability. The advantages of cocrystals, e.g., improved drug solubility, and/or stability, the possibility of being used as masking taste agent, are helpful to formulate improved age-appropriated formulations for TB treatment. Solvent (co-) crystallisation is still one of the most used methods in the pharmaceutical industry due to its simplicity and good results obtained. However, the use of organic toxic solvents is still an issue. The use of Deep Eutectic Solvents (DES) is a way to solve the environmental problem. Natural Deep Eutectic Solvents (NADES) are a sub-group of DES, in which their constituents are plants metabolites, such as organic salts, amino acids and sugars. The advantages of these solvents include low volatility, low melting point, biodegradability, high capacity of dissolving organic molecules, easy to prepare, stable, and low cost. In this project, NADES based on sugars will be included to prepare and to dissolve co-crystals. The use of sugars to prepare the NADES will also have a taste masking effect in the final formulation. Circa 1 million children became ill with TB and 233,000 children died of TB in 2007. Although children represent about a quarter of the global TB burden, paediatric TB R&D accounts for just 2% of the total funding. One of the identified problems is the lack of child-friendly Pharmaceutical Formulations (PFs). PFs adapted to paediatric patients need to be improved. Recently, the European Medicines Agency (EMA) and the World Health Organization (WHO) issued guidelines concerning the need of medicines design especially for children, increasing awareness and encouraging research on the paediatrics’ drug delivery filed.

Supervisors: Cristina Maria Fernandes Delerue Alvim de Matos (REQUIMTE|LAQV-ISEP (GRAQ)), Pedro Fontes Oliveira (REQUIMTE|LAQV-UA (Bio)Chemistry & Omics groups)) and Maria de Fátima de Sá Barroso (REQUIMTE|LAQV-ISEP (GRAQ)).

Project Title: Electrochemical MultiSNPgenosensor applied to cardiovascular pharmacogenetic: Detection of polymorphisms associated to the therapeutically response of the antithrombotic agents’ warfarin and clopidogrel.

Summary:

Cardiovascular diseases (CVD) are the lead cause of mortality and disability worldwide. Every year, about 32.4 million CVD´s events occur, being the myocardial infarctions and strokes the most reported cases. To combat CVD, two anticoagulants agents are being prescribed: warfarin and clopidogrel. Nevertheless, both agents present narrow therapeutic windows due to patient age, size, nutritional status, organ function and genetic factors, namely single nucleotide polymorphisms (SNP). Three genes have been identified as the main genetic determinants to warfarin and clopidogrel sensitivity: the CYP2C9, VKORC1 and CYP2C19 genes. These genes have been identified as major pharmacogenetic markers. This project proposes the development of low-cost advanced electrochemical paper-based analytical devices (ePAD) to answer the demands on multitarget DNA analysis able to determine genetic variables, namely SNP, related to this therapy. The proposed multitarget DNA detection will be based on several genosensors design assembled in innovative ePAD. This cost-effective platform will allow the simultaneous screening of several SNP in one assay, moreover, the simple design, small dimension and low power requirement are added advantages. To meet the challenges of sensitivity, the electrochemical signal amplification of the genosensors will be performed using quantum dots: CdSe/ZnS. Results will be validated using PCR-amplified DNA samples. This application presents for the first time a new device useful to health workers, by performing pharmacogenetic testes that allow to genotype a patient to estimate the dose to be administered. Besides, this proposal highlights the use of non-invasive biomarkers (e.g. tears/saliva) and the design of a cost-effective paper platform.

Supervisors: M. Beatriz P. P. Oliveira (REQUIMTE-LAQV, FFUP), Manuel António Coimbra (REQUIMTE-LAQV, Universidade de Aveiro) and Rita Carneiro Alves (REQUIMTE-LAQV, Universidade do Porto).

Project Title: Towards a deep knowledge of coffee silverskin composition in view of its valorization.

Summary:

Silverskin (CS) is the major by-product of coffee roasting, with 300 t/year produced by this industry, just in Portugal. Currently, CS is used as firelighters or dispatched for landfills, but as a relevant source of nutrients and bioactive compounds, it deserves innovative applications to increase its value. Previous studies show its richness in dietary fiber and antioxidants. Although it is known that the coffee bean composition varies according to the species, the influence of this factor on CS characteristics has been poorly studied. Moreover, as far as we know, the influence of the type of production (conventional or organic) has not been explored till the date. Having in view the valorization of this by-product, it is essential to know the factors that influence its chemical composition. The aim of this work is to ascertain the influence of the species and type of production on the CS composition. Taking advantage of an already existent collaboration with coffee industry, CS samples will be obtained from the roast of different commercial coffee blends, species and types of production. Their nutritional composition, caffeine and 5-hydroxymethulfurfural contents, free and total amino acids, vitamin E, and phenolics profile will be assessed at FFUP. Minerals, melanoidins, and carbohydrates structures will be analysed at UA. Moreover, structural modifications due to industrial thermal processing will be also studied to find structure-function relationships. Statistical tools will be used to compare data and discriminate samples.
In sum, the expected impact of this application remains in finding ways to valorize CS. By this way, an environmental challenge might become an economic opportunity, according to the principles of circular economy. Moreover, the proposed project is totally integrated in the scientific strategy of the host institution, since food quality, safety, and sustainability are areas in which REQUIMTE/LAQV is focused.

Supervisors: Samuel Guieu (Chemistry Department, Universidade de Aveiro) and Maria Manuel B. Marques (FCT NOVA).

Project Title: Exploiting tunable functionalization of heterocycles for the future generation of organic lightning devices.

Summary:

The efficiency of currently used organic light emitting diodes is intrinsically limited, because the electric energy collected by the organic fluorophores cannot be entirely converted into light. One way to overcome this limitation is to use organic fluorophores presenting thermally activated delayed fluorescence, a phenomenon which allows the dye to collect thermal energy, in order to cross from the excited triplet state to the excited singlet state and emit from there. Such organic fluorophores usually rely on carbazoles as key substituents, but the derivatives available are limited, which restrains the accessible substitution patterns, and indoles or azaindoles have rarely been used. As a consequence, the luminescent devices built with these dyes are limited in color. Therefore, the implementation of synthetic strategies toward substituted (aza)indoles and (aza)carbazoles is a necessary step in order to improve the efficacy of these luminescent devices. In addition, these strategies should be sustainable and scalable. During this project, highly substituted indoles, azaindoles and carbazoles will be synthesized, following one-pot synthetic strategies developed in our team. New strategies will also be implemented, in order to turn the synthesis more selective, more versatile, and more environmentally friendly. These building blocks will then be used in the synthesis of fluorophores bearing different substituents, to fine-tune their photophysical properties, which will be characterized and evaluated. Finally, a simple electroluminescent device will be built using the most promising dyes as emitting layer, as a proof of concept, to demonstrate the potential of these new dyes.
If successful, these dyes are expected to be used in the next generation of organic lightning devices, overcoming the drawbacks of the devices currently on the market.

Supervisors: Clara Isabel Barbosa Rodrigues Pereira (FCUP), César António Tonicha Laia (FCT NOVA) and André Miguel Trindade Pereira (FCUP).

Project Title: Advanced Multifunctional Nanocomposites for a new Generation of Flexible and Wearable All-in-One Electrochromic Supercapacitor Technologies.

Summary:

In the era of the Internet of Things (IoT) and with the escalating growth of wearable technologies market, the development of clean and safe energy storage devices became a major priority. Supercapacitors (SCs) are a greener and safer energy storage solution when compared to batteries, presenting longer cycle life and faster charging. One of the current challenges relies on the development of smart SC technologies with sensing properties, which are able to store energy and, at the same time, can exhibit an optical change upon variations in the level of stored energy, to monitor in real-time energy consumption. The hybridization of SCs and electrochromic (EC) technologies in a single multi-tasking more compact device – electrochromic supercapacitor (ECSC) – emerged as a promising strategy to meet the demands of the next-generation of multifunctional miniaturized/wearable electronics. The design of flexible ECSCs integrated in textiles or directly produced as fabrics is now a major challenge. In this project, new efficient, lightweight and multicolored all-in-one flexible and wearable ECSCs will be developed through scalable eco-sustainable processes. To achieve that goal, multifunctional nanomaterials and nanocomposites with synergistically enhanced electrical conductivity, electrochromism and/or pseudocapacitance will be produced by combination of non-toxic carbon nanomaterials, redox-active metal oxide nanoparticles and conjugated polymers, and used as active electrode materials. Afterwards, they will be deposited on textile/flexible plastic substrates through dyeing and advanced technologies and assembled with safe solid-gel electrolytes.
This project will have a major contribution to the advance of affordable, clean and modern energy storage technologies, ensuring sustainable production and consumption patterns, fulfilling Goals 7 and 12 of the UN 2030 Agenda. Moreover, it will foster innovation on high-tech smart textiles for Society benefit.

Supervisors: Jorge Manuel Alexandre Saraiva (LAQV-REQUIMTE, Departamento de Química da Universidade de Aveiro) and Susana Isabel Pereira Casal Vicente (LAQV-REQUIMTE, Laboratório de Bromatologia e Hidrologia, Faculdade de Farmácia da Universidade do Porto).

Project Title: A novel non-thermal technological food preservation approach to assure microbial food safety and extend the shelf-life of raw meat.

Summary:
Raw meat is a highly perishable food, as its high aw, ≅neutral pH and nutritional composition create an ideal environment for microbial growth and so poses high safety concerns and relevant economical losses. Although its short shelf-life can be extended by refrigeration (RF), microbial safety cannot be assured since RF causes no microbial inactivation. No other possible technologies are available to ensure microbial safety (by inactivation of microorganisms) of raw meat, except high-pressure pasteurization, but this causes extensive colour changes with no possibility of commercial application. Hyperbaric storage (HS), defined as food storage under pressure (≤100MPa) at room temperature (RT) was recently reported as effective to extend raw meat shelf-life by inhibiting/slowing down microbial growth, allowing colour preservation, while causing additionally some microbial inactivation. HS is also considered an environmentally friendlier preservation methodology over RF since energy is only needed for a short period (compression/decompression of the pressure vessel). The aim of this research is to study, for the first time, a new possibility of microbial inactivation discovered during HS studies, called hyperbaric inactivation (HI), applied to raw pork/bovine meat, using pressures between 125-300MPa to assure raw meat microbial safety by microbial inactivation without color changes. HI effect on microbial load/shelf-life and quality/sensorial parameters will be studied, envisaging microbial safety of raw pork/bovine meat without color changes, allowing its commercialization as raw meat with extended shelf-life. This approach is herein tested as a green preservation technology for raw meat, with low energy expenditure, as an attempt to prolong its physicochemical/sensorial characteristics at RT with improved microbial safety. This, besides reducing food losses, increases the feasibility of RT transportation of raw meat, inconceivable presently.

Supervisors: Clara Grosso (REQUIMTE-LAQV, ISEP), Pedro Miguel Calado Simões (REQUIMTE-LAQV, FCT NOVA) and Alexandre Babo de Almeida Paiva (REQUIMTE-LAQV, FCT NOVA).

Project title: Development of new strategies for biotoxin elimination from bioactive plant extracts using green technologies.

Summary:

1,2-Unsaturated pyrrolizidine alkaloids (PAs) is a class of emerging plant toxins mainly found in honey, tea, infusions and food supplements. European authorities (EMEA and EFSA) have stipulated a maximum level of these contaminants in herbal products due to their adverse side effects. This project aims to develop clean-up strategies to decontaminate medicinal plant extracts from 1,2-unsaturated PAs without compromising their bioactivities. In the first part of the proposal, two model plants known for their high content in PAs will be used – borage (Borago officinalis L.) and comfrey (Symphytum officinale L.) – in order to optimize the conditions for selective extraction of PAs. A multi-step sub/supercritical fluid extraction schema will be adopted, using water-saturated supercritical CO2 (ScCO2) and subcritical water (sCW). Several extraction parameters will be optimized in both processes to obtain PAs free residues that can be further used to extract bioactive compounds. In the second part of the proposed plan, herbal samples obtained from the market will be subjected to the same extraction conditions determined in the first part to perform a quality control assessment of the presence/absence of PAs. Robust analytical tools will be developed to screen and quantify PAs in the samples. Toxin-free fractions will be tested for their neuroprotective, antidiabetic and cardioprotective effects and their chemical profile analyzed through HPLC. At the end, the most promising contaminant-free bioactive extract(s) will be micronized to increase their stability. The supervisor and co-supervisors have been collaborating for several years and have complementary experience and expertise in the biomass fractionation/purification of extracts using green technologies (FCT) and development and validation of chromatographic methodologies and bioassays (ISEP).

Principal Supervisor: Luísa Pinto Ferreira (FCT NOVA), Patrícia Carla Ribeiro Valentão (FF UP) and João Aires de Sousa (FCT NOVA).

Project title:Multi-target-directed ligand strategy for Alzheimer's disease.

Summary:

Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative brain disorder and the most common form of dementia, whose prevalence is expected to more than triplicate during the next 30 years. The few therapeutic drugs available focus on the development of acetylcholinesterase (AChE) inhibitors, which increases the amount of the neurotransmitter acetylcholine (ACh) in the synaptic cleft. The structures of the acetylcholinesterase inhibitors, approved drugs for the treatment of AD present some structural characteristics that can be identified as a flat motif in tacrine, a spacer unit on Donepezil by the piperazine ring, the presence of amide, carbamate and nitrogen motives in Rivastigmine and others. From our recent work we have observed an unusual reactivity associated with N-heterocycle olefins (NHO) derived from 1,2-dimethyl-3-ethylimidazolium iodide namely, the oxidation of aromatic aldehydes to the corresponding carboxylic acids in the presence of a mild base or the synthesis of a new heteroarylidene-9(10H)-anthrone structure. When DBU or DBN were used as base we disclosed a new role of NHO species as catalysts for the ring opening of DBU or DBN upon reaction with aldehydes to form the corresponding ε-caprolactam and γ-lactam derived imines further reduced to lactam-based 1,3-diamine. Herein, we propose to develop a new family of compounds using a multi-target-directed ligand (MTDL) approach, by combining in the same molecular entity, different pharmacophores able to interact with different receptors - the AChE and the histamine H3 receptor, the latter being associated with release of procognitive neurotransmitters like acetylcholine (ACh). The new libraries of compounds to be developed will be assisted with docking studies on the specific receptors and biological assays of the synthesized compounds. This work accounts for Goal 3 (Good health and well-being) of Sustainable development Goals from UN.

Supervisores: Maria Ascensão Ferreira Silva Lopes (LAQV/REQUIMTE, Universidade do Porto), Inês Alexandra Morgado do Nascimento Matos (LAQV/REQUIMTE, FCT NOVA) e José Domingos Santos (LAQV/REQUIMTE, Universidade do Porto).

Título do projecto: Desenvolvimento de vestuário de proteção individual de alto desempenho e sustentável.

Sumário:

O desconforto associado aos equipamentos de proteção individual é um problema muito comum para os utilizadores deste tipo de vestuário, nomeadamente quando este é desenhado com particular ênfase na proteção contra fogo/chama. Esse vestuário deve proteger o utilizador do calor recebido, permitindo que o excessivo calor metabólico gerado pelo corpo durante determinada atividade evapore para o ambiente, atuando como uma barreira para a transferência de calor e humidade. Os utilizadores de vestuário de proteção pessoal estão também comumente sujeitos a radiação ionizante de grande poder penetrante (radiação gama). A proteção contra a radiação depende do nível de controlo da contaminação, tempo de exposição, assim como, da distância da fonte de radiação. O presente projeto visa o desenvolvimento de funcionalizações de estruturas fibrosas complexas, com pré-forma e orientações multidireccionadas de elevado desempenho mecânico, para dotá-las de capacidade de resistência ao fogo/calor e à radiação ionizante, com recurso a tecnologias emergentes, incluindo a nanotecnologia. A sua sustentabilidade é também um fator determinante a ter em conta, nomeadamente na utilização de compostos químicos orgânicos e inorgânicos de reduzido impacto ambiental e com relevância na economia circular, para utilização em vestuário orientado para aplicações nos domínios da proteção humana contra riscos ocupacionais e recreativos, aumentando as propriedades de conforto termofisiológico proporcionadas ao utilizador.

Supervisors: Simone Barreira Morais (REQUIMTE-LAQV-ISEP) and Luís Cobra Branco (REQUIMTE-LAQV, FCT NOVA).

Project title: 4+SusAquac: Novel Tools for a Sustainable Aquaculture Sector: Ionic Liquids-based Membranes and (Bio)Sensors for Emerging Organic Contaminants.

Summary:

Fishery commodities are one of the most traded food commodities worldwide and the increasing potential of the aquaculture sector in the contribution to economic growth have been internationally recognized. This is particularly relevant for the EU and Portugal considering their actual economic strategy, geographical characteristics, but also their traditional diets. Pharmaceuticals and plasticizers, as emerging organic contaminants (EOC), are being released uncontrollably into the environment potentially causing hazardous effects to aquatic ecosystems and consequently to human health. In the absence of well-established monitoring programs, one can only imagine the full extent of this problem and so there is an urgent need for the development of sustainable and efficient water purification processes as well as extremely sensitive, portable, and low-cost devices to perform analysis. The remarkable characteristics of the tailored ionic liquids (IL) and nanomaterials will ensure enhanced performance, allowing the development of innovative and recyclable supported IL membranes (SLIM) for effective treatment of EOC such as pharmaceuticals and plasticizers from aquaculture systems. At the moment, there are scarce studies on the development and application of (i) SLIM for water purification and (ii) (bio)sensors in aquatic matrices, especially in fish, arising therefore a good opportunity, which justifies the present project. The obtained results are expected to respond to diverse scientific, socioeconomic, and environmental challenges (at least 3 sustainable goals from Agenda 2030), generating relevant data and recommendations for the aquaculture sector, and environmental and food authorities. This application is fully supported by the expertise and facilities of LAQV Environmental Chemistry-ISEP (Simone Morais; (bio)sensors, environment monitoring & analysis, environmental and health risks) and LAQV CHARM-FCT-NOVA (Luis Branco; functional materials and health & wellbeing).

Supervisors: Maria Eduarda da Cunha Pereira (LAQV-REQUIMTE, Universidade de Aveiro), Nuno Carlos Lapa dos Santos Nunes (LAQV-REQUIMTE, FCT NOVA) and Bruno Manuel Galinho Henriques (LAQV-REQUIMTE, Universidade de Aveiro).

Project title: Viability of living macroalgae as an ecologically sustainable sorbent for the removal of classic and emerging contaminants from contaminated waters.

Summary:

Living macroalgae have recently been highlighted as an efficient sorbent for the remediation of contaminated waters. Sorption capabilities of green, brown, and red macroalgae can range from classic contaminants such as heavy metals (Hg, Cd, Pb…) to emerging contaminants from e-waste such as the rare-earth elements (La, Ce, Gd, Nd, Dy…). Although macroalgae-based technologies represent a promising ecologically viable alternative to conventional water remediation methods, their application at the industrial level would require extensive knowledge about the sorption process under relevant realistic conditions. Thus, mixtures of classic and emerging contaminants at varying initial concentration will be used to determine the extent of the contamination scenarios in which living macroalgae can be efficiently used, also including the effect of nutrient availability and photoperiod variation. To assess the viability of the living biomass compared to dried biomass, parallel experiments using dried biomass will also be conducted. Sorption of metals onto living and dried macroalgae biomass may be governed by different mechanisms, depending on biomass properties (such as surface area, porosity, pH at the point of zero charge, functional groups at the surface of biomass,…) and medium conditions (such as pH, temperature, concentration of competing ions, mass diffusional constraints,…). Kinetic and equilibrium models are very powerful tools to define the sorption kinetic constants and mechanisms. The most accepted ones it will be used, aiming to explain the sorption results. Sustainability is a critical issue for new processes being developed. Among the tools dealing with sustainability, Life Cycle Analysis (LCA) is the preferred methodology by UN and EC for environmental sustainability assessment. The technology of removing metals and rare-earth elements through macroalgae will be analysed for environmental sustainability by using LCA modelling.

Supervisors: Miguel M. Santos (LAQV-REQUIMTE, FCT NOVA) and Sofia Costa Lima (LAQV-REQUIMTE, Faculdade de Farmácia da Universidade do Porto).

Project title:Tackling microbial resistance: transdermal delivery of antibiotic drugs as Ionic Liquids and Organic Salts using nanostructured biomaterials.

Summary:

Bacterial resistance to antibiotics is a worldwide public health threat, causing an estimated 700k+ deaths every year (Figure 1). The conjugation of antibiotics with chemical adjuvants is one of the most promising strategies to overcome the lack of novel antimicrobial drugs. Over the last years, our group has focused on the combination of Active Pharmaceutical Ingredients (APIs) with biocompatible organic counter-ions yielding APIs as Organic Salts and Ionic Liquids (API-OSILs). The use of this type of chemical adjuvants with the studied APIs has rendered very promising pharmaceutical properties, in particular increases in the APIs’ bioavailability and permeability, reduction or elimination of polymorphism, low toxicity and enhanced therapeutic activity (Figure 2). In the case of antibiotics, namely β-lactams, we have observed elimination of resistance in MRSA and E. coli strains in in vitro studies. Transdermal drug delivery systems offer controlled drug release through the skin layers into the subdermal vascularization with high bioavailability by avoiding the first-pass metabolism. As the exposure of gut microbiota to the drugs is reduced, the rise of resistant strains is limited. Moreover, systemic side effects are reduced, and dosage efficacy is improved by enabling steadier serum drug levels throughout treatment. Hence, this PhD scholarship will focus on the synthesis of novel API-OSILs from two of the most endangered antibiotic classes: carbapenems and aminoglycosides. In vitro stability, water solubility, partition, toxicity and antimicrobial activity studies against sensitive and resistant Gram-(+) and Gram-(-) bacteria strains will be performed. The most promising AB-OSILs will be incorporated into biocompatible and stable lipid nanoparticles dispersed in hydrogels for sustained delivery of highly stabilized drugs (Figure 3). The ability of the most promising AB-OSILs systems to permeate the skin will be evaluated by in vitro human skin models.

Supervisors: Ana V.M. Nunes (LAQV REQUIMTE, Faculdade de Ciências e Tecnologia da Universidade NOVA de Lisboa), Susana Luísa Henriques Rebelo (LAQV-REQUIMTE Faculdade de Ciências Universidade do Porto) and Mário Manuel Quialheiro Simões (LAQV-REQUIMTE – Departamento de Química, Universidade de Aveiro).

Project title: Continuous process for the indirect methanol production from CO₂ .

Summary:

The possibility of using CO2 as a carbon source in alternative to fossil resources can dramatically impact the future of our energy system. The aim of this project is to develop a continuous flow process for the reduction of CO₂-derived molecules into methanol. Methanol is believed to be a key vector for a feasible energy transition since it can be integrated in the existing energy flows and infrastructures. The utilization of intermediate liquid stable CO₂-derived molecules (e.g. cyclic carbonates) for the indirect reduction of CO₂ into methanol allows the reaction to proceed under relatively milder conditions compared to direct routes. Furthermore, cyclic carbonates are particularly attractive as intermediate CO₂ derivatives as they can be formed readily from the reaction of CO₂ with the corresponding epoxides or diols. The high-pressure hydrogenation reaction of organic carbonates into methanol will be explored using metalloporphyrins for the first time as heterogeneous catalysts for this application.

Supervisores: Teresa Casimiro (LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa), André Alberto de Sousa Melo (LAQV-REQUIMTE, Faculdade de Ciências, Universidade do Porto) e Raquel Viveiros (LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa).

Título do Projecto: Polímeros molecularmente impressos (MIPs) com afinidade para biomoléculas: Síntese em CO₂ supercrítico e optimização por estudos computacionais de modelação molecular.

Sumário:

Este projeto de doutoramento tem como objetivo principal desenvolver materiais de afinidade sintéticos – polímeros de impressão molecular (BioMIPs - Molecularly Imprinted Polymers) com a capacidade de reconhecer biomoléculas, e serem capazes de competir com anticorpos naturais. Estes materiais serão preparados usando tecnologias verdes através da tecnologia de fluidos supercríticos. Estes novos materiais serão investigados na separação/purificação e deteção de biomoléculas obtidas em bioprocessos e na catálise de reações químicas com interesse industrial.

No âmbito desta proposta, será estabelecida uma estreita colaboração LAQV, entre a FCT/UNL (projeto BioMIPs, PTDC/EQU-EQU/32473/2017, com a participação da empresa CEV-Converde) e a FCUP (Projeto REALM, PTDC/QUI-QIN/30649/2017). Esta parceria permitirá, de forma dinâmica, usar o know-how adquirido no LAQV, pelas unidades académicas (síntese de BioMIPs para reconhecimento de biomoléculas usando tecnologia de scCO2, FCT/UNL e desenvolvimento de modelos moleculares apropriados à previsão do comportamento destas matrizes poliméricas e da sua capacidade para reconhecerem biomoléculas, FCUP) para resolver os problemas de biopurificação, tendo como objetivo final, o desenvolvimento de um protótipo a ser testado no ambiente industrial desta empresa, bem como a escolha dos modelos que melhor caracterizam a performance destes materiais.

Supervisores: Maria João Melo (LAQV-REQUIMTE, FCT NOVA), Natércia do Carmo Valente Teixeira (REQUIMTE-LAQV, FCUP) e Fernando Pina (LAQV-REQUIMTE, FCT NOVA).

Título do Projecto: Dos estudos fundamentais das moléculas da cor na arte à descoberta de aplicações sustentáveis com recursos naturais renováveis: em redor do azul da Chrozophora tinctoria, também conhecido na idade média como folium.

Sumário:

Este projeto enquadra-se na nova linha temática da Requimte dedicada à salvaguarda da Herança Cultural. Mais precisamente, à (re)descoberta de cores do passado como inspiração para novos materiais. A nossa motivação é tanto direcionada para a salvaguarda de um património precioso, como para o estudo dos mecanismos de resiliência destas cores para desenvolvimento de novas aplicações, amigas do ambiente.
Assim, este projecto de doutoramento será desenvolvido dentro da equipa interdisciplinar que recentemente desvendou a estrutura de um corante medieval, folium, presente nos frutos da Chrozophora tinctoria, uma pequena planta que se encontra em Portugal. Esta descoberta foi festejada pela comunidade científica, tendo tido grande impacto nos media. Assim, a identificação desta pequena, mas complexa molécula responsável pela cor azul, chrozophoridina, contribuiu para o reconhecimento internacional do grupo LAQV. Esta descoberta só foi possível pela colaboração sem precedentes de cientistas dos pólos de Caparica, Porto e Aveiro. Agora, com a estrutura conhecida, propõe-se um estudo completo que abrirá caminho a novas aplicações sustentáveis do extrato desta planta. No seio do grupo LAQV-NOVA, a química-física da chrozophoridina será estudada para compreensão dos mecanismos de estabilidade desta molécula. A identificação, isolamento e caraterização dos restantes compostos presentes nos frutos, folhas e caule será efectuada em conjunto com o grupo LAQV-FCUP, especialistas na identificação e isolamento de compostos naturais. Neste polo, serão ainda investigadas novas aplicações destes extratos na indústria têxtil e alimentar. Como ponto de partida para o uso dos extratos como corantes alimentares, serão pesquisadas fontes históricas que descrevem a produção do folium. Estas receitas serão testadas e otimizadas. Os casos de maior sucesso serão caracterizados usando tecnologias de ponta, inseridas numa abordagem multi-analítica, numa colaboração Caparica & Porto.

Supervisors: Maria da Conceição Branco Montenegro (LAQV-REQUIMTE, Faculdade de Farmácia da Universidade do Porto) and Carla Alexandra Moreira Portugal (LAQV-REQUIMTE, FCT NOVA).

Project Title: Development sustainable magnetic-responsive (bio)sensors for diagnosis of chronic kidney and cardiovascular diseases.

Summary:

While the increased life expectancy is being reflected on a higher prevalence of chronic kidney disease (CKD) different external factors have been associated with its grim progression to end-stage renal disease (ESRD) irreversible condition. The diagnosis of CKD also fails because it is often only done when the glomerular filtration rate has already been lost. This project aims the development of electrochemical sensors for neutrophil gelatinase-associated lipocalin (NGAL) and asymmetric dimethylarginine (ADMA) as predicting protein biomarkers of CKD. For that, (bio)sensors will be developed by using hydrogels based on food waste polymers to bind the recognition element. Antibodies will be firstly selected as a recognition element, being aptamers or dendrimers alternatives to them. Low cost components such as graphite from pencil mines will be used as conductive support and natural anti-oxidants as electrochemical mediators in the development of the biosensor. The proposed hydrogels exhibit tunable chemical and structural properties which will be explored to address biofouling and limited diffusion of biomarkers. Selective sensors based on simple, low cost and green materials will enable lower detection limits, with whole blood samples, providing analysis in real-time to prevent the subsequent risks leading to high morbidity and mortality of CKD patients. The validation of the innovative analytical tools will be done by using clinical commercially available kits. This PhD project will be developed in the LAQV. FFUP in collaboration of FCT.NOVA, supervised by Prof. Conceição Montenegro (CM) with expertise in development of electroanalytical sensors with electrochemical transduction and co-supervised by Dr. Carla Portugal (CP) with expertise in membrane bioprocessing and design of functional porous materials, thus enabling to strengthen a collaborative relationship between Analytical Development and Bio(chemical) Process Engineering from these two LAQV units.

Supervisors: Nuno M. M. Moura (Department of Chemistry, University of Aveiro), Carlos Lodeiro (NOVA Science and Technology School, Caparica Campus, NOVA University Lisbon, 2829-516, Caparica, Almada Setubal, Portugal) and Idalina Gonçalves (Department of Chemistry, University of Aveiro).

Project Title: SENSIBIOMAT - Development of porphyrin-doped biobased materials with photosensitizing and sensing properties.

Summary:

The photodynamic inactivation (PDI) of microorganisms has been recognized by the scientific community as an effective alternative to fight the antimicrobial resistance growth. On the other hand, due to the worldwide high pollution levels, an efficient monitorization of the presence of pollutants in-situ and in real-time has become a major issue. Immobilization of active agents is as an essential requirement for stablishing strategies that answer both these scientific fields in a practical and environmentally feasible way.
SENSIBIOMAT project aims to study the feasibility of developing photoactive materials containing β-functionalized porphyrin derivatives able to act as photosensitizers (PS) in microorganisms PDI and as sensors (e.g. thermometers, iono- or vapochromic materials), using accessible, low-cost, and ecological polymeric supports. With SENSIBIOMAT it is expected that the new developed photoactive materials effectively produce reactive oxygen species (ROS) increasing their efficiency as PSs. Moreover, it is aimed that their polymeric network will be permeable to analytes in the surrounding area, allowing their interaction and detection. For this project, 1,3-dioxopyrroloporphyrin (1,3-DPP) was selected as template, due to the possibility of finely tuning its physicochemical properties by synthetic modifications, to afford derivatives suitable for the proposed applications. It is forecasted that the modification of 1,3 DPP macrocycle with appropriate functional groups will allow its covalent immobilization on biobased polysaccharide formulations (e.g. starch), thus conferring them the photophysical/photochemical properties required in a good PS and sensor material. Furthermore, the presence of proper functional terminal groups in 1,3 DPP derivatives will allow their anchorage in nanoparticles (NPs) and/or to be used as doping agents in a non-covalent fashion through a low-cost, environmental-friendly and reusable polymeric films and hydrogels.

Supervisors: Zeljko Petrovski (LAQV-REQUIMTE, FCT NOVA), Patricia Poeta (LAQV-REQUIMTE, FCT NOVA/UTAD) and Paula Gameiro (LAQV-REQUIMTE, FC UP).

Project Title: Highly Efficient Novel Antibiotics against Resistant Bacteria based on Ionic Liquids Containing Active Pharmaceutical Ingredients (Highness IL-APIs).

Summary:

The goal of this project is focused in the synthesis of ionic liquids containing active pharmaceutical ingredients (IL-APIs) and subsequent screening of its antimicrobial activities as well as to explore their biophysical interactions in order to elucidate a potential effect against resistant bacteria.
Bacterial resistance has been increasing drastically over last years. Recent efforts in this field by big pharma companies have been disappointing. The bacteria resistance reached alarming dimensions and still is increasing. IL-APIs have been studied academically and they showed significant activity against some resistant bacteria such as MRSA and E. coli species (RDIC>1000). We believe that the higher activity can be attributed to API transportation or some other specific contribution of counterion, but more systematic studies are needed. The workplan is divided in three main tasks: 1) synthesis of IL-APIs, 2) Activity studies with resistant bacteria and 3) Biophysical studies. The first part of this work will be performed at chemistry lab (Zeljko Petrovski, FCT-NOVA), the second in microbiological lab (Patricia Poeta, UTAD) and finally the third part in biophysics lab (Paula Gameiro, UPorto). For the more promising compounds molecular dynamic and docking simulations, will also be developed as well as the toxicological and enzymatic interaction studies. Combination strategy against antibiotic resistant bacteria has been suggested as a possible solution for drug resistance [14]. IL-APIs can perhaps provide a powerful combination strategy and in addition, they offer virtually limitless number of new compounds. The expertise of the supervisors team in synthetic and medicinal chemistry, microbiology and biophysics combined with LAQV facilities and ongoing projects (Tuberculosis: PTDC/QUI-QOR/32406/2017; Bacterial Antibiotic Resistance SAF2012-35474) can contribute for the success of this project and it is aligned with sustainable development goal 3 from Agenda 2030.

Supervisors: Maria Salete Balula (LAQV-REQUIMTE, FCUP), Luísa Alexandra Graça Neves (FCT NOVA) and Luís Manuel Cunha Silva (LAQV-REQUIMTE, FCUP).

Project Title: Designing a New Route to Promote Desulfurization of Maritime fuels: From Bulk catalysts to Membranes.

Summary:

The aim of this PhD research project is to develop a novel effective desulfurization route based in catalytic membranes to treat diesel and maritime fuel. Heavy fuel oil (HFO) has been used as the main fuel for marine transportation. HFO is inexpensive and widely available; however, has high sulfur content (3-6% of S), contributing extensively for global SOx emissions. The actual refinery method to treat diesel (hydrodesulfurization, HDS), can´t be used to treat HFO, due to it’s high viscosity and heavy molecular composition. To guarantee the use of HFO in marine transportation, it is crucial to develop a novel desulfurization process able to desulfurize HFO to accomplish the actual legislation (maximum of 0.5% of S). Oxidative desulfurization (ODS) will asset this purpose, promoting the selective removal of S-compounds by changing their polarity via oxidation. The catalyst design is decisive to oxidize efficiently the S-compounds in Fuels. Using the previous know-how gained to treat diesel using Bulk heterogeneous Catalysts, novel Metal-Organic Frameworks (MOFs) supporting polyoxometalates (POMs; as active centers) will be prepared and tested in ODS reactions of model HFO. The next advance step is to mitigate catalyst mass loss, frequently occurred during recycle process, and also to increase Bulk Catalysts stability by their incorporation in ceramic Membranes. These will promote an effective separation and will avoid catalyst deactivation caused by aggregation. Catalytic Membranes will be tested in model Fuels (diesel and HFO), and the reactional conditions optimized to improve catalyst performance and sustainability. Further, these will be used to treat real Fuels. The project is supervised by members of LAQV from FC-UP and FCT-UNL, sharing expertise and facilities that assure the development of the work plan, as well as the financial support of PTDC/CTM-CTM/31983/2017 project and also from Galp (will guarantee all the analysis involving real fuels).