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Information for Candidates

The PhD in Sustainable Chemistry is directly funded by Fundação para a Ciência e Tecnologia with 10 new doctoral fellowships per year. These will be ascribed to the best ten candidates chosen in the selection process.

The overall admission target for the programme is 50 students per year, so candidates with alternative sources of funding , such as individual grants from the annual call of Fundação para a Ciência e a Tecnologia, will also be admitted.

The PhD in Sustainable Chemistry welcomes diversity and aims at recruiting students with a passion to perform research in one of the fields of Sustainable Chemistry. It will seek students with the intellectual maturity to be able to put forward the foundations of a well designed career plan, and who have successfully completed Masters degree in any area of Science and Technology with a sufficient Chemistry content.

 

Starting date for the lective year 2016/17

20th of February 2017

 

Admission criteria

Candidates should meet the following criteria:

  1. 1. Masters degree in any area of Science and Technology, with at least 18 (Bologna) credits in Chemistry or equivalent subjects (if you will complete your Masters degree until the 31st December, you can also apply).
  2. 2. Minimum Grade-Point Average (GPA) of 14/20 (Portuguese Scale or equivalent by conversion in case of foreign candidates) is legally mandatory for admission in a PhD course in Portuguese Universities. The GPA is calculated using the following formula: 0.6 GPA Undergraduate Degree + 0.4 GPA Masters Degree. Exceptionally, the directors of the doctoral program may admit applicants with GPA lower than 14, provided that the candidate holds an excellent scientific curriculum.
  3. 3. Solid knowledge of English language is mandatory.

Required Documents

  • Academic Certificates - A digital copy of all academic certificates (stating the final classification), and the respective official transcripts (listing the grade/classification of each discipline/subject attended to get each degree).
  • Curriculum Vitae - This document must include personal details, education and qualifications, research interests and additional skills. You also should mention your research and academic/professional standing, teaching and demonstrating experience, administrative experience, professional memberships and public engagement, prizes and references. This document must be organized so that crucial elements for the evaluations are clearly presented:

1) Final marks obtained for the undergraduate degree and the Master.

2) Other relevant achievements as undergraduate and Master’s student, such as marks obtained in the most relevant courses, projects and theses, mobility, academic prizes, results from introductory research work.

3) Research publications:

3.1- Papers published with original research

3.2 – Review papers

3.3 – Oral communications to scientific conferences actually delivered by the candidate.

3.4 – Other presentations to conferences

  • Motivation Letter - This document should be written in English, and should include your objectives and goals as well as your main areas of interest in the Program. Your letter should refer to specific research topics in which you wish to focus and should give your reasons for wishing to do graduate in the field you have chosen. Your statement of interest should be approximately 500 to 800 words in length.
  • Two Reference Letters - You must provide to your two referees the email address for the course to which you are applying, and the reference letters must then be emailed to This email address is being protected from spambots. You need JavaScript enabled to view it. This email address is being protected from spambots. You need JavaScript enabled to view it. by each referee. The letters should be printed on official stationery of the institution at which the referee works, and must include a URL for the institution so the affiliation can be checked. The letters must be signed by the referee and then attached to an email sent to the address mentioned above. It is the candidate's responsibility to ensure that Coordination Committee of the Doctoral Programme receives both letters before the application deadline.

 

How to Apply

The candidates have to use the application platform provided and fill in all the information in the application form. Please ignore the fields concerning the submission of the PhD work plan and the supervisor justification.

The deadline for application submission in the academic year 2016/17 is the 23rd of December 2016.

 

Selection Process

The process of selecting and ranking applicants is carried out by the Coordination Committee, with the collaboration of members of the Scientific Council and, whenever necessary, external experts.

Evaluation is a two-step process: in the 1st step a careful analysis of each candidate's curriculum vitae, including the academic background, scientific experience, letter of motivation and reference letters is evaluated and a short list of candidates is prepared; in the 2nd step the candidates in the short list are invited for a personal interview.

Applicants will receive a final mark (1 to 5) and will be ranked accordingly.

Evaluation in the 1st step considers:

  1. 1. Previous academic achievements
    Masters final average mark, classifications obtained in relevant courses, especially interesting written coursework, communications in meetings and conferences, mobility, academic prizes.
  2. 2. Scientific background
    Research experience, research results, and impact of scientific publications are considered, taking into consideration the role played in those publications.
  3. 3. Motivation letter and recommendation letters
    The motivation letter should refer the goals and expectations for joining this specific Program. The reference letters will be requested in a standard template.

Evaluation in the 2nd step includes:

o Personal interview
This is carried out by the whole committee, to confirm (or not) the impressions on the applicant’s quality generated by the appreciation of all other elements of evaluation.

The final ranking score of each candidate is determined by:

(1) Previous academic achievements (30 %)

(2) Scientific background (20 %),

(3) Interview, recommendation letters and motivation letter (50 %)

 

PhD Projects Available (incomplete)

Universidade de Aveiro

Tema UA1: Exploitation of novel methodological tools for breath and urine analysis towards clinical applications

In the site of their current interest, breath and urinary metabolomics continue away for the clinical usage, as right now they are based on time consuming and complex methodologies that generate big data. Despite the huge importance of these common metabolomics approach, in order to go further on the breath and urinary exploitation, this project aims to develop rapid, sensitive, and selective sample preparation based on solvent-free microextraction tools combined with chromatography and mass spectrometry, using expedite chromatographic and mass spectrometry instrumental configurations and signal data processing. Also, it is planed the development of portable and ready-to-use tools that may be used further used at the point-of-care or patient-home. Finally, it is expected that the applicability of the develop methodologies and tools will be tested in specific clinical scenarios.

Supervisor: Sílvia Rocha (QOPNA)

 

Tema UA2: Tuning MOFs structure by post-synthetic modification to enable and improve their catalytic activity or light emission

Metal organic frameworks (MOFs) are hybrid materials consisting of organic linkers bridging metal clusters, having very high surface areas up to 5200 m2 g−1, and a variety of chemical functionalities. MOFs have potential application in the absorption and separation of gas molecules (such as CO2, N2, CH4, and H2), microelectronics, sensing, ion conductivity, optics, pollutant sequestration, drug delivery, contrast agents, micromotors, bioreactors and catalysis.

An outstanding feature of nanoporous MOFs is that the chemical makeup of the channel walls may be adjusted by post-synthetic modification (PSM) of the organic linkers. In this way, new organic functionalities and metal cations may be introduced enabling or improving gas sorption, catalytic activity or light emission, among others.

The objective of this PhD project includes: i) the synthesis of new MOF structures bearing bigger channels, based on aromatic carboxylates with rigid and larger carbon skeletons; ii) the PSM functionalization of some known and of the new MOF structures with fluorescent bodipy dies, and organocatalysts; iii) the study of the absorption and fluorescence properties of the bodipy-based MOFs aiming at their application in photoelectronic devices; iv) the study of the catalytic activity of the organocatalysts-based MOFs in some organic reactions, mainly in asymmetric synthesis; v) the PSM functionalization of some known and of the new MOF structures with appropriate moieties to chelate lanthanides to prepare fluorescent sensors and light-emitting devices.

Supervisors: João Rocha (CICECO) and Artur Silva (QOPNA)

 

Tema UA3: SPYMOL - Unveiling the structure of surface species in heterogeneous acid catalysts with spy molecules

The nature of acid species in micro- and mesoporous borosilicate zeolite materials will be studied with a combination of experimental solid state NMR (ssNMR) and computational density functional theory (DFT) approaches using trialkylphosphine oxide (TAPO) probe molecules. These molecules can engage in hydrogen bonding with Brønsted and Lewis acid site environments in the zeolite materials, leading to the formation of TAPOacid complexes, which can be detected experimentally. The benchmarking of calculated NMR chemical shifts with the experimental information will be used to design accurate structural models of the TAPOacid complexes, which will enable an unprecedented picture of the type, strength, location, and amount of the acid sites in these fascinating and industrially relevant materials.

Supervisor: Supervisor: José Richard Baptista Gomes (CICECO)

Co-Supervisors: Luís Miguel Monteiro Mafra and João Rocha (CICECO)

 

Tema UA4: Novel MOFs with Bisphosphonates for in situ Osteoporosis Treatment

Bisphosphonates (BPOs) are widely prescribed to prevent and treat osteoporosis because of their ability to lower the activity of osteoclasts, thus preventing bone loss. The treatment with BPOs is often combined with calcium and magnesium intake, important oligo-elements for bone health. The present proposal aims at preparing Metal Organic Frameworks composed by calcium or magnesium and BPOs suitable for local action on the bone, which are expected to provide a more efficient therapy by exerting a local and sustained release. MOFs will be studied using in-house techniques as X-Ray Diffraction (powder and, when available, single crystal), Nuclear Magnetic Resonance, Scanning Electron Microscopy, Termogravimetry, FT-IR.  Drug release profile and biomineralization properties will be studied in vitro in Simulated Body Fluid.

Supervisors: Filipe A. Almeida Paz (CICECO) and Susana Santos Braga (QOPNA)

 

Tema UA5: Design of organized structures based on proteins for biomedical applications.

The project aims at developing new protein-based materials with controlled degrees of orientation and organization and improved mechanical properties, keeping the functional character unchanged. These structures will be obtained through well-designed chemical modifications and adequate processing methodologies under special conditions. We intend to replicate fundamental aspects of the extra-cellular matrix found in native tissues and to provide favorable instructive signals for controlling the cell behavior. The biomaterials to be developed may have the potential to be used as cell expansion devices or as tissue engineering platforms, significantly adding value of the raw materials obtained from renewable sources.

Supervisors: Cármen Freire and João Mano (CICECO)

 

Tema UA6: Natural deep eutectic solvents (NADES): a promising media for the design of new functional biobased materials.

The development of new functional biobased materials is a key challenges for the sustainable development of society. The use of green processing conditions, and the adequate tailoring of target properties are essential for the success of this approach.

Natural deep eutectic solvents, are based on natural and intrinsically nontoxic and biocompatible components and therefore inherently safe, and have emerged in recent years as one of the most promising and sustainable class of solvents, with applications in a many domains of chemistry. Nonetheless their used as media for the formulation of new materials, e.g. hydrogels, aerogels and films,  from natural biopolymers or from in situ polymerization of adequate monomers, which are increasingly searched notably in the biomedical domains has not been explored.

In this perspective the aim of this project is precisely to address the production, in NADES media of hydrogels, aerogels and films from natural biopolymers or from in situ polymerization of adequate monomers, and to deeply study both the influence of NADES on the properties of the final materials as well as their potential applications.

Supervisors : Armando Silvestre and João Coutinho (CICECO)

 

Tema UA7: Functionalization of polysaccharides from by-products to be used as chelating agents of metals for bioremediation

Polysaccharides (POS), can be easily obtained from by-products of food industry, such as galactomannan from spent coffee grounds, arabinoxylans from brewers spent grain, cellulose from agriculture by-products and starch from potato chips industries. Thus the aim of this work is to accomplish the functionalization of POS, after extraction, using a synthetic route with alfa hydrpxy-acids, to promote the formation of chelating moieties able to trap metal ions. Modified POS will be characterized by mass spectrometry and their chelating capabilities evaluated. Functionalized POS will be proposed for bioremediation and preservatives as antioxidants in food, feed and pharmaceutical products. This project proposes an ecofriendly reuse of wastes, in accordance with biorefinery concepts and sustainable circular bioeconomy.

Supervisor: Manuel António Coimbra (QOPNA)

Co-supervisors: Rosário Domingues and Augusto Tomé (QOPNA)

 

Tema UA8: Bioelectronic tongue for the detection of paralytic shellfish toxins.

Most coastal countries are affected by harmful algal blooms and resulting episodes of marine toxin poisoning. Due to unpredictability of these outbreaks routine monitoring of marine toxins in bivalves is mandatory. Paralytic shellfish toxins (PSTs) are of particular concern due to the life-threatening neurological symptoms they can cause in humans.

This project aims to develop a bioelectronic tongue system for the rapid detection of PSTs commonly found in bivalves. Development of electrochemical biosensors based on PST transforming enzymes and PST specific antibodies is proposed. Novelty of this work lays in the development of biosensors for detection of PSTs from N-sulfocarbamoyl and decarbamoyl groups, which are commonly detected in bivalves from the Portuguese coast, and in the utilization of PST transforming enzymes.

Supervisors: Maria Teresa S.R. Gomes and Alisa Rudnitskaya (CESAM)

 

Tema UA9: Atmospheric variability of water-soluble organic matter composition: new perspectives using nanomanipulated collection substrates and high-resolution techniques

Atmospheric water-soluble organic matter (WSOM) play an important role in climate system, yet little is known about its molecular composition on timescales closer to atmospheric variability. This doctoral research project proposes the development of a new approach for capturing short-term changes of the chemical features of particulate WSOM. The research plan focuses on a strategy to incorporate polymer functionalized magnetic nanoparticles into different collection substrates for in-situ preconcentration, with subsequent solid-phase microextraction and offline characterization of WSOM through high-resolution techniques (multidimensional NMR spectroscopies, mass spectrometry, and 2D liquid chromatography). Besides gaining highly time-resolved data on the chemical properties of atmospheric WSOM, this project will also provide a deeper insight into its structure-origin relationship.

Supervisor: Regina Maria B. O. Duarte (CESAM)

Co-Supervisor: Armando da Costa Duarte (CESAM)

 

Tema UA10: Risk assessment of pharmaceuticals’ photodegradation on the aquatic environment – aquaculture waters, a case study

Sunlight-induced photochemical processes should be considered as a major pathway to mitigate the impact of pharmaceuticals, namely antibiotics, in the environment. However, this is not reached if photoproducts retain/increase parent compounds’ hazardous properties. This project aims to study the environmental conditions of aquatic matrices that affect the photo-degradation of some pharmaceuticals used in aquaculture, namely antibiotics, to know which photoproducts (mass spectrometry) are formed, and to assess their effect in non-target organisms. Also, synthetic photo-catalysts (e.g., magnetic nanoparticles with porphyrins, TiO2/graphene oxide composites) will be tested for solar light-induced photocatalytic degradation of these contaminants, and the most effective will be tested in real conditions of intensive aquacultures industries.

Supervisor: Valdemar Esteves (CESAM)

Co-Supervisores: Maria Eduarda B. H. Santos and Diana Lima (CESAM) 

 

Temas InterUniversidades

UAR1: Development of biocatalysed synthetic routes to improve stereo and regioselectivity

Despite the numerous efforts that have been made in developing new drugs, the emerging resistance to the currently used ones as well as their recognised side effects indicates that new and more effective drugs are needed. The development of new organic molecules with precise three-dimensional structure is difficult, especially if the usual synthetic organic methodologies are employed. Moreover, the classical organic synthetic methodologies are far from being environmental benign. Consequently it is necessary the development of new efficient synthetic methodologies in the green chemistry contest.

Taking into consideration that nitrogen heterocycles such as indoline (1), tetrahydroisoquinoline (2) and dihydroquinolinone (3) or (4), are known to be useful in the treatment of several infections, the establishment of new methodologies towards the synthesis of their derivatives in a regio, diastereo and enantioselective way is an important goal. These scaffolds are classically obtained through several procedures involving organic solvents and several catalysts systems, for example, tetrahydroisoquinolines (2) can be obtained from the reaction of dopamine (5) derivatives with aldehydes in the presence of appropriate catalyst, usually POCl3, P2O5 or ZnCl2, to form an iminium intermediate that promptly cyclizes into a 3,4-dihydroisoquinoline. Or the reductive cyclization of 3-(2-nitrophenyl)acrylic acids (6) with a stoichiometric amount of zinc dust and ammonium formate to obtain dihydroquinolinones (3).

The efficiency of a procedure that allowed the synthesis of the above mention nitrogen heterocycles with the appropriate substitution pattern will be an objective but the main goal will be the development of environmentally benign methods, accordingly the use enzymes as biocatalysts will be developed not only to the scaffold core synthesis but as well to their biotransformation, for instance the introduction of hydroxyl groups with appropriate peroxidases to enhanced their pharmacological application.

Supervisor: Diana Pinto (QOPNA)

Co-Supervisor: Lígia Martins (ITQB)

 

UAR2: Development of theranostic nanomaterials based on tetrapyrrolic macrocyles

During the last two decades, tetrapyrrolic macrocycles (porphyrins and analogues) are being explored as important tools for new applications. In fact, interdisciplinary studies have pointed out the great potentialities of these compounds.

The increase cost of healthcare joined to the restrictions in using diagnostic tests promote the appearance of new multifunctional agents to simultaneously monitor and treat disease, namely based on nanoparticles. In fact, theranostic nanomedicine is emerging as a promising therapeutic paradigm.

The aim of this proposal is to develop new and promising theranostic nanomaterials based on tetrapyrrolic macrocycles and to assess the applicability of this novel procedure for disease’s diagnostic and treatment.

Supervisores: Maria Amparo Ferreira Faustino, Maria Graça P. M. S. Neves (QOPNA) and Carlos Lodeiro Espiño (FCT-UNL)

 

UAR3: Design, synthesis and evaluation of novel potential anti-leishmanial inhibitors

Leishmaniasis is a neglected infectious disease endemic in almost one hundred countries (tropics, subtropics and Europe), currently affecting 12 million people. It is caused by 20 different Leishmania parasite species and can have skin, mucocutaneous and visceral presentations. To date, there are no vaccines against this parasitic diseases, and chemotherapy is the main weapon against. Current drugs are toxic and expensive, and are losing their effectiveness due to parasite resistance. In this way the development of new effective chemotherapeutic agents for the treatment of leishmaniasis is greatly needed.

Since some drug targets for the treatment of leishmaniasis are already know (e.g. arginases and asparaginases…), in this project we will perform a virtual screening of some novel quinolone, acridones, chromones and related compounds in these targets. For those presenting better binding interactions we will design and refine computationally a series of structural analogues and then proceed with the chemical synthesis and biological evaluations.

Supervisor: Artur Silva (QOPNA)

Co-Supervisor: Pedro Alexandrino (REQUIMTE-FCUP)

 

UAR4: Sustainable materials for adsorption and electroreduction of carbon dioxide to high-value compounds

Polysaccharides such as chitosan, alginate, carrageenan, which are abundant sources and easily extracted from biomass, can be excellent starting materials for adsorbent materials (e.g CO2 capture or separation). These polymers can be pyrolised to achieve conductive carbon based materials at relative low cost to be used as effective electroreductive catalysts. This proposal aims to reuse biomass residues and to turn them useful as environmental friendly adsorbents of CO2, reducing the greenhouse effect, or upgrading biogas as alternative energy source and contributing to CO2 transformation by electroreduction into applicable compounds (e.g. acetic acid, acetone or methanol). Computational tools will be used in combination with laboratorial experiments to design a more sustainable development of these materials.

Supervisor: Paula Ferreira (CICECO)

 

Co-Supervisors: José R. B. Gomes (CICECO) and Cristina Freire (REQUIMTE, FCUP)

 

Universidade do Porto

UP1 - INOLEVine - Desenvolvimento de um produto inovador à base de um extracto proteico de leveduras para a estabilização química e melhoramento da qualidade sensorial de vinhos.

Keywords : Leveduras, Polifenóis, Vinhos, Biotecnologia, Estabilidade.

Descriçao: Neste trabalho pretende-se desenvolver um extratos proteicos de levedura (EPLs) com excelentes capacidades preventivas na oxidação de vinhos e na sua clarificação, para substituição da maioria dos agentes de colagem existentes que são de origem animal. Para atingir este objetivo definiram-se as seguintes etapas:

  1. a) Desenvolvimento do processo de produção e de formulação dos EPLs adaptados às condicionantes bioquímicas e aplicacionais do produto em colaboração com uma empresa de biotecnologia, a PROENOL;
  2. b) Caracterização do material proteico do extrato de leveduras por proteómica recorrendo a espectrometria de massa: LC-MS/MS usando um ion trap/Orbitrap (LTQ-Orbitrap), recorrendo à tecnologia multidimensional de identificação proteica (MudPIT);
  3. c) Estudo da reatividade dos EPLs com os polifenóis do vinho que são responsáveis pela cor (antocianijnas) e sabor (taninos), usando para o efeito diferentes técnicas: nefelometria, extinção da fluorescência intrínseca e Saturation Tranfer Difference-NMR (STD-NMR), entre outras;
  4. d) Caracterização da composição polifenónica dos vinhos antes e após tratamento com as EPLs. Estudo da interação com diferentes famílias de proteínas salivares. Este estudo será efetuado diretamente com saliva humana;                                                                                                                                             
  5. f) Validar analiticamente as propriedades das EPLs no vinho, nomeadamente na sua clarificação, na remoção de compostos amarelos de oxidação, na prevenção da oxidação e melhoramento do sabor (redução da adstringência) - em colaboração com uma empresa vinícola;

Orientador: Victor Freitas (REQUIMTE, FCUP)

 

UP2 - Naturally-occurring alkaloids: Green chemistry approaches for increased bioactivity and lower toxicity

Alkaloids are among the most biologically active metabolites in Nature, being the basis of several medicines.

In many cases, however, the marked pharmacological activity of alkaloids is accompanied by high toxicity and, often, carcinogenicity. Frequently, this toxicity is a consequence of metabolic transformation, leading to the formation of toxic metabolites, such as hydroxylated and dehydrated derivatives.

In this project, we will screen several classes of alkaloids for biological activity in cancer and inflammation models. The most potent molecules will be selected for subsequent studies in which green chemistry tools will be used for the structural modification of these molecules, aiming to lower toxicity whilst maintaining or enhancing therapeutic potential.

Supervisor: Paula B. Andrade (REQUIMTE, FFUP)

Co-supervisors: Patrícia Valentão and David M. Pereira (REQUIMTE, FFUP)

 

UP3 - Theoretical study o ionic liquids using polarizable potentials

Research on ionic liquids (ILs) is certainly one of the most active and passionate areas of work on chemistry nowadays. ILs have been generally considered as green solvents, which can be used as efficient alternatives to volatile organic solvents. This is due to their high thermal and chemical stability, almost negligible vapor pressure and non-flammability. These solvents also present a high conductivity and are associated with the formation of both polar and hydrophobic domains.

ILs have been employed in diverse fields of science and engineering. As far as analytical chemistry is concerned, ILs have been extensively used in recent years in the development of methodologies that fulfill the principles of green chemistry. These included extractions, gas chromatography, liquid chromatography, capillary electrophoresis, mass spectrometry, electrochemistry, sensors, and spectroscopy. Other main applications of ILs have been directed to the extraction and separation of target analytes from environmental, food, clinical and pharmaceutical samples.

The ILs have a great tunability potential, in the sense that by a judicious choice of the cation and the anion, one can design the best IL for a particular application. More subtle modifications on the structure of the ILs, such are the substituent effect or the length of the alkyl chain, have been also related with a more effective tuning of ILs’ physical-chemical properties.

From a theoretical perspective, ILs represents a significant challenge. In general, ILs are characterized by a subtle interplay of different physical interactions [1]. Pairwise addictive contributions, associated with two-body Coulombic and van der Waals interactions, can be reasonably described by the classic force fields developed for ILs [2-6]. Classical molecular dynamics (MD) simulations, using pairwise potentials, have been a powerful tool for understanding the IL properties at an atomistic level. MD simulations have extensively used to evaluate structural, thermodynamic and dynamical properties.

However, ILs are complex fluids whose ions have usually a significant delocalized charge and the importance of the quantum effects cannot be neglected [1]. The use of potentials, which explicit include polarization of the constituent ions, is very important for accurately reproducing both the cohesive and dynamical properties of an IL [7]. The polarizable potential, introduced by Son et al [7], is one of the most successful model of this type. Its parameterization is based on symmetry-adapted perturbation theory (SAPT) calculations involving the homomolecular species.

This project concerns the accurate simulation, using polarizable potentials, of several ILs families in order to understand how their physical-chemical properties can be fine-tuned. The evaluation of the effect of structural changes on an IL (such as the cation, the anion, the length of the alkyl chain or the nature of the functional groups) in its physical-chemistry properties will be also analyzed in detail. Therefore based on this study it will be possible not only to give a profound thermodynamic view/interpretation of these systems, to develop estimative methods, as well as to give support to computational methods in order to be able to evaluate/predict the applicability of the ILs.

References

[1] K. Wendler, F. Dommert, Y. Y. Zhao, R. Berger, C. Holmb , L. D. Site, Faraday Discuss., 154, 111-132 (2012).

[2] J. N. Canongia Lopes, J. Deschamps, Agílio A. H. Pádua, J. Phys. Chem. B, 108, 2038–2047 (2004).

[3] S. V. Sambasivarao, O. Acevedo, J. Chem. Theor.Comp., 5, 1038-1050 (2009).

[4] X. Zhong, Z. Liu, D. Cao, J. Phys. Chem. B, 115, 10027-10040 (2011).

[5] B. L. Bhargava, S. Balasubramanian, J. Chem. Phys., 127, 114510 (2007).

[6] I. V. Voroshylova, V. V. Chaban, J. Phys. Chem. B, 118, 10716-10724 (2014).

[7] C. Y. Son, J. G. McDaniel, J. R. Schmidt, Q. Cui, A. Yethiraj, J. Phys. Chem. B, 120, 3560-3568 (2016).

Orientadores: Maria Nat ália Dias Soeiro Cordeiro (REQUIMTE, FCUP)

 

UP4 - Project Title: Living in extreme conditions: extremozymes for industrial application.

Abstract

The project aims to understand how enzymes of extremophile organisms work. This will provide the knowledge to use them in industry for our benefit.

The application of enzymes in industry is a multibillion dollar field. However, the fact that the majority of industrial processes require harsh conditions is limiting their application. To solve this, science is now searching for extremozymes, which are the enzymes of organisms that live in extreme environments (i.e. extremophile organisms), as they can endure the extreme industrial conditions.

We aim to explore and unveil with atomistic detail, using state of the art computational approaches, the catalytic mechanisms and the folding stability of two extremozymes, the Sulfur Oxygenase Reductase (SOR) from Acidianus ambivalens and the Mannosylglycerate synthase (MGS) from Rhodothermus marinus, which have the rare ability of being catalytically active and efficient under extreme conditions.

SOR and MGS are suited for biotechnological applications in biomining of precious metal sulphide ores and in the preservation of biomaterials, respectively.

Based on this, we will explore possible ways to enhance their turnover rates.  This will further contribute to the understanding of extremozymes and to lay the bases to rational enzyme engineering, to make them even more attractive for biotechnological application.

Objective

Despite their desirability, only a few extremozymes have been commercially exploited, particularly due to difficulties found in the culture and production of extremophiles. However, the continuous progresses in cloning and expressing the genes of extremophiles in mesophilic hosts will certainly increase the interest in this field and the biocatalytic applications of extremozymes.

Here we propose to study two extremozymes with potential industrial applicability, using computational approaches:

  • - The sulphur oxygenase reductase (SOR), which is the initial enzyme of the sulfur oxidation pathway in the thermoacidophilic Archaeon Acidianus ambivalens that grows optimally at 80ºC and pH between 1 and 3. SOR catalyzes an oxygen-dependent sulfur disproportionation to H2S, sulfite and thiosulfate and may have important biotechnological applications in processes such as biomining of base and precious metal sulfide ores. Control of biological sulfur oxidation is important in bioleaching operations for the industrial bioleaching of metal sulfides or heavy metal recovery from industrial wastes.
  • - The mannosylglycerate synthase (MGS), which catalyzes the synthesis of α-mannosyl-D-glycerate using GDP-mannose as the preferred donor species. This enzyme has a crucial role in the protection of the extremophile organism from the harsh conditions it endures through the formation of molecules that confer tolerance to osmotic stress and thermostability. The properties of these molecules have been demonstrated to be industrially applicable in the preservation of biomaterials.

The computational methods that we intend to apply have been a major contributor in the study of proteins. In particular, quantum mechanics/molecular mechanics (QM/MM) schemes have helped to unveil several catalytic mechanisms with atomistic detail and have allowed to obtain the energy profile of the catalytic reactions. This enables a better understanding of the reaction and aids on the rational prediction of mutations, which would enhance the catalytic rate. The merits of this methodology have been recognized by the attribution of the Nobel prize in 2013 to Michael Levitt and Arieh Warshel, who originally formulated the model, along with Michael Karplus for the development of multiscale models for complex chemical systems.

The central goal of this project is to study the intriguing structural features and to unveil the catalytic mechanisms of SOR from Acidianus ambivelns and MGS from Rhodothermus marinus applying state of the art computational methods, namely QM/MM schemes. The obtained results will contribute to a better understanding of the unique characteristics that the enzymes from extremophile microorganisms possess in order to be active and effective under extreme conditions, in fact unbearable for most life forms. Given the potential biotechnological applications of extremozymes, our data may also further stimulate the search and study of extremophiles. For that reason, we intend, also, to explore ways to make these extremozymes more efficient, using an innovative approach of rational optimization of the turnover rates through point mutations, based on the study of the catalytic mechanism with QM/MM methodology. This would make SOR and MGS even more attractive for biotechnological applications.

In short, our project intends to:

  • - Identify the unique structural characteristics SOR and MGS possess that allow them to be catalytically active under extreme conditions.
  • - Obtain an atomistic level description and the energy profile of the catalytic mechanisms of SOR and MGS and to identify their rate-limiting step.
  • - Find ways to enhance the turnover rates of the studied enzymes to make them more attractive for biotechnological applications.

Supervisors: Maria João Ramos e Pedro Alexandrino Fernandes (REQUIMTE, FCUP)

 

UP5 - IONERA – IONic liquids and organic salts to ERAdicate tropical diseases

Synopsis

Based on our long-term interest in finding new value for old medicines, we have been focusing our research in what is called the 3R’s of drug development (DRRR or DR3 – Drug Rescuing, Repurposing, and Recycling).[1] The DR3 approach is particularly useful when dealing with diseases that are endemic to low income countries, as it potentially delivers new therapeutic approaches at a very low cost. In this connection, we have recently started a new line of work where we combine drugs with opposed polarities (acids and bases) to produce therapeutically-relevant Organic Salts (OSs) and Ionic Liquids (ILs); this is a remarkably simple, cost-effective and eco-friendly strategy where known active pharmaceutical ingredients (APIs) can be combined to produce multi-action water-soluble drugs by means of simple acid-base titrations in aqueous or hydro-alcoholic media.[2,3]

Motivated by our recent and quite promising results with new ILs derived from classical antimalarial drugs,[3] we now wish to engage into a new doctoral project aimed at the chemical synthesis, and physico-chemical and biological profiling of novel OSs/ILs obtained by combination of carboxylate drugs with trypanocidal phosponium cations;[4,5] although other classes of anti-infective drugs are also envisaged, antiparasitics (antimalarial, leishmanicidal and trypanocidal drugs) and anti-retrovirals (anti-HIV drugs) will be our main focus, as they target diseases that are frequently established as co-infections in low-income tropical countries.[6,7] The long experience of the supervisor (http://orcid.org/0000-0002-6018-4724) in applying the DR3 concept to classical antiparasitics, and the expertise of the co-supervisor (http://orcid.org/0000-0002-1761-117X) in APIs-derived ILs, as well as their well-established collaborations with experts in biophysics and parasitology/microbiology, altogether provide excellent prospects on the success of this project.

Cited references

[1] Teixeira et al., Chemical Reviews, 114, 11164-11220 (2014); [2] Ferraz et al., RSC Advances, 4, 4301-4307 (2014); [3] Ferraz et al., RSC Advances, 6, 56134-56138 (2016); [4] Taladriz et al., Journal of Medicinal Chemistry, 55, 2606-2622 (2012); [5] Alkhaldi et al., International Journal for Parasitology: Drugs and Drug Resistance, 6, 23-34 (2016); [6] Cohen et al., Clinical Infectious Diseases, 41, 1631-1637 (2005); [7] Kagira et al., Journal of Tropical Medicine, 2011, Article ID 248914 (2011).

Supervisor: Paula A. C. Gomes, (REQUIMTE, FCUP)

Co-supervisor: Ricardo J. V. Ferraz, (ESS-PPorto, REQUIMTE)

 

UP6 – Exploiting the potential of Deep Eutectic Solvents (DES) and Natural Deep Eutectic Solvents (NADES) in (bio)chemical analysis

A new generation of solvents, named Deep Eutectic Solvents (DES), has emerged at the beginning of this century as a new alternative for the implementation of more sustainable and greener chemical processes. DESs are less toxic and often biodegradable solvents that are minimally prepared from easily obtainable, low-cost, and eventually recyclable materials.

Preparation of these DESs can be obtained by simply mixing together two safe components such as choline chloride, as hydrogen bond acceptor (HBA), and urea, glycerol or several carboxylic acids (levulinic, glutaric, malonic, oxalic, and glycolic) as hydrogen bond donors (HBD), which are then capable of forming an eutectic mixture, liquid at ambient temperature. Natural Deep Eutectic Solvents (NADES) further emphasize the green characteristic of these solvents by resorting to natural primary metabolites such as sugars, sugar alcohols, organic acids, amino acids and amines, often complemented with variable water amounts. In its synthetic process a theoretical E-factor of 0 can be achieved and a value of nearly 100% can be assumed regarding carbon efficiency.

The objective of this project is the preparation, characterization and exploitation of the potential of DES and NADES. It includes the study and evaluation of distinct precursors for DES preparation aiming at tailoring their properties for specific purposes. The as-prepared materials will be characterized regarding their thermophysical and thermodynamical properties. Also, the evaluation of its toxicology, biodegradability and reusability is mandatory for the assessment of its safety, health and environmental impacts. With the data obtained structural elements/properties relationships will be established for the implementation of a generation of eco-friendly alternatives.

The potential of the developed DES and NADES will be exploited in (bio)catalysis, for the implementation of fast oxidations, in greener extractive processes and as either solvents or precursors in the synthesis of nanomaterials. In a final stage, and profiting from the advantages features arising from DES and NADES utilization the research will be focused on the implementation of more environmental friendly analytical methods in the biomedical and environmental fields. When justified on-line approaches using automated flow methodologies will be also contemplated.

Ultimately it is aimed alternative solvents (DES and NADES), that can boost the development of sustainable processes, complying directly or indirectly with some principles of green chemistry (1st, 3rd, 4th, 5th, 7th, 10th, 12th).

Supervisor : Maria Lúcia Marques Ferreira de Sousa Saraiva

 

UP7 – Early biomarkers of renal dysfunction (beta-trace protein), tubular lesions (neutrophil gelatinase-associated lipocalin, NGAL) and renal endothelial dysfunction (asymmetric dimethylarginine, ADMA)

The prevalence of chronic kidney disease (CKD) is increasing worldwide and is associated with high morbidity and health care costs. Biomarkers of kidney function, such as glomerular filtration rate, blood urea nitrogen, serum creatinine, albuminuria and proteinuria, are usually used in clinical practice for diagnosis and prognosis of CKD. However, these traditional biomarkers show significant increases only when about 50% of renal function was lost; thus, they increase when several injuries have already occurred in renal cells.

The detection of early kidney injury and of progression of the disease is an emergent area of research in this increasing public health problem.

ELISA methods are the main tools for the analysis of circulating biomarkers of CKD and are commonly used in clinical analysis. Some of these methods are not sufficiently sensitive for the detection of the low biomarker concentrations, especially in the early stages of the disease. To overcome some of these problems, electrochemical (bio)sensors can be adequate alternatives because of their high selectivity and sensitivity, which allows early detection of many diseases. Furthermore, these sensors are excellent to be included into point-of-care devices due to their fast response, simplicity, low cost, easy miniaturization and integration into microfluidic (lab-on-a-chip) devices. Another advantage is the possibility of incorporating individual sensors into multiplexed detection systems. Like this, they can provide fast recording of biomarker profiles, which can play an important role in early detection, progression, outcome of the disease and personalized medicine.

The aim of this proposal is to develop and validate innovative detection technologies for reliable biomarkers of early renal injury that would allow a i) more premature treatment of renal injury; ii) avoid or minimize the progression of the disease; iii) improve diagnosis, prognosis and self-management of CKD patients; iv) contribute to economic growth through innovation.

In a first approach, sensing tools will be developed for biomarkers of renal (dys)function (beta-trace protein), tubular lesions (neutrophil gelatinase-associated lipocalin, NGAL) and renal endothelial dysfunction (asymmetric dimethylarginine, ADMA).

For this project, CKD patients (stage 1-5) from the Nephrology Outpatient Clinic of Centro Hospitalar do Porto, and end stage renal disease patients, under dialysis, from different Hemodialysis Clinics from the north region of Portugal, will be enrolled in the study. The biomarkers under study will be evaluated by traditional assays and used to validate and to correlate and with those obtained by the new technologies and with other analytical and clinical data of CKD patients.

These studies will strength the linkage between research, new technologies and innovation, and will contribute to scientific knowledge, concerning CKD, a public health issue with a high economic regional and national impact; moreover, the out coming results have potential for technologic transfer. 

Supervisor: Alice Santos Silva (REQUIMTE)

 

UP8 - Stimuli-Responsive Nanovesicles from Ionic Liquid-based Surfactants for Nanomaterial Templating and Delivery Applications

Stimuli-responsive self-assembled structures—such as micelles, vesicles, nanotubes and liquid crystalline particles—built from surfactants, and amphiphiles in general, are fascinating bottom-up soft materials for a wide variety of applications in nanotechnology, such as templating of “hard” inorganic nanomaterials and smart delivery of biomolecules (e.g. drugs, genes and proteins). In particular, nanovesicles of high stability, low polydispersity and spontaneous formation are interesting and challenging from a thermodynamic and colloidal point of view. Besides, they may also open doors for a plethora of applications if their formation and response is “smartly” controlled and they bear sustainable credentials (environment- and cost-wise). Building on our previous experience with catanionic vesicles from conventional surfactants and amino acid-based surfactants, this project follows a novel approach by selecting ionic liquid-based surfactants (ILS)—i.e. surfactants combining the unique properties of ILs—of opposite charge that bear stimuli-responsive motifs, namely with respect to temperature, pH and light. The basic aim of the project is thus to: (i) develop responsive, robust nanovesicles fabricated from mixed ILS in aqueous media, using a systematic approach (chain length or headgroup variation); (ii) to characterize the nanovesicles in terms of size, shape, stability, equilibrium properties and liability to programmed stimuli, using a toolbox of methods, e.g. SEM, TEM, scattering (light, SAXS, SANS) and self-diffusion NMR; (iii) to develop specific and sustainable applications using the most promising systems, namely for soft-templating of nanoparticles and controlled encapsulation/release of biomolecules (viz. genetic materials).

Supervisor: Eduardo F. Marques

 

UP9 - Avaliação energética e de reatividade em fragrâncias e aromas

As fragrâncias oferecem uma pluralidade de odores que estimulam os sentidos e induzem várias reações sensoriais. Estas substâncias estão presentes numa grande variedade de produtos no nosso dia-a-dia, como em cosméticos, champôs, perfumes, óleos essenciais, produtos de higiene pessoal e noutros materiais de consumo, como produtos de limpeza e purificadores de ar, entre outros. A exposição humana a este tipo de materiais é elevada, desde o contacto com a pele à inalação de vapores, a que se adiciona o facto de surgirem como poluentes em sistemas aquáticos, tornando-se assim numa cada vez maior preocupação em termos de saúde. Duas principais organizações científicas internacionais – Research Institute for Fragrance Materials, Inc (RIFM) e International Fragrance Association (IFRA) - regulam o setor de fragrâncias, de acordo com as normas da European Chemical Agency para produtos químicos (REACH - Registration, Evaluation, Authorization and Restriction of Chemicals) e da US Environmental Protection Agency. O RIFM tem como missão gerar, monitorizar e avaliar os dados de segurança de cerca de 5000 ingredientes utilizados em formulações de fragrâncias, designadamente as suas propriedades físico-químicas, regulamentares e toxicológicas. O elevado número de substâncias existentes e a escassez de dados experimentais disponíveis para avaliar os potenciais riscos levou a que as autoridades governamentais recomendem o uso de modelos de estimativa, por exemplo [Q]SARs (Quantitative Structure-Activity Relationships) como alternativa para avaliar riscos para a saúde humana e segurança ambiental. Embora a confiança nos modelos QSAR e SAR seja relativamente elevada, as limitações dos modelos disponíveis poderão ser subestimadas ou mesmo desconhecidas. De facto, a maioria dos dados físico-químicos apresentados e utilizados pela RIFM na avaliação da segurança de fragrâncias são valores estimados, sendo a falta de dados experimentais um obstáculo para o estabelecimento de esquemas de estimativas fiáveis. Este trabalho pretende suprimir parte das lacunas existentes, pela obtenção de dados experimentais, sua validação, expansão e, consequente, aperfeiçoamento dos métodos de estimativa. A estratégia do projeto será baseada numa combinação de estudos experimentais e computacionais de compostos chave, para se obter o máximo de informação de modo a estabelecer e validar esquemas de previsão robustos para estimativa de propriedades de compostos cujo estudo seja inviável. A interligação das diferentes propriedades termoquímicas experimentais obtidas a partir destas técnicas será fundamental para o sucesso do projeto. Pretende-se que o principal objetivo deste projeto seja atingido através de uma programação cuidada das seguintes atividades: 1) Caracterização térmica das fases sólida e líquida por calorimetria diferencial de varrimento. 2) Calorimetria de combustão para determinar entalpias de combustão e formação na fase condensada de fragrâncias “chave”. 3) Determinação de pressões de vapor, entalpia e entropia de transição de fase (sólido-gás e líquido-gás) por cromatografia gasosa, microcalorimetria Calvet, método de efusão de Knudsen e, quando necessário, pelo método estático. Parte deste trabalho deverá ser realizado num laboratório estrangeiro. 4) Os estudos energéticos em fase gasosa serão realizados com base nas entalpias de combustão e de transição de fase e, ainda, computacionalmente. Esquemas de previsão de entalpias de formação de compostos semelhantes serão desenvolvidos. 5) Estudos computacionais. A otimização de geometria de moléculas chave por métodos computacionais de alto nível proporcionará uma melhor compreensão da sua estrutura, reatividade e da entalpia de formação na fase gasosa. Os cálculos computacionais também serão úteis na avaliação de outras propriedades iónicas termodinâmicas. A termoquímica computacional será um recurso complementar na avaliação dos resultados experimentais e na previsão de propriedades de compostos relacionados cujo estudo experimental seja inviável. 6) A análise por espectroscopia de UV-Vis irá permitir a identificação da gama de absorção de UV dos compostos em diferentes solventes e permitirá a determinação de energias de excitação espectroscópica. Estas propriedades serão analisadas e comparadas com as obtidas pela via computacional. 7) Os estudos de solubilidade, utilizando diferentes técnicas tais como calorimetria de solução e espectroscopia UV-VIS, proporcionarão informação sobre a dispersão aquosa no meio ambiente.

Supervisors: Maria das Dores Melo da Cruz Ribeiro da Silva and Vera Lúcia de Sousa Freitas

 

UP10 - Imprinted hollow TiO2 microspheres for selective photocatalysis

Supervisors: Manuel Augusto Gomes de Oliveira Azenha and António Fernando Sousa da Silva

 

UPR1: Chemical changes and off-flavour development in beer during storage.

The flavour of beer, a complex balance of characters from malt, hops and yeast, deteriorates from the moment it is packaged, through the development of stale flavours. Delaying flavour staling, to prolong shelf life, is therefore one of the greatest challenges facing the brewing industry today. Most pathways contributing to the changes which take place in the flavour chemistry of beer interact in a complicated and dynamic way.

This project aims at identifying and characterizing factors potentially involved in the process of beer staling. Novel analytical methodologies will be developed for the determination of compounds having extremely low flavour thresholds, whose sensorial impact is noticed when present in very small quantities. A vacuum distillation system specifically developed for volatile species coupled to one and two dimensional chromatographic techniques with mass spectrometric detection will be used. The use of headspace solid phase microextraction, followed by qualitative mass spectrometric analysis, is also envisaged for the characterization of the volatile fraction in beer.

This project will be conducted in close collaboration with the brewing company UNICER, which will supply samples and provide access to the production lines.

Supervisors: Luís Guido (FCUP) e Marco Gomes da Silva (FCT/UNL)

 

UPR2: Nanostructured biomarkers sensor integrating membrane purification processes for the on spot evaluation of chronic kidney disease.

Chronic kidney disease (CKD) is a silent threat pathological condition with an increasing prevalence worldwide. The prevalence of CKD increases with age to about 40% in adults with more than 65 years. Sooner or later, the prognosis of cardiovascular disease (CVD) is established as being associated with a systemic inflammatory condition. Laboratory evaluation of kidney function such as the estimated glomerular filtration rate, blood urea nitrogen, serum creatinine, albuminuria and proteinuria, are usually used for diagnosis and prognosis of CKD. These clinical indicators have no specificity for the pathological condition and become significant too late, generally when half of kidney function is irreversibly compromised. The urgent need of CKD and CVD risk biomarkers is thus justified in several stages of the disease: early detection, prognosis, personalized medication and treatment follow-up and of patients. The development of microfluidic systems has been motivated by the need of implementing efficient on spot analytical systems requiring the use of minute sample volumes, rendering cheaper and faster analysis. In this sense, microfluidic systems acquire a particular relevance in the development of micro scale devices for medical diagnosis, promoting the access of populations to basic health conditions. Major challenges of the implementation of these devices refers to their ability to process minute volumes of complex biologic fluids, such as blood, with minimal interferences from further fluid components/impurities on the detection of a specific biomarker. The aim of this project regards to neutrophil gelatinase-associated lipocalin (NGAL); asymmetric dimethylarginine (ADMA) and cystatin content in blood as biomarkers. For these a disposable nanostructured electrochemical biosensor with integrated membrane purification process will be developed for each biomarker to be used in the future as a point-of-care device. Membranes processes will allow sample pre-cleaning (before it reaches the detector) by selective removal of sample contaminants, leading to the production of permeates enriched in the biomakers, thus facilitating the detection of low concentrations of them, anticipating the diagnosis. The design of magnetic-responsive membranes is proposed to attempt the attenuation of membrane biofouling.

Supervisor: Maria da Conceição Branco Montenegro (LAQV/Requimte)

Co-Supervisor: Carla Portugal (FCT-UNL)

 

 

NOVA

 

NOVA1.Title: CO2 Capture Strategies using Bio-based Ionic Liquid Materials

Supervisor: Isabel Marrucho (ITQB-NOVA)

Abstract

One of the most interesting characteristics of ionic liquid-based materials is their remarkable CO2-afinity. The last decade has been very fruitful in the identification of new chemical functionalities and structures that provide good performances for the preparation of advanced materials with superior CO2 absorption and membrane separation. Simultaneously, to impart sustainability to CO2 capture processes new nature inspired materials have also been recently proposed.

Our recent studies have been unveiling the use of ionic liquid-based materials, such as ionic liquids, poly(ionic liquid)s and deep eutectic solvents as a powerful strategy to design improved CO2 separation membranes, since these materials offer a pathway to fine-tune their gas permeation properties and affording performances that could not be achieved by conventional polymers.

The aim of this project is to prepare new efficient membranes, based on nature inspired functionalities, to deliver high performances in CO2 separation processes.  

 

NOVA2. Title: Biocatalysis for tackling lignocellulose recalcitrance and valorisation

Supervisor: Lígia O. Martins (ITQB-NOVA)

Abstract :The proposal focuses on the investigation of bacterial DyP-type peroxidases.[1 ] DyPs are potential important biocatalysts for industrial oxidations and redox conversion processes in particular for lignin deconstruction. This is considered a key step for utilization of lignocellulosic biomass for bulk and fine chemicals, materials and biofuels. Biocatalysis offers an environmentally friendly tool for lignin degradation, potentially holding the key for its successful valorisation. The multidisciplinary research in this proposal aims at: (i) advance the understanding of the catalytic, stability and structural fingerprints of bacterial DyPs,  (ii) improve their performance and robustness using protein engineering approaches, including directed evolution [2 ], (iii) identify intermediates and products of enzymatic reactions with lignin model compounds through complementary information derived from Nuclear Magnetic Resonance (NMR) and Mass Spectrometry [3 ], (iv) exploit their potential in multi-enzymatic bioprocesses [4 ] in combination with pyranose 2-oxidases [5 ] in the valorization of lignin/lignocellulose waste preparations. This research has potential to generate results that represent progress beyond the state of the art contributing to the full exploitation of plant biomass, a top priority area in the EU and worldwide.

 

  1. Santos, A., Mendes, S., Brissos, V. and Martins, L. O. (2014) New dye-decolorizing peroxidases from Bacillus subtilis and Pseudomonas putida MET94: towards biotechnological applications. Appl Microbiol Biotechnol. 98, 2053-2065
  2. Brissos, V., Ferreira, M., Grass, G. and Martins, L. O. (2015) Turning a hyperthermostable metallo-oxidase into a laccase by directed evolution. ACS Catalysis. 5, 4932-4941
  3. Pereira, L., Coelho, A. V., Viegas, C. A., Canachaud, C., Iacazio, C., Tron, T., Robalo, M. P. and Martins, L. O. (2009) On the mechanism of biotransformation of the anthraquinonic dye Acid Blue 62 by laccases. Adv. Synth. Catal. 351, 1857-1865
  4. Mendes, S., Farinha, A., Ramos, C. G., Leitao, J. H., Viegas, C. A. and Martins, L. O. (2011) Synergistic action of azoreductase and laccase leads to maximal decolourization and detoxification of model dye-containing wastewaters. Bioresource Technol. 102, 9852-9859

Mendes, S., Banha, C., Madeira, J., Santos, D., Miranda, V., Manzanera, M., Ventura, M. R., van Berkel, W. J. H. and Martins, L. O. (2016) Characterization of a bacterial pyranose 2-oxidase from Arthrobacter siccitolerans. J. Mol. Cat. B: Enzymatic, in press. DOI: 10.1016/j.molcatb.2016.11.005

 

NOVA3. Title: On the Development of Green Catalytic Systems Based on DNA

Advisor: Ana Petronilho (ITQB-NOVA)

Abstract: DNA-mediated catalysis is an emerging area in the field of bioinspired catalytic processes. It exploits the chirality of DNA in asymmetric synthesis using hybrid catalysts comprised of a metal complex anchored to a DNA strand. However, controlling metal coordination and defining the number of active sites remains a considerable challenge. Developing synthetic systems that allow for the incorporation of a defined number of metal sites, obtaining one DNA catalysts with multiple catalytic tasks is thus highly desirable.

In this project we aim to develop DNA functionalized catalytic systems bearing transition metals with well-defined connectivity, via N-Heterocyclic carbenes derived from nucleobases. Nucleobases form strong hydrogen bonds, which are responsible for DNA structure and functions. Application of these interactions in catalytic processes will be employed as a catalytic strategy to provide substrate recognition, proton-transfer facilitated processes and metal coordination.

This methodology constitutes a unique approach combining a strong donating carbene ligand with the additional coordination sites that nucleobase provides, allied with high propensity of nucleobases to form strong hydrogen bonds. When successful this project will fabricate a DNA based compound bearing different catalytic functionalities. This feature will enable to perform an array of catalytic processes with only one molecule, and will constitute a great advance in the field of sustainable catalytic processes.

 

Nova 4. Title: Development of Theragnosis Dry Powder Formulations Using scCO2 technology

Supervisor: Ana Aguiar Ricardo (FCT-NOVA)

Abstract

Lung diseases are currently among the top ten causes of death worldwide. In patients with such diseases, inhalation is considered the most relevant administration route but the least straightforward one when it comes to formulation development. This project aims at developing dry powder formulations with chemical targeting ability, imaging modality, highly flexible drug dose loading, and aerodynamic properties using more sustainable technologies.

Major objectives will consist on:

  1. i) Integration of scCO2–based processes with nanotechnologies, namely living polymerization and layer-by-layer deposition for preparation of complex nano sensing and delivery systems (NDS).
  2. ii) Micro encapsulation of engineered NDS using supercritical CO2 spray-drying.
  • iii) Evaluation of powder properties, in-vitro performance, manufacturability and environmental impact.
  1. iv) Systematic quality by design approach to create design space platforms for production guidance of DPIs.

 

NOVA 5.Title: Self-Assembly of polythiophene derivatives with carbon based materials for electrochromic devices

Supervisors: A. Jorge Parola, César A.T. Laia (FCT-UNL, LAQV-REQUIMTE) and Davide Bonifazzi (Cardiff University)

Abstract

Carbon nanomaterials in their different allotropic forms (fullerene, nanodiamonds, quantum dots, nanotubes, graphene, etc.) hold great promises both as green organic material constituents and as dopant of other organic polymeric materials. Synthetic semi-conducting thiophene polymers with specific monomers with groups such as pyrene lead to improved photo- and electroactive materials, enhancing at the same time the composite mechanical and optical properties.  Recent results from a combined effort by FCT-UNL, YNVISIBLE company and Cardiff University have shown that the simple mixing of carbon nanotubes with a pyrene-modified PEDOT polymer lead to electrochromic devices featuring unexpectedly high coloration efficiency, fast switching kinetics, and extremely long lifetimes (patent recently submitted). In this context, new polythiophene materials with aromatic anchors such as pyrene will be synthesized to develop stable inks with carbon materials such as quantum dots and graphene’s. Mastering the interaction between the carbon derivatives and the polymer via non-covalent interactions should allow the control of the nanostructure of the composite leading to superior electrochromic materials, with different colors and enhanced switching times and durability. The work will be carried out in the context of the Marie Skłodowska-Curie Action “Research and Innovation Staff Exchange (RISE)” (project “INFUSION”, Engineering optoelectronic INterfaces: a global action intersecting FUndamental conceptS and technology implementatION of self organized organic materials), with FCT-UNL and Cardiff University.

 

NOVA 6. Title: Fluorinated Ionic Liquids as Novel Task-specific Fluids

Supervisors: Ana B. Pereiro, João M. Araújo (FCT-NOVA)

Abstract

The pharmaceutical market is evolving in a context of increasing economic pressure due to the reduction of healthcare costs by public authorities, the increase of generic substitution, and the rate of failure during drug development, 90% in general. Therapeutic proteins have been shown to be able to control and cure diseases, and a market for them has recently sprung up. However, protein instability still limits protein-based pharmaceuticals and therapeutics. It is therefore important to develop methods that can maintain the proteins in a stable and active state. The unique features of ionic liquids (ILs) and the possibility of tailoring them to have certain desired properties and interactions represent major advantages of these systems compared to the more traditional solvents and surfactants. These properties are driving the application of ILs into biological systems. This project will explore the potential use of novel ILs as drug delivery systems by studying their effect in the solubility, stability, activity, and structure of therapeutic proteins.

 

NOVA 7. Title: Cascade processing of Mediterranean food industry waste streams using green solvents

Supervisors: Alexandre Paiva, Susana Barreiros, Pedro Simões (FCT-NOVA)

As stated in the H2020 directives, cleaner processes are crucial for a sustainable future. Although several advances to the state of the art have been achieved in the field of green chemistry, the implementation of green chemistry principles in industry is far from being a reality. That requires the integration of different green chemistry approaches, such as a better use of raw materials, clean solvents, and energy, as well as the production of minimal amount of waste.

Mediterranean food is known for its health benefits, and the food waste feedstocks still hold large potential for the production of high added-value materials with applications in, e.g., the pharmaceutic and cosmetic and nutraceutical industries.

The main objective of this project is the design of a cascade process for the valorization of by-products from the winery and coffee industries, using green solvents such as deep eutectic solvents (DES), hot compressed water (HCW), and supercritical carbon dioxide (scCO2), as schematically shown in Figure 1. The smart design of the integrated processes will allow for the extraction and fractionation of added-value products with minimal waste production, energy load and environmental impact, thus following the green chemistry principles.

 

NOVA 8. Title: A CHALLENGING GUANIDINE MOLECULE – synthesis and applications

Supervisors: Paula Branco, Luísa Ferreira (FCT-NOVA)

Abstract

The production of sufficient material of new lead structures for broad biologic studies and applicability by, chemical modifications to improve therapeutic action, complete syntheses, and semisyntheses, is of utmost importance [1]. Cernumidine identified by our research team [2], is a natural (2-aminopyrrolidin-1-yl)carboxamidine alkaloid condensed with an isoferulic (3-hydroxy-4-methoxycinnamic) acid unit that was present in the leaves of Solanum cernuum Vell (Solanaceae), endemic in southern and southeastern Brazil (Fig 1). This compound presents a singular and not yet reported C4-N aminoguanidine core and display inhibition of interleukine-8 production by HT-29 colon carcinoma cells. These two facts led us to study this challenging molecule as much as lead compound for therapeutic intervention by targeting tumours environment and as a structure core for organocatalysis. The main goals of this project are:

1) synthesis of cernumidine and cernumidine analogs. Proline, as a natural amino acid and building block of recognized importance is an expected starting material for the construction of the C4-N aminoguanidine core.

2) study the biological behaviour of the synthesized compounds against IL-8 production.

3) apply the C4-N aminoguanidine core in organocatalysis. New chiral guanidine catalyst will be developed and applied in the formation of new C-C bonds which is a valuable approach to a more sustainable chemistry.

It’s expect the project to strongly contribute to the establishment of new lead structures that can play their role against inflammation-cancer. The supervisor and co-supervisor are experienced scientists with expertise not only in organic synthesis, but also in structural identification.

 

NOVA 9. Title: Chemical Characterization of Amphora Wines

Supervisors: Marco R. da Silva

Abstract

In the south of Portugal, in Alentejo region, there still is a tradition of making wine in the ancient way using clay amphoras, like the Greeks and the Romans did. The amphoras are impermeabilized using pitch, and these wines called “Vinhos de Talha” (Amphora wines) are made from red grapes (Red wines), white grapes (White wines) and a mixture of red and white grapes (Palhete wines). The technology associated with these wines is the same for red, white or “palhete” , but due to its unusual technology, “Vinhos de Talha” has unique characteristics, yet no reports can be found in literature about the physical-chemical characteristics of these wines. Actually, “vinho de talha” is now being apply to world cultural or natural heritage as described in the UNESCO World Heritage Convention, established in 1972.

 

Since the technology associated to these wines are very different from the usual way of winemaking, and the materials that are in contact with the fermenting musts and wines are also different from the traditional inox or wood vessels, the main objective of this work is:

  • 1) to characterize the volatile composition of these wines. Volatile composition of wines will be analyzed by head-space solid phase microextraction hyphenated with gas chromatography – mass spectrometry (HS-SPME-GC/MS and GCxGC-FID fingerprinting).
  • 2) To characterize the mineral composition of these wines. Mineral composition will be done by ICP/OES or ICP/MS
  • 3) To characterized the amino acid and volatile phenols profile of these wines by HPLC/DAD

Wines under study will be 10 of each (white, red and palhete) collected at Vidigueira region each year. An assay will also be made in order to have in house made samples: with the same pool of grapes wines will, be made in inox and clay vessels. Clay vessels will also be impermeabilized with pitch and epoxy resins. This assay will allow us to seek for the compounds that can be used as markers of the use of clay vessels with pitch, the most traditional way of doing amphora wines.

 

NOVA 10. Title: Sustainable strategy towards a key peptidoglycan involved in bacteria/host interactions

Supervisor: Maria Manuel Marques , Sérgio Raposo Filipe (FCtNOVA)

Abstract

Conversion of chitin fragments into high-value oligosaccharides opens room for a straightforward access to biological important carbohydrates that are difficult to produce by multistep assembly of the (1,4) glycosidic bond. Over the last ten years one-pot regioselective protection of monosaccharides has emerged as an excellent and sustainable alternative to decrease the number of synthetic and purification steps. However the regioselective protection of disaccharides has been rarely explored, in particular one-pot regioselective protection of chitooligosaccharides has not yet been investigated. Glucosamine is a challenging scaffold, and many problems have been associated with the sequestration of the catalyst by the N-containing functionalities.

Peptidoglycan (PGN), a major component of the bacterial cell wall, is associated with many bacteria/host interactions and bacterial infections. Despite great progress, the chemical synthesis of PGN is still a challenging task and a major limitation for progress in the investigation of PGN role in bacterial infection diseases.

In this project a novel synthetic strategy will be investigated to address the challenging synthesis of PGN carbohydrate backbone. A one-pot regioselective protection of oligosaccharides, obtained from controlled depolymerization of chitin, will be investigated allowing a straightforward and innovative access to the PGN carbohydrate backbone while avoiding the problems associated with the use of glucosamine scaffolds. A library of PGN fragments of varied composition will be prepared and applied in molecular recognition studies with different PGN binding proteins (bacterial proteins involved in the maturation of PGN that recognize the stem peptide and Drosophila PGN receptors that are required to trigger an host innate immune response upon recognition of PGN in the Drosophila). The synthesis of complex carbohydrate oligomers is a puzzling task and often requires high degree of functionalization, and preparation of glycosyl donors and acceptors. The discovery of new synthetic approaches to functionalized chitooligosaccharides will improve the assembly of biological relevant compounds such as the complex PGN carbohydrate backbone in a straightforward route. The contribution of bacterial infectious diseases to the leading cause of death worldwide is increasing PGN role in host recognition is still not understood, thus it is emergent to determine the influence of PGN composition on the recognition by targets from the innate immune system. The results obtained in this project will allow the understanding of how bacteria are recognized by the host, and how PGN composition allows bacteria to infect the host, ultimately and undoubtedly contribute to the field of bacterial infections.

 

Nova 11. Title: Luminescent Au(I) water soluble supramolecular aggregates and gels in metamorphic  sensing.

Supervisors: João Carlos Lima (FCT-NOVA), Jorge Artur Carneiro Moro, (FCT-NOVA) Jorge Ascensão Oliveira (FF-UP)

Abstract

This project will develop supramolecular structures and hydrogels soluble in water that can aggregate based on the ability to establish aurophilic interactions together with other weak interactions (hydrogen bonding,  stacking…). The linear structure of Au(I) complexes is ideal to promote self-assembly via intermolecular aurophilic bonds, yielding elongated structures with new luminescence properties, a phenomenon known as Aggregation Induced Emission (AIE). The project consists of using Au(I) complexes as new sensor systems for biooligomers with repeated motifs, namely polyglutamine (PolyQ), a biopolymer that occurs in vivo and is abnormally expanded in the mutant proteins associated with Huntington’s disease and several spinocerebellar ataxias. The complexes will comprise fluorescent ligands (e.g. naphthyridine) which forms stable hydrogen bonds with the target (e.g. PolyQ), allowing for a cooperative effect in the formation of successive aurophilic bonds, yielding linear Au(I) elongated polymers. The intrinsic emission changes upon changes in the morphology of the supramolecular assemblies will be used as a new sensing strategy for biological relevant species. Water-soluble compounds with cell penetrating capabilities will be tested in cellular models of polyglutamine expansion diseases, for their detection capabilities and for their ability to modulate the aggregation profile of the mutant proteins.

 

NOVA 12. Title: Synthesis and applications of Biodegradable Luminescent Silica@Nanoparticles (mSiO2) as Drug Delivery carriers in Cancer Cells

Supervisors: Elisabete Oliveira, Carlos Lodeiro (FCT-NOVA), Maria da Graça Neves (U Aveiro)

Abstract

Luminescent inorganic mesoporous silica nanoparticles (mSiO2) are a new generation of nanocarriers acting as all-in-one diagnostic and therapeutic tools. They can be used to visualize and treat various diseases. Among fluorescent agents, inorganic quantum dots (QDs) have excellent optical properties; however, depending of the components they also are highly toxic, and non-biodegradable, due to the use of heavy metal elements in the core of the nanoparticles [1]. Silicon QDs emerged in the last years as a new promising biocompatible emissive nanomaterials [2, 3]. Such properties make mSiO2, and SiQDs excellent nanomaterials to be used in the design of new nanocarriers for smart drug delivery in cancer cells. However, the major concern in these drug delivery systems using nanomaterials is that they must be biocompatible and safely eliminated in a timely fashion yet, surprisingly little effort has been put into engineering self-destruction of errant nanoparticles into non-toxic products [4, 5, 6]. Regarding such aspect, herein it is proposed a PhD project based on the synthesis and characterization of a new generation of biocompatible and biodegradable luminescent inorganic nanomaterials (SiQDs@mSiO2) for the screening of new biomarkers in liquid biopsies and for multiple drug delivery in cancer cells.

The project aims are:

  • - Synthesis of biocompatible Silicon Quantum Dots (SiQDs) and red emissive porphirins
  • - Synthesis of mesoporous silica nanoparticles doped with SiQDs (NANO).
  • - In vitro biodegradability and characterization of these nanomaterials
  • - Screening of overexpressed biomarkers by the use of NANO , in human liquid biopsies. Nanomaterials with different pores will be tested to find the best separation system.
  • - Toxicological studies in cancer cells of all nanoparticles synthetized.
  • - Targeting of the nanocarriers and encapsulation of multiple drugs molecules
  • - Use of synthesized biodegradable nanomaterials as stimulated drug delivery, as theranostic nanovectors.