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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.

Applications open until January 15th 2018

The call for applications for 10 (ten) individual fellowtships is open for the 2017/18 class of the PhD programme in Sustainable Chemistry (PDQS), organized by the Universities of Aveiro, Nova Lisbon and Porto, and financing by the Portuguese Foundation of Science and Technology (FCT- Fundação para a Ciência e Tecnologia).

The PDQS PhD grants are for four consecutive years and, subject to the FCT regulations, currently include:

- A monthly salary of 980 € (tax free);
- Annual co-payment for tuition or fees;
- Rotation laboratories (at Portuguese institutions located in different towns).

Admission requirements

- Candidates must hold a Master degree in any area of Science and Technology, with at least 18 ECTS credits in Chemistry or equivalent subjects.

- Minimum Grade-Point Average (GPA) of 14/20 (Portuguese Scale or equivalent by conversion in case of foreign candidates. The GPA is calculated using the following formula: 0.6 GPA Undergraduate Degree + 0.4 GPA Master 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.

- Foreign degrees must be registered or recognized by the Portuguese State Higher Education Agency (DGES). Academic degrees awarded by foreign higher education institutions must be submitted for the recognition of foreign academic degrees (Decree-Law No. 341/2007, 12th October), or alternatively, the holder of a foreign academic degree may present proof of previous recognition or equivalence provided by an acceptable organization (Decree-Law No. 283/83, 21st June).

- Solid knowledge of English language is mandatory.

Selection criteria

- 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 written curriculum vitae, including the academic background, scientific experience, letter of motivation and reference letters is evaluated and the 2nd step will consist in a personal interview (in person or by video conference), of the 20 best-ranked candidates. Candidates will receive a final mark (1 to 5) and will be ranked accordingly.

- Evaluation in the 1st step considers:

-Previous academic achievements: Masters final average mark, classifications obtained in relevant courses, especially interesting written coursework, communications in meetings and conferences, mobility, academic prizes.

-Scientific background: Research experience, research results, and impact of scientific publications are considered, taking into consideration the role played in those publications.

-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:

-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%)

How to apply

- Formalisation of application – applications should be made exclusively via Internet, at the following address

- List of documents necessary for the processing of applications, being considered obligatory, at risk of exclusion, those indicated below, with the exception of 4.2.4:

- 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:

-Final marks obtained for the undergraduate degree and the Master.

-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.

-Research publications:

- Papers published with original research
- Review papers
- Oral communications to scientific conferences actually delivered by the candidate.
- 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 Prof. Baltazar de Castro  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

Note: In the case of qualifications awarded abroad, the documents should be authenticated by the official educational body of the respective country and recognised by the diplomatic authorities, or Portuguese consular authorities, or carry the apostille of the Hague Convention. The same applies to translations of documents not originally written in Spanish, French or English (translation into one of these languages is obligatory).


Dissemination of results
The results of the evaluation and ranking will be sent to the applicants by email and posted at . After being notified of the results, the candidates have 10 working days to request a hearing according to the Code of Administrative Proceedings (Código do Procedimento Administrativo). Formal contestations of the final decision can be sent to the Directive Council of Fundação para a Ciência e Tecnologia, IP within 15 workdays after the notification. 8. Discrimination and equal access policy: The institutions hosting the Doctoral Programme promote a policy of non-discrimination and equal access, so that no candidate can be privileged, benefited, harmed or deprived of any right or exempt from any duty due, specifically, to their ancestry, age, gender, sexual orientation, marital status, family situation, economic situation, education, origin or social status, genetic heritage, reduced working capacity, disablement, chronic illness, nationality, ethnic origin or race, territory of origin, language, religion, political or ideological convictions or trade union membership.


The grants awarded under this call for applications shall be supported by appropriations from the State Budget of the MCTES (Ministry of Science, Technology and Higher Education/FCT) and when eligible, by funding from the European Social Fund through the Operational Programmes for the 2014-2020 programming period, of Portugal 2020, particularly the Thematic Operational Human Capital Programme, the Regional Operational Programme in the North, Centre and Alentejo region, in line with the provisions of the applicable Specific Regulation.

The funding of the grants is dependent on the receipt of the required documentation and the budgetary availability of the Funding entity.

Evaluation of applications
The applications will be evaluated by a panel composed by members of the Scientific Committee of the Doctoral Program in Sustainable Chemistry, according to regulation.

Application deadline
Applications will be received until the 15th of January 2018.

The fee for application is the fee established by the University at the time of application. Payment must be made through the payment methods provided by the application platform.

Academic Calendar
The academic calendar of this programme starts in March 2018 (i.e. 1st semester of this programme corresponds to the 2nd semester of the normal academic year).

Study plan
Consult the webpage:


PhD Projects 2017/2018

Universidade de Aveiro

AV1 -Molecular recognition of the biologically relevant anions: a theoretical investigation

In nature, several interactions rely on hydrogen bonding (HB) interactions. However, other recognition processes can also occur through the Halogen (XB) or Chalcogen (ChB) bonds, σ-hole based interactions, which can be explored in anion binding, anion transmembrane transport, chiral discrimination, drug design among others.  The molecular Modelling and Computational Biophysics Group has a comprehensive theoretical research activity in anion binding and chiral discrimination via these unconventional interactions, using both QM approaches as well as with classical force field calculations. The group has an extensive know-how in the modelling of XB-based receptors able to bind biologically relevant oxyanions and halides. Moreover, we have pioneered the development of force field parameters to describe the interactions of a ChB-based macrocycle with halides in competitive aqueous solvent mixture. These ground-breaking works open new perspectives for the design and development of new XB/ChB based molecules for use in health, green chemistry, structural biology, and other fields. This project primarily aims the development of force field parameters of general use on the molecular modelling of chalcogen compounds incorporating selenium or tellurium centres. Subsequently, these parameters will be use on the investigation of the recognition of anions by synthetic, typically interpenetrated molecules, and natural receptors. This research is partially developed in collaboration with researchers from University of Oxford.

Supervisor: Vitor Félix (CICECO – UA)


AV2 - Green chemistry approaches to extract bioactive components from natural resources to valuable applications

One of the main concerns of the exploitation of bioactive compounds from natural sources is to find sustainable, eco-friendly and economical feasible extraction methods. In this work it is proposed to characterize the lipophilic and phenolic fractions of selected agricultural/forest by-products, studying the most promising bioactivities (anti-inflammatory/antibacterial/anti-proliferative). Promising molecules will be selected for subsequent eco-friendly extraction methodologies studies (microwave assisted extraction, ultrasound assisted extraction or using natural deep eutectic solvents (NADES)). Mathematical models, including Response Surface Methodology will be used to maximize the biocompounds yield, enhancing the anticipated bioactivities. NADES will be also evaluated to perform liquid formulations, increasing the lifetime of active ingredients and allowing their incorporation in different food or pharmaceutical applications.

Supervisor: Sónia Santos (CICECO, UA)
Co-supervisor: Sílvia Rocha (QOPNA, UA)


AV3 -Sustainable porous functional carbon nanospheres – novel synthetic routes and application in water treatment

Carbon nanospheres are receiving increasing attention due to their excellent performance in environmental, energy, health fields. Very recently our group has developed a novel strategy for the preparation of spheroidal organic-inorganic hybrid nanoparticles, highly enriched in biopolymers extracted from renewable sources. This research work aims to investigate new routes for the production of porous functional carbon-based nanospheres, with tailored surface properties (polarity, chemical functionality) using these bio-hybrid nanoparticles as precursors and methodologies based on carbonization or hydrothermal carbonization. The performance of the carbon nanospheres as sorbents for water treatment, for the uptake of organic pollutants and ions from water, will be assessed in the frame of a project with the company Bosch.

Supervisor: Ana Luísa Daniel da Silva (CICECO, UA)
Co-supervisor: Tito Trindade (CICECO, UA)


AV4 -Development of improved in-tube solid-phase microextraction method coupled to high-resolution techniques for assessing the atmospheric variability of water-soluble organic matter composition

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 green strategy using novel extractive phases as capillary coatings for the concentration and microextraction of WSOM, and subsequent offline/online characterization through high-resolution techniques (multidimensional NMR, mass spectrometry, and 2D liquid chromatography). Besides gaining highly time-resolved data on the chemical properties of atmospheric WSOM, this project will also allow the development of a miniaturized and green approach for a wide range of applications in environmental analysis.

Supervisor: Regina Duarte (CESAM, UA)
Co-Supervisor: Armando da Costa Duarte (CESAM, UA)


AV5 -Toward energy-saving WOLED technologies: a rational design of luminescent dendrimers-lanthanide materials

This research proposal explores a new concept to address the possibility that each lanthanide (Ln) ion can actually emit light without self-quenching by neighboring complexes in order to achieve white light for WOLED. Therefore, is devoted to the development of Ln dendritic architectures for white-light luminescence from a high-site isolation single-component with 3 different Ln centers [Eu3+, Tb3+, Tm3+)] emitting simultaneously primary colors. To achieve light antenna harvesting and high site-isolation, the concept of surrounding the Ln3+ ion by new dendritic shells of thenoylacetophenone moieties with increasing generations of poly(benzyl aryl ether) dendrons arranged in a supramolecular assembly provided by neutral 1,3,5-tris-[2-(2´-pyridyl)benzimidazolyl]benzene starburst ligands is explored. To predict and support the photoluminescence properties, two different computational approaches will be applied.

Supervisor: Mariela Martins Nolasco (CICECO, UA)
Co-supervisors: Vera Lúcia Marques da Silva (QOPNA, UA) and Paulo Ribeiro-Claro (CICECO, UA)


AV6 -Design of organized nanostructures based on proteins for biomedical applications.

The project aims at developing new fibrous protein-based biomaterials with controlled degrees of orientation and organization and improved mechanical properties, keeping their functional character unchanged. These nanostructures will be obtained through well-designed chemical modifications and processing methodologies under adequate and sustainable conditions (e.g. use of alternative solvents and nanofabrication methodologies). 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: Carmen Freire e João Mano


AV7: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, UA) and Artur Silva (QOPNA, UA)



AV8 –Cucurbituril Containers for Therapeutic Delivery of Carbon Monoxide Releasing Molecules

Carbon monoxide has attracted attention as a therapeutic agent for a wide range of conditions. CO-releasing molecules (CORMs) have been investigated with the goal of targeted CO delivery. However, pure CORMs exhibit some drawbacks, such as instability in the plasma and in biological media, poor bioavailability, and undesired toxic effects. In this proposal, transition metal-based CORMs will be encapsulated in cucurbiturils (CBs) with the aim of obtaining safe and efficient systems that deliver intact CORMs to tissues. The CO-release properties of CORMs and CB@CORM will be studied in different media and under different conditions and various techniques will be used to characterize the CORMs before and after CO liberation. The toxicity of CORMs and CB@CORM will also be studied. Successful completion of the work will afford new bio-compounds that may have potential for the delivery of CO to treat various diseases of high socioeconomic impact such as inflammatory disorders.

Supervisor: Isabel S. Gonçalves(CICECO, UA)
Co-supervisors: Martyn Pillinger(CICECO, UA) and Rita Ferreira (QOPNA, UA)


AV9 –Polyoxometalate Based Chiral Heterogeneous Catalysts for Asymmetric Epoxidation under Sustainable Conditions

The catalytic transformation of organic compounds into oxygenated derivatives is indubitably an important area of research. Polyoxometalates (POMs) present chemical and structural versatility that leads to properties which have been explored in catalysis. This plan aims to: (1) prepare chiral heterogeneous catalysts based on POMs; (2) test these catalysts in the asymmetric epoxidation of prochiral alkenes and terpenes; (3) use an environmentally safe oxidant such as hydrogen peroxide. The POMs will be supported by electrostatic interactions with chiral functionalized silica materials or Merrifield resins. The oxidation reaction studies will be carried out under conventional heating and using microwave irradiation. All the catalysts and the oxidation products will be characterized using the standard experimental techniques.

Supervisors: Mário Manuel Quialheiro Simões (QOPNA, UA) and Helena Isabel Seguro Nogueira (CICECO, UA)


AV10 -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, UA)
Co-supervisores: Maria Eduarda B. H. Santos (CESAM, UA) and Diana Lima (CESAM, UA)


IN-AV1 -Metabolic biomarkers of chemotherapeutic efficacy of novel lower toxicity drugs for triple negative breast cancer: a metabolomics study

This project aims at identifying metabolic biomarkers of the efficacy of potential new therapeutic agents (Pd complexes) towards triple negative breast cancer (TNBC), which may convey lower biotoxicity and environmental toxicity (upon excretion) than conventional Pt-based drugs. Pd quelates with polyamines will be synthesized (Coimbra) and tested for cytotoxic properties in a selected human TNBC cell line. NMR untargeted metabolomics and targeted MS metabolomics (Aveiro) will evaluate in vitro antitumoral activity both in single-drug protocols and in combination with doxorubicin and methotrexate (mimicking clinical cocktails comprising cisplatin), to account for synergetic effects on cellular metabolism. Pd complexes will differ in number of metal centers and nature of the ligand (uni- and poly-dentate polyamines). The best performing compounds will be evaluated for pharmacokinetics, in vivo (Porto) through metabolic profiling of organs and biofluids to evaluate drug biotoxicity/efficacy, as well as metabolized/excreted drug amounts. Statistically valid metabolic profiles of drug efficacy will help generate hypotheses as to the corresponding deviant metabolic pathways. This should reveal biomarkers of drug efficacy in TNBC therapy, while minimizing biotoxicity and environmental toxicity issues.

Supervisor: Ana M. Gil (CICECO, UA)
Co-supervisors: Maria Paula Marques (Department of Life Sciences,University of Coimbra) and Carmen Pereira, LAQV/REQUIMTE,Faculty of Pharmacy, University of Porto



IN-AV2 -Immobilization of Ionic Liquids in Porous Metal-Organic Frameworks based on Photo-Active Linkers

This Ph.D. project aims to answer the following scientific challenge: “Can we induce order/disorder structural changes of confined ionic liquids in the pores of Metal-Organic Frameworks based on photo-active organic linkers by simple visible light absorption?”

To address this challenge the candidate will design, prepare and structurally characterize mixed-metal Metal-Organic Frameworks (MOFs) based on large and rigid organic ligands (based on porphyrin or phthalocyanine organic cores), ultimately expected to induce nanometric-sized accessible structural pores. Ligands and networks will be prepared using quick, economically-viable and environmentally responsible synthetic procedures such as microwave-assisted synthesis and ultrasonic irradiation, but also using classical approaches. Materials will be scrutinized using a combination of single-crystal and high-resolution X-ray data (synchrotron), electron microscopy, solid-state NMR and photoluminescence data. In a second stage, porous MOFs will be evacuated and ionic liquids with specific melting points will be included into the channels. Hyperthermia studies will explored so to investigate if the photo-active MOFs can induce, by simple light absorption, order/disorder structural changes of the confined ionic liquids.

Supervisor: Leandro M. O. Lourenço (QOPNA, UA)
Co-supervisors: Filipe A. Almeida Paz (CICECO, UA) and João C. Lima (UNL)


IN-AV3 – Porphyrin–thiazolothiazole conjugates for dye-sensitized solar cells

Molecules containing porphyrin units covalently linked to the bicyclic thiazolo[5,4-d]thiazole system will be synthesized and their structural and photophysical properties evaluated. The new molecules will be used for the construction of dye-sensitized solar cells (DSSCs). Porphyrins are among the compounds with higher molar absorption coefficients and are excellent dyes for DSSCs. In fact, the current record of energy conversion efficiency for a DSSC was achieved using a porphyrin as a dye. The new molecules should display strong absorption in a significant part of the visible spectrum and possess a donor-π-acceptor geometry, allowing the production of DSSCs with a high conversion efficiency of solar radiation into electricity.

Supervisors: Augusto Tomé, Maria da Graça Neves (QOPNA, UA) and A. Jorge Parola (UNL)


IN-AV4 –Influence of arabinose-rich polysaccharides on the modulation of astringency perception of polyphenolic-rich foods

Astringency perception is due to the interaction of the polyphenols present in foods and salivary proteins. Polysaccharides may interfere in these interactions having, as a consequence, changes the foods taste perception. Arabinose, a pentose constituent of many polysaccharides, due to its amphiphilic peculiar character, when present in polysaccharides, may play a key role on the modulation of the perception of astringency of polyphenol-rich foods.

To study this hypothesis, different polysaccharides-containing arabinose residues, including arabinans, arabinogalactans, arabinogalactan-proteins – AGP, and arabinoxylans will be prepared. The affinity of these polysaccharides with different classes of polyphenols (extracted from natural sources and synthetic ones) will be studied in aqueous solutions. Competition studies of the interaction of polyphenols with different salivary proteins (PRPs, statherin, mucins, and cystatins) in the presence of the polysaccharides will be performed.

The main methodologies to be used to characterize the interactions will be the NMR (DOSY, STD, 1H), mass spectrometry (ESI, MALDI), fluorescence, dynamic light scattering (DLS), and chromatography (HPLC, GC-FID, and GC-MS).

Supervisor: Manuel A. Coimbra (QOPNA, UA)
Co-Supervisor: Victor Freitas (FCUP)





The clinical management of tuberculosis (TB) and other mycobacterial diseases remains a difficult task. TB is an infectious disease that is far from being eradicated and controlled. The standard treatment for tuberculosis is associated with noncompliance because it consists of a long-term treatment, appearance of side effects, and degradation of drug before reaching the target. Nanotechnology has provided a huge improvement to pharmacology using drug delivery systems, due to the capacity to carry other compounds and target tissues and cells, controlling drug release. Previously work by us, have demonstrated that rifampicin-loaded mannosylated nanostructured lipid carriers (NLCs) were more efficient in inducing a decrease of intracellular growth of mycobacteria [1].


In this project, new formulations will be evaluated consisting of modified NLCs containing anti-tuberculosis antibiotics. The use of a bone marrow-derived murine macrophage model, will allow the evaluation of the cell viability effect, cell uptake and antimycobacterial efficacy of the new nanoformulations. The results obtained will be useful for the development of new TB treatments.


[1] Vieira, A. C., Magalhaes, J., Rocha, S., Cardoso, M. S., Santos, S. G., Borges, M., Reis, S. (2017). Targeted macrophages delivery of rifampicin-loaded lipid nanoparticles to improve tuberculosis treatment. Nanomedicine (Lond), 12(24), 2721-2736. doi:10.2217/nnm-2017-0248.


Supervisor: Prof. Doutora Margarida Maria Coutinho Nogueira Marta Borges.






Keywords: microfluidics, nanostructured sensors, molecular imprinted polymers, quantum dots


This project proposes the development of chemical sensors for detection of common drugs used in crimes. The exploitation of molecularly imprinted polymers (MIP) for chemical recognition, combined with the use of fluorescent probes quantum dots (QD) or nanoparticles based on noble metals, like gold or silver, for the detection, can provide an effective chemical sensing technology with high selectivity and sensitivity for those drugs. The MIP technology is in this project further used as chemosensory material through the conjugation MIP@NP, assuring high selectivity and sensitivity. The QD, due to the quantum confinement, exhibit excellent photostability and high quantum yield, are attractive nanomaterials to use as fluorescent probes. The nanoparticles based on noble metals allow the development of analytical methodologies based on colorimetric properties, sensitive to naked eye detection. The implementation of the proposed chemical sensing technology in a cellulose paper-based support will allow the future development of commercial, rapid and easy to use kits for drug screening. Microfluidic paper-based analytical devices (uPAD) exploiting MIP@NP nanosensors provides the necessary technology for analytical screening of some drugs of possible use in crimes, while at the same time, allows the development of disposable, low-cost and easy to deal devices, thus, with potential for commercialization. More important, the inherent chemical nanotechnology exploited in these paper-based devices embrace many of the criteria of Sustainable Chemistry, of outmost importance nowadays. The main tasks to be considered will be the definition of diverse flow-paths in paper support, the optimized synthesis of quantum dot nanoparticles and selective analyte MIPs, and methods validation.


Supervisors:      Alberto da Nova Araújo (LAQV@Requimte, FFUP) | João Alexandre Velho Prior (LAQV@Requimte, FFUP)






According to the Food and Agricultural Organization of the United Nations (FAO) it is expected that the world population rise about 2.3 billion till 2050. Also, the burden of malnutrition is expected to decrease around the world through several food programs. Such evidences clearly point to a higher food demand in the next 30 years. This will constitute a challenge for the agricultural activity once we are losing arable land due to urbanization, salinization and desertification. To face these challenges it is urgent to increase crop yield per unit land area which, according to FAO, will only be feasible with a strong alliance between technology and agriculture.


In this context, the MAIN GOAL of this work is to contribute to increase Vaccinum corymbosum (Vc) crop yield. Blueberries are currently recognized as functional food, mainly due to its high anthocyanin content, and as possessing a strong potential in the treatment of cancer, diabetes, cardiovascular diseases and dementia. The expected higher food demand along with the health benefits from including functional foods in the daily dietary and the recommendations from World Health Organization to increase fruit and vegetables consumption will certainly lead to an increase demand for fruits like blueberries.


To achieve the MAIN GOAL, it is proposed the use of a totally non-invasive, quick and in-situ technique (Near infrared spectroscopy) to early detect metabolic alterations in Vc leaves responsible for fruit quality and fruit and seed abortion which are major limiting factors in crop yield. The early detection will allow the application of preventive/corrective measures in the farms, mostly related with water and substrates feeding, leading to a production quality and quantity increase.


The SPECIFIC GOALS of this work are:


-To identify Vc leaves metabolites mainly associated with the carbon and nitrogen cycles which are known to strongly influence the crop quality and yield;


-To determine physical and chemical blueberries quality parameters;


-To recognize already known leaves key metabolites which strongly impact fruit quality and crop yield and search for new ones;


-To correlate such leaves key metabolites with the corresponding infrared spectra of the Vc leaves;


In order to accomplish these goals, it is proposed the follow WORKFLOW:


1-To perform four sampling campaigns in each year corresponding to the (1st) bud burst stage; (2nd) blossom stage; (3rd) presence of the first immature fruits and (4th) plenty berries maturation. During the sampling campaigns, leaves and fruits (whenever possible) will be collect and infrared spectra of all the samples will be acquired prior to collection;


2-To identify leaves metabolites from the carbon and nitrogen cycles through Fourier Transform Ion Cyclotron Resonance mass spectrometry (FTICR-MS);


3-Determination of several physical and chemical parameters of the fruits as skin colour values, firmness and the maximum penetration force and total polyphenols, flavonoids and carbohydrates contents, caffeic acid derivatives and antioxidant activity, soluble solid content, pH-value and titratable acidity;


4-Correlation between the presence/absence of leaves metabolites with fruit quality parameters through multivariate data analysis. This will allow to recognize some KEY metabolites already known as having strong impact in fruit quality parameters in other species as well as identify potential new ones;


5-Correlate the presence/absence of such KEY metabolites with the previously obtained leaves infrared spectra through multivariate data analysis;


6-Approach validation with data collect in the last year of this work. Data collected in first two years will be used for the development of the correlations stated above and data from the campaigns of the last year will be used to validate our approach.


Supervisor: Doutora Clara Cecília Santana de Sousa


Co-supervisors: Professor Doutor José Luís Fontes da Costa Lima e Professor Doutor João Pedro Almeida Lopes






The contamination of the environment with pharmaceuticals has received great attention in the last decade [1]. After their elimination/excretion, pharmaceuticals and their metabolites (PhM) are released in wastewaters, which are treated in Wastewater Treatment Plants (WWTPs). However, WWTPs are not designed to completely remove these emergent pollutants, allowing the entrance of pharmaceuticals and their metabolites in surface water, ground water, coastal water, and even drinking water [2].


This project will evaluate the efficiency of Technosol [3] and Typha latifolia [4] in the treatment of urban and hospital wastewaters contaminated with PhM. For this purpose, controlled laboratorial tests will be performed using: (i) Technosol with different compositions to find the most suitable composition and soil structure and (ii) Typha latifolia. The most promising treatments resulting from these tests will be applied in pilot scale studies.


The innovative approach of this project could lead to an alternative tertiary treatment method of wastewaters contaminated by PhM with low-cost and minimal environmental impact.


[1] Jiang, J.Q.; Zhou, Z.; Sharma, V.K., Microchem. J. 110 (2013), 292–300.


[2] Jelic A., GrosM, Ginebreda A., Cespedes-Sánchez R., Ventura F., Petrovic M., Barceló D., Water. Res. 45 (2011) 76–1165.


[3] Xunta de Galicia. ITR / 01/08, January 8, 2008, of the General Directorate of Quality and Environmental Assessment, concerning the production of soils (Technosols) derived from waste. Santiago de Compostela: Xunta de Galicia (2008).


[4] Dordio A., Palace Carvalho A.J., Teixeira D.M., Dias C.B., Pinto A. P., Bioresour. Technol. 101 (2010) 886–892.


Supervisors: Cristina Maria Fernandes Delerue Alvim de Matos (REQUIMTE/LAQV-ISEP), Felipe Macias-Vázquez (Universidade de Santiago de Compostela) e Maria Manuela Martins de Carvalho (REQUIMTE/LAQV-ISEP)






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, and are increasingly being used as efficient alternatives to volatile organic solvents. This is due to their high thermal and chemical stability, almost negligible vapour pressure and non-flammability. These solvents also present a high intrinsic conductivity, wide electrochemical windows, good solvating ability, and are associated with the formation of both polar and hydrophobic domains. Plentiful applications of ILs exist today, ranging from catalysis, extractions and separations to sensors. In particular, much attention has been paid lately to the potential use of ILs as an advantageous media for the development of stable and robust CO2 gas sensors, either optical-based or electrochemical-based sensors [1].


From a theoretical perspective, ILs or their mixtures with organic solvents represent a significant challenge. In general, ILs or ILs mixtures are characterised by a subtle interplay of different physical interactions [2]. Pairwise addictive contributions (i.e. two-body Coulombic and van der Waals interactions) have been reasonably described by the force fields (FFs) developed for ILs so far. Classical molecular dynamics (MD) simulations using these pairwise FFs have been a powerful tool for understanding the IL structural and dynamic properties at an atomistic level [3]. However, ILs are complex fluids whose ions have usually a significant delocalized charge and the importance of the quantum effects cannot be neglected [2]. 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, of its mixtures and reactive processes. The polarizable potential, introduced by Son et al. [4], is one of the most successful models of this type. Its parameterisation is based on symmetry-adapted perturbation theory (SAPT) calculations involving the homomolecular species.


This project aims at theoretically studying the effect of using polarizable force fields for modelling imidazolium-based ILs and mixtures plus the inherent processes, typically applied and occurring in optical and in electrochemical CO2 sensors [1]. To do so, classical MD simulations will be carried out using the new developed polarizable FFs. Therefore based on this study it will be possible not only to gather deep insight views/interpretation of these ILs and of their mixtures, to develop estimative methods, as well as to give support to computational methods in order to be able to evaluate/predict their applicability for the detection of CO2.




[1] Ionic liquid-based optical and electrochemical carbon dioxide sensors, K. Behera, S. Pandey, A. Kadyan, S. Pandey, Sensors 2015, 15, 30487-30503.


[2] Ionic liquids studied across different scales: A computational perspective, K. Wendler, F. Dommert, Y.Y. Zhao, R. Berger, C. Holmb, L.D. Site, Faraday Discuss. 2012, 154, 111-132.


[3] What does an ionic liquid surface really look like? Unprecedented details from molecular simulations, G. Hantal, M. Natália D.S. Cordeiro, M. Jorge, Phys. Chem. Chem. Phys. 2011, 13, 21155-21662; A systematic molecular simulation study of ionic liquid surfaces using intrinsic analysis methods, G. Hantal, I.V. Voroshylova, M. Natália D.S. Cordeiro, M. Jorge, Phys. Chem. Chem. Phys. 2012, 14, 5200-5213.


[4] First-principles united atom force field for the ionic liquid BMIM+BF4–: An alternative to charge scaling, C. Y. Son, J. G. McDaniel, J. R. Schmidt, Q. Cui, A. Yethiraj, J. Phys. Chem. B 2016, 120, 3560-3568.


Orientador: M. Natália D. S. Cordeiro


Co-orientador: Iuliia V. Voroshylova






Metal ion chelation is a common chemical tool used in living organisms either to incorporate essential transition metal ions or to address situations in which their concentration has to be amended. In the latter case, upon the choice of appropriate ligands to target the metal ion, from the coordination chemistry point of view, it is necessary to consider the biological target and to tune the properties of the ligand to successfully increase or decrease the metal ion concentration.


The objective of the project is to design multifunctional and synthetically versatile chelators that allow tuning their properties according to the specific target in view. Moreover, it is often advantageous to have the possibility to use chelators marked with spectroscopic probes in order to understand their distribution and location in a cell or organism.


Supervisors: Maria da Conceição Rangel and Baltazar de Castro






The main aim of this project is to develop degradable materials with a mechanical performance for technical applications, which are currently non-existent in the market but responds to a need of European and global markets. The focus will be biomedical engineering applications, and biocompatible composite materials based on sustainable polymers will be developed.”


Supervisors: Maria Ascenção Lopes (FEUP); José Domingos Santos (FEUP) and Maria Helena Fernandes (FMDUP)






O receptor da vitamina D (VDR) pertence à familia dos receptores nucleares das hormonas esteroidais e consta de aproximadamente 400 amino ácidos.[1] A forma hormonal da Vitamina D3 (calcitriol), forma um complexo com o VDR e esse complexo forma um dímero com o receptor do ácido retinóico (RXR), o qual provoca uma serie de respostas em termos de transcrição genómica [2,3]. O calcitriol intervem numa grande diversidade de funções biológicas, nomeadamente, regula o metabolismo mineral, promove a diferenciação celular, inibe a proliferação celular e controla o sistema imunológico através de um modo de ação genómico [2-4]. Atualmente, apenas o calcitriol e mais oito análogos seco-esteróides sintéticos são usados na quimioterapia de pacientes com hipertiroidismo secundário, osteoporose e psoríase, e apenas quatro análogos estão em fase de testes clínicos avançados para a terapia de cancro.


A investigação que se propõe neste projecto de tese é a síntese de novos seco-esteróides, análogos do calcitriol, como potenciais ligandos do receptor da vitamina D. Estes novos análogos trans-hidrindánicos e de configuração Z (1A-1D), de estrutura alquilidénica no que diz respeito à posição C-17 (olefinas tri e tetra-substituídas), foram selecionados, neste projeto, após estudos preliminares de docking que forneceram resultados promissores em termos de afinidade ao recetor da vitamina D.  Os compostos finais serão biologicamente avaliados por forma a obter informação valiosa acerca das suas potencialidades como fármacos, principalmente como agentes anti-tumorais. As tarefas serão realizadas na Universidade do Porto (REQUIMTE/DQB-FCUP, 36 meses no grupo do Prof. E. Borges) e na Universidade de Santiago (DEP. QUÍMICA ORGÁNICA, 12 meses no grupo do Prof. A. Mouriño).



(1)      Vitamin D receptor as a drug discovery target. Pinette KV et al. Mini. Rev. Med. Chem. 2013, 3, 193–204.


(2)      Vitamin D, third ed.; Feldman D et al, Eds.; Elsevier Academic Press: San Diego, CA,  2011.


(3)      Nuclear receptors. Muñoz A et al. Cell Cycle2009, 8, 1675-1680.


(4)      Aplicaciones actuales y futuras de la vitamina D: (a) Special Issue: Role in cancer causation, progression and therapy. D. Trump Ed. Cancers2014 (ISSN 2072-6694). (b) The role of vitamin D in reducing cancer risk and progression. Feldman D et al. Nat. Rev. Cancer2014, 14, 342-357. (c) Vitamin D receptor ligands: The impact of crystal structures. Mouriño A et al. Expert Opin. Ther. Pat. 2012, 22, 417-435.



P9_Valorização de subprodutos das indústrias agroalimentares: sementes de melão como ingredientes de alimentos funcionais

Um dos maiores desafios da indústria alimentar consiste na redução dos subprodutos produzidos diariamente e que, contrariamente aos conceitos de economia circular, são descartados.

A produção de melão gera grandes quantidades de subprodutos, especialmente sementes. Neste projeto pretende-se fazer a sua caracterização (nutrientes, anti-nutrientes, fitoquímicos) e avaliação de bioactividades (antioxidantes, anti-inflamatórios, antitumorais e antimicrobianos) visando o estudo da sua segurança e características funcionais. Serão desenvolvidas novas formulações, que incorporam ingredientes de sementes de melão obtidos por metodologias de extração eco-amigáveis e efetuados ensaios de bioacessibilidade e biodisponibilidade. Para avaliar a aceitação dos consumidores será feita uma análise sensorial.

Este projeto pretende criar sinergias entre investigadores e indústria alimentar através de uma abordagem sustentável.

Supervisor: Prof. Doutora Beatriz Oliveira


P10_ Optimization of ionic liquid/electrode material interface for enhanced energy storage

Summary: The project aims to contribute with experimental results to fill the gaps between the knowledge gained at the macro scale with the advanced theoretical comprehension of the confinement of ionic liquids at nano or micro scale.

This PhD Thesis project will be focused on the study of the charge storage mechanisms obtained from traditional monocationic ionic liquids based on pyrrolidinium cations, deep eutectic solvents based on choline chloride, mixtures between the selected ionic liquid models and solvents (e.g. acetonitrile polypropylene carbonate) and on the electrode material (e.g. nanostructured carbon material).

Previous work in the field of electrified interfaces between ionic liquids and electrodes, gathered by the research group will significantly contribute to success of the present PhD thesis.

Objectives: Pyrrolidinium based ionic liquids electrochemical performance on glassy carbon electrodes will be used to establish the standard performance of the electrode / ionic liquid material and from this starting ground, the effect of deep eutectic ionic solvent formulation and the introduction of organic solvent will be assessed aiming to understand the contributions of each of the constituents and to select the best performing systems. After selecting the best performing systems the characteristics of the electrochemical system will be optimized by introduction of nanostructured carbon material (graphene and modified graphene).

The project final goals are to design and develop of more efficient uptake/storage systems based on electrostatic energy storage grounded in an electric double layer structure and to contribute to the formation of a young researcher in a field that is important to the long term sustainability of our country, energy storage and management.


[1] A. Pandolfo, A. Hollenkamp, Carbon properties and their role in supercapacitors, J. Power Sources 2006, 157, 11–27.

[2] A. Lee, S. Kondrat, G. Oshanin, A. Kornyshev, Charging dynamics of supercapacitors with narrow cylindrical nanopores, Nanotechnology 2014, 25, 315401 – 8.

[3] D. Macfarlane, M. Forsyth, P. Howlett, J. Pringle, J. Sun, G. Annat, W. Neil, E. Izgorodina, Ionic liquids in electrochemical devices and processes: managing interfacial electrochemistry, Acc. Chem. Res., 2007, 40, 1165–1173.

[4] C. Gomes, R. Costa, C. Pereira, A. Silva, The electrical double layer at the ionic liquid/Au and Pt electrode interface, RSC Adv., 2014,4, 28914-28921.

[5] R. Costa, C. M. Pereira, A. F. Silva, Insight on the effect of surface modification by carbon materials on the Ionic Liquid Electric Double Layer Charge Storage properties, Electrochimica Acta, 2015, 176, 880–886.

Supervisor: Prof. Doutor Carlos Manuel de Melo Pereira.


P11_Stimuli-Responsive Vesicles from Surface-Active Ionic Liquids for Nano-Templating and Biodelivery

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 controlled 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 fundamental thermodynamic and colloidal point of view. Besides, they may be used for important applications in nanotechnology and biomedicine if their behavior is smartly controlled and they offer sustainable credentials (health and environment safety and cost). Building on our work and contributions with cationic/anionic vesicles from conventional [1-2] and amino acid-based surfactants [3], this project follows an innovative route by selecting surface-active ionic liquids (SAILs)—i.e. surfactants combining the unique properties of ionic liquids—that bear stimuli-responsive motifs, namely with respect to temperature, pH and/or light. The basic aims of the project are: to develop robust and responsive nanovesicles fabricated from SAILs in aqueous media, using a systematic approach regarding structural motifs; to characterize the nanovesicles in terms of size, shape, stability, equilibrium properties and liability to programmed stimuli, using a toolbox of advanced methods (SEM, TEM, scattering and self-diffusion NMR); to develop specific and sustainable applications using the most promising systems, namely for soft-templating of nanoparticles and controlled encapsulation and release of biomolecules.

[1] Silva, B. F. B.; Marques, E. F.; Olsson, U., Unusual Vesicle-Micelle Transitions in a Salt-Free Catanionic Surfactant: Temperature and Concentration Effects, Langmuir, 2008, 24, 10746-10754.

[2] Marques E.F., “Surfactant Vesicles: Formation, Properties and Stability”, in Encyclopedia of Surface and Colloid Science. P. Somasundaran (Ed.), Taylor & Francis Group, New York, 3rd edition, 2015, 7190-7209.

[3] Silva, S. G.; Vale, M. L. C.; Marques, E. F. Size, Charge, and Stability of Fully Serine-Based Catanionic Vesicles: Towards Versatile Biocompatible Nanocarriers. Chem Eur. J., 2015, 21, 4092-4101.

Supervisor: Prof. Doutor Eduardo Jorge Figueira Marques

P12_ Energetic Properties of Fragrance and Flavour Materials.

Fragrances offer a plurality of odors that stimulate the human senses and elicited various sensory reactions. These chemicals are present in a wide variety of products in our daily lives as in cosmetics, shampoos, perfumes, essential oils, personal care and other consumer products such as household cleaners and air fresheners, among others.

Considering the human exposure to these materials is high, ranging from skin contact to inhalation, and adding that they are emerging as pollutants in aquatic systems, such chemicals are becoming a concern. Currently, the Research Institute for Fragrance Materials, Inc (RIFM) and the International Fragrance Association (IFRA) have as mission to generate, monitor and evaluate safety data on over 5000 ingredients used in fragrance formulations, and that means to look for physicochemical, regulatory and toxicological properties.

The limited experimental data available to assess potential hazards of these substances has prompted governmental authorities to recommend the use of estimation models as an alternative to assess risks to human health and environmental safety. The majority of physicochemical data presented and used to assess the safety of fragrance compounds are predicted. There is a large absence of experimental data which poses an impediment for the establishment of reliable properties estimation schemes.

This work aims to develop an interchange of experimental and computational thermochemical studies of key fragrance ingredients in order to collect as much information as possible to establish well supported structure-energetic-reactivity relationships, to create and validate reliable prediction schemes for the compounds that cannot be studied directly. This research will address existing needs by filling the experimental data gap, validate, and expand refining predictive methods.

The interplay of the different experimental thermochemical properties obtained from the different techniques will be fundamental to the project success.

The main objective of this project will be achieved through careful planning of several activities:

1) Calorimetric studies for the thermal characterization and determination of enthalpies of formation and phase transition of fragrances; 2) Determination of vapor pressure by effusion methods;

3) Theoretical studies to calculate the structure and energy of the local minima on the potential energy surface and to determine the gas-phase enthalpy of formation; 4) solubility studies using calorimetric and spectroscopy techniques.

Supervisors: Prof. Dra. Maria das Dores Melo da Cruz Ribeiro da Silva & Dra. Vera Lúcia de Sousa Freitas







Keywords: biosensors, microfluidics, electrochemistry, kidneys function impairment.


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 this, disposable nanostructured electrochemical  biosensors with integrated membrane purification process are envisaged  for each biomarker to be used in the future as a point-of-care devices.  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 will be studied to attempt  the attenuation of membrane biofouling.


Supervisor: Célia Gomes Amorim (LAQV/Requimte)/ Conceição Branco (LAQV/Requimte)

Co-Supervisor: Carla Portugal (FCT-UNL)





Scope and aim of the doctoral project


Malaria eradication remains an unmet goal, and implies a yearly burden of about half a million deaths, most of which of children under 5 years old, and 220 million new cases worldwide. About 90% of these cases, including malaria-related fatalities, occur in Africa, whereas most of the remaining cases prevail in tropical and sub-tropical regions of the globe. Yet, several social, economic, political and environmental factors underpin an increased risk of disease spread to non-endemic regions, and cases have been recently reported in malaria-free countries; while some of these are imported by travellers (see, e.g., ), some others are apparently of autochthonous origin (see, e.g, ). Regardless of the origins or factors underlying malaria onset and dissemination, the urgent need to tackle with this worldwide menace is clear when one becomes aware that one African child dies every minute from malaria, and that children in non-endemic countries are equally at risk of dying from this disease (see, e.g., ).


Malaria parasites have developed resistance to virtually all antimalarials clinically available (see, e.g., ), including first-line drugs such as artemisinin and derivatives. Given that malaria mostly affects low-income countries, new approaches to fight this disease must be low cost sustainable ones. In this connection, the group at UP has a long track record in the “recycling of classical antimalarials”, where from simple chemical modifications to targeted delivery strategies have been explored in order to enhance the antimalarial therapeutic profile of known drugs. Recently, this group showed that ionic liquids (ILs) based on the classical antimalarial drug primaquine were active against the three stages of malaria infection in the mammalian host. In parallel, the group at UA demonstrated that use of water/ILs mixtures to extract bioactive molecules from their natural plant sources produces extracts with enhanced bioactivity as compared to the aquous extract alone.


In view of the above, we now wish to explore use of ILs, both classical and antimalarial-derived ones, towards extraction of artemisinin from biomass (Artemisia annua plants) in higher yields and with improved antimalarial profiles. This is a timely and highly relevant topic, as artemisinin is currently the first-line antimalarial drug, but its chemical synthesis is a high-cost difficult one, whereas standard extraction procedures from biomass are low yield ones. As such, improved extraction yields are highly desirable, and ILs may have a crucial role to this end. Moreover, using ILs that are antimalarial per se represents an unprecedented approach that might deliver extracts of wider spectrum antimalarial activity.


The following specific goals are set for this doctoral project:


1. chemical synthesis of ILs, both classical and based on antimalarial drugs;


2. study of the solubility profile of artemisinin in the aqueous solutions of the ILs;


3. extraction of artemisinin from biomass using aqueous solutions of ILs;


4. in vitro evaluation of extracts activity against blood-stage, liver-stage and gametocytes of malarial parasites;


5. assessment of in vitro cytotoxicity of the extracts against HepG2 cells, and of their permeability profile by means of Caco-2 permeability assays.


Supervisors: Paula A. C. Gomes ( ) and João A. P. Coutinho ( ).






Summary: The main aim of this project is the development of new catalytic processes to reduce the level of sulfur in diesel and gasoline fuels. The principal objectives are: i) preparation of novel catalysts based on advanced organic:inorganic hybrids (OIH) incorporating active oxometal complexes; ii) optimization of catalyst desulfurization efficiency and stability, using green oxidants such as hydrogen peroxide and ionic liquids as extraction agents; iii) performing deep desulfurization of untreated diesel supplied by Galp Energia. The application of heterogeneous oxometal catalysts will be a new development for oxidative desulfurization technology. This research project arises from a recent collaboration with Galp Energia dedicated to investigating alternative processes for the desulfurization of fuels.


Objectives: The major scientific challenge and objective of the project is the development of novel sustainable ODS systems to produce ultra-low sulfur fuels, with potential to improve the industrial desulfurization process (hydrodesulfurization), turning it more attractive, cost-effective and environmentally friendly. This proposal will use unexplored approaches to improve the catalytic efficiency for oxidation of sulfur compounds and to increase the extraction potential in the same organic:inorganic hybrid) materials, together with optimization of the experimental conditions of the ODS process.


The main objectives of this doctoral research project are:


Developed of noncovalent encapsulation strategies to prepare silica- or organically modified silica-based organic:inorganic hybrid (OIH) materials containing oxometal complexes. Compared with covalent strategies, the noncovalent approach has the advantage of not needing a preparative step to obtain oxo-complex-containing silica precursors. The oxometal complexes may be encapsulated during the formation of the OIH composite (Method A: Sol-Gel) or incorporated into a pre-formed mesoporous host (Method B: Impregnation). Steps must be taken to overcome incompatibility of the nonpolar and hydrophobic organic guest molecules with either polar sol-gel precursor solutions or hydrophilic silica-based host frameworks. These materials will conciliate the high activity and selectivity for the oxidation of sulfur compounds present in fuels and at the same time will present enhanced adsorption capacity to remove the oxidized sulfur compounds from fuel media.


ii). Application of the new catalytic materials in ODS technology, evaluation of heterogeneous catalytic capacity between different materials. Select the most efficient and robust catalysts to be used in an oxidative desulfurization process with untreated fuel (supplied by Galp Energia), by the combination of efficient oxidative catalysis and extraction.




[1] D. Julião, A.C. Gomes, M. Pillinger, L. Cunha-Silva, B. de Castro, I.S. Gonçalves and S.S. Balula, Fuel Processing Technology, 131 (2015) 78.


[2] C.M. Granadeiro, A.D.S. Barbosa, S. Ribeiro, I. Santos, B. de Castro, L. Cunha-Silva and S.S. Balula, Catal. Sci. Technol., 4 (2014) 1416.


[3] C.M. Granadeiro, S.O. Ribeiro, M. Karmaoui, R. Valenca, J.C. Ribeiro, B. de Castro, L. Cunha-Silva and S.S. Balula, Chemical Communications, 51 (2015) 13818.


[4] T. R. Amarante, P. Neves, A. A. Valente, F. A. A. Paz, M. Pillinger, I. S. Gonçalves, J. Catal. 340 (2016) 354–367.


[5] P. Beyazkilic, A. Yildirima, M. Bayindir, Nanoscale 6 (2014) 15203-15209.


[6] S. Kirmayer, E. Dovgolevsky, M. Kalina, E. Lakin, S. Cadars, J. D. Epping, A. Fernández-Arteaga, C. Rodríguez-Abreu, B. F. Chmelka, G. L. Frey, Chem. Mater. 20 (2008) 3745-3756.


[7] A. J. Cadby, S. H. Tolbert, J. Phys. Chem. B 109 (2005) 17879-17886.


[8] L. Grösch, Y.J. Lee, F. Hoffmann, M. Fröba, Chem. Eur. J. 21 (2015) 331-346.


Supervisor: Salete S. Balula (Porto); Martyn Pillinger (Aveiro) and Isabel Gonçalves (Aveiro)



P/UA3_On the Study of speciation and phase equilibria of Protic Ionic Liquids as a key for the optimization of Biomass Processing

This project engages the physico chemical and quantum chemical study of some Protic Ionic Liquids (PILs) focused on the molecular understanding of the speciation, phase equilibria and chemical reactivity related with the biomass processing. The most promising PILs for the biomass processing will be explored: combination of superbases with the organic carboxylic acids. This project will part of ongoing project and R&D field. [1-3]

The gaseous phase composition along the Knudsen effusion experiments will be additionally analyzed by NMR. Infrared low-temperature Ar and Kr matrix spectra. Quantum chemical calculation will used in the speciation study of PILs in the gaseous phase.

The thermodynamic study of pure PILs will be focused in the vapor-liquid equilibrium exploring the effect of different base/acid compositions, the identity of bases and acids, as well as their relative acidity/basicity on the speciation equilibrium, cohesive energy and volatility. The study will be extended to mixtures of PILs with solvents, such as, water, simple alcohols, sugars and carbohydrates, with the main target of explore the solvation capabilities of the PILs.

Ab-initio based quantum chemical calculations will be carried out and used to estimate some properties of the PILs, such as, heat capacity, ionic dissociation energies, enthalpies and entropies as well as the acid/base equilibrium in gas phase.

High accurate thermodynamic properties concerning the vapor-liquid equilibrium, solvation thermodynamics, gaseous phase speciation, solution calorimetry data (dissolution, mixing and solvation enthalpies) will be used to the rationalization and understand the capabilities of some PILs in the biomass processing as well as, evaluate the ability and functionalities of PILs needed for the process design and economical application of the PILs.

[1] Ribeiro F.M.S., Lima C.F.R.A.C., Vaz I.C.M., Rodrigues A.S.M.C., Sapei E., Melo A., Silva A.M.S., Santos L.M.N.B.F. (2017). Vaporization of Protic Ionic Liquids Derived from Organic Superbases and Short Carboxylic Acids. Phys. Chem. Chem. Phys., 19, 5326-5332.

[2] Rodrigues A.S.M.C., Lima C.F.R.A.C., Coutinho J.A.P., Santos L.M.N.B.F. (2017). Nature of the C2-Methylation Effect on the Properties of Imidazolium Ionic Liquids. Phys. Chem. Chem. Phys., 19, 5326-5332.

[3] Rodrigues A.S.M.C., Rocha M.A.A., Almeida H.F.D., Neves C.M.S.S., Lopes-da-Silva J.A., Freire M.G., Coutinho J.A.P., Santos L.M.N.B.F. (2015). Effect of the Methylation and N−H Acidic Group on the Physicochemical Properties of Imidazolium-Based Ionic Liquids. J. Phys. Chem. B, 119, 8781-8792.

Supervisors: Luis M N B F Santos (UP) & João Coutinho (UA)



PhD Projects 2016/2017

PhD Projects Available

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.


[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.


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.


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


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 ( in applying the DR3 concept to classical antiparasitics, and the expertise of the co-supervisor ( 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)





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

Supervisor: Isabel Marrucho (ITQB-NOVA)


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)


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)


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)


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)


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


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)


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)


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)


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.
  • Nova 1. Title: Sustainable methods for the synthesis of biologically active molecules

    Supervisors: Beatriz Royo    ITQB AX/NOVA   email: This email address is being protected from spambots. You need JavaScript enabled to view it.

                Co-supervisor: Artur Silva QOPNA, U Aveiro

    Abstract: The pharmaceutical industries are under increasing economic, ecological and regulatory pressure to develop sustainable methods for the synthesis of new drugs. An elegant approach to the synthesis of relevant biologically active compounds is catalytic hydrogen transfer processes mediated by metal catalysts.

    In this project, we will develop new methods for the preparation of heterocycles and C-N bonds found in pharmaceuticals using hydrogen transfer methodology, a green process that generates no-byproducts, avoids the use of hazardous reagents, and uses renewable starting materials.


    Nova 2. Title: Tailor hyperthermostable oxidoreductases for efficient oxidation of lignin-related phenolics

    Supervisor: Lígia O. Martins     ITQB AX/NOVA   email: This email address is being protected from spambots. You need JavaScript enabled to view it.

                         Co-supervisor: Artur Silva QOPNA, U Aveiro

    Abstract Lignocellulose biorefineries are promising alternative sources of renewable bulk and fine chemicals, materials, energy and fuels for sustainable development. In order to be economically feasible, future biorefineries need to overcome the recalcitrance of lignocellulose to degradation that mostly originates in the lignin molecular architecture, which relies on different non-phenolic phenylpropanoid units linked by a variety of ether and carbon-carbon bonds that form a complex, irregular and insoluble three dimensional networks. Biocatalysis offers an environmentally friendly alternative for lignin degradation, representing additionally the key approach for the successful valorisation of lignin bio-wastes. In this proposal a multidisciplinary approach combining cutting-edge protein engineering techniques, with biochemical, biophysical and chemical studies, will allow to i) tailor the hyperthermostable evolved McoA laccase(1 ) for the oxidation of lignin-related phenolics, ii) provide catalytic, stability and structural fingerprints of new enzyme variants, and iii) set-up enzymatic reactions targeted at the degradation of lignin preparations and production of valuable aromatic fine and bulk chemicals.

    1. 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.


    Nova 3. Title: Integrated Manufacture of Nano-in-Micro Dry Powder Formulations: towards enzyme encapsulation

    Supervisor: Ana Aguiar Ricardo /FCT-NOVA  email: This email address is being protected from spambots. You need JavaScript enabled to view it.

    Abstract: The global enzymes market is expected to reach EURO 17 kM in 2024, due to its increasing application in detergents, food processing, pharmaceuticals, and growing usage demand to promote a more sustainable industry in various applications such as paper bleaching, energy, fine chemistry among others. However, its practical industrial and biomedical applications in many fields are often limited by their short lifetime in vivo, high sensitivity to the environmental conditions and low operational stability. In addition, enzymes manufacture result in high production costs resulting from the difficulties in recovery and reusability.

    This PhD project focus on the development of a green integrated manufacturing process to produce liposomal dry powder formulations for enzymatic stabilization, combining microfluidic devices and supercritical CO2-assisted spray-drying (SASD). Two model enzymes, an anti-oxidant therapeutic enzyme, Cu,Zn-superoxide dismutase (SOD), and the pulp bleaching xilanase will be studied. Nanoformulations of enzymes incorporated in liposomes will be prepared using green methodologies combining a parallel multiple microfluidic chip (PDMS/glass microfluidic chips designed using photolithography and soft lithography techniques) coupled to SASD to produce dry powders in continuous process overcoming the lack of batch-to-batch reproducibility. To improve the powder in-vitro performance without compromising the product manufacturability, a systematic quality-by-design approach and design-of experiments tool, followed by a statistical analysis will be implemented to carefully perform a balance between the process optimization and powder requirements in terms of enzyme functionality and formulation stability.


    Nova 4. Title: New Versatile and Environmentally Friendly Routes for Arylation and Amidation Reactions


    Supervisor: Maria Manuel Marques, FCTNova  email: This email address is being protected from spambots. You need JavaScript enabled to view it.


    Abstract: The development of new chemical transformations and greener approaches for the current methodologies is one of the main goals of modern organic chemistry. Novel reactions and reagents allow known structures to be made more efficiently. In this aspect compounds of iodine in higher oxidation states, which are known as “hypervalent iodine compounds” allowed the development of electrophilic synthons by the umpolung of normally nucleophilic species and have emerged as a great alternative to emulate more toxic and expensive late transition metals.

    The cyclic structure of benziodoxole-derived reagents allows them to have an enhanced stability when compared to their acyclic counterpart’s due to a higher overlap of the nonbonding electrons on the iodine atom with the π-orbitals of the benzene.

    Thus, considering the potential of the hypervalent iodine compounds in the transfer of functional groups, in this project novel approaches to current methodologies will be developed. In particular the N-arylation of amines in a metal-free method will constitute a great contribution not only to the academia but also for industry.

    Thus it is expected to develop a versatile, simple, atom-economy and metal-free method for N-arylation of several amines.

    Amide bond formations is one of the most common transformations carried out in pharmaceutical synthesis and is of major importance in the structure of proteins. It was reported, in 2006, that 25% of all pharmaceuticals currently on the market have an amide bond. In order to overcome the harsh conditions of direct thermal amidation, amides are traditionally formed by the reaction of a pre-activated carboxylic acid with stoichiometric amounts of a coupling reagent such as carbodiimides and an amine or alternatively turning the carboxylic acid into the corresponding acid chloride.  However, these methods generally present a poor atom economy and are not necessarily green.

    In this project a new amidation reaction will be developed using the hypervalent iodine chemistry. The versatility of the method and reaction scope will be explored. Moreover, a solid-phase approach will be implemented to achieve amides with high conversion and in an atom-economy process.



    Nova 5. Title: Biodegradable Magneto-Luminescent Mesoporous Nanoparticles as

    new Nano BioMedical tools in Cancer Treatment


    Supervisor: Carlos Lodeiro, FCTNova  email: This email address is being protected from spambots. You need JavaScript enabled to view it.

    Co-Supervisor: Elisabete Oliveira, FCTNova  email: This email address is being protected from spambots. You need JavaScript enabled to view it.


    Abstract: Despite the advances in early diagnosis and treatment, precise-targeted nanoformulations containing the most effective drug combination for colorectal cancer (CRC) have not been yet reported. The present project aims to create for the first time, a forefront and powerful Magneto-luminescent nanocarrier, combining silicon

    quantum dots, iron oxide nanoparticles and mesoporous silica nanoparticles with biodegradable materials for diagnosis and for controlled (via stimuli) release of multiple drugs (Irinotecan hydrochloride, 5-fluorouacil, folinic acid, oxaliplatin, cisplatin, capecitabine, and doxorubicin) in colorectal cancer and its design for via oral form. The target samples will be colorectal cancer, but at the end, these nanocarriers could be applied to other types of cancer or disease. It is expected with this strategy a decrease in drug dosage and in the side effects of conventional chemotherapy. The proposed research will cover a broad range of interdisciplinary research in health sciences, chemical, environmental and nanotechnology fields, starting with the design of new target biodegradable magneto-luminescent nanocarriers, their full characterization,

    multiple drug encapsulation, as well as their utility for diverse practical applications, including drug delivery/theranostics and as magnetic sorbents for pollutant removal.

    The aims of this project are:

    1. Syntheses of biocompatible Silicon Quantum Dots and of iron oxide nanoparticles.

    2. Covering of the iron oxide nanoparticles (SPIONs), the silicon quantum dots (SiQDs), and the combination of both (SPIONs@SiQDs) with different layers of silica mesoporous nanoparticles (MNs).

    3. Characterize all nanomaterials (NANO 1: SPIONs@MNs; NANO 2: SiQDs@MNs; NANO 3:SPIONsSiQDs@MNs).

    4. Extraction and identification of membrane proteins in colorectal cancer cells. 5. Targeting of biodegradable and biocompatible polymers PEG, PGLA, with target ligands, the analogs of proteins found in point 4, and further coupling into the surface of the magneto-luminescent mesoporous nanoparticles

    6. Encapsulation and release of drug molecules

    7. In vitro biodegradability and toxicological studies of these nanomaterials.

    8. 8. Use of synthesized biodegradable nanomaterials as stimulated drug delivery, as theranostic nano-vectors in vitro (colorectal cancer cells) and in vivo (in zebrafish embryos and in a tumor xenograft mice model).

    9. Evaluate the magneto-luminescent silica mesoporous as magnetic sorbents for pollutant removal in real water samples via magnetic assistance.

    10. Creation of the oral form of the most promising nanocarriers, by the use of biodegradable polymers for functional enteric coatings (to prevent its degradation in the stomach): preparation to the preclinical assays.


    Nova 6. Title: Unlocking the secrets of phosphorylation-code by pinpointing critical

    switching sites that impact cellular biological functions

    Supervisor: José Luis Capelo (FCTNova) email: This email address is being protected from spambots. You need JavaScript enabled to view it.

    Co-supervisor: Hugo M Santos


    Abstract: Reversible protein phosphorylation regulates almost all aspects of cellular function, while abnormalphosphorylation is a cause or consequence of cellular malfunction and diseases, uncovering hidden biomarkers and potential drug targets [1]. At any given time, as many as 60% of cell proteins are phosphorylated, most on multiple sites, and different phosphorylation patterns and sites often elicit diverse cellular responses [2]. At the level of a single protein, the binding of a negatively charged phosphate group leads to changes in the protein structure, altering the way it functions, essentially acting as a switch, turning it on and off in a coordinated manner, and facilitating binding to and between partner proteins. In this way, phosphorylation regulates protein-protein interactions, protein turnover and crosstalk with other protein modifications, and regulates a broad spectrum of biological cellular functions [3]. While much is known about the importance of protein phosphorylation we have not been able to cover more than 20% of the universe of ~106 phosphorylation sites [2]. Existing methods of protein phosphorylations analysis favour a candidate approach where one focuses on the function of one or few phospho-sites at a time in any particular biological context [4, 5]. Therefore, to unlock the secrets of the phosphoproteome it is necessary a robust and unbiased approach for largescale identification and quantification of phosphorylation sites. Our preliminary data shows that La3+ nano-IMAC allow for 3-fold increase in detection of phosphorylates peptides in comparison to the current methods for phosphopeptide enrichment. To attain this goal this Ph.D. project aims to combine:

    (i) Engineered design of new nano Immobilized Metal Affinity Chromatography (nano-IMAC)

    with and lanthanides for high-throughput phosphopeptide enrichment. These new adsorbents are exciting as the lanthanide ions provide more coordination sites for phosphopeptide binding than any other transition-metal used so far as an affinity material.

    (ii) Multiplex-quantitative mass spectrometry. This strategy allows gaining deeper phosphoproteome quantification by MS and as an approach holds the potential to uncover low-abundance tyrosine phosphorylation sites often missed in classic phosphoproteomics studies. Because of the multiplexing capabilities it allows to compare up to 12 experimental conditions simultaneously, reducing instrument-time and regents consumption, as well as reduces experimental variation ensuing increased statistical confidence.


     Nova 7. Title: Hybrid Ionic Liquids Frameworks for CO2 Separation

    Supervisor: Isabel Esteves (FCTNova) email: This email address is being protected from spambots. You need JavaScript enabled to view it.

    Co-supervisor: José M. Esperança, FCTNova


    Abstract:  The removal of CO2 from both flue gas, biogas and natural gas is of great environmental and economic importance. Currently, CO2 capture technology that has been applied in industry is through chemical absorption using an aqueous amine solution – amine scrubbing, which has serious drawbacks (solvent loss, corrosion and high energy demand). Thus, many research efforts have been devoted to seeking new solvents/materials for CO2 capture/separation.

    Over the past decade, a new class of structured nanoporous materials - Metal Organic Frameworks (MOFs) - have been synthesized and structurally characterized. MOFs are crystalline materials composed of metal centers and organic ligands, infinitely connected by coordinative bonds. Due to their high porosity, high adsorption capacity, and thermal stability, these materials have shown great potential for applications in gas storage, gas separation and catalysis.

    Ionic liquids (ILs) possess many unique features such as negligible vapor pressure, high thermal stability and tunable functionality by the choice of cation/anion combination. Therefore, ILs offer a new opportunity for developing novel capture systems capable of reversibly capturing CO2 with a high capacity. Used alone, ILs suffer from low absorption and desorption rates because of the troublesome high viscosity and relatively small gas–liquid interfaces. However, if they are immobilized or encapsulated into a MOF in an adsorption process, it will circumvent the problems of mass transport limitation and the need for high amounts of ILs.

    The aim of this work is to take advantage of the best of the two worlds – ILs and MOFs - by understanding the behavior of ILs in MOFs, as well as the separation performance of the resulting composites for gas mixtures.


    Nova 8. Title: Sustainability Assessment of the Subcritical Water Treatment of Grape Pomace

    Supervisor: Alexandre Paiva FCTNova, email: This email address is being protected from spambots. You need JavaScript enabled to view it.

    Co-supervisors: Pedro Simões, Susana Barreiros, FCTNova


    Abstract: 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.

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

    Subcritical water (SBW) is a common designation for liquid water at temperatures above 150 °C and pressures above its vapor pressure. SBW treatment does not require the use and further disposal of added chemicals, does not cause corrosion, generates lower concentrations of fermentation inhibitors, is fast, and has moderate energy requirements. SBW has facilitated mass transfer over water at ambient temperature, and its higher ionic product facilitates the deconstruction of lignocellulose, which in turn releases acetyl groups that further acidify the medium.

    SBW has the potential to sustainably treat and valorize agro-industrial residues. Nevertheless the sustainability of SBW-based processes is not yet firmly established, mainly regarding its economic viability and environmental impact.  

    The main purpose of this proposal is the development of a mathematical model for the SBW processing of an abundant agro-industrial by-product: grape pomace. SBW is a complex, simultaneous process of extraction and reaction involving a heterogeneous system with an inhomogeneous solid phase, where catalytic and diffusional processes occur. A robust mathematical model can be obtained by considering two separate phases, namely the solid biomass phase and the solvent mobile phase. Unsteady-state extraction model equations can be obtained by integrating the differential mass balance to the conservation of solutes in a finite section of a fixed bed assumed to be made up of spherical biomass particles. A kinetic model to describe the hydrolysis of the main components of lignocellulose will also be developed, assuming sequential pseudo homogeneous, first order reaction mechanisms, and integrated into the differential mass balance equations for these components and derived ones, in the mobile phase. The resulting multicomponent mass balance equations will be coupled with an energy balance equation.

    The model will be developed using both literature and/or experimental data, and computational tools such as CFD, gPROMs and ASPEN.

    A process and supply chain characterization will be conducted to develop an economic model assessment. OPEX (operating expenses) and CAPEX (capital expenditures) calculations will include analysis of factors such as feedstock variability and availability, utility supplies, transportation and effort required, target products. A second model will be developed following the LCA methodology, to determine environmental impacts. These models will allow an engineering approach to the assessment of the sustainability of the SBW-based treatment of grape pomace.


    Nova 9. Title: New structured substrates and chromatographic processes for downstream processing of complex biopharmaceuticals


    Supervisor: José Paulo Mota FCTNova,   email: This email address is being protected from spambots. You need JavaScript enabled to view it.


    Abstract: This PhD project proposal is built upon the M-ERA.NET European Project NESSIE (Newstructured substrates and chromatographic processes for downstream processing of complex biopharmaceuticals), which started in June 2017. This project will support the material execution of the PhD project and make available to the PhD student its network of expertise and partners’ facilities. Virus-like particles (VLPs) and viral vectors (VVs) are used to produce targeted and safer vaccines. These macro-biomolecules mimic pathogens (the invaders of our body) and trick the immune system into believing that it is under attack thus creating memory cells (immunity). Examples of such vaccines protect us against hepatitis B and human papilloma

    viruses. VPLs and VVs are produced in cell cultures. Together with the desired viral product, other compounds are produced, thus requiring downstream purification to generate safe materials. Purification processes are complex, costly and a combination of several operations is normally used. Chromatography has been widely employed in the downstream processing of VVs and VLPs. However, the existing packed bed materials have a series of disadvantages that limit their application: trade-off between particle size and pressure drop is problematic and slow pore diffusion leads to product degradation. In addition, packed resin beds display a low dynamic binding capacity for viruses at common process conditions. In this project, we aim to overcome these problems by applying a new approach straight on the manufacture of the components used.

    The main goal of this project is to produce new structured adsorbents as selective chromatographic media to separate complex biopharmaceuticals. New customized surfaces will be attached to innovative shapes produced by ceramic-based additive manufacturing (AM). The main advantage of our approach is the possibility to tailor flow inside the column and adjust surface modifications accordingly and precisely to obtain improved chromatographic separation. The mechanical properties will be improved by addition of ceramic oxide additives and tailoring the composition and shape of the structure. The surface properties will be tuned by addition and post-modification of nanoparticles to introduce multimodal functionality incorporating hydrophobicity and ion exchange. These are the preferred mechanisms for achieving high performance, which allow the chromatographic medium to operate over a wide range of pH and salt concentration. The final flow properties and selectivity of the new chromatographic structure will be fine-tuned through optimization of different aspects such as: (1) fluid distribution and residence time, (2) content and distribution of nanoparticles in the material used for production, (3) extent and type of post-surface treatment, and (4) new

    adsorber configurations to improve process performance of the new substrates.

    Lithography-based Ceramic Manufacturing (LCM) with ~150 μm accuracy will be used.

    Novel combinations of materials and process improvements will be developed to provide strength and increased post-modification possibilities to new shapes. Modeling-based optimization of the monolith shape and its specific volumetric surface area, as well as the nanoparticle coating concentration, will maximize the selective retention of impurities at reduced pressure drop. The target is to obtain an improved final distribution of post-modified nanoparticles with controlled dual functionality of hydrophobicity and ion exchange in the same chromatographic unit. The new chromatographic materials will be tested for downstream processing of clarified bio-reaction bulks of adenoviruses and retro- VLPs as model cases. Based on the experimental data, new adsorber configurations will be developed to optimize the performance of the downstream process and to improve economic indicators.

    The components of the project will be manufactured at TRL 5 even though the utilization of ceramic-based AM for this type of application has never been tested before. Testing the technology at this TRL will allow an estimation of the cost savings introduced by the new materials and processes, enabling alternative strategies for using nanotechnology in AM with the purpose of production of high added-value compounds.


    Nova 10. Title: Development of biocompatible composites with advanced antibiofilm function, based on natural products from “green” (phytochemicals) and “blue” (marine actinomycete) sources enhanced by fullerene (C60) and biopolymers (HPC)

    Supervisor: Svitlana Lyubchyk

    Abstract: Recent insights into bacterial biofilm matrix structures have induced a paradigm shift toward the recognition of amyloid fibres as common building block structures (along with bacterial cells) that confer stability to the exopolysaccharide matrix. To address this challenge, the candidate will design, develop, structurally characterize and test a set of the advanced nanocomposites from natural sources (phytochemicals and marine actinomycete) enhanced by nanomaterials and polymers as tools to inhibit the biofilms formation aimed at further biomedical applications. The research strategy is to explore the possibility to prevent the biofilm formation using advanced biocompatible composites suitable to act in both directions, i.e. against main biofilm components, such as bacteria and amyloids structures (Fig. 1). Namely, natural antibiotic bioagents isolated from the marine actinomycete collected at Madeira Archipelago and enhanced by hydroxypropylcellulose will be able to kill/inhibit the bacteria growth. While, innovative composite design, which is water-soluble phytochemicals (flavonoids)-based fullerene (C60) enhanced composite, will be able to destabilize bacterial biofilms through the inhibition mechanism of the kinetics of the amyloid fibrils formation.


    WP1. Inhibition/killing of the functional bacterial systems related to biofilm matrix formation in both Gram-negative and Gram-positive bacteria using advanced Marine Actinomycete isolates Hydroxypropylcellulose (HPC)-enhanced composites.

    WP2. Destruction of the functional amyloid systems related to biofilm matrix formation using advanced water-soluble Phytochemicals (flavonoid family) Fullerene (C60)-enhanced composite

    WP3. Elaborated composites (both from “green” and “blue” sources) testing for their practical application as antifouling and pharmaceutics band-aids bioagents.


    Projects in collaboration:


    Nova 11. Title: Integrated green strategy to intensify extraction and formulation of anthocyanin-based pigments: from red to blue hues


    Supervisors: Supervisor: Ana A. Matias | iBET e ITQB-NOVA email This email address is being protected from spambots. You need JavaScript enabled to view it.

    Co-supervisor: Joana Oliveira | REQUIMTE FC-UP, This email address is being protected from spambots. You need JavaScript enabled to view it.


    Abstract: The use of natural and naturally-derived pigments as an alternative to synthetic colourants is receiving increased interest. Nevertheless, naturally-derived pigments applications are being limited by several bottlenecks such as their lower stability. This proposal focused on the development of a strategy based on the integration of different greener methodologies for the extraction, downstream and formulation of anthocyanins and anthocyanin-derivatives, targeting a wide range of hues (red, orange, violet and blue) with potential application as natural colorants in food and cosmetic industries. Overall, the main goal of the integrated process is a significant reduction of processing steps; increased recovery yields of anthocyanins and anthocyanins-derived pigments; increased stability and efficiency, while decreasing the use of chemicals, waste water and energy with impact on production costs and environmental impact. Renewable sources will be used as a raw material, and high pressure-based technologies will be explored to extract, fractionate and formulate the anthocyanins(-derived) pigments.


    Nova 12. Title: Playing with ionic liquids to obtain new ABS systems to extract added value proteins


    Supervisors: Supervisor: José MSS Esperança, FCTNOVA email This email address is being protected from spambots. You need JavaScript enabled to view it.

    Co-supervisor: Mara G Freire, CICECO/UAveiro  

    Abstract: In today’s world there is a continuous search for the development of more sustainable processes.

    Ionic liquids are by definition salts that are liquid at temperatures below 100°C. In general, they present properties that make them attractive, namely negligible vapour pressure, a broad liquid range, and a very rich and complex behaviour as solvents. The possibility of tailoring ionic liquid ions to reach the desired properties, interactions and toxicity is driving them to novel industrial applications. Many toxicological studies are becoming available and show that there are important differences between cations and anions. Moreover, due to their nature, with an intricate balance between van der Waals, pi-pi, hydrogen bonding and coulombic forces, ionic liquids have shown the potential to revolutionize some processes with results that are not achievable with currently used industrial/laboratorial schemes.

    In this project we will focus on the synthesis of functionalized ionic liquids with null toxicity to be used as key components on the development of distinctive Aqueous Biphasic Systems. Playing with both cation and anion we will create unconventional separation systems that show important advantages in protein separation schemes. The expected benefits from the project will reveal both at laboratory scale by facilitating the analytical work and at an industrial scale by easing the scale up of these new processes with expectable cost advantages.


    Nova 13. Title: Advancing structural diversity on heterocycles via sustainable approaches: novel metal-catalyzed routes towards azaindoles

    Supervisors: Supervisor: Maria Manuel Marques, FCTNOVA email  This email address is being protected from spambots. You need JavaScript enabled to view it.

    Co-supervisor: Artur Silva, QOPNA/UAveiro 


    Abstract: Azaindoles are indole bioisosteres and key scaffolds of various biologically active compounds, often employed in drug discovery programs. Synthesis of azaindoles can prove challenging, due to the electron-deficient nature of the pyridine ring, therefore indole formation methods give poor results or do not work. Despite great progress on azaindoles assembly, there are still drawbacks such as poor regioselectivity, restriction to isomers and limited substrate scope. Additionally N-arylation of azaindoles, in particular 2-substituted azaindoles is difficult.

    In this project innovative and sustainable approaches will be explored towards substituted azaindoles, in particular olefin ring-closing metathesis (RCM), one of the most powerful and reliable methods to access heterocycles via ring formation, with its limits continually being probed and expanded.

    For the first time a RCM and an enyne RCM will be investigated to prepare substituted azaindoles, while opening room for exploring structural diversity. Additionally, one-pot procedures involving metal-catalyzed cross-coupling reactions will be implemented as well as a traceless solid-phase version of these reactions.

    In addition, C–H activation enables one to construct the same C–C bond without using any functionalized substrate. As a result, this privileged strategy is an efficient as well as an atom economic route. Thus, in this project a novel method to construct azaindoles will be developed based on C–H activation.

    These will constitute atom-efficient strategies to improve access and purification of these key scaffolds, overcoming limitations of previous approaches while simultaneously establishing difficult functionalization on these moieties. These advances will undoubtedly impact medicinal chemistry and the pharmaceutical industry.