Mara Guadalupe Freire Martins

Coordinating Researcher

Short CV

Mara G. Freire graduated in Chemistry in 2003 by the University of Aveiro, Portugal, receiving the “Best Chemistry Student Award” from Dow Portugal. In 2007 she completed her PhD in Chemical Engineering by the University of Aveiro, with trainees at Federal University of Rio de Janeiro, Brazil, and Claude Bernard University, Lyon, France, followed by post-doctoral activities at ITQB2, New University of Lisbon, Portugal. In 2012, Freire was an invited professor at Tiradentes University, Sergipe, Brazil. In 2013, Freire was an Assistant Researcher and since 2014 she is a Coordinator Researcher at CICECO - Aveiro Institute of Materials, Chemistry Department, University of Aveiro, Portugal. Currently, Freire is the Coordinator of Group 5 - Biomedical and Biomimetic Materials - of CICECO, and Deputy Chair of the Scientific Council of the University of Aveiro. She is member of the European Academy of Sciences and of the Lisbon Academy of Sciences. In addition to being member of several journal editorial boards, Freire is one of the 17 Chairs of the Content Selection Advisory Board (CSAB) from Scopus.

Freire published +300 papers in peer reviewed journals, +30 book chapters and two books, and has +16,000 citations and h-index of 71. She coordinated/participated in 25 R&D projects, among which two European Research Council (ERC) grants and 2 PathFinder projects from the European Innovation Council (EIC). She has filled +15 national/international patents, and is the co-founder of the RYAPURTECH spin-off.

In addition to other awards and recognitions, Freire received the ECTP-NETZSCH Young Scientist Award in 2014, was recognized amongst the top 20 “Women in Science” in Portugal in 2016, was recognized as one of the 14 rising stars in the Green Chemistry field by the Green Chemistry journal in 2017, was recognized as one of the 100 women in Chemistry by the Royal Society of Chemistry in 2018, was awarded with the “Vicente de Seabra Medal” in 2018, and received the 2021 Best Researcher Award from the University of Aveiro. Related to technology transfer and business ideas, she received the Born from Knowledge award by Agência Nacional de Inovação in the Health field in 2018, was finalist in the Everis Awards (2019) with the RYAPURTECH business case, and was awarded (2021) with the spin-off RYAPURTECH by the Macao Young Entreperneur Incubation Centre (MYECI).

Up to date, Freire has completed the supervision of 18 post-doctoral researchers, and 17 PhD, 60 MSc and 40 BSc students.

Scientific Interests

Freire performs research in the following scientific domains: Biotechnology, Chemical Engineering/Bioengenering, Chemistry/Physical Chemistry and Health Sciences. Her research interests cover the following topics:

Development of cost-effective purification processes for high-value biopharmaceuticals

The production cost of high-quality biopharmaceuticals for large-scale applications still remains higher than other drug therapies due to the current lack of efficient purification strategies. To overcome this drawback, we are focused on the development of cost-effective purification processes for several value-added biopharmaceuticals, namely antibodies, recombinant proteins, and nucleic-acids-based products. Simultaneously to the development of separation processes, we are also working on the optimization of immunization protocols and on the biopharmaceuticals production.

Development of efficient pre-treatment techniques for biological samples envisaging early-stage diagnoses

The early detection of some diseases, including cancer, is pivotal and can increase their therapeutic success rate. Nowadays, there are some well-known biomarkers which are indicative of the presence of cancer or other diseases; yet, in most situations, their concentrations in human fluids, such as in urine and serum, are well below the detection limit of the currently used analytical equipment. To overcome these limitations, our research team is focused on the development of pre-treatment strategies for biological fluids (simultaneous purification and concentration approaches) to improve the detection and quantification of several diseases biomarkers.  

Development of sustainable recovery processes for high-value compounds with therapeutic properties from biomass

The consumption of natural compounds with therapeutic features is highly advantageous compared to their synthetic counterparts (which usually lead to adverse effects). However, these products are typically extracted by volatile and often toxic solvents, and obtained with low yields and low purity levels. Trying to overcome these drawbacks, we have been investigating the use of aqueous solutions of ionic liquids and deep eutectic solvents as alternative solvents for the selective extraction of target compounds, mainly with therapeutic features from biomass, as well as from biomass by-products and wastes. Attempts on integrated/biorefinery approaches, always bearing in mind the new challenges of the circular economy and the need to reduce and reuse waste and raw materials, are priority issues in this line of research. The cytotoxicity and biological activities of the extracted compounds also are usually appraised. 

Synthesis and applications of ionic liquids as therapeutic drugs

Several therapeutic drugs exhibit low solubility in biological fluids, displaying thus low bioavailability, and sometimes requiring the use of vehicles for drug delivery which, in turn, may be toxic. To overcome these drawbacks, we are focused on the synthesis of novel ionic-liquid-based drugs with analgesic, anti-inflammatory and/or antioxidant activities for pharmaceutical and medical applications, and on the evaluation of their in vitro and in vivo toxicity and their neuroprotection capacity. These novel drugs display a high potential to prevent neurodegeneration-based conditions, such as Parkinson’s and Alzheimer’s diseases. 

Selected Publications

  1. Passos, H.; Costa, S. H.; Fernandes, A. M.; Freire, M. G.; Rogers, R. D.; Coutinho, J. A. P., “A Triple Salting-Out Effect is Required for the Formation of Ionic-Liquid-Based Aqueous Multiphase Systems”, Angew. Chem. Int. Edit. 56 (2017) 15058-15062. 
  2. e Silva, F. A.; Pereira, J. F. B.; Kurnia, K. A.; Ventura, S. P. M.; Silva, A. M. S.; Rogers, R. D.; Coutinho, J. A. P.; Freire, M. G., “Temperature Dependency of Aqueous Biphasic Systems: an Alternative Approach for Exploring the Differences between Coulombic-dominated Salts and Ionic Liquids”, Chem. Commun. 53 (2017) 7298-7301.
  3. Ferreira, A. M.; Cláudio, A. F. M.; Valega, M.; Domingues, F. M. J.; Silvestre, A. J. D.; Rogers, R. D.; Coutinho, J.A.P.; Freire, M. G., “Switchable (pH-driven) aqueous biphasic systems formed by ionic liquids as integrated production-separation platforms”. Green Chem. 19 (2017) 2768-27773.
  4. Neves, C. M. S. S.; Silva, A. M. S.; Fernandes, A. M.; Coutinho, J. A. P.; Freire, M.G., “Towards an Understanding of the Mechanisms behind the Formation of Liquid-Liquid Systems formed by Two Ionic Liquids”, J. Phys. Chem. Lett. 8 (2017) 3015-3019.
  5. Ventura, S. P. M.; Silva, F. A.; Quental, M. V.; Mondal, D.; Freire, M. G.; Coutinho, J. A. P., “Ionic-Liquid-Mediated Extraction and Separation Processes for Bioactive Compounds: Past, Present, and Future Trends”, Chem. Rev. (2017) 6984-7052. 
  6. Capela, E. V.; Quental, M. V.; Domingues, P.; Coutinho, J. A. P.; Freire, M. G., “Effective Separation of Aromatic and Aliphatic Amino Acids Mixtures using Ionic-Liquid-based Aqueous Biphasic Systems”, Green Chem. 19 (2017) 1850-1854.
  7.  Mondal, D.; Sharma, M.; Quental, M. V.; Tavares, A. P. M.; Prasad, K.; Freire, M. G., “Suitability of Bio-Based Ionic Liquids for the Extraction and Purification of IgG Antibodies”, Green Chem. 18 (2016) 6071-6081.
  8. Passos, H.; Luís, A.; Coutinho, J. A. P.; Freire, M. G., “Thermoreversible (Ionic-Liquid-Based) Aqueous Biphasic Systems”, Sci. Rep. 6 (2016) Article number: 20276.
  9. Dinis, T. B. V.; Passos, H.; Lima, D. L. D.; Esteves, V. I.; Coutinho, J. A. P.; Freire, M. G., “One-step Extraction and Concentration of Estrogens for an Adequate Monitoring of Wastewaters Using Ionic-Liquid-Based Aqueous Biphasic Systems”, Green Chem. 17 (2015) 2570–2579
  10. Taha, M.; Almeida, M. R.; Silva, F. A.; Domingues, P.; Ventura, S. P. M.; Coutinho, J. A. P.; Freire, M. G., “Novel Biocompatible and Self-buffering Ionic Liquids for Biopharmaceutical Applications”, Chem. Eur. J. 21 (2015) 4781–4788.
  11. Passos, H.; Freire, M. G.; Coutinho, J. A. P., “Ionic liquid Solutions as Extractive Solvents for Value-Added Compounds from Biomass”, Green Chem. 16 (2014) 4786-4815.
  12. Cláudio, A. F. M.; Swift, L.; Hallett, J.; Welton, T.; Coutinho, J. A. P.; Freire, M. G., “Extended Scale for the Hydrogen-Bond Basicity of Ionic Liquids”,  Phys. Chem. Chem. Phys. 16 (2014) 6593-6601.
  13. Pereira, J. F. B.; Rebelo, L. P. N.; Rogers, R. D.; Coutinho, J. A. P.; Freire, M. G., “Combining Ionic Liquids and Polyethylene Glycols to Boost the Hydrophobic-hydrophilic Range of Aqueous Biphasic Systems”, Phys. Chem. Chem. Phys. 15 (2013) 19580-19583.
  14. Freire, M. G.; Cláudio, A. F. M.; Araújo, J. M. M.; Coutinho, J. A. P.; Marrucho, I. M.; Canongia Lopes, J. N.; Rebelo, L. P. N., “Aqueous Biphasic Systems: A Boost Brought About by using Ionic Liquids”, Chem. Soc. Rev. 41 (2012) 4966-4995.
  15. Tariq, M.; Freire, M.G.; Saramago, B.; Coutinho, J. A. P.; Canongia Lopes, J. N.; Rebelo, L. P. N., “Surface Tension of Ionic Liquids and Ionic Liquid Solutions”, Chem. Soc. Rev. 41 (2012) 829-868.
  16. Freire, M. G.; Pereira, J. F. B.; Francisco, M.; Rodríguez, H.; Rebelo, L. P. N.; Rogers, R. D.; Coutinho, J. A. P., “Insights into the Interactions that Control the Phase Behaviour of Novel Aqueous Biphasic Systems Composed of Polyethylene Glycols and Ionic Liquids”, Chem. Eur. J. 18 (2012) 1831-1839.
  17. Freire, M. G.; Neves, C. M. S. S.; Marrucho, I. M.; Canongia Lopes, J. N.; Rebelo, L. P. N.; Coutinho, J. A. P., “High-Performance Extraction of Alkaloids using Aqueous Two-Phase Systems with Ionic Liquids”, Green Chem. 12 (2010) 1715-1718.
  18. Freire, M. G.; Neves, C. M. S. S.; Carvalho, P. J.; Gardas, R. M.; Fernandes, A. M.; Marrucho, I. M.; Santos, L. M. N. B. F.; Coutinho, J. A. P., “Mutual Solubilities of Water and Hydrophobic Ionic Liquids”, J. Phys. Chem. B 111 (2007) 13082-13089.
  19. Freire, M. G.; Gomes, L.; Santos, L. M. N. B. F.; Marrucho, I. M., Coutinho, J. A. P., “Water Solubility in Linear Fluoroalkanes Used in Blood Substitute Emulsions”, J. Phys. Chem. B 110 (2006) 22923-22929.
  20. Freire, M. G.; Dias, A. M. A.; Coelho, M. A. Z.; Coutinho, J. A. P.;Marrucho, I. M., “Aging Mechanisms of Perfluorocarbon Emulsions using Image Analysis”, J. Colloid Interface Sci. 286 (2005) 224-232.

Ongoing Supervisions

Projects

Aeration of multiphase biological reactors (POCTI/EQU/44427/2002)

PartnerFundação para a Ciência e a Tecnologia
Biological reactors Aeration Multiphase Perfluorocarbons

Anchoring Basic Parameters for fundamental predictive models in Liquid Salt Systems (PTDC/QUI/72903/2006)

PartnerFundação para a Ciência e a Tecnologia
Ionic Liquids Vapor Pressure Enthalpy of vaporization Vapor Liquid Equilibrium

Anticorpos de aves com elevada pureza e estabilidade como biofármacos alternativos no combate à resistência antimicrobiana (antYmicrob)

CoordinatorIndustry National
O projeto antYmicrob ambiciona aumentar e validar à escala pré-industrial um processo de purificação desenvolvido para anticorpos imunoglobulina Y, e validar o processo com ovos hiperimunes para bactéria Staphylococcus aureus resistente à meticilina (MRSA), assegurando a atividade, estabilidade e não toxicidade dos anticorpos obtidos por ensaios...

Aplicação de SAB constituídos por líquidos iónicos no desenvolvimento de diagnósticos de câncer do sistema adrenalina (MCT/CNPq 14/2010 Universal)

Local CoordinatorOther International

DeepBiorefinery - Natural Deep Eutectic Solvents: A platform to Boost Eucalyptus globulus and Quercus suber cork integrated Biorefinerie (DeepBiorefinery )

PartnerFundação para a Ciência e a Tecnologia
natural deep eutetic solvents, biorefinery, green separation processes

Desenvolvimento de nanomateriais sustentáveis para a purificação de fármacos anti-leucémicos (NanoPurAsp)

PartnerFundação para a Ciência e a Tecnologia

Development of a sustainable technology for the extraction and purification of chlorophylls from biomass (EXPL/QEQ-PRS/0224/2013 )

PartnerFundação para a Ciência e a Tecnologia
chlorophyll extraction bioresources ionic liquids

Development of Ionic-Liquid-based Devices for the Removal of Cytostatic Drugs From Urine Excreted by Cancer Patients (IonCytDevice)

CoordinatorFundação para a Ciência e a Tecnologia

Development of New Oxygen Therapeutics using Fluorinated Ionic Liquids (PTDC/EQU-FTT/118800/2010)

Local CoordinatorFundação para a Ciência e a Tecnologia
Fluorinated Ionic Liquids Perfluoroalkanes Phase Equilibria Oxygen Solubility

Equilibrium and Interfacial Properties of Water + Oil Systems (POCI/EQU/58239/2004)

PartnerFundação para a Ciência e a Tecnologia
Phase Equilibria Interfacial Tension Aqueous Systems Modeling

EXIL - Exchange on Ionic Liquids (EXIL)

PartnerEuropean Comission
The objective of this Action is to coordinate European research activities and knowledge exchange on ionic liquids (ILs, low melting salts, many of them liquid at room temperature and below) and to explore their full potential in the context of fundamental and applied chemistry, materials science and engineering. The COST Action will provide a c...

Extraction and Purification of Biomolecules (FAPITEC/FUNTEC/CNPq n. 10/2011)

Local CoordinatorOther International

Igy Technology: A Purication Platform using Ionic-Liquid-Based Aqueous Biphasic Systems (IGYPURTECH)

CoordinatorEuropean Comission
With the emergence of antibiotic-resistant pathogens the development of antigen-specific antibodies for use in passive immunotherapy is, nowadays, a major concern in human society. Despite the most focused mammal antibodies, antibodies obtained from egg yolk of immunized hens, immunoglobulin Y (IgY), are an alternative option that can be obtaine...

Integration of human fluids pretreatment and detection of cancer biomarkers using ionic-liquid-based aqueous biphasic systems in microfluidic devices (ILSurvive)

PartnerFundação para a Ciência e a Tecnologia
Cancer biomarkers Detection Ionic liquids Microfluidic devices

Ionic liquid-based supports for pre-miRNAs purification targeting Alzheimer's disease (PUREmiRSILs)

Local CoordinatorFundação para a Ciência e a Tecnologia

Ionic Liquids as Promoters of Aqueous Biphasic Systems: The Role of van der Waals and Coulomb Interactions (PTDC/QUI-QUI/121520/2010)

PartnerFundação para a Ciência e a Tecnologia
Aqueous Biphasic System Ionic Liquid Inorganic Salt Polymer

MultiBiorefinery - Multi-purpose strategies for broadband agro-forest and fisheries by-products valorization: a step forward for a truly integrated biorefinery (SAICTPAC/0040/2015)

PartnerFundação para a Ciência e a Tecnologia
Biorrefinaria; Subprodutos e resíduos; Novos processos de extração e conversão; Bioprodutos

Nanostructured ZnO and ZnO/nanocarbon composites for biosensing applications (NANOBIOSENSE)

PartnerFundação para a Ciência e a Tecnologia
The expanding interest regarding biosensing and early diseases’ diagnosis has led to an exponential growth of R&D efforts in order to find the most suitable materials and sensing mechanisms to achieve high sensitivity and selectivity at low production cost. In this framework, the present project envisages the development of ZnO-based nanostructu...

Nova abordagem terapêutica para desacelerar a progressão da doença de Parkinson; (PDSolve)

Local CoordinatorIndustry National
A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais prevalente no mundo, com profundos impactos económicos e sociais. O objetivo deste projeto é provar a eficácia farmacológica e aplicação terapêutica à DP do i...

Optimization and Scale-up of Novel Ionic-Liquid- based Purification Processes for Recombinant Green Fluorescent Protein produced by Escherichia coli (FAPESP/19793/2014)

PartnerFundação para a Ciência e a Tecnologia
biopharmaceuticals, fluorescent proteins, purification, aqueous biphasic systems

The best of two worlds: Ionic liquids as Active Pharmaceutical Ingredients (PTDC/EQU-EPR/104554/2008)

Local CoordinatorFundação para a Ciência e a Tecnologia
Ionic Liquids Fluoroquinolones Bioavailability Solubility related properties

Vapour Liquid Equilibrium of Pure Ionic Liquids and their Mixtures with Organic Solvents (PTDC/EQU-FTT/65252/2006)

PartnerFundação para a Ciência e a Tecnologia
Ionic Liquids Vapour pressure Molar enthalpies and entropies of vaporization Vapour Liquid equilibrium

Publications

Nucleic Acids Stabilization with Ionic Liquids and Deep Eutectic Solvents

In Noureddine Abidi and Julia Shamshina (Eds.), Properties and Applications of Ionic Liquids
Almeida J.S.; Capela E.V.; Tavares A.P.M.; Freire M.G.
2023, Properties and Applications of Ionic Liquids, 181-218, Nova Science Publisher Inc..
ISBN: 979-888697873-5; 979-888697635-9

Microbial Enzymes in the Bioremediation of Pollutants

In Inamuddin, M.Phil (Eds.), Bioremediation for Environmental Pollutants
Flávia F. Magalhães, Maria I. Bonifácio, Ana M. Ferreira, Mara G. Freire and Ana P. M. Tavares
2023, 1-37, Benthan Science.
ISBN: 978-981-5123-53-1

Relevance on the Recovery of High Economic Value Elements and Potential of Ionic Liquids

Handbook of Solid Waste Management: Sustainability through Circular Economy
Almeida, J. C.; Cardoso, C. E. D.; Trindade, T.; Freire, M. G.; Pereira, E.
2022.

Anti-Cancer Biosurfactants

In Springer (Eds.), Microbial Biosurfactants
Flávia F. Magalhães, João C. F. Nunes, Marília T. Araújo, Ana M. Ferreira, Mafalda R. Almeida, Mara G. Freire, Ana P. M. Tavares
2021, 159-196.
ISBN: 10.1007/978-981-15-6607-3_8

Recovery and Purification of (Bio)Pharmaceuticals Using (Nano)Materials

In Bentham Science (Eds.), Recent Advances in Analytical Techniques Volume: 4
Ana P. M. Tavares, Márcia C. Neves, Tito Trindade and Mara G. Freire
2020, 58-93.
ISBN: 978-981-14-0510-5

Aqueous biphasic systems formed by cholinium-based ionic liquids and mixtures of polymers

In Rasmus Fehrmann, Catherine Santini (Eds.), Ionic Liquids: Synthesis, Properties, Technologies and Applications
Teresa B.V Dinis, Catarina M.S.S. Neves, Luís Barbosa, João A.P. Coutinho, Mara G. Freire
2019, 29-54, Berlin, Walter de Gruyter GmbH.
ISBN: 978-3-11-058201-7

Application of Ionic Liquids in Separation and Fractionation Processes

In Buxing Han and Tianbin Wu (Eds.), Green Chemistry and Chemical Engineering
Capela, EV; Coutinho, JAP; Freire, MG
2019, 637-665, New York, NY, Springer.
ISBN: 978-1-4939-9059-7

Immobilization of Ionic Liquids, Types of Materials, and Applications

In Zhang S. (Eds.), Encyclopedia of Ionic Liquids
Augusto Q. Pedro, João A. P. Coutinho, Mara G. Freire
2019, Springer.
ISBN: 978-981-10-6739-6

Ionic Liquids and Deep Eutectic Solvents in the Field of Environmental Monitoring

In Płotka-Wasylka, Justyna, Namieśnik, Jacek (Eds.), Green Analytical Chemistry: Past, Present and Perspectives
Cardoso I.S., Pedro A.Q., Silvestre A.J.D., Freire M.G.
2019, 203-240, Singapore, Springer.
ISBN: 978-981-13-9104-0

Use of Nanomaterials in the Pretreatment of Water Samples for Environmental Analysis

In Bhat AH, Jawaid M, O Sulliman FE, Al-Kindy SM (Eds.), Nanomaterials for Healthcare, Energy and Environment
Bernardo S, Sousa ACA, Neves MC, Freire MG
2019, 103-142, Aveiro, Springer Nature.
ISBN: 978-981-13-9832-2

Application of Ionic Liquids in Separation and Fractionation Processes

In Robert A. Meyers (Eds.), Encyclopedia of Sustainability Science and Technology
Capela, EV; Coutinho, JAP; Freire, MG
2018, 1-29, New York, USA, Springer.
ISBN: 978-1-4939-2493-6

Ionic Liquids in Bioseparation Processes

In Toshiyuki ItohYoon-Mo Koo (Eds.), Advances in biochemical engineering/biotechnology
Belchior D.C.V., Duarte I.F., Freire M.G.
2018, 1-29, Springer, Berlin.
ISBN: 978-3-030-23080-7

Monoclonal Antibodies – Addressing the Challenges on the Manufacturing Processing of an Advanced Class of Therapeutic Agents

In Atta-ur-Rahman (Eds.), Frontiers in Clinical Drug Research-Anti Infectives
Capela, EV; Aires-Barros, MR; Freire, MG; Azevedo, AM
2017, 142-203, Sharjah, UAE, Bentham Science.
ISBN: 978-1-68108-488-6

Imunoglobulina Y (IgY): uma Alternativa Promissora aos Anticorpos de Mamíferos

In Manuel A. Coimbra (Eds.), Bioquímica e Bem-Estar
M. V. Quental, M. R. Almeida, J. Gomes, J. Resende,P. Domingues, M. G. Freire
2017, Lisboa, Edições Afrontamento.
ISBN: 978-972-36-1560-9

Aplicação de Sistemas Aquosos Bifásicos na Purificação de Biomoléculas

In Á. S. Lima and C. C. Santana (Eds.), Processos de Extração e Purificação de Biomoléculas
Á. S. Lima, N. S. O. Placido, R. L. S. França, I. O. A. Reis, M. M. Pereira, M. G. Freire
2017, Brazil, EDUNIT - Editora Universitária Tiradentes.

CHAPTER 8:Ionic Liquids as Efficient Tools for the Purification of Biomolecules and Bioproducts from Natural Sources

In Rafal Bogel-Lukasik (Eds.), Ionic Liquids in the Biorefinery Concept : Challenges and Perspectives
Matheus M. Pereira, João A. P. Coutinho and Mara G. Freire
2016, 227-257, Royal Society of Chemistry.
ISBN: 978-1-84973-976-4

Introduction to Ionic-Liquid-Based Aqueous Biphasic Systems (ABS)

In Mara G. Freire (Eds.), Ionic-Liquid-Based Aqueous Biphasic Systems: Fundamentals and Applications
Mara G. Freire
2016, 1-25, Springer Berlin Heidelberg.
ISBN: 978-3-662-52875-4

Predicting the Thermodynamic Behavior of Water & Ionic Liquids Systems Using COSMO-RS

In Gaune-Escard M, Seddon K R (Eds.), Molten Salts and Ionic Liquids: Never the Twain?
Freire MG, Santos LMNBF, Marrucho IM, Coutinho JAP
2010, John Wiley & Sons, Inc..
ISBN: 978-0471773924

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