Mara Guadalupe Freire Martins
  Research Coordinator  
  phone: 234401422  
  extension: 24922  
  department: Chemistry  
  office: 29.3.33  
  group: 5 - biomedical and biomimetic materials
  line: 4 - health
  direct url:  
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.
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