Mara G. Freire graduated in Chemistry in 2003 by the University of Aveiro, Portugal, receiving the “Best Chemistry Student Award” from Dow Portugal. By the end of 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 of CICECO - Biomedical and Biomimetic Materials, and Deputy Chair of the Scientific Council of the University of Aveiro. She is member of the Portuguese Chemical Society and of the Portuguese Biotechnology Society. From 2017-2021 she was member of the Young Scientists Seminar of the Lisbon Academy of Sciences. She is member of the editorial board of several scientific journals, being Associated Editor of the Separation and Purification Technology journal. Since 2021, Freire is one of the 17 Chairs of the Content Selection Advisory Board (CSAB) from Scopus.
Freire published +270 papers in peer reviewed journals, +30 book chapters and two books, and has +15,000 citations and h-index of 69. 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 elected member of the Young Scientists Seminar of the Lisbon Academy of Sciences in 2017, 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, was recognized as an influential researcher by the journal Industrial Research and Chemical Engineering and as a highly cited researcher by the Journal of Chemical and Engineering Data of the American Chemical Society in 2019, 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 15 PhD, 58 MSc and 40 BSc students.
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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.
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- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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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L-asparaginase production review: bioprocess design and biochemical characteristicsCastro, D; Marques, ASC; Almeida, MR; de Paiva, GB; Bento, HBS; Pedrolli, DB; Freire, MG; Tavares, APM; Santos-Ebinuma, VC 2021, APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 105, 11, 4515-4534.
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Enhancing Artemisinin Solubility in Aqueous Solutions: Searching for Hydrotropes based on Ionic LiquidsSales, I; Abranches, DO; Costa, P; Sintra, TE; Ventura, SPM; Mattedi, S; Coutinho, JAP; Freire, MG; Pinho, SP 2021, FLUID PHASE EQUILIBRIA, 534,
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Integrated Biocatalytic Platform Based on Aqueous Biphasic Systems for the Sustainable Oligomerization of RutinMuniz-Mouro, A; Ferreira, AM; Coutinho, JAP; Freire, MG; Tavares, APM; Gullon, P; Gonzalez-Garcia, S; Eibes, G 2021, ACS SUSTAINABLE CHEMISTRY & ENGINEERING, 9, 29, 9941-9950.
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Purification of green fluorescent protein using fast centrifugal partition chromatographySoares, BP; Santos, JHPM; Martins, M; Almeida, MR; Santos, NV; Freire, MG; Santos-Ebinuma, VC; Coutinho, JAP; Pereira, JFB; Ventura, SPM 2021, SEPARATION AND PURIFICATION TECHNOLOGY, 257,
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Advances Brought by Hydrophilic Ionic Liquids in Fields Involving PharmaceuticalsDinis, TBV; Silva, FAE; Sousa, F; Freire, MG 2021, MATERIALS, 14, 21,
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Insights into coacervative and dispersive liquid-phase microextraction strategies with hydrophilic media - A reviewPacheco-Fernandez, I; Gonzalez-Martin, R; Silva, FAE; Freire, MG; Pino, V 2021, ANALYTICA CHIMICA ACTA, 1143, 225-249.
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Efficient Isolation of Bacterial RNAs Using Silica-Based Materials Modified with Ionic LiquidsPereira, P; Pedro, AQ; Neves, MC; Martins, JC; Rodrigues, I; Freire, MG; Sousa, F 2021, LIFE-BASEL, 11, 10,
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Superior operational stability of immobilized l-asparaginase over surface-modified carbon nanotubesAlmeida, MR; Cristovao, RO; Barros, MA; Nunes, JCF; Boaventura, RAR; Loureiro, JM; Faria, JL; Neves, MC; Freire, MG; Santos-Ebinuma, VC; Tavares, APM; Silva, CG 2021, SCIENTIFIC REPORTS, 11, 1,
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A purification platform for antibodies and derived fragments using a de novo designed affinity adsorbentMatos, MJB; Trovao, F; Goncalves, J; Rothbauer, U; Freire, MG; Barbosa, AMJB; Pina, AS; Roque, ACA 2021, SEPARATION AND PURIFICATION TECHNOLOGY, 265,
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Recovery of lactose and proteins from cheese whey with poly(ethylene) glycol/sulfate aqueous two-phase systemsGonzalez-Amado, M; Tavares, APM; Freire, MG; Soto, A; Rodriguez, O 2021, SEPARATION AND PURIFICATION TECHNOLOGY, 255,
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Purification of anthocyanins from grape pomace by centrifugal partition chromatographyLima, AS; de Oliveira, BS; Shabudin, SV; Almeida, M; Freire, MG; Bica, K 2021, JOURNAL OF MOLECULAR LIQUIDS, 326,
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PrefaceFreire, MG; Coutinho, JAP 2020, FLUID PHASE EQUILIBRIA, 512,
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Distinct roles of salt cations and anions upon the salting-out of electro-positive albuminMadeira, PP; Freire, MG; Coutinho, JAP 2020, JOURNAL OF MOLECULAR LIQUIDS, 301,
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Bacterial nanocellulose membranes loaded with vitamin B-based ionic liquids for dermal care applicationsChantereau, G; Sharma, M; Abednejad, A; Vilela, C; Costa, EM; Veiga, M; Antunes, F; Pintado, MM; Sebe, G; Coma, V; Freire, MG; Freire, CSR; Silvestre, AJD 2020, JOURNAL OF MOLECULAR LIQUIDS, 302,
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Aqueous biphasic systems comprising copolymers and cholinium-based salts or ionic liquids: Insights on the mechanisms responsible for their creationDimitrijevic, A; Tavares, APM; Jocic, A; Maric, S; Trtic-Petrovic, T; Gadzuric, S; Freire, MG 2020, SEPARATION AND PURIFICATION TECHNOLOGY, 248,
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Anti-Cancer BiosurfactantsFlávia F. Magalhães, João C. F. Nunes, Marília T. Araújo, Ana M. Ferreira, Mafalda R. Almeida, Mara G. Freire, Ana P. M. Tavares In Springer (Eds.), Microbial Biosurfactants 2021, 159-196.
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Recovery and Purification of (Bio)Pharmaceuticals Using (Nano)MaterialsAna P. M. Tavares, Márcia C. Neves, Tito Trindade and Mara G. Freire In Bentham Science (Eds.), Recent Advances in Analytical Techniques Volume: 4 2020, 58-93.
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Aqueous biphasic systems formed by cholinium-based ionic liquids and mixtures of polymersTeresa B.V Dinis, Catarina M.S.S. Neves, Luís Barbosa, João A.P. Coutinho, Mara G. Freire In Rasmus Fehrmann, Catherine Santini (Eds.), Ionic Liquids: Synthesis, Properties, Technologies and Applications 2019, 29-54. Berlin: Walter de Gruyter GmbH.
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Application of Ionic Liquids in Separation and Fractionation ProcessesEmanuel V. Capela, João A.P. Coutinho, Mara G. Freire In Buxing Han and Tianbin Wu (Eds.), Green Chemistry and Chemical Engineering 2019, 637-665. New York, NY: Springer.
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Immobilization of Ionic Liquids, Types of Materials, and ApplicationsAugusto Q. Pedro, João A. P. Coutinho, Mara G. Freire In Zhang S. (Eds.), Encyclopedia of Ionic Liquids 2019, Springer.
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Ionic Liquids and Deep Eutectic Solvents in the Field of Environmental MonitoringCardoso I.S., Pedro A.Q., Silvestre A.J.D., Freire M.G. In Płotka-Wasylka, Justyna, Namieśnik, Jacek (Eds.), Green Analytical Chemistry: Past, Present and Perspectives 2019, 203-240. Singapore: Springer.
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Use of Nanomaterials in the Pretreatment of Water Samples for Environmental AnalysisBernardo S, Sousa ACA, Neves MC, Freire MG In Bhat AH, Jawaid M, O Sulliman FE, Al-Kindy SM (Eds.), Nanomaterials for Healthcare, Energy and Environment 2019, 103-142. Aveiro: Springer Nature.
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Application of Ionic Liquids in Separation and Fractionation ProcessesEmanuel V. Capela, João A.P. Coutinho, Mara G. Freire In Robert A. Meyers (Eds.), Encyclopedia of Sustainability Science and Technology 2018, 1-29. New York, USA: Springer.
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Ionic Liquids in Bioseparation ProcessesBelchior D.C.V., Duarte I.F., Freire M.G. In Toshiyuki ItohYoon-Mo Koo (Eds.), Advances in biochemical engineering/biotechnology 2018, 1-29. Springer, Berlin.
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Monoclonal Antibodies – Addressing the Challenges on the Manufacturing Processing of an Advanced Class of Therapeutic AgentsEmanuel V. Capela, M. Raquel Aires-Barros, Mara G. Freire, Ana M. Azevedo In Atta-ur-Rahman (Eds.), Frontiers in Clinical Drug Research-Anti Infectives 2017, 142-203. Sharjah, UAE: Bentham Science.
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Imunoglobulina Y (IgY): uma Alternativa Promissora aos Anticorpos de MamíferosM. V. Quental, M. R. Almeida, J. Gomes, J. Resende,P. Domingues, M. G. Freire In Manuel A. Coimbra (Eds.), Bioquímica e Bem-Estar 2017, Lisboa: Edições Afrontamento.
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Aplicação de Sistemas Aquosos Bifásicos na Purificação de BiomoléculasÁ. S. Lima, N. S. O. Placido, R. L. S. França, I. O. A. Reis, M. M. Pereira, M. G. Freire In Á. S. Lima and C. C. Santana (Eds.), Processos de Extração e Purificação de Biomoléculas 2017, Brazil: EDUNIT - Editora Universitária Tiradentes.
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CHAPTER 8:Ionic Liquids as Efficient Tools for the Purification of Biomolecules and Bioproducts from Natural SourcesMatheus M. Pereira, João A. P. Coutinho and Mara G. Freire In Rafal Bogel-Lukasik (Eds.), Ionic Liquids in the Biorefinery Concept : Challenges and Perspectives 2016, 227-257. Royal Society of Chemistry.
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Introduction to Ionic-Liquid-Based Aqueous Biphasic Systems (ABS)Mara G. Freire In Mara G. Freire (Eds.), Ionic-Liquid-Based Aqueous Biphasic Systems: Fundamentals and Applications 2016, 1-25. Springer Berlin Heidelberg.
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Predicting the Thermodynamic Behavior of Water & Ionic Liquids Systems Using COSMO-RSFreire MG, Santos LMNBF, Marrucho IM, Coutinho JAP In Gaune-Escard M, Seddon K R (Eds.), Molten Salts and Ionic Liquids: Never the Twain? 2010, John Wiley & Sons, Inc..
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