BOOK OF A3BSTRACTS...Book of Abstracts - 2nd International Meeting on Deep Eutectic Systems 7 Bárbara Socas-Rodríguez, David M. Alonso García, José A. Mendiola, Alejandro Cifuentes

Book of Abstracts - 2nd International Meeting on Deep Eutectic Systems

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BOOK OF A3BSTRACTS 2nd INTERNATIONAL MEETING ON DEEP EUTECTIC SYSTEMS

ONLINE 15th-17th JUNE 2021

The Organizing Committee invites you for the 2nd International Meeting

on Deep Eutectic Systems. Due to the pandemic context we are living, the Meeting

will be held exclusively online, from 15th to 17th of June 2021. After the success

of the 1st event, we expect to continue a fruitful series of meetings, where scientists,

students and industry partners can discuss current developments and innovations

in the field of Deep Eutectic Systems. Themes like fundamental properties, scale up

of processes, and development of new products, techniques and approaches will be

addressed. The main objective is to join a group of specialists in this emerging field

and be able, not only to hear the newest developments and discoveries, but also to

discuss and interact with students and other participants. This way, we intend to

provide you a unique opportunity of results dissemination and discussion of new

ideas. This Meeting will have plenary lectures, oral communications, and poster

sessions, which we believe to cover all the most innovative scientific developments.

Hope to see you there!

The Organizing Committee


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Title: The Book of Abstracts of the 2nd International Meeting on Deep Eutectic Systems Publishes abstracts from the following fields: Fundamentals, Pharma, Food, Extraction & Separation, Materials and Biotech. Publishers: Des Solutio - Soluções e Consultoria Científica, Lda ISBN: 978-989-33-1955-0

ORGANIZING COMMITTEE: ▪ Ana Rita C. Duarte, FCT-Universidade Nova de Lisboa, Portugal ▪ Alexandre Paiva, FCT-Universidade Nova de Lisboa, Portugal ▪ Rita Craveiro, FCT-Universidade Nova de Lisboa, Portugal ▪ Luísa Pereira, FCT-Universidade Nova de Lisboa, Portugal

SCIENTIFIC COMMITTEE:

▪ Andrew Abbott – University of Leicester, UK ▪ Francisco Del Monte – CSIC, Madrid, Spain ▪ Gary Baker - Missouri University, EUA ▪ Gregory Warr – University of Sydney, Australia ▪ Jeongmi Lee – Sungkyunkwan University, South Korea ▪ Josué Mota-Morales – CFATA-UNAM, Mexico ▪ Karen Edler – Bath University, UK ▪ Karine Vigier – IC2MP, Poitiers University, France ▪ Maan Hayyan – Sohar University, Sultanate of Oman ▪ Rob Verpoort – Leiden University, Netherlands ▪ Sona Raeissi – Shiraz University, Iran ▪ Zhan-Hui Zhang – Hebei Normal University, Shijiazhuang, China


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Sponsors


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Program


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*Western European Summer Time Zone (WEST, UTC±1:00) Detailed program Tuesday, 15th June 2021

* 09:00 Opening session

Plenary lecture

09:15 Understanding the Physicochemical Behavior of Deep Eutectic Solvents Using Computational Modelling: From fundamentals to practical applications Félix Llovell

Oral presentations – FUNDAMENTALS

10:00 Simulation of Equilibrium Phase Diagram and Physicochemical Characterization of Natural Eutectic Solvents

Maha M. Abdallah, Simon Muller, Andres Gonzalez de Castilla, Pavel Gurikov, Maria do Rosário Bronze, Ana A. Matias, Naiara Fernandez

10:15 ATR-IR Spectroscopy for Rapid Quantification of Water Content in Deep Eutectic Solvents

Suha Elderderi, Charlotte Leman-Loubière, Laura Wils, Hugh J. Byrne, Igor Chourpa, Cécile Enguehard-Gueiffier, Emilie Munnier, Abdalla A. Elbashir, Leslie Boudesocque-Delaye, Franck Bonnier

10:30 Is There Depth to Eutectic Systems?

Adriaan van den Bruinhorst, Mark Vis, Gijsbertus de With, Agilio Padua, and Margarida Costa Gomes

10:45 Coffee break and poster sessions

11:45 Micellization of Ionic Surfactants in a Ternary Deep Eutectic System

Ria Atri, Iva Manasi, Adrian Sanchez Fernandez, Oliver Hammond, James Doutch and Karen J. Edler

12:00 DES? Solutions? The Influence of Water on the phase behaviour of Ternary Liquid Mixtures

Ana Roda, Christoph Held, Filipa Santos, Yeong Zen Chua, Aarti Kumar, Hoang Tam Do, Alexandre Paiva and Ana Rita C. Duarte

12:15 Carvone and its eutectic mixtures introduced as tunable, green solvents

Ke Li, Seulgi Kang, Yuli Liu, Inseon Hwang, Jeongmi Lee

12:30 Structure and Interactions in p-Toluene Sulfonic Acid based Deep Eutectic Solvent

Iva Manasi, Elly K Bathke, Stephen M King, Daniel T Bowron and Karen J Edler

12:45

On the Betaine:Urea:xWater NADES system

Maria F. Nava-Ocampo, Lamya Al Fuhaid, Adriano Santana, Szilárd S. Bucs, Robert Verpoorte, Young Choi, Johannes S. Vrouwenvelder, Geert J. Witkamp, Andreia S. F. Farinha

13:00

Biosourced Non-Ionic Low Transition Temperature Mixtures Composed of Fructose and Glycerol: Water and Temperature Impact on the Supramolecular Organization Caprin Benoît, Charton Virginie, Rodier Jean-David, Vogelgesang Boris, Charlot Aurélia, Da Cruz-Boisson Fernande, Fleury Etienne

13:15 Lunch

Oral presentations – PHARM

14:45 Solubility of Mesalazine in Natural Deep Eutectic Solvents

Debora Procopio, Carlo Siciliano, Sonia Trombino, Roberta Cassano, Federica Curcio, Maria Luisa Di Gioia

15:00 Delivery of Deep Eutectic Solvents Comprising Nonsteroidal Anti-inflammatory Drugs using Biopolymer-Based Systems

Sónia N. Pedro, Maria S. M. Mendes, Bruno Miguel Neves, Mara G. Freire, Armando J. D. Silvestre and Carmen S. R. Freire

15:15 Unravelling the target-specific anticancer action of THEDES

Filipe Oliveira, Joana Pereira, Eduardo Silva, Joana M. Silva, Rui L. Reis, Ana Rita C. Duarte

15:30 Eutectic Mixtures as Promising Formulation Strategy for Poorly Water-Soluble Drugs Sarah El Masri, Sophie Fourmentin, Steven Ruellan, Maha Zakhour and Lizette Auezova

15:45 Impact of hydrophilic natural deep eutectic solvents on hydrogels intended for skin application

Iron Mike Ardeza, L. Boudesocque-Delaye. Laura Wils, Xavier Perse, Sybille de La Motte, Emilie Munnier


Oral presentations – FOOD

17:00 Safety assessment of valorised food by-products using novel analytical procedures based on natural deep eutectic solvents


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Bárbara Socas-Rodríguez, David M. Alonso García, José A. Mendiola, Alejandro Cifuentes and Elena Ibáñez

17:15

A Green Method based on Natural Hydrophobic Deep Eutectic Solvents for Plastic Migrants Determination in Beverages using UHPLC-MS/MS Ruth Rodríguez-Ramos, Álvaro Santana-Mayor, Antonio V. Herrera-Herrera, Bárbara Socas-Rodríguez, Miguel Ángel Rodríguez-Delgado

17:30 NADES in the stabilization of phenolic compounds from sunflower meal

Fernanda de Sousa Bezerra, Danielly C. Ferraz da Costa and Maria Gabriela Bello Koblitz

17:45

Could NaDES assisted one-pot extraction and biotransformation be a relevant strategy to boost activity of natural extracts? Millena Cristina Barros Santos, Nathalie Barouh, Bruno Baréa, Mélina Robert, Pierre Villeneuve, Luiz Cláudio Cameron, Valérie-Lullien, Claire Bourlieu-Lacanal, Mariana Simões Larraz Ferreira and Erwann Durand

Wednesday, 16th June 2021

Plenary lecture

09:00 Design of biobased supramolecular solvents dedicated to plant extraction for cosmetic actives, from research to industrial implementation

Caprin Benoît, Charton Virginie, Vogelgesang Boris

Oral presentations - EXTRACTION & SEPARATION

09:45 Application of Deep Eutectic Solvents for the Extraction of Textile Dyes from Water

L. Villar, J. Páez, A. Domínguez, B. González

10:00 Extraction and Stabilization of Bioactive Compounds From Aromatic Plants Using Sustainable NADES

Sílvia Rebocho, Rita Craveiro, Alexandre Paiva, Ana Rita C. Duarte

10:15 Valorization of vine shoots biomass assisted by acidic deep eutectic solvents

Bruno D. A. Pinheiro, Maria Hijosa-Valsero, André M. da Costa Lopes, Armando J. D. Silvestre

10:30 Using Eutectic Mixtures For The Extraction And Recovery of the Carotenoid Bacterioruberin

Mariam Kholany, Nicolas Schaeffer, Inês P.E. Macário, Telma Veloso, Tânia Caetano, Joana Luísa Pereira, Sónia P.M. Ventura, João A. P. Coutinho


11:45 Sustainable waste management from wine production

Manuela Panić, Veronika Gunjević, Mia Radović, Kristina Radošević, Marina Cvjetko Bubalo, Natka Ćurko, Karin Kovačević Ganić, Ivana Radojčić Redovniković

12:00

Non-Ionic Hydrophobic Deep Eutectic Solvents as Promising Extraction Agents for the Evaluation of Endocrine Disruptors in Environmental Waters

Álvaro Santana-Mayor, Bárbara Socas-Rodríguez, Ruth Rodríguez-Ramos, Antonio V. Herrera-Herrera, and Miguel Ángel Rodríguez-Delgado

12:15 Insulinotropic effects of apple pomace extracts in Deep Eutectic systems

Heleena Moni Bottu, Lorraine Brennan, Lorrenzo Guazzelli, Angelica Mero, Elena Husanu, Serge Tavernier

12:30 Natural Deep Eutectic Solvents for the Green Extraction of Soy By-Products

Felipe Sanchez Bragagnolo, Bárbara Socas-Rodríguez, Cristiano Soleo Funari, Elena Ibáñez

12:45 Lunch

Oral presentations – MATERIALS

14:15 Deep Eutectic Solvents for wood cellulose purification

Andrea Mezzetta, Greta Colombo Dugoni, Lorenzo Guazzelli, Monica Ferro, Andrea Mele

14:30 A critical study on the influence of DES on the formation of organic biphasic systems

Jean-Baptiste Chagnoleau, Nicolas Papaiconomou, Mona Jamaly, João A. P. Coutinho, Dinis O. Abranches, Xavier Fernandez, Thomas Michel

14:45 Dissolution and Recovery of Lithium-Ion Battery Cathode Materials Using Deep Eutectic Solvents

Dana L. Thompson, Jennifer M. Hartley, Chunhong Lei, Ioanna M. Pateli, Andrew P. Abbott


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15:00 Separation of Lithium from a Simulated Salt-lake Brine using Synergistic Deep Eutectic Solvents

Takafumi Hanada and Masahiro Goto

15:15 Furfural production from xylans through acidic deep eutectic-based systems

Eduarda S. Morais, Mara G. Freire, Carmen S. R. Freire, João A. P. Coutinho, Armando J. D. Silvestre


16:30 Synthesis of Sugar-Based Polymers From Reactive Natural Low Transition Temperature Mixtures

Gabriel Duaux, Etienne Fleury, Daniel Portinha

16:45 Extraction of Ferulic Acid from Aqueous Systems Using Deep Eutectic Solvents

O. G. Sas, M. López, M. Pita, B. González, A. Domínguez

17:00 Lignin conversion into value-added compounds using an acidic deep eutectic at mild conditions

Filipe H. B. Sosa, Ana Bjelic, João A. P. Coutinho, Mariana C. Costa, Edita J. Grojzdek, Miha Grilc, Andre M. da Costa Lopes

17:15 Indium Mediated Barbier Allylation of Carbonyl Compounds in Deep Eutectic Solvents

Nerea González-Gallardo, Beatriz Saavedra, Gabriela Guillena and Diego J. Ramón

17:30 Make it or Break it: Cu3(BTC)2 Metal-Organic Framework in Reline DES

Renata Avena Maia, Benoît Louis, Stéphane Baudron

Thursday, 17th June 2021

Plenary lecture

09:00 Conversion of Carbohydrates to Value Added Chemicals in the presence of DES

Karine De Oliveira Vigier

Oral presentations – BIOTECH

09:45

Unravelling the in vitro and in vivo toxicity of deep eutectic solvents consisting of safe compounds including choline chloride

Dasom Jung, Jae Back Jung, Seulgi Kang, Ke Li, Inseon Hwang, Ji Hoon Jeong, Hyung Sik Kim and Jeongmi Lee

10:00 Stabilization of Horseradish Peroxidase Using Natural Deep Eutectic Systems

Liane Meneses, Ana Rita C. Duarte, Alexandre Paiva

10:15 Natural deep eutectic solvents as biofilm structural breaker

Maria F. Nava-Ocampo, Lamya Al Fuhaid, Szilárd S. Bucs, Robert Verpoorte, Young Choi, M.C.M. van Loosdrecht, Johannes S. Vrouwenvelder, Geert J. Witkamp, Andreia S. F. Farinha

10:30 Natural deep eutectic solvents for microalgae biorefinery: Spirulina as case of study

Laura Wils, Soukaina Hilali, Suha Elderli, Mervé Yagmur, Charlotte Leman-Loubière, Barbara Clément-Larosière, Franck Bonnier and Leslie Boudesocque-Delaye


11:30 Poster Award

11:45 NADES for microalgae biorefinery: biomass pre-treatment and comparison with bio-sourced solvents

Laura Wils, Soukaina Hilali, Mervé Yagmur, Barbara Clément-Larosière, and Leslie Boudesocque-Delaye

12:00

Towards Mechanistic Understanding of Naturally Derived Deep Eutectic Solvents Effect on Enzyme Catalyzed Reactions

Attila Kovács, Erik C. Neyts, Iris Cornet and Pieter Billen

12:15 Enhanced Solubilization Of Essential Oils By Combining Deep Eutectic Solvent, Cyclodextrins And Water

Lamia Nakhle, Miriana Kfoury, Isabelle Mallard, Hélène Greige-Gerges, David Landy

12:30 Natural deep eutectic solvents: the future of natural cosmetic formulation?

Iron Mike Ardeza, Leslie Boudesocque-Delaye, Laura Wils, Alexandra Despres, Franck Bonnier, Xavier Perse, Charles Bodet, Igor Chourpa, Emilie Munnier

12:45 Closing session


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PLENARY

LECTURES


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Design of biobased supramolecular solvents dedicated to

plant extraction for cosmetic actives, from research to

industrial implementation

Caprin Benoît *, Charton Virginie, Vogelgesang Boris,

Gattefossé SAS, 36 chemin de Genas, 69804, Saint-Priest cedex, France

* [email protected]

Keywords: NaDES, NaLTTM, Cosmetics, Green chemistry, Eco-friendly plant extraction

process, Sustainable actives, Phytochemical footprint, Biological activity

Natural Deep Eutectic Solvents (NaDES), and more recently Natural Low Transition

Temperature Mixtures (NaLTTM), have emerged as a promising and ecofriendly alternative to

petrochemicals to dissolve plant metabolites. The demand for sustainable and green cosmetics

is in permanent growth and those solvents represent unexplored opportunities to develop

innovative extracts with unique phytochemical footprints and biological activities. However,

despite the number of NADES or NaLTTM described in the literature, only a few can be used

for cosmetic applications because of safety or regulatory issues. This presentation will first

introduce the regulatory framework, the green chemistry and naturalness requirements that a

cosmetic active ingredient has to comply with. In this frame, the research strategy adopted by

Gattefossé to develop and characterize green solvents dedicated to the obtention of fully

biobased plant extracts will be described. A peculiar attention on the value-added of these

systems compared to traditional extraction solvents in terms of phytochemical composition and

biological efficacy on human skin will be then presented. In a second part, this presentation will

introduce some of the technological choices that have been made during scale-up activities to

make the implementation of such extraction processes possible. Finally, the industrial reality

and benefits of biobased actives obtained will be presented through concrete examples.

Figure 1 : Illustration of biological efficacy of an industrialized NaDES plant extract design by Gattefossé.


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Understanding the Physicochemical Behavior of Deep

Eutectic Solvents Using Computational Modelling: From

fundamentals to practical applications

Fèlix Llovell

Department of Chemical Engineering, Universitat Rovira i Virgili, Avinguda Països Catalans

26, 43007, Tarragona, Spain.

*E-mail: [email protected]

In the last decade, Deep Eutectic Solvents (DESs) have emerged as a new family of compounds

with fascinating properties that can be implemented in a wide variety of industrial processes.

Although there is not full agreement on finding an exact definition for the denomination of

DESs, they are typically understood as the combination of a Hydrogen Bonding Acceptor

(HBA) compound, which is normally a halide salt, and a Hydrogen Bonding Donor (HBD),

which is a neutral complexing agent. The hydrogen-bonding effect causes a substantial decrease

of the melting point compared to that of the individual components, becoming an eutectic

mixture. This fact widens the range of the liquid state, while keeping a negligible volatility.

Compared to Ionic Liquids (ILs), DESs have an easier preparation, which reduces their cost. In

addition, many of them can be formed using natural compounds, originating a subclass known

as Natural Deep Eutectic Solvents (NADES). For this reason, DES are also associated to

greener processes, which can contribute to improve the sustainability of industrial operation

units. [1]. However, as it happened with ILs, the number of possible combinations to form a

DES is enormous, complicating a full characterization of all options to screen the best

compound for a particular application. Nowadays, the mechanisms behind their

physicochemical properties are still not well understood, and this becomes a constraint for the

design of any process involving DESs. In this regard, the use of multiscale simulation provides

a useful path to obtain additional information to guide the experimental work into the right

direction. In this contribution, a general overview of the possibilities that computational

modelling tools can offer to better understand the mechanisms that drive the physicochemical

behavior of DESs is presented [2]. In particular, the use of advanced equations of state or

models explicitly considering hydrogen bonds will be shown, highlighting some practical

examples related to the screening of DESs for greenhouse gases capture applications [3,4].

Acknowledgements

This research is supported by project PID2019-108014RB-C21, funded by the Spanish Ministry of Science and

Innovation, and project KET4F-Gas, SOE2/P1/ P0823, which is co-financed by the European Regional

Development Fund within the framework of the Interreg SUDOE Program.

References

[1] A. Paiva, R. Craveiro, I. Aroso, M. Martins, R. L. Reis, A. R. C. Duarte, ACS Sustainable Chemistry &

Engineering, 2(5) (2014)1063–1071.

[2] I. Alkhatib, D. Bahamon, F. Llovell, M. Abu-Zahra, L.F. Vega, Journal of Molecular Liquids, 298 (2020)

112183.

[3] R.M. Ojeda, F. Llovell, J. Chem. Eng. Data (2018) 63 (2018) 2599−2612.

[4] I.I.I. Alkhatib, M. L. Ferreira, C. G. Alba, D. Bahamon, F. Llovell, A. B. Pereiro, J. M.M. Araújo, M. R.M.

Abu-Zahra, L. F. Vega, Journal of Chemical & Engineering Data 65 (2020) 12, 5844–5861.


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Conversion of Carbohydrates to Value Added Chemicals

in the presence of DES

Karine De Oliveira Vigier

IC2MP, UMR CNRS 7285, Université de Poitiers

1 rue Marcel Doré, Poitiers, France, [email protected]

The catalytic conversion of carbohydrates to value added chemicals or platform molecules is

the topic of numerous research. One of the challenges is the conversion of a highly concentrated

solution of carbohydrates in an environmentally friendly process. The effect of the solvent

nature will be discussed. An interesting class of solvents is gaining more and more attention:

Deep Eutectic Solvents (DES) or Low Melting Mixtures (LMM). One of the most widespread

components used for the formation of these solvents is choline chloride (ChCl). ChCl is a very

cheap, biodegradable and non toxic quaternary ammonium salts which can be either extracted

from biomass or readily synthesized from fossil reserves (million metric tons) through a very

high atom economy process. In combination with safe hydrogen bond donors such as

carbohydrates, ChCl is capable of rapidly forming a DES/LMM. We have studied several

catalytic systems in the synthesis of furanic derivatives (5-hydroxymethylfurfural and furfural)

showing the benefit effect of these solvents in such reactions. Some examples will be presented

where ChCl can help to control the selectivity of the reaction by providing interactions with the

furanic derivatives avoiding their degradation starting from highly concentrated solutions of

carbohydrates. Some insights of the mechanism will be provided. The hydrogenation of

carbohydrates was also investigated in the presence of DESs and the nature of the solvent was

also studied in order to improve the yield of alditol and the catalyst stability.


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ORAL PRESENTATIONS


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Is There Depth to Eutectic Systems?

Adriaan van den Bruinhorsta,b*, Mark Vis,b,a Gijsbertus de With,b Agilio Padua,a and

Margarida Costa Gomesa a École Normale Supérieure Lyon, Laboratoire de Chimie, 46 allée d’Italie, 69364 Lyon, FR b Eindhoven University of Technology, Chemistry & Chemical Engineering, P.O. Box 513,

5600 MB Eindhoven, NL

*[email protected]

Keywords: eutectic depth, S–L equilibria prediction, fusion properties, calorimetry

The key aspect of a deep eutectic system (DES) is the formation of a liquid over a wide

composition range upon mixing its constituents. Easy access to the liquid phase via melting

point depression is at the basis of the broad spectrum of DES applications reported in literature.

We aim to determine the eutectic depth – i.e. the difference between the actual and ideal eutectic

temperature – for a large number of systems to confirm the existence of a distinct group of

mixtures with exceptional melting temperature depressions: the deep eutectic systems. The

depth of a simple eutectic is governed by (i) pure component fusion properties and (ii)

intermolecular interactions between the constituents in the liquid phase. Fusion properties are

available in literature for many pure components. Measuring unknown fusion properties is in

principle straightforward, but can be challenging in practice due to sublimation or thermal

decomposition. Here we present an overview of experimental methods to indirectly obtain the

fusion properties for components that decompose before or upon melting, showcasing the use

of isothermal calorimetry for choline chloride – one of the archetypal DES constituents. The

interaction energies in the liquid phase can be derived from isothermal calorimetry data or from

phase diagrams summarising the solid–liquid equilibria (SLE) of eutectic mixtures. Although

such data is available for common mixtures, it would be unfeasible to experimentally evaluate

all possible (D)ESs owing to the ubiquity of eutectic behaviour. We therefore predicted over

100000 binary phase diagrams from the excess Gibbs energy of mixing using COSMO-SAC1

for components with known fusion properties2 and sigma-profiles1. Comparison of the large

number of predicted and reported SLE phase diagrams showed which fusion properties

typically contribute to deeper eutectics. No discrete groups emerged with respect to eutectic

depth, complicating a strict definition for DESs. However, the presented methodologies to

quantify fusion properties and liquid interactions resulted in a roadmap towards developing

eutectic systems with the desired liquid window, deep or not.

1 F. Ferrarini, G. B. Flôres, A. R. Muniz and R. P. de Soares, AIChE J., 2018, 64, 3443–3455.

2 Fusion properties were extracted from the WolframAlpha database on 04-12-2019.


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Non-Ionic Hydrophobic Deep Eutectic Solvents as

Promising Extraction Agents for the Evaluation of

Endocrine Disruptors in Environmental Waters

Álvaro Santana-Mayor a,*, Bárbara Socas-Rodríguez b, Ruth Rodríguez-Ramos a,

Antonio V. Herrera-Herrera c, and Miguel Ángel Rodríguez-Delgado a a Departamento de Química, Unidad Departamental de Química Analítica, Facultad de

Ciencias, Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, s/n, 38206 San

Cristóbal de La Laguna, España, b Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera

9, 28049 Madrid, Spain, c Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna

(ULL), Avda. Astrofísico Fco. Sánchez, 2, 38206 San Cristóbal de La Laguna, España

* [email protected]

Keywords: deep eutectic solvent, plastic migrants, microextraction, water samples

Deep eutectic solvents (DESs), labelled as 21st century solvents, have emerged within scientific

community as a promising sustainable alternative to conventional organic solvents. DESs have

remarkable properties that can be tuned depending on the components and their molar ratios.

Since some of their main characteristics are their liquid nature, great stability at room

temperature and high biocompatibility, these neoteric mixtures have been used in analytical

extraction procedures. Furthermore, these eutectic solvents have shown high capacity to extract

a wide variety of compounds with different polarities, as well as metallic species from all types

of matrices, even using low volumes of DESs. In this way, they not only allow the development

of versatile procedures, but also provide a significant degree of pre-concentration and,

therefore, low detection limits. This is especially important in the determination of pollutants,

such as plastic migrants, whose presence even at very low concentrations can result in

significant damage to living beings and the environment. In this work, a terpene-based natural

hydrophobic DES (thymol:menthol, 2:1) has been used as extraction solvent in a simple liquid-

liquid microextraction of 14 phthalates and one adipate from environmental waters (treated

wastewater, runoff and pond waters). The separation and quantification of target analytes were

carried out using an ultra-high performance liquid chromatography-tandem mass spectrometry

system. Good linearity was achieved (R2 higher than 0.9954) and few parameters were

optimised (DES molar ratio and volume) to reach good recovery values (70–120%) and very

low limits of quantification (0.013–0.425 µg/L). Finally, the methodology was applied for the

evaluation of plastic migrants in different waters from Canary Islands destined to agricultural

activities.


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DES? Solutions? The Influence of Water on the phase

behaviour of Ternary Liquid Mixtures Ana Roda a, Christoph Held b,*, Filipa Santos a, Yeong Zen Chua b, Aarti Kumar c, Hoang

Tam Do c, Alexandre Paiva a and Ana Rita C. Duarte a a LAQV, REQUIMTE, Chemistry Department, FCT-NOVA, 2829-516 Caparica, Portugal

b Institute of Physics, University of Rostock, Albert-Einstein-Str. 23-24, 18051

Rostock, Germany c Laboratory of Thermodynamics, Department of Biochemical and Chemical

Engineering, TU Dortmund, 44227 Dortmund, Germany

* [email protected]

Keywords: Solution, water, solid-liquid equilibria, PC-SAFT, spectroscopy, characterization

The influence of water in on the phase behaviour of liquid mixtures like deep eutectic systems

(DES) is a question that has been addressed by different researchers from several perspectives

[1–4]. In the present work, solid liquid equilibria (SLE) studies and spectroscopy analysis were

used to study the impact of water in the liquefaction of ternary mixtures. PC-SAFT predictions

were validated using experimental data of the DES choline chloride:urea (1:2 molar ratio) upon

water addition from ref. [5]. Hence, PC-SAFT was further applied to predict the water influence

on the SLE of the mixture L-arginine:citric acid:H2O using new melting data for L-arginine. A

decrease of about 100K in the melting temperature was predicted when water is added to the L

arginine:citric acid 1:1 (mol) mixture. One possible explanation for this are water-mediated

effects that turned the positive deviations from Raoult’s law (γ>1) into negative deviations

(γ<1), highlighting stronger interactions between the mixture components upon water addition.

Additionally, NMR and FTIR studies were performed to study the hydrogen-bonding

interactions of the system and the possibility of salt formation between L-arginine and citric

acid, which could also explain decreased melting temperatures upon water addition. The

hypothesis of salt formation was refuted by FTIR, while NMR supported an altered hydrogen

bonding network for the ternary systems L-arginine:citric acid:H2O with respect to the

individual aqueous solutions. In sum, both the terms of negative deviation from Raoult’s law

and hydrogen-bonding mediated liquefaction were herein identified for the L-arginine:citric

acid:H2O mixture. Although both terms are compliant with the DES definition, they are also

applicable to strongly non-ideal solutions. Given the complexity of these type of mixtures, this

work aims to emphasize the urge of a more comprehensive definition and the need for additional

tools for fully characterizing these systems.

[1] Y. Dai, et al. Food Chem. 187 (2015) 14–19. doi:10.1016/j.foodchem.2015.03.123.

[2] O.S. Hammond et al. Angew. Chemie - Int. Ed. 56 (2017) 9782–9785. doi:10.1002/anie.201702486.

[3] H. Passos, et al. ACS Sustain. Chem. Eng. 4 (2016) 2881–2886. doi:10.1021/acssuschemeng.6b00485.

[4] J. Baz, et al. Phys. Chem. Chem. Phys. 21 (2019) 6467–6476. doi:10.1039/c9cp00036d.

[5] X. Meng, et al. New J. Chem. 40 (2016) 4492–4499. doi:10.1039/c5nj02677f.

Acknowledgements This project has received funding from the ERC-2016-CoG 725034 and was supported by the Associate Laboratory for Green Chemistry-LAQV, financed by national funds from FCT/MCTES (UID/QUI/50006/2019. C.H. and Y.Z.C. thank German Science Foundation (DFG) for funding (HE 7165/6-1 and CH 1922/1-1).


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Lignin conversion into value-added compounds using an

acidic deep eutectic at mild conditions

Filipe H. B. Sosaa,b, Ana Bjelicc, João A. P. Coutinhoa, Mariana C. Costab, Edita J. Grojzdekc,

Miha Grilcc, Andre M. da Costa Lopesc,d* aCICECO, Department of Chemistry, University of Aveiro, Campus Universitário de

Santiago, Aveiro, Portugal. bSchool of Chemical Engineering (FEQ), University of Campinas (UNICAMP), Campinas,

Brazil. cDepartment of Catalysis and Chemical Reaction Engineering, National Institute of

Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia dCECOLAB - Collaborative Laboratory Towards Circular Economy, R. Nossa Senhora da

Conceição, 3405-155 Oliveira do Hospital

*[email protected]

Keywords: lignin, deep eutectic solvents, depolymerisation, value-added compounds.

The heterogeneous and complex structure of lignin and its low reactivity undermines the

valorisation of this macromolecule, thus the development of novel lignin conversion processes

is demanding. In this study, an acidic DES ([Ch]Cl:Oxa) in presence or absence of co-catalysts

(H2SO4 and H2O2) was used as benign solvent to valorise Kraft lignin (KL) and Organosolv

(OL) by breaking down their structure into value-added aromatic compounds. The obtained

data showed maximum yields between 25.3 wt% and 27.7 wt% of lignin depolymerisation

products after OL and KL breakdown. Moreover, the profile of depolymerisation products was

distinct between examined lignins as well as between acidic ([Ch]Cl:Oxa and

[Ch]Cl:Oxa/H2SO4) and acidic oxidative treatments ([Ch]Cl:Oxa/H2O2). The acidic treatments

of KL favoured the formation of syringol and acetosyringone, while vanillic and syringic acids

were the main products in the acidic treatments of OL. On the other hand, the presence of H2O2

in DES promoted electrophilic substitutions of chloride from [Ch]Cl in the aromatic ring of

lignin monomers. In both cases, lignin oligomers were detected in depolymerization extracts.

Moreover, the regenerated lignin samples after depolymerisation disclosed different

characteristics in contrast to their precedent technical lignins, including esterification with

oxalic acid, lower molecular weight and increase of phenolic group content. These

physicochemical modifications are expected to give functionalization to regenerated lignins.

Therefore, the integration of lignin depolymerisation into valued added monomers and

oligomers with functionalization of remaining lignin towards new bio-based materials seems

promising with this DES technology.

Acknowledgments: This work was financed in part by the CAPES, FAPESP, CNPq, and partially developed

within the scope of the project CICECO, FCT Ref. UIDB/50011/2020 & UIDP/50011/2020. Authors would like

to thank COST Action CA17128 for financing the STSM of Filipe H. Sosa enabling collaboration with National

Institute of Chemistry in Ljubljana.


18

Deep Eutectic Solvents for wood cellulose purification

Andrea Mezzetta*, a Greta Colombo Dugoni,b Lorenzo Guazzelli,a Monica Ferro,b Andrea

Meleb

a Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy, b Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Politecnico di

Milano, Piazza L. da Vinci, 32, 20133 Milano, Italy

* [email protected]

Keywords: lignin, hemicellulose, Kraft cellulose purification, choline acetate based DESs

In the last decade the urgency to find alternative renewable sources brought to global attention

the possibility to convert lignocellulosic biomass into energy, value-added products and biofuel.

Lignocellulosic biomass is the most abundant biomass on earth with an annual production of

170-200 billion tons and it is mainly composed by lignin (10-30%), cellulose (38-50%) and

hemicellulose (23-32%). In consideration of the biorefinery processes, the robust structure of

biomass represents an obstacle for the fractionation of the components in order to produce

substrates to be converted in platform chemicals or biofuel.1

Deep eutectic solvents (DESs) hold great promises in the area of biomass processing. Indeed,

a few DESs displayed remarkable efficiency in the solubilization of lignocellulosic

biopolymers.2,3 However, more investigations are needed to fully unveil DESs potential in this

area of research.

Herein, we present three novel DESs composed of choline acetate (ChOAc) as hydrogen bond

acceptor (HBA) and three different hydrogen bond donors (HBD): glycolic acid (GlyA),

levulinic acid (LevA) and imidazole (Im). DESs were tested neat and in presence of water for

their ability to solubilize a reference hemicellulose as well as for the treatment of wood cellulose

containing 16% of hemicellulose. High values of hemicellulose dissolution (40-45% wt)

demonstrated the potential of the proposed DESs as solvents for this biopolymer. DESs also

exhibited a selective solubility towards hemicellulose, leading to cellulose purification.

References

1. Loow, Y.-L., New, E. K., Yang, G. H., Ang, L. Y., Foo, L. Y. W., Wu, T. Y. Cellulose 2017, 24, 3591–3618.

2. Zdanowicz, M., Wilpiszewska, K., Spychaj, T. Carbohydr. Polym. 2018, 200, 361–380

3. Sheldon, R. A. Chem. – A Eur. J. 2016, 22, 12984–12999


19

On the Betaine:Urea:xWater NADES system

Maria F. Nava-Ocampoa, Lamya Al Fuhaida, Adriano Santanaa, Szilárd S. Bucsa, Robert

Verpoorteb, Young Choib, Johannes S. Vrouwenveldera, Geert J. Witkampa, Andreia S. F.

Farinhaa* a Water Desalination and Reuse Center, King Abdullah University of Science and

Technology, Thuwal, Saudi Arabia. b Institute Biology Leiden, Leiden University, Leiden, The Netherlands.

* [email protected]

Keywords: betaine, urea, NADES, NMR, Modelling

This study focuses on the structures within the betaine-urea-water (B:U:W) NADES system.

Solutions spanning a range of molar ratios of betaine, urea, and water were prepared, varying

the temperature and preparation times. On the clear transparent liquids, attenuated total

reflection Fourier-transform infrared spectroscopy (ATR-FTIR) and liquid Nuclear Magnetic

Resonance (1H and 13C NMR) were done. In addition, Density Functional Theory (DFT) and

the Natural Bond Orbital (NBO) analyses were performed using Gaussian software. Our

experimental results show that, in non-anhydrous conditions, for one mole of betaine mixed

with one mole of urea, a minimum of three moles of water are needed to obtain a stable NADES.

However, a metastable transparent liquid can be formed with less water molecules. In such

liquids, betaine crystals easily grew when seeded. Comparison of the 13C NMR spectra of

B:U:W 1:1:2 and 1:1:3 showed for the latter that the carbonyl groups from betaine and urea

formed stronger hydrogen bonds, and the CH3 group of betaine becomes more deprotected (less

electron rich) by the addition of the extra water molecule. After simulating the less energetic

conformation from different supramolecular structures of B:U:W (1:1:2 and 1:1:3), we

compared the experimental with simulated 13C NMR spectra. The compared spectra resulted

in similar chemical shifts tendencies which makes us confident that this is the most probable

supramolecular structure on the ternary B:U:W 1:1:2 and 1:1:3 NADES system (Figure 1).

Figure 1. Structural conformations of B:U:W 1:1:2 (A) and 1:1:3 (B) based on the minimum

energy obtained by computational modelling.


20

Towards Mechanistic Understanding of Naturally Derived

Deep Eutectic Solvents Effect on Enzyme Catalyzed

Reactions

Attila Kovács a,*, Erik C. Neyts b, Iris Cornet c and Pieter Billen a

a iPRACS research group, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp,

Belgium, b PLASMANT research group, University of Antwerp, Universiteitsplein 1, 2610 Antwerp,

Belgium, c BioWAVE research group, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp,

Belgium

* [email protected]

Keywords: Biocatalysis, Molecular dynamics, Reaction modeling

Natural deep eutectic solvents (NADES) are a novel class of solvents, offering more benign

properties compared to common organic solvents. NADES are mixtures of naturally derived

compounds (usually a quaternary ammonium salt and a hydrogen bond donating component,

like organic acids or polyols) forming a strong intermolecular hydrogen bonding system. This

network stabilizes the liquid mixture, which results in a significantly decreased melting point

compared to the initial compounds. This property allows the use of NADES as reaction

media/solvents for various chemical reactions. This is typically in the food, feed, cosmetic and

pharmaceutical industries, where biocompatibility is required. However, to efficiently design

NADES for biocatalysis, a better understanding of their effect on these reactions is needed.

Fundamentally, this comes down to the description of the exact hydrogen bonding network and

its interaction with the reaction actors. Modeling methods, allowing for such fundamental

descriptions (like density functional theory or molecular dynamics), suffer from limitations of

accessible time and length scales, which makes their application impractical for bulk media.

We hypothesize that describing the effect that the NADES have on enzymatic reactions is

feasible solely through solvation energies of the substrates, medium viscosities and enzyme

stability in NADES. If these effects describe indeed their behavior sufficiently, this simpler

model could be developed to design neoteric solvents.

As a case study, we monitored the initial enzyme activity and the final conversion rate of lipase

catalyzed vinyl laurate transesterification in n-hexane together with various choline chloride

based NADES with different compositions and molar ratios. We determined the solubility of

substrates and the viscosity of solvents by experimental methods and we used MD based

simulation to investigate enzyme stability and to calculate solvation free energies of substrates

in NADES. Also, we determined the relationship of these properties to the enzyme activity and

conversion rate to evaluate their utility in predicting the reaction parameters.


21

Safety assessment of valorised food by-products using

novel analytical procedures based on natural deep eutectic

solvents

Bárbara Socas-Rodríguez *, David M. Alonso García, José A. Mendiola, Alejandro Cifuentes

and Elena Ibáñez

Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera

9, Madrid, 28049, Spain

Keywords: natural deep eutectic solvent; food assessment; by-product; green extraction

In recent years, the application of deep eutectic solvents (DESs) as alternative materials has

sharply increased in different fields. Their low toxicity and great versatility make them excellent

candidates to replace conventional organic solvents. Besides, the broad spectrum of raw

materials and their high availability provide great versatility to DES-based approaches.

Particular attention has been paid to the so-called natural-DESs (NaDESs). These materials are

exclusively constituted by natural components that enhance the low toxicity nature and

biocompatibility of DESs and favour their use in biological and food applications [1].

Globalisation of food industry has led to important economic benefits, but it has also brought

about the increase of food waste with negative effects on the environment. This concern

requires the establishment of effective strategies to reduce the impact of the organic residues

generated. In this sense, the valorisation of food by-products has been suggested as a suitable

approach to tackle this issue. However, as occur with the rest of food products, the

commercialization of valorised by-products also requires a strict control to ensure consumers’

safety. In this sense, the development of sustainable methodologies allowing the reliable

assessment of food by-products’ safety while complying with the principles of sustainability

constitute an issue of great importance [2].

In this work a novel and sustainable approach based on the application of betaine-based

hydrophilic NaDESs as extraction solvents has been proposed for the evaluation of food safety

in combination with chromatographic separation and mass spectrometry detection. The

methodology has resulted suitable for the efficient and reliable determination of pesticides in

fruit by-products.

References:

[1] Liu et al. Natural Deep Eutectic Solvents: Properties, Applications, and Perspectives. J. Nat. Prod., 2018, 81,

679–690.

[2] A. Nayaka, Brij Bhushan, An overview of the recent trends on the waste valorization techniques for food

wastes. J. Environ. Manage., 233 (2019) 352–370


22

Biosourced Non-Ionic Low Transition Temperature

Mixtures Composed of Fructose and Glycerol: Water and

Temperature Impact on the Supramolecular Organization

Caprin Benoît a,b,*, Charton Virginie b, Rodier Jean-David b, Vogelgesang Boris b,

Charlot Aurélia a, Da Cruz-Boisson Fernande a, Fleury Etienne a a Laboratoire Ingénierie des Matériaux Polymères, UMR CNRS 5223, INSA Lyon, bâtiment

Jules Verne, 17 avenue Jean Capelle, 69621 Villeurbanne, France b Gattefossé SAS, 36 chemin de Genas, 69804, Saint-Priest cedex, France

* [email protected]

Keywords: LTTM, H-bonds, DOSY & NOESY NMR, green chemistry

Deep Eutectic Solvents (DES), Natural Deep Eutectic Solvents (NaDES) or Low Transition

Temperature Mixtures (LTTM) constitute an appealing class of neoteric solvents generally

meeting some criteria of green chemistry. Most of the time, their high viscosity compromises

their industrial implementation, and water addition is an effective means to valuably increase

their fluidity. Therefore, the effect of water on the internal organisation and the physical and

chemical properties of these solvents is an emerging issue in scientific literature.1,2 In this frame,

the present contribution deals with the preparation and the thorough characterization of entirely

biobased ternary mixtures composed of glycerol (G), fructose (F) and water (W). We previously

shown that combination of glycerol and fructose with water allows for engineering efficient

eco-friendly solvents in the field of vegetal extraction and understanding interactions at the

molecular level is a fundamental starting point that must be studied.3 In order to meet this

objective, this work focuses on i) the elucidation of a ternary diagram from a homemade library

of F/G/W mixtures ii) the examination of molecular interactions between the three components

from NOESY and pulsed field gradient NMR experiments with an accent on the effect of the

molar composition and temperature variation iii) the analysis of thermal and rheological

properties in order to establish relationships between the structure at the molecular level and

the resulting properties. This comprehensive study is expected to be helpful for further

applications of F/G/W mixtures in green and sustainable chemical technologies.

1. Delso, I.; Lafuente, C.; Muñ

oz-Embid, J.; Artal, M. NMR study of choline chloride-based deep eutectic solvents. Journal of Molecular Liquids,

2019, 290, 111236.

2. López, N.; Delso, I.; Matute, D.; Lafuente, C.; Artal, M. Characterization of xylitol or citric acid: Choline

chloride:water mixtures: Structure, thermophysical properties, and quercetin solubility. Food Chemistry, 2020, 306,

125610.

3. Caprin, B.; Charton, V.; Demarne, F.; Extraits végétaux destinés à la cosmétique, solvants et procédés pour les obtenir.

Brevet FR 3 036 618 B1. 2 novembre 2018

4. Caprin, B.; Charton, V.; Rodier, J.D.; Boisson-Da Cruz, F.; Charlot, A.; Fleury, E.; Elucidation of the Supramolecular

Structure of Non-Ionic Biobased Low Transition Temperature Mixtures. Submitted, 2020.


23

Valorization of vine shoots biomass assisted by acidic deep

eutectic solvents

Bruno D. A. Pinheiroa, Maria Hijosa-Valserob, André M. da Costa Lopesa,c, Armando J. D.

Silvestrea aCICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro,

3810-193, Aveiro, Portugal bCentro de Biocombustibles e Bioproductos, Instituo Agrario de Castilla y Léon (ITACyl),

Villarejo de Órbigo, 24358, Léon, Spain cCECOLAB – Collaborative Laboratory Towards Cicrcular Economy, R. Nossa Senhora da

Conceição, 3405-155, Oliveira do Bairro, Portugal

[email protected]

Keywords: deep eutectic solvents, vine shoots, phenolic compounds, anthocyanins.

Wine production is an essential economic engine in most regions across the Iberian Peninsula.

However, this activity generates a high amount of by-products, such as vine shoots, which need

to be handled and valorized within a circular economy perspective. Therefore, sustainable and

cheap processes capable of extracting value from these raw materials are required. In this work,

acidic deep eutectic solvents (DES) were tentatively used as green solvents in the extraction of

value-added compounds from vine shoots prior to its fractionation. DES combining cholinium

chloride ([Ch]Cl) as hydrogen bond acceptor (HBA) with different hydrogen bond donors

(HBD), such as p-toluenesulfonic acid (pTSA), malic acid (MA), glycolic acid (GLY), tartaric

acid (TART), citric acid (CIT), were studied. These acidic DES showed capacity to extract

phenolic compounds, including anthocyanins, where [Ch]Cl:pTSA demonstrated the best

performance among them. The extraction of these compounds with [Ch]Cl:pTSA was further

examined by studying HBA:HBD molar ratio, time, temperature and water content in DES (25

wt% and 50 wt%). A higher molar ratio of [Ch]Cl enabled a better selectivity towards the

extraction of anthocyanins, possibly due to the stabilization of the anthocyanin flavylium cation

by the Cl- as counterion. In addition, the presence of water (25 wt%) improved anthocyanin

extraction, although decreasing its selectivity. Moreover, prolonged extraction (> 1 h)

negatively affected the extraction performance due to anthocyanins degrading. The optimal

conditions towards selective extraction of anthocyanins was obtained with [Ch]Cl:pTSA (3:1)

at 80 °C for 1 h reaching a maximum yield of 6.46 (± 0.02) mg.gbiomass-1. These anthocyanin-

rich extracts not only may provide antioxidant activity, but also disclose potential to be used in

natural dyeing applications, due to its deep red color.

Acknowledgements: This work was performed in the frame of BIOVINO (0688_Biovino_6_E) and financed by

the research program INTERREG V-A España-Portugal (POCTEP) 2014-2020. The authors also acknowledge

FCT/MCTES for the financial support to CICECO (UIDB/50011/2020 & UIDP/50011/2020).

https://www.sciencedirect.com/science/article/pii/S0926669020303666#gs0005

https://www.sciencedirect.com/science/article/pii/S0926669020303666#gs0005


24

Dissolution and Recovery of Lithium-Ion Battery Cathode

Materials Using Deep Eutectic Solvents

Dana L. Thompson a, Jennifer M. Hartley a*, Chunhong Lei a, Ioanna M. Pateli a,b, Andrew P.

Abbott a a School of Chemistry, University of Leicester, Leicester, LE1 7RH, UK

b Stephenson Institute for Renewable Energy, University of Liverpool, Liverpool, L69 7ZF,

UK

* [email protected]

Keywords: lithium ion batteries, recycling, circular economy, dissolution, recovery

The decarbonisation of transport necessitates the proliferation of electric vehicles, resulting in

a significant increase in demand for lithium-ion batteries (LIBs). To prevent a build-up of

hazardous waste when electric vehicles reach end-of-life, a circular economy model is required

whereby the LIB is recycled and used in new electric vehicles. The majority of value within the

LIB lies with metals such as Co and Ni. The metal ratios vary across different battery

chemistries. In this work, a deep eutectic solvent consisting of oxalic acid and choline chloride

is utilised to develop a recycling procedure for the selective dissolution and recovery of

Ni/Mn/Co (NMC) elements. Through the addition of water or oxalic acid (OxA) to the leachate,

the solubility of Mn and Co decreases and results in the precipitation of metal oxalate species

(Figure 1). This allows for the recovery of the metals as precursors suitable for use in LIBs,

with 97-99 % efficiency.

Figure 1: Images of the mixed element solutions (left to right) before any additions, and after

the addition of water or the anti-solvents 0.5, 1.0 and 1.8 M OxA solution at t=0 min.

I. M. Pateli, D. Thompson, S. S. M. Alabdullah, A. P. Abbott, G. R. T. Jenkin and J. M. Hartley, Green Chem.,

2020.

D. L. Thompson, J. M. Hartley, S. M. Lambert, M. Shiref, G. D. J. Harper, E. Kendrick, P. Anderson, K. S. Ryder,

L. Gaines and A. P. Abbott, Green Chem., 2020.


25

Synthesis of Sugar-Based Polymers From Reactive Natural

Low Transition Temperature Mixtures

Gabriel Duaux, Etienne Fleury, Daniel Portinha,*

Université de Lyon CNRS, UMR 5223, INSA Lyon, IMP@INSA Villeurbanne F-69621,

France

* [email protected]

Keywords: Natural Low transition temperature mixture ; Polymerization ; crosslinking.

Deep Eutectic Solvents (DES) [1] or Low Transition Temperature Mixtures (LTTM) [2], have

appeared as a new class of solvents obtained by mixing two or more substances, which form

mixtures with melting point or glass transition temperature much lower than that of their

individual components. Like ionic liquids, many of such solvents have numerous attractive

physicochemical properties (chemical and thermal stability, non-flammability, low volatility

high electrical conductivity etc..) and in the field of polymers, present the potential of replacing

conventional organic compounds as solvents, plasticizers, additives etc. Moreover, similarly to

functional ionic liquids, some DES/LTTM have been designed such as one over their

components act as a monomer (DEMs : Deep Eutetic Monomers) [3], opening the scope for a

large variety of novel possible uses of these renamed Deep Eutectic Systems. More recently,

combinations of agro-based, natural, metabolites or renewable components have appeared and

been named Natural DES (NaDES) [4] or LTTM (NaLTTM) [2], which undoubtedly represent

a very interesting family of raw materials to be developed in the framework of green chemistry.

So far, the academic and industrial uses of NaDES have mainly concerned the extraction of

molecules of interest for food, pharmaceuticals, and cosmetics or as solvent for organic

synthesis. In this communication, the synthesis of carbohydrate polymers from Natural Low

Transition Temperature Monomer Mixtures (NaLTTMM) made of functional natural polyols

and organic acids will be presented [5]. The preparation process and physicochemical properties

(viscosity, transition temperature, pH etc) of the mixtures will first be presented. Then their

polymerization will be discussed, in particular as a function of the reaction temperature that is

always lower than the melting points of monomers taken separately. Structural parameters of

the polymer (chemical bonds type, molecular weight, topology etc) can be adjusted by operation

conditions and careful selection of the starting raw materials, which will be discussed during

this communication.

[1] E. L. Smith et al., Chem. Rev., vol. 114, no. 21, pp. 11060–11082, 2014.

[2] E. Durand et al., Biochimie, vol. 120, pp. 119–123, 2016.

[3] M. Isik et al., Macromol. Rapid Commun., vol. 37, no. 14, pp. 1135–1142, 2016.

[4] Y. H. Choi et al., Plant Physiol., vol. 156, no. 4, pp. 1701–1705, 2011.

[6] G. Duaux et al., submitted.


26

Solubility of Mesalazine in Natural Deep Eutectic Solvents

Debora Procopio, Carlo Siciliano, Sonia Trombino, Roberta Cassano, Federica Curcio,

Maria Luisa Di Gioia*

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria,

87036, Arcavacata of Rende (CS), Italy

*[email protected]

Keywords: Natural deep eutectic solvents, drug solubility, choline chloride

Natural deep eutectic solvents (NADESs) are recognised as the third liquid state in the living

organisms, beside water and lipid. As such, they have recently gained great attention in many

fields of science and technology. They show a potential as solvents for pharmaceutical

applications thanks to their biodegradability, low toxicity and ability to dissolve several water-

insoluble compounds and macromolecules. Choline chloride represents the most commonly

used hydrogen bond acceptors (HBA) in the formation of DESs. Due to it being a complex B

vitamin, commonly used as food additive, the choline-based NADESs can be considered

harmless and non-toxic. In the present work, we report the solubility of low water-insoluble

mesalazine in several choline chloride-based NADESs. These were prepared combining the

ChCl with several natural HBDs at different molar ratio. The solubility profile of mesalazine

were measured employing the shake flask method at different temperatures. Moreover, the

molecular interactions between the DESs and drug have been investigated using dynamic light

scattering (DLS) and polarized optical microscope (POM) measurements, as well as nuclear

molecular resonance (NMR) techniques. The results showed that the DES formed by choline

chloride and lactic acid exerted the strongest ability to promote the solubility of mesalazine

among all DESs. The increase in solubility is justified by the establishment of hydrogen bonds

between mesalazine and the DES components. These early observations laid the foundation for

the development of a new DES-based mesalazine delivery system.


27

Furfural production from xylans through acidic deep

eutectic-based systems

Eduarda S. Morais a,*, Mara G. Freire a, Carmen S. R. Freirea, João A. P. Coutinhoa, Armando

J. D. Silvestrea a CICECO—Aveiro Institute of Materials, Department of Chemistry, University of Aveiro,

3810-193, Aveiro, Portugal

* [email protected]

Keywords: deep eutectic solvents, furfural, acid catalysis, xylans

Furfural has been identified as a key platform chemical derived from biomass. This chemical

can be obtained from hemicelluloses through acid hydrolysis and subsequent dehydration,

followed by separation from the reaction media using organic solvents [1]. However, nowadays

it is imperative to find more sustainable ways of producing furfural. Deep eutectic solvents

(DES) emerged as a greener alternative to conventional solvents used in chemical processes

due to their simple preparation and unique physicochemical properties. Moreover, they may be

of natural origin, and may be designed to be biodegradable and recyclable [2]. Therefore, DES

are good candidates to be used in biotechnological processes, such as in the extraction and

conversion of polysaccharides into added-value chemicals.

In this work, we report the use of acidic based deep eutectic solvents for the hydrolysis of xylans

into xylose and further dehydration into furfural. The effects of the DES molar ratio,

temperature, solid/liquid ratio and amount of water were investigated, and the process was

optimized for maximum furfural production. The DES [Ch]Cl:Malic acid was used in

microwave-assisted reactions as both solvent and catalyst for furfural production [3]. The

process developed allowed an outstanding 75.0% of furfural yield in 2.5 minutes of reaction

time with microwave heating. The recovery and recyclability of the solvents was evaluated,

being possible to reuse the DES in at least three cycles. The obtained results highlight the

potential of greener and recyclable solvents based on deep eutectic mixtures for the creation of

integrated platforms for the valorization of hemicellulose fractions in biomass.

[1] Mika L., et al. Chemical Reviews, 2018, 118, 505–613

[2] Khandelwal S., et al. Journal of Molecular Liquids. 2016, 215, 345–86.

[3] Morais E. S., et al. ChemSusChem. 2020, 13, 784-790.

This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, 640

UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MCTES. The work was

funded by FCT/MCTES through the project MultiBiorefinery (POCI-01-0145- 654 FEDER-016403) and

DeepBiorefinery [PTDC/AGR-TEC/1191/2014], E. S. Morais acknowledges FCT/MCTES for the PhD grant

[SFRH/BD/129341/2017].


28

Natural deep eutectic solvents: the future of natural

cosmetic formulation?

Iron Mike Ardeza a,b, Leslie Boudesocque-Delaye a, Laura Wils a, Alexandra Despres c,

Franck Bonnier b, Xavier Perse b, Charles Bodet d, Igor Chourpa b, Emilie Munnier b,*

a SIMBA EA 7502 Synthèse et isolement de molecules bioactives, Université de Tours,

Faculté de Pharmacie, 31 avenue Monge 37200 Tours, France

b NMNS EA 6295 Nanomédicaments et Nanosondes, Université de Tours,

Faculté de Pharmacie, 31 avenue Monge 37200 Tours, France. c RCP design Global- CERTESENS,

56 avenue Marcel Dassault, 37200 Tours, France d EA 4331 LITEC Laboratoire Inflammation, Tissus épithéliaux et Cytokines, Université de Poitiers,

1 rue Georges Bonnet 86073 Poitiers, France

* [email protected]

Keywords: NaDES, extraction, stability, toxicity, formulation, sensoriality

Natural Deep Eutectic Solvents (NaDES) constitute a new generation of green ionic liquids,

first introduced as solvents with unique properties in chemistry by Abbott et al. in 20031

Recently, NaDES have focused the interest of cosmetic industry due to their unique properties.

Their high solvent power, combined with their stabilizing ability, make NaDES suitable as a

sustainable alternative to prepare greener active ingredient from vegetal or biotechnological

biomasses. Unlike organic solvent ordinary used to extract active molecules from plants or

algae, NaDES are not volatile and will persist in the final cosmetic formulation. The present

talk will expose the principal points that must be particularly taken into account at every step

of the development of a NaDES- based cosmetic product, from the NaDES composition to the

sensory impact on final product and their harmlessness towards skin. Concrete examples will

illustrate each key points to give a global overview of the benefice/risk balance of NaDES in

cosmetics.

1 Abbott, A.P., Boothby, D., Capper, G., Davies, D.L., Rasheed, R.K., 2004. Deep Eutectic Solvents Formed

between Choline Chloride and Carboxylic Acids: Versatile Alternatives to Ionic Liquids. J. Am. Chem. Soc. 126,

9142–9147.


29

Natural Deep Eutectic Solvents for the Green Extraction

of Soy By-Products

Felipe Sanchez Bragagnolo a,b, Bárbara Socas-Rodríguez a, Cristiano Soleo Funari b, Elena

Ibáñez a* a Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera

9, 28049 Madrid, Spain b Faculty of Agricultural Sciences, São Paulo State University, Av. Universitária 3780,

18610-034, Botucatu, São Paulo, Brazil

* E-mail: [email protected]

Keywords: Soy By-Products, Natural Deep Eutectic Solvents, Hansen Solubility, Green

Chemistry

Soybean is the major oilseed crop worldwide, with 336.47 million tons produced in 2019/2020.

However, this vast production has been leaving by-products (roots, branches, leaf, and pods)

behind that could be valorised considering their composition in high-added compounds such as

fatty acids, saponins, tannins, organic acids, isoflavones, etc. This approach can be of interest

to reduce the environmental impact of leaving the wastes in the landfield. For this purpose, a

green approach combining Natural Deep Eutectic Solvents (NaDES) and Pressurized Liquid

Extraction (PLE) has been employed for generating extracts with potential bioactivity

properties. Besides, Hansen Solubility Parameters (HSP) have been used for guiding the

selection of the best NaDES composition targeting the most valuable compounds. Two

sequential processes have been tested; a) firstly, a defatting process, in which n-heptane as a

benchmark solvent in PLE (at three temperatures (40, 80, 120 °C)), has been compared to

natural hydrophobic DES (NaHDES composed of the secondary metabolites identified in n-

heptane soy by-products extracts by GC-Q-TOF-HRMS). Moreover, NaHDES with more HSP

similarity with n-heptane have also been selected. b) Secondly, EtOH:H2O (7:3) (v/v), as the

reference solvent in PLE, and hydrophilic NaDES were considered. Different bioactivities,

depending on extracts’ composition, can be expected, such as antioxidant, anti-inflammatory,

and anti-neurodegenerative activities.


30

NADES in the Stabilization of Phenolic Compounds from

Sunflower Meal

Fernanda de Sousa Bezerra a,*, Danielly C. Ferraz da Costa b and Maria Gabriela Bello

Koblitz a a Federal University of the State of Rio de Janeiro - UNIRIO, Food and Nutrition Graduate

Program – PPGAN. 296 Pasteur Av. 2nd floor. Urca, Rio de Janeiro - RJ. Brasil. 22290-240. b State University of Rio de Janeiro – UERJ, Nutrition Institute. 524 São Francisco Xavier St.,

12th floor F. Maracanã, Rio de Janeiro - RJ. Brasil. 20550-900.

* [email protected]

Keywords: natural deep eutectic solvents, chlorogenic acid, ultrasound, storage

Sunflower meal is the main by-product generated from the extraction of the oil from this seed

and is normally destined for animal feeding. However, it is a bioactive rich material with up to

4% of phenolic compounds, in which 70% are represented by the chlorogenic acid family.

Traditionally, organic solvents are used to extract polyphenols, but there is a search for more

sustainable solvents to avoid the purification steps necessary for the application of these extracts

by the food, cosmetics, and pharmaceutical industries. Natural deep eutectic solvents (NADES)

have already demonstrated to be a more biodegradable and efficient alternative. Moreover,

NADES may also improve the stability of phenolic compounds in the extracts. The objective

of this work was to obtain phenolic extracts from sunflower meal applying two different

formulations of NADES and to evaluate the stability of the phenolic compounds in these

extracts under different storage conditions, using a hydroethanolic extract (40%) as the control.

All extracts were obtained by ultrasound assisted extraction (UAE) and stored at -18ºC, 8ºC

other 25ºC. Samples were analysed immediately after extraction and after 1, 7, 15, 30 and 60

days of storage. Extraction with lactic acid:glucose (5:1), choline chloride:glycerol (1:1) and

hydroethanolic solution resulted in 95.54 mg of chlorogenic acid/L, 60.39 mg of chlorogenic

acid/L and 33,72 mg of chlorogenic acid/L, respectively. The lactic acid:glucose NADES was

the most efficient in stabilizing phenolic compounds over storage time, regardless of

temperature. However, all extracts showed significant phenolic loss after 7 days and the choline

chloride:glycerol NADES showed a decrease of 71% in chlorogenic acid on the 30th day of

storage. These assays are under reiteration to confirm the results.


31

Unravelling the target-specific anticancer action of THEDES Filipe Oliveira a*, Joana Pereira a, Eduardo Silva b, Joana M. Silva b, Rui L. Reis b, Ana Rita

C. Duarte a a LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, Caparica, Portugal b 3B’s Research Group, University of Minho, Avepark 4805-017 Barco, Guimaraes, Portugal

c ICVS/3B’s PT Government Associated Laboratory, Braga/Guimaraes

* [email protected]

Keywords: Green chemistry, THEDES, Terpenes, NSAIDs, Solubility, Cancer therapy

The remarkable bioactive properties of DES have now been widely described. Eutecticity has

proven to be a promising tool in the development of new and effective therapeutic agents,

contributing to modern medicine most challenging battles, such as antibacterial and antibiofilm,

antifungal, and anticancer. Additionally, the tailor-made versatility and compliance with the

green chemistry metrics, have pushed forward the possible therapeutic applications of eutectic

formulations. In this work, we aim to unravel what we consider to be the next step in the

comprehension and consolidation of such therapeutic systems – target-specificity. By allying

the anticancer and anti-inflammatory properties of terpenes with nonsteroidal anti-

inflammatory drugs (NSAID), we have already observed and described THEDES selective

action towards cancer cells (Colorectal cancer cells), without compromising normal intestinal

cells viability. So, what are the specific cellular targets and consequent responses from the

eutectic exposure? Using a multidisciplinary approach, from the design, preparation and

characterization of THEDES, to the study of their bioavailability and bioactivity; to the

evaluation of THEDES specific cell target, we expect to untangle THEDES cytotoxic

mechanisms and establish this technology as an innovative approach in the cancer challenge.

Acknowledgments: This project has received funding from the European Union’s Horizon 2020 (European

Research Council) under grant agreement No ERC-2016-CoG 725034. This work was also supported by the

Associate Laboratory for Green Chemistry (LAQV) financed by national funds from FCT/MCTES

(UIDB/50006/2020).


32

Separation of Lithium from a Simulated Salt-lake Brine

using Synergistic Deep Eutectic Solvents

Takafumi Hanadaa and Masahiro Goto a,* a Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744

Motooka, Nishi-ku, Fukuoka, Japan.

* [email protected]

Keywords: Liquid-Liquid extraction, Lithium, Salt-lake brine

Lithium (Li) recovery from salt-lake brines have attracted much attention owing to the

abundance of the resources much greater than that of ores. However, current situation in Li

production from salt-lake brines is facing challenges such as long-term process of the solar

evaporation. To meet the increasing demand of Li, the liquid-liquid extraction which is the

developed metal refining technique is expected to be applied for the Li recovery from salt-lake

brines. To date, various Li extraction system such as ion-recognition using crown ethers or

synergistic extraction using two or more mixed extractants have been investigated. On the other

hand, due to the environmental impacts of volatile and toxic organic diluents used in the liquid-

liquid extraction procedure, benign alternatives such as ionic liquids and deep eutectic solvents

(DESs) are desired.

Here, we show a novel concept “synergistic DESs” for the selective recovery of Li from salt-

lake brines. We found that the mixture of the synergistic extractants for Li, beta-diketones and

phosphine oxides, shows the melting point depression deeper than that of their ideal mixture.

The extraction performance of Li using the DES was compared with the traditional solvent

extraction system using toluene as diluent, as shown in Fig. 1. Interestingly, the DES performed

the synergy in Li extraction, which both beta-diketones and phosphine oxides could coordinate

to Li to form stable extracted complexes. Finally, we successfully applied the DES for the

selective recovery of Li from the simulated salt-lake brine.

Fig. 1. Comparison of Li extraction performance between the traditional solvent extraction

using toluene as diluent, and DES without dilution

0

20

40

60

80

100

1M-HTTA 0.5M-TOPO HTTA/TOPO intoluene

HTTA/TOPO-DES

%E

HTTA/TOPO-DESP

O

O

FF

F

S

O

Thenoyltrifluoroacetone

(HTTA, m.p. 317 K)

Trioctylphosphine oxide

(TOPO, m.p. 325 K)


33

Insulinotropic effects of apple pomace extracts in Deep

Eutectic systems

Heleena Moni Bottua, Lorraine Brennana*, Lorrenzo Guazzellib, Angelica Merob, Elena

Husanub, Serge Tavernierc a Institute of Food and Health, University College Dublin, Dublin 4, Ireland

b Department of Pharmacy, University of Pisa, Italy

c iPRACS, University of Antwerp, Belgium

* [email protected], [email protected]

There is growing interest in the potential of new environment friendly solvent systems for

extracting bioactive compounds from foods. Our objective is to investigate the ability of

different extraction systems to extract bioactives from apple pomace a food waste. The

bioactivity was focused on antioxidant potential and ability to secrete insulin from pancreatic

beta cells (BRIN BD11). We assessed 20 wet and dry apple pomace extracts. Their antioxidant

effects were examined using DPPH antioxidant capacity as % of scavenging activity and by

FRAP antioxidant capacity expressed as µM TE/mg d.w sample. The effects of the extracts on

cell viability and cell proliferation were assessed and at lowest concentration where the cell

viability was not affected, we examined the ability to stimulate insulin secretion. Statistical

analysis was performed with graph pad prism using Analysis of Variance (ANOVA) and

Benferroni post hoc comparisons. The results demonstrate that the dry apple pomace extracts

from classical extraction system exhibit potential insulinotropic effects and in vitro antioxidant

effects. Among extracts from various DES systems lyophilized dry extracts of apple pomace in

DES ChCl:EG (1:4) demonstrated an ability to promote insulin secretion. Research is on-going

to examine these effects further.


34

Impact of hydrophilic natural deep eutectic solvents on

hydrogels intended for skin application

Iron Mike Ardeza a,b,*, L. Boudesocque-Delayea, Laura Wils a, Xavier Perse a, Sybille de La

Motte b, Emilie Munnier b a SIMBA EA 7502 Synthèse et isolement de molecules bioactives, Université de Tours,

Faculté de Pharmacie, 31 avenue Monge 37200 Tours, France b NMNS EA 6295 Nanomédicaments et Nanosondes, Université de Tours,


* [email protected]

Keywords: Natural deep eutectic solvents, cosmetics, hydrogels, physicochemical

charcteristics

NaDES as a novel green solvent has gained, in recent years, a positive momentum for cosmetic

ingredients preparation from vegetal biomasses. Many combinations particularly

betaine/glycerol and glucose/glycerol has displayed a great potential for both extraction and

stabilization of several phenolic compounds and epigallocatechin-3-gallate respectively 1,2.

This study aims to evaluate the impact of the incorporation of these well-known NaDES in a

cosmetic gel intended for skin application. Betaine/glycerol (BG) and glucose/glycerol (GG)

were incorporated at 3 different concentrations (1%, 5% and 10%) in two different hydrogels

one based on a hemisynthetic cellulose derivative and the other on vegetable gum. The

organoleptic and physico-chemical characteristics of the NaDES-enriched gels were observed

before and after 30 days at room temperature (25°C) and in accelerated aging conditions (40°C,

75°C humidity). Obtained results showed that the incorporation of NaDES in gels does not

change significantly the pH of the formulations, but has a variable impact on the viscosity of

the gels depending on the composition of the NaDES, their concentration and the incorporation

method. These results highlight how important it is to understand the NaDES interaction with

the formula ingredients for an efficient predictive approach of their compatibility as ingredients

in cosmetic formulations.

1Fanali, C.; Della Posta, S.; Vilmercati, A.; Dugo, L.; Russo, M.; Petitti, T.; Mondello, L.; De Gara, L. Extraction,

Analysis, and Antioxidant Activity Evaluation of Phenolic Compounds in Different Italian Extra-Virgin Olive

Oils. Molecules 2018, 23, 3249. 2Jeong, K.M.; Ko, J.; Zhao, J.; Jin, Y.; Yoo, D.E.; Han, S.Y.; Lee, J. Multi-functioning deep eutectic solvents

asextraction and storage media for bioactive natural products that are readily applicable to cosmetic products.J.

Clean. Prod.2017,151, 87–95.


35

Structure and Interactions in p-Toluene Sulfonic Acid

based Deep Eutectic Solvent

Iva Manasia*, Elly K Bathkea,, Stephen M Kingb, Daniel T Bowronb and Karen J Edler a a Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AX, UK.,

b ISIS Neutron and Muon Source, Rutherford Appleton laboratory, Oxford, OX11 0QX, UK

*[email protected]

Keywords: Deep-eutectic solvent; p-toluene sulfonic acid; choline chloride; DES structure;

surfactants assembly.

Changing the H-bonding components and their ratios can alter the physicochemical properties

of deep eutectic solvents (DES). Recent studies have shown p-toluene sulfonic acid (pTSA)

forms room temperature liquids with choline chloride (ChCl) at different molar ratios: 1:1, 1:2

and 2:1 (Rodriguez Rodriguez et al., 2019). They also showed that the composition affects the

physical properties of these liquids and their ability to dissolve metal oxides. In this work we

look at the structure of pTSA/ChCl based liquid mixtures at two molar ratio, 1:1 (eutectic point)

& 1:2, using total neutron scattering experiments and Empirical Potential Structure Refinement

(EPSR) modelling to understand how composition impacts structure which in turn influences

properties and interactions in these mixtures.

Additionally, we also evaluate the solubility of cationic surfactants; alkyltrimethyl ammonium

bromides (CnTAB), in these pTSA/ChCl based liquids. CnTABs are insoluble in

1pTSA:2ChCl, whereas in 1pTSA:1ChCl and 2pTSA;1ChCl they form micelles. We

characterise CnTAB (n=12, 14, 16) micelles at these two compositions using Small Angle

Neutron Scattering and also look at interaction of water with the micelles. These studies help

determine the interaction of DES components with the surfactant and the influence of varying

pTSA and water ratios on these interactions. This provides potential for controlled surfactant

templating and allowing rheology modification in such systems.

References:

Rodriguez Rodriguez, N., MacHiels, L., & Binnemans, K. (2019). P-Toluenesulfonic Acid-Based Deep-

EutecticSolvents for Solubilizing Metal Oxides. ACS Sustainable Chemistry and Engineering, 7(4), 3940–3948.

https://doi.org/10.1021/acssuschemeng.8b05072


36

Sustainable waste management from wine production

Manuela Panića, Veronika Gunjević a, Mia Radović a, Kristina Radošević a, Marina Cvjetko

Bubalo a, Natka Ćurko a, Karin Kovačević Ganić a, Ivana Radojčić Redovnikovića a Faculty of Food Technology and Biotechnology, University of Zagreb, Pieroti street 6,

10000 Zagreb, Croatia

* [email protected]

Keywords: COSMO-RS, green extraction, natural deep eutectic solvents, polyphenols

Food processing generates a substantial volume of solid organic by-products. Only small

amounts of these by-products are up-graded or recycled and used usually for composting or

even discarded in open areas potentially causing environmental problems. Wine production by-

products, such as grape pomace, are the most abundant worldwide and have been lately often

evaluated as a source of biological active compounds due to high content of polyphenolics. In

the last few years, the extraction and identification of phenolic compounds from natural sources

has become a major area of scientific research. Due to their complex structure, there is no

universal extraction method suitable for extraction of all plant phenolic, whereby conventional

extraction techniques are usually associated with high organic solvent consumption and long

extraction times. One of the organic solvents replacement could be natural deep eutectic

solvents (NADES) since NADES can dissolve both polar and non-polar compounds. They may

be used for very efficient extraction of natural products from plants, such as polyphenols. Since

NADES has high safety profile it is expected that extract obtained by NADES may be directly

used in food, pharmaceutical, cosmetical and agrochemical products without the need for

expensive downstream purification steps.

NADES is designed solvents, so to save time and money, it should be designed rationally for

polyphenolics extraction. Currently, COSMO-RS can design new solvent structures with

tailored properties and thus the trial-and-error method of NADES preparation can be avoided

Therefore, the aim of this stufy is to design efficient NADES for extraction of polyphenols from

wine production by-products.

Acknowledgements: The work was supported by the European Union through the European regional development

fund, Competitiveness and Cohesion 2014-2020 (KK.01.1.1.07.0007.)


37

Unravelling the in vitro and in vivo toxicity of

deep eutectic solvents consisting of safe compounds

including choline chloride

Dasom Jung a, Jae Back Jung a, Seulgi Kang a, Ke Li a, Inseon Hwang a, Ji Hoon Jeong a,

Hyung Sik Kim a and Jeongmi Lee a,* a School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of

Korea

* [email protected]

Keywords: deep eutectic solvents; toxicity; toxico-metabolomics; oxidative stress

Safety of deep eutectic solvents (DESs) has been taken for granted because their constituents

generally have low toxicity. Herein, we prepared eight different DESs using edible components,

including choline chloride (ChCl), organic acids (lactic acid and malic acid), polyols (glycerol,

xylitol, and sorbitol), sugars (glucose and fructose), and urea. In in vitro cytotoxicity assessment

on HepG2 and HEK293T cell lines, both DESs and the simple aqueous mixtures of the DES

components were generally more cytotoxic than the individual components. Moreover, some

DESs presented lower IC50 than the aqueous mixtures. Next, a toxico-metabolomics study was

performed on CU (1:2) that consists of ChCl and urea (1:2 molar ratio) because its popular

usage in many applications. The animal study was based on five groups of mice that were orally

administered saline, ChCl, urea, aqueous mixture of ChCl and urea, and CU (1:2). After 24 h,

serum, kidney, and liver samples were collected and analysed for metabolic profiling using gas

chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Metabolic

profiles of the DES-treated mice were generally distinct from the others, as evidenced in the

principal component analysis and orthogonal projection to latent structure discriminant

analysis. The identified differential marker metabolites suggest that the DES toxicity may be

associated with oxidative stress and ammonia stress. The DES-induced oxidative stress was

confirmed by several biochemical assays including superoxide dismutase activity, catalase

activity, and malondialdehyde assays. The ammonia assay showed that blood of the DES-

treated mice had significantly increased ammonia levels compared with the control mice.

Ammonia could be produced during DES preparation from ChCl and urea with and without

heating and also could be produced from ChCl and organic acids with heating. Collectively,

our study suggests that ChCl-based DESs may not be simply considered as pure and safe

mixtures. The current presentation is based on our recent publication in Green Chemistry (2021,

in press).


38

Micellization of Ionic Surfactants in a Ternary Deep

Eutectic System

Ria Atri,a,b Iva Manasi,b Adrian Sanchez Fernandez,b Oliver Hammond,a,b James Doutchc and

Karen J. Edlerb,*

a EPSRC Centre for Doctoral Training in Sustainable Chemical Technologies, University of

Bath, Bath, BA2 7AY, UK b Department of Chemistry, University of Bath, Bath, BA2 7AY, UK

c ISIS Pulsed Neutron and Muon Source, Science & Technology Facilities Council,

Rutherford Appleton Laboratory, Didcot, OX11 0QX, UK

* [email protected]

Keywords: surfactant self-assembly, ternary systems, small angle scattering, micelles

Deep eutectic systems (DES), have shown the ability to support the self-assembly of both

anionic and cationic surfactant molecules. In order to use this in applications such as templated

materials synthesis, it is of interest to study a system which simultaneously facilitates the

synthesis of metal oxides and is capable of solubilising suitable surfactant molecules.

We have previously developed solvothermal syntheses of metal oxides using the choline

chloride:urea DES [1, 2] and aim to extend our method to include the surfactant templated

synthesis of porous materials. The urea component in the DES is essential to the reaction

pathway, however we have not been able solubilise both cationic and anionic surfactants in

choline chloride:urea. To overcome this, we have turned to a three component DES comprising

choline chloride, urea and glycerol which is capable of supporting the self-assembly of both

cationic (CnTAB) and anionic (sodium dodecyl sulfate) surfactants. The micellization of these

surfactants in the ternary DES at various urea:glycerol ratios has been investigated using small

angle neutron scattering (SANS) techniques. [3]

Fitting of the SANS data has revealed that elongated micelles are obtained in both cases. We

have demonstrated that the micelle morphology displays composition dependence, with a

higher glycerol content in the DES giving rise to more spherical micelles. This could be due to

a higher counterion solubility with increased glycerol, whereas at higher urea content the

counterions may preferentially pack at the micelle corona.

References:

[1] O.S. Hammond, K.J. Edler, D.T. Bowron, L. Torrente-Murciano, Nature Commun. 8 (2017) 14150.

[2] O.S. Hammond, S. Eslava, A.J. Smith, J. Zhang, K.J. Edler, J. Mater. Chem. A 5 (2017) 16189

[3] R.S. Atri, A. Sanchez-Fernandez, O.S. Hammond, I. Manasi, J. Doutch, J.P. Tellam, K.J. Edler, J. Phys.

Chem. B 124 (2020) 6004.


39

Carvone and its eutectic mixtures introduced as tunable,

green solvents

Ke Li, Seulgi Kang, Yuli Liu, Inseon Hwang, Jeongmi Lee*

School of Pharmacy, Sungkyunkwan University, Suwon, 16419 Republic of Korea.

* Corresponding author. E-mail: [email protected]; tel.: +82-31-290-7784; fax: +82-31-

292-8800.

Keywords: carvone; eutectic solvents; tunable green solvent; liquid-liquid extraction.

Development of tunable and renewable solvents has been the Achilles's heel in green extraction

processes. In this study, R-(-)-carvone and its eutectic mixtures were investigated as green and

tunable solvents with low viscosity. A series of carboxylic acids, terpenes and a benzoate ester

could apparently form stable eutectic mixtures with carvone at various mole fractions of

carvone. The solid-liquid equilibrium diagrams of the mixtures unveiled that most of the

mixtures remained liquid at room temperature within a wide range of mole fractions and that

some combinations could be classified as deep eutectic solvents. The examined eutectic

mixtures at certain mole fractions showed varying properties in terms of density and polarity,

but they had low viscosity and reasonable biodegradability. Finally, taking advantage of these

favourable solvent properties, we applied these mixtures to liquid-liquid extraction system

using model dyes and high-value natural pigments from red algae. The results suggest that the

carvone-based eutectic mixtures could extract hydrophobic dye and pigments with varying

efficiencies and selectivity depending on the type of eutectic mixtures. Thus, this study

proposes carvone and its eutectic mixtures as promising green solvents.


40

Enhanced Solubilization Of Essential Oils By Combining

Deep Eutectic Solvent, Cyclodextrins And Water

Lamia Nakhlea,b, Miriana Kfourya, Isabelle Mallardb, Hélène Greige-Gergesa, David Landy*b

a Bioactive Molecules Research Laboratory, Faculty of Sciences, Lebanese University, 90656

Jdaidet el-Metn, Lebanon

b Unité de Chimie Environnementale et Interactions sur le Vivant (UCEIV, EA 4492), SFR

Condorcet FR CNRS 3417, Université du Littoral Côte d’Opale (ULCO), 145 Av. M.

Schumann, F-59140 Dunkerque, France

⁎ Email of the corresponding author: [email protected]

Keywords: cyclodextrin, deep eutectic solvents, essential oil, solubility.

There is a strong demand to overcome the poor solubility of active natural molecules in

pharmaceutics and food technology. Many efforts are therefore devoted to develop

formulations based on delivery systems and/or biodegradable and sustainable green solvents

[1] [2]. This study focuses on developing formulations combining native, modified or

polymerized cyclodextrins (CD) with choline chloride/ urea deep eutectic solvent (DES) and

water. The formulations were characterized for their density and viscosity, before being

investigated for their ability to reduce the volatility of essential oils (EO) using Headspace Gas

Chromatography (HSGC). A solubility increase was observed for various EO with all the tested

systems (water/CD, DES/water¸ DES/water/CD), when compared to water alone. Besides being

able to reduce the viscosity of the solvent, the presence of a certain amount of water (20-30

wt%) favor the retention of EO in the formulation when using CD, since water molecules

improve the complexation phenomena and therefore the solubilizing efficiency of the DES/CD

mixture. For a better understanding of the solubilization mechanisms, the affinity of DES and

of EO components for CD was assessed by isothermal titration calorimetry.

[1] M. Kfoury, L. Auezova, H. Greige-Gerges, and S. Fourmentin, “Promising applications of cyclodextrins in

food: Improvement of essential oils retention, controlled release and antiradical activity,” Carbohydrate Polymers,

vol. 131, pp. 264–272, Oct. 2015, doi: 10.1016/j.carbpol.2015.06.014.

[2] T. El Achkar et al., “New generation of supramolecular mixtures: characterization and solubilization studies,”

International Journal of Pharmaceutics, p. 119443, May 2020, doi: 10.1016/j.ijpharm.2020.119443.


41

NADES for microalgae biorefinery: biomass pre-treatment

and comparison with bio-sourced solvents

Laura Wils a,*, Soukaina Hilali a, Mervé Yagmur a, Barbara Clément-Larosière b,

and Leslie Boudesocque-Delaye a

a SIMBA EA 7502 Synthèse et isolement de molécules bioactives, Université de Tours,


b Aqua Eco Culture,

7 rue d’Armor Maroué, 22403 Lamballe, France

* [email protected]

Keywords: microalgae, biorefinery, pre-treatment, bio-sourced solvent, NADES

Microalgae are a unique sustainable resource of biomolecules for cosmetic, pharmaceutical,

food and feed industries. In this markets, microalgae are usually used as powder or global

extract, targeting one class of metabolite for one defined species. For example, Spirulina

(Arthrospira platensis) is extracted for its high content of a phycobiliprotein, the phycocyanin.

Phycocyanin is a highly promising metabolite exhibiting antioxidant, anti-cancer and anti-

inflammatory activity. The high demand for phycocyanin concentrated product in food and

cosmetic market had led to an exponential increase amount of microalgal biomass by-product.

This by-product can be further valorized since most of the lipophilic pigments were not

recovered as well as other high value metabolites like free fatty acids (FFA).

One crucial aspect to investigate to develop microalgae biorefinery is the biomass pre-

treatment. In fact, microalgae cell-wall are well-known to be robust and to limit dramatically

the access of intracellular metabolites, like FFA. Here we report the investigation of the impact

of biomass pre-treatment of A. platensis on FFA biorefinery using NADES and bio-sourced

solvents. Three pre-treatments were compared: cell disruption by freezing, air-drying and by-

product from phycobiliprotein extraction with water. The impact on biomass integrity, FFA

recovery and profile were investigated and NADES extraction performance were compared to

bio-sourced solvents. In our work, fatty acid based NADES were highlighted as the most

promising to recover FFA from Spirulina, after and before phycocyanin extraction. These data

open the way to the design of a multi-step Spirulina biorefinery scheme using NADES.


42

Natural deep eutectic solvents for microalgae biorefinery:

Spirulina as case of study Laura Wils a, Soukaina Hilali a, Suha Elderli b, Mervé Yagmur a, Charlotte Leman-Loubière a,b

Barbara Clément-Larosière c, Franck Bonnier b and Leslie Boudesocque-Delaye a,*



b NMNS EA 6295 Nanomédicaments et Nanosondes, Université de Tours,


c Aqua Eco Culture,

7 rue d’Armor Maroué, 22403 Lamballe, France

* [email protected]

Keywords: NADES, microalgae, biorefinery, fatty acids, phycobiliprotein

Microalgae are promising renewable resources of various biomolecules of interest like protein,

pigments (phybiliprotein, carotenoids, chlorophylls), polysaccharides and lipids especially

polyunsaturated (PUFA), for various markets (food, feed, pharmaceutics, cosmetic).1,2

Microalgae were usually used as powder or global extract, targeting one class of metabolite for

one defined species. For example, Spirulina (Arthrospira platensis) is extracted for it high

content of phycocyanin.1 The increasing demand of phycobiliprotein concentrated product in

food marked led to the extraction of increasing amount of microalgal biomass, using water as

the main solvent.3 By-product generated were usually used as is, even if other high value

metabolites like free fatty acids (FFA), especially polyunsaturated one, or carotenoids could be

still valorised. A sustainable biorefinery approach would be a good opportunity for microalgae

industry. In this context, Natural Deep Eutectic Solvents (NADES) represent an exciting

opportunity. In the DERMIC project, the use of NADES for the extraction of both

phycobilliproteins and apolar metabolites (FFA and carotenoids) were investigated. Biomass’

pre-treatment, NADES library screening and intensification of unitary operation were

investigated highlighting the high potential of NADES to generate concentrated extracts. The

sequential used of NADES for the valorization of all metabolites was conducted and

demonstrated the feasibility of the integration of NADES in all steps of biorefinery scheme.

1 Dolganyuk, V.; Belova, D.; Babich, O.; Prosekov, A.; Ivanova, S.; Katserov, D.; Patyukov, N.; Sukhikh, S.

Microalgae: A Promising Source of Valuable Bioproducts. Biomolecules 2020, 10, 1153.

https://doi.org/10.3390/biom10081153 2 Guillerme, J.-B.; Couteau, C.; Coiffard, L. Applications for Marine Resources in Cosmetics. Cosmetics. 2017, 4

(3), 35. https://doi.org/10.3390/cosmetics4030035. 3 Fernando Pagels, A. Catarina Guedes, Helena M. Amaro, Anake Kijjoa, Vitor Vasconcelos, Phycobiliproteins

from cyanobacteria: Chemistry and biotechnological applications, Biotechnology Advances, Volume 37, Issue 3,

2019, Pages 422-443, https://doi.org/10.1016/j.biotechadv.2019.02.010.


43

Stabilization of Horseradish Peroxidase Using Natural

Deep Eutectic Systems

Liane Meneses a, Ana Rita C. Duarte a,b, Alexandre Paiva a,b*

a LAQV/REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal b Des Solutio, Avenida Tenente Valadim nº17 2ºF, 2560-275 Torres Vedras, Portugal

* [email protected]

Keywords: Natural Deep Eutectic Solvents, Enzymes, Horseradish Peroxidase, Enzymatic

Activity, Stabilization

The applications of deep eutectic systems (DES) have grown over the past few years and they

have become a viable alternative as media for preservation of different compounds, such as

antioxidants, phenolics or even proteins. Some choline-based systems had already been

reported effective for the stabilization of the enzyme Horseradish Peroxidase (HRP). However,

they face restrictions in which concerns their utilisation on some industries making it of the

utmost importance to replace such compounds in their formulations. Hence, in this work, the

application of natural deep eutectic systems (NADES) for the stabilization of HRP was

assessed. Betaine and sugar-based systems were used in different combinations and molar

ratios. Phosphate buffer saline (PBS) was used for control experiments. The enzyme’s stability

was tested at 37, 60 and 80 ⁰C for different incubation times. The effect on HRP’s stability was

evaluated through enzymatic activity assays. Preliminary results shown that, upon 6h

incubation in Betaine:Sorbitol:Water (1:1.3), HRP’s enzymatic activity has a 2-fold increase,

when compared to the control experiments performed in PBS. The possibility to extrapolate

these findings to more relevant and sensitive molecules could open new possibilities for the

pharmaceutical or cosmetic industries.


44

Application of Deep Eutectic Solvents for the Extraction of

Textile Dyes from Water

L. Villar, J. Páez, A. Domínguez, B. González*

Advanced Separation Processes Group, Isaac Newton Building, Department of Chemical

Engineering, Universidade de Vigo, Lagoas-Marcosende, 36310, Vigo, Spain

* [email protected]

Keywords: Deep Eutectic Solvents, Liquid-Liquid Extraction, Malachite Green, Industrial

Wastewater.

Currently, textile industry is continuously growing due to the fast-fashion trend, which involves

the consumption of huge number of garments in a short period. The dyeing process is a critical

step in this industrial activity that generates the discharged of high amount of coloured

wastewater due to the presence of textile dyes. These dyes are responsible of water

contamination due to their high toxicity and their contribution to water opacity, which caused

the kill of aquatic life. Among these dyes is Malachite Green which is an artificial dye

traditionally used for leather, cotton and silk fabrics dyeing.

With the aim of removing Malachite Green from water, Liquid-Liquid Extraction (LLE)

technique was useful applied for the extraction of pollutants from water, due to its efficiency

and versatility. However, the main drawback is the use of Volatile Organic Compounds (VOCs)

that have a high toxicity. In this line, Deep Eutectic Solvents (DESs) are presented as replacing

agents for VOCs.

In this work, three hydrophobic DES based on Thymol and Decanoic acid in different molar

proportions were applied for the extraction of Malachite Green from water. Samples were

prepared by mixing aqueous solutions of Malachite Green in different concentrations with a

known amount of DES as extraction agent. Then both phases were separated and the extraction

efficiency of the process was studied measuring Malachite Green absorbance in aqueous phase

using an UV-Vis spectrophotometer.

As a result, all DESs presented extraction efficiencies higher than 95% for all studied

concentrations, proving that can be suitable to remove Malachite Green from water that

contributes to the recycle of water promoting the decrease of its consumption.


45

Simulation of Equilibrium Phase Diagram and

Physicochemical Characterization of Natural Eutectic

Solvents

Maha M. Abdallaha, b *, Simon Muller c, Andrés Gonzalez de Castilla c, Pavel Gurikov d,

Maria do Rosário Bronze a, b, e, Ana A. Matias a, Naiara Fernandez a a Institute of Experimental Biology and Technology, Portugal

b Institute of Chemical and Biological Technology, New University of Lisbon, Portugal c Institute for Thermal Separation Processes, Hamburg University of Technology, Germany

d Laboratory for Development and Modelling of Novel Nanoporous Materials, Hamburg

University of Technology, Germany e FFULisboa, Faculty of Pharmacy, University of Lisbon, Portugal

* E-mail address of corresponding author: [email protected]

Keywords: Deep eutectic solvents, physicochemical characterization, equilibrium phase

diagram

Eutectic solvent systems are prepared from natural terpene-based components, including

menthol, thymol, camphor and borneol. The solid-liquid equilibrium (SLE) phase diagrams are

predicted using the models UNIFAC and COSMO-RS with two different parametrization

levels. The ideal, experimental and predicted eutectic points are obtained for each system. The

deviation from ideality is studied to assess if the system could be considered as deep eutectic

solvents (DES). For instance, Thymol:Borneol system has shown a clear negative deviation

from ideality in the SLE curves using the models and experimentally and may be considered as

DES (Figure 1). The thermodynamic parameters, including the degradation, glass transition and

crystallization temperatures, are measured using DSC and TGA. Furthermore, the chemical

structure and interactions are analyzed on the basis of FTIR and 1H NMR to confirm the

presence of intermolecular hydrogen bonding in the eutectic systems. The difference in the

chemical interactions between the pure compounds and the eutectic systems, observed

experimentally and analyzed by simulation, proves that in fact the systems do not act as an ideal

mixture, which confirms their behavior as possible DES.

Figure 1: Ideal, experimental and predicted SLE

phase diagrams of the terpene-based solvent

systems. (Thy: Thymol, Bor: Borneol)


46

Natural deep eutectic solvents as biofilm structural

breaker

Maria F. Nava-Ocampoa, Lamya Al Fuhaida, Szilárd S. Bucsa, Robert Verpoorteb, Young

Choib, M.C.M. van Loosdrechtc, Johannes S. Vrouwenveldera, Geert J. Witkampa, Andreia S.

F. Farinhaa*

a Water Desalination and Reuse Center, King Abdullah University of Science and


c Department of Biotechnology, Faculty of Applied Sciences, Delft University of Technology,

Delft, The Netherlands.

*[email protected]

Keywords: green solvent, aerobic granular sludge, EPS, biofilm

Natural Deep Eutectic Solvents (NADES) are composed of supramolecular interactions of two

or more natural compounds, such as organic acids, sugars, and amino acids. In this study, using

NADES is presented as a possible technology for biofilm structural breaker in complex systems.

The NADESs were analyzed before and after the biofilm treatment by attenuated total reflection

Fourier-transform infrared spectroscopy and fluorescence excitation-emission matrix

spectroscopy. Our results indicate that the green solvents could extract up to ≈70 percent of the

main components of the biofilms extracellular matrix. The weakening of the biofilm structure

enhanced its solubilization and removal. NADES have the potential to be an environment

friendly, green biofilm solvent to extract valuable compounds from the extracellular polymeric

substance (EPS) and to control biofouling in membranes system used for water treatment and

cooling towers.


47

Using Eutectic Mixtures For The Extraction And Recovery

Of The Carotenoid Bacterioruberin

Mariam Kholany a, Nicolas Schaeffer a, Inês P.E. Macário a,b, Telma Veloso a,b, Tânia Caetano

b, Joana Luísa Pereira b, Sónia P.M. Ventura a,*, João A. P. Coutinho a a CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro,

3810-193 Aveiro, Portugal b CESAM – Centre for Environmental and Marine Studies, Department of Biology,

University of Aveiro, 3810-193, Aveiro, Portugal

* [email protected]

Keywords: Bacterioruberin, carotenoid, eutectic mixture, extraction

In the biorefinery context, both bulk and specialty chemicals can be produced and extracted

from biomass, resulting in a potentially more sustainable alternative to petroleum-derived

products. An example of this is Haloarchaea, an interesting class of extremophile

microorganisms, also present in the Aveiro salt pans. Amongst these, Haloferax mediterranei

is a highly promising candidate for the production of bacterioruberin owing to its rapid growth

and ability to consume a variety of carbon sources. Bacterioruberin is an uncommon C50

carotenoid with great biotechnological interest. This type of carotenoid exhibits a higher

antioxidant capacity than the C40 carotenoids such as β-carotene, which can be explained due

to the higher number of pairs of conjugated double bonds. This makes this carotenoid

remarkably interesting for the food, pharmaceutical and biomedical industries. In this work, the

valorization of Haloferax mediterranei ATCC 33500 was pursued through the recovery of

bacterioruberin and its separation and purification from the remaining cell components. In an

effort to formulate food and cosmetic grade compatible extracts, pigment recovery was

accomplished through the use of bio-derived eutectic solvents. Operational conditions such as

the solid-liquid ratio, concentration of eutectic mixture, hydrogen bond-donor and hydrogen-

bond acceptor ratio and the time of extraction were accessed. These eutectic mixtures arise as

more sustainable and appropriate solvents compared to the typical solvents used in chemical

processes because of their simple preparation, extraction efficiency and integration of the

extraction and separation in a “one-pot” method by using water as counter-solvent.

Acknowledgments: This work was developed within the scope of the project CICECO-Aveiro Institute of

Materials, UIDB/50011/2020 & UIDP/50011/2020 and CESAM, UIDB/50017/2020 & UIDP/50017/2020,

financed by national funds through the FCT/MCTES. The authors are also grateful to the FCT for the doctoral

grants of M. Kholany (SFRH/BD/138413/2018), I.P.E. Macário (SFRH/BD/123850/2016) and T. Veloso

(SFRH/BD/147346/2019).


48

Could NaDES assisted one-pot extraction and

biotransformation be a relevant strategy to boost activity

of natural extracts? Millena Cristina Barros Santos1,2; Nathalie Barouh3,4; Bruno Baréa3,4, Mélina Robert4, Pierre

Villeneuve3,4, Luiz CláudioCameron2; Valérie-Lullien5, Claire Bourlieu-Lacanal5, Mariana

Simões Larraz Ferreira1,2* and Erwann Durand3,4*

¹LabBio - Laboratory of Bioactives, Food and Nutrition Graduate Program - PPGAN, Federal

University of State of Rio de Janeiro – UNIRIO, Rio de Janeiro, Brazil. 2IMasS-LBP - Center of Innovation in MS-Laboratory of Protein Biochemistry, UNIRIO, Rio

de Janeiro, Brazil. 3CIRAD, UMR QualiSud, F-34398 Montpellier, France

4QualiSud, Univ Montpellier, CIRAD, Institut Agro, IRD, Univ Réunion, Montpellier,France. 5IATE, Univ Montpellier, INRAE, Institut Agro, Montpellier, France.

* [email protected] and [email protected]

Keywords: NaDES, extraction, biotransformation, natural extracts, rice bran.

NaDES have been already proposed as a promising strategy to improve extraction efficiency of bioactive

compounds from plant biomass. What makes NaDES interesting is their unpredictable and strong

solubilization capacity, providing enriched extracts with higher phytochemical concentration. In

addition, NaDES have been reported to be excellent liquids to stabilize and protect molecules from

degradation, mostly due to the supramolecular network of tightly interconnected molecules. Last but not

the least, NaDES may offer all characteristics to design atom economy, efficient, low cost and

sustainable development for ready-to-use formulation, while being fully compatible with food and feed

applications. Concomitantly, the structural modification of molecules has been recognized as an

effective approach to strengthen the chemical efficiency of bioactive compounds. For example,

modification of antioxidant molecules could further result in a better capacity to retard oxidation of

lipid-based formulations. Although more challenging, such a strategy is even more interesting when the

modification takes place enzymatically; for safety and potential health benefits reasons, but also for

many others that align with the green chemistry principles. Here, metabolomics approaches focusing on

phenolic compounds (PC) was applied to characterize the complexity of pigmented rice bran NaDES

extracts. Compared to a binary mixture of water and ethanol (60:40 v/v), NaDES showed a specificity

to extract PC and demonstrated an interesting radical scavenging activity. In parallel, a characterization

of the lipid extraction profile showed the presence of different classes of lipids, which confirmed the

richness and abundance of diverse classes of bioactive compounds (PC/lipids). Our scientific

challenging aimed at investigating whether, and how, NaDES could sublimate activity of natural

occurring molecules in plant biomass. Thus, our strategy was to use these media properties to develop

a sustainable one-pot extraction and biotransformation environment to (i) promote antioxidant

enrichment (including PC and lipids) of a natural extract, and to (ii) enzymatically modify the structure

of compounds. Lipase was used to modify structures of enriched NaDES extract, and the samples were

tested for their ability to prevent lipid oxidation in an oil-in-water emulsion system. PV and TBARS,

determined during an incubation period, demonstrated an efficient antioxidant activity of our

biotransformed extracts. Thus, NaDES could favor the extraction and the biotransformation of natural

extracts, resulting in new functionalized compounds with improved antioxidant activities in emulsions.

These extracts can be used as natural additives at doses higher than the levels naturally found in cereals.

Omics tools will be applied to elucidate the structural rearrangement between the extracted compounds

from rice bran that justify the protection against lipid oxidation.


49

Indium Mediated Barbier Allylation of Carbonyl

Compounds in Deep Eutectic Solvents

Nerea González-Gallardo, Beatriz Saavedra, Gabriela Guillena* and Diego J. Ramón*

Departamento de Química Orgánica and Instituto de Síntesis Orgánica (ISO), Facultad de

Ciencias Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain.

* E-mail: [email protected], [email protected]

Keywords: Indium, Barbier Allylation, Deep Eutectic Solvent, Green Chemistry

This study describes, for the first time, the in-situ generation of indium organometallic reagents

in environmentally-friendly Deep Eutectic Solvents (DESs). The allylation process of different

carbonyl compounds was achieved mediated by indium metal, and using cheap allyl chloride

derivatives. The unique DESs properties allowed the reaction to be performed at room

temperature and under air obtaining yields from 52 to 99%. It was possible to recycle the

reaction medium at least 4 consecutive cycles without any decrease on the results. Also, a linear

correlation between the yield of the reaction and the densities of the DESs was observed. Thus,

this methodology could represent a practical and sustainable alternative to traditional protocols.

mailto:[email protected]


50

A critical study on the influence of DES on the formation

of organic biphasic systems

Jean-Baptiste Chagnoleau1, Nicolas Papaiconomou1*, Mona Jamaly1, João A. P. Coutinho2,

Dinis O. Abranches and Xavier Fernandez1, Thomas Michel1,

1Université Côte d'Azur, CNRS, Institut de Chimie de Nice, UMR 7272, Nice, France. 2CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro,

3810-193 Aveiro, Portugal.

*Corresponding author: [email protected]

Keywords: DES, organic biphasic systems, phase diagrams, natural compounds, partition

coefficients, COSMO-RS.

In the current context of sustainable development and circular economy, new sustainable

processes and techniques for obtaining pure natural compounds is subject of intense studies.

Recent works1,2 have reported that Deep Eutectic Solvents (DES) added to two miscible organic

solvents (e.g., ethanol and heptane) trigger a phase demixion and the formation of a biphasic

system, that can be further applied to the partitioning of natural compounds. A critical study on

the relevance of using DES was however lacking.3

In this talk, in order to get a better understanding at the mechanisms in play for the formation

of biphasic systems and on the partitioning of natural compounds, we studied six systems based

on heptane and ethanol and a third compound being either glycerol, ethylene glycol, levulinic

acid, or the corresponding DES formed with choline chloride. Phase diagrams for these six

systems are reported and compared together. Measurements of the partition constants of five

natural compounds (quercetin, apigenin, coumarin, b-ionone and a-tocopherol) within these

systems was also measured. Finally, all phase diagrams and partition coefficients measured in

this work were compared to calculations carried out with the help of COSMO-RS model.

Figure 1. Comparison

between experimental

and calculated values

for log(KD) of several

natural compounds.

Yellow: H/E/LevA.

Blue: H/E/Ch:EG.

Grey: H/E/Glyc. Light

blue: H/E/Ch:LevA.

Orange: H/E/Ch:EG.

Green: H/E/Ch:Glyc.

Full colour:

Experimental. Dashed

colour: Calculated.

1: Bezold F.; Weinberger M. E.; Minceva M. Fluid Phase Equilibria 2017, 437, 23–33.

2: Bezold F.; Minceva M. A J. Chrom. A 2019, 1587, 166–171.

3: Chagnoleau J.-B.; Papaiconomou N.; Jamali M.; Abranches D.O.; Coutinho J.A.P; Fernandez X.; Michel T.

ACS Sus. Chem. Eng. 2021, submitted.


51

Extraction of Ferulic Acid from Aqueous Systems Using

Deep Eutectic Solvents

O. G. Sas, M. López, M. Pita, B. González, A. Domínguez*

Advanced Separation Processes Group, Isaac Newton Building, Department of Chemical

Engineering, Universidade de Vigo, Lagoas-Marcosende, 36310, Vigo, Spain

* [email protected]

Keywords: Deep Eutectic Solvents, Liquid-Liquid Extraction, Ferulic acid, UV-Vis

spectrophotometry.

Ferulic acid is one of the most common bioactive compounds that belongs to cinnamic acid

derivatives of phenol, it is presented on cell walls of many vegetables. This compound is

suitable for more and more applications, such as cosmetic, medical or food field. Consequently,

this high demand make necessary the recovery of ferulic acid from wastewater of some

industrial processes, as palm oil or beer production.

Among different used extraction techniques is Liquid-Liquid Extraction (LLE), which main

advantage is the possibility of recovering the target compound, as well as, the extraction agent.

In the last years, Deep Eutectic Solvents (DESs) have emerged as versatile solvents replacing

volatile organic compounds (VOCs) used conventionally in LLE.

In this work, one hydrophobic DES, Thymol:Menthol (1:1), was used in order to remove ferulic

acid from water samples of different initial concentrations. Ternary system formed by {DES +

Acid + Water} were mixed at controlled conditions, immediately DES-rich phase and water-

rich phase were separated using a centrifuge. The concentration of acid that remains in water-

rich phase was measured by UV-Vis spectrophotometry and the extraction capability of DES

was assessed.

The obtained results showed that the extraction percentage was higher than 90% for all studied

initial concentrations.

To conclude, Thymol:Menthol (1:1) is an appropriated solvent for the extraction of ferulic acid

from water, allowing the posterior reuse of both DES and extracted compound contributing to

a circular economy.


52

Make it or Break it: Cu3(BTC)2 Metal-Organic

Framework in Reline DES

Renata Avena Maia a, Benoît Louis b,*, Stéphane Baudron a,* a CNRS, CMC UMR 7140, Université de Strasbourg, 4 rue Blaise Pascal, F-67000

Strasbourg, France. b CNRS, ICPEES UMR 7515, Université de Strasbourg, 25 rue Becquerel, F-67087

Strasbourg, France.

* [email protected], [email protected]

Keywords: Metal-Organic Frameworks • reline • structure transformation • CuBTC

The fate of the Metal-Organic Framework (MOF) Cu3(BTC)2 (BTC = 1,3,5-

benzenetricarboxylate) in reline DES (choline chloride/urea 1:2) was investigated,

demonstrating that not only reline can be used to make this MOF but also to transform it into

another crystalline material. Cu3(BTC)2 synthesized in reline showed good textural properties

and a particular rose morphology. Upon optimizing the reaction conditions such as

concentration, temperature, and metal/ligand ratio, it was found that another structure

Cu2(BTC)Cl, also forms. Furthermore, it was unequivocally demonstrated that, upon heating in

reline, Cu3(BTC)2 behaves as a metastable architecture, converting to the non-porous chloride-

incorporating material. Thus, a novel feature of DES in MOF synthesis is uncovered: its role as

a structure-directing agent, triggering the transformation between two different MOF

structures.1

1 R. A. Maia, B. Louis, S. Baudron, Dalton Trans. 2021, doi: 10.1039/D1DT00377A.


53

A Green Method based on Natural Hydrophobic Deep

Eutectic Solvents for Plastic Migrants Determination in

Beverages using UHPLC-MS/MS

Ruth Rodríguez-Ramos a,*, Álvaro Santana-Mayor a, Antonio V. Herrera-Herrera b, Bárbara

Socas-Rodríguez c, Miguel Ángel Rodríguez-Delgado a a Departamento de Química, Unidad Departamental de Química Analítica, Facultad de

Ciencias, Universidad de La Laguna (ULL). Avda. Astrofísico Fco. Sánchez, s/n. 38206 San

Cristóbal de La Laguna, España, b Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna

(ULL), Avda. Astrofísico Fco. Sánchez, 2, 38206 San Cristóbal de La Laguna, España, c Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera


* [email protected]

Keywords: phthalate ester, green solvent, microextraction, soft drink

Among the plastic additives applied in the manufacture of polymers, phthalic acid esters (PAEs)

constitute the most widely used to improve the properties of final products such as flexibility.

Due to the ease of PAEs to migrate from plastic materials in contact with food to the immediate

environment, the development of analytical protocols capable of quantitatively determining

these organic contaminants at low concentration levels, at which detrimental effects for human

health have been demonstrated, is extremely necessary. In this context, natural hydrophobic

deep eutectic solvents (NaHDESs) have emerged as a green alternative to reduce the use of

conventional extraction solvents, due to their inherent advantages such as high biocompatibility

and biodegradability, easy synthesis, high availability of raw materials and low cost. Moreover,

the application of small volume of NaHDES is compatible with the development of

microextraction techniques which resulted in a lower environmental impact. In this work, a

sustainable analytical method based on NaHDES as extraction solvent in vortex-assisted-

dispersive liquid-liquid microextraction has been developed for the extraction of 15 plastic

migrants from soft drinks. With this aim, different eutectic mixtures formed by the monoterpene

thymol and medium-chain fatty acids (octanoic acid and decanoic acid) in different molar ratios

have been firstly evaluated. Once the molar ratio that led to the highest absolute recovery of

PAEs was determined, other parameters that also showed a remarkable influence on extraction

efficiency were optimised by univariate protocol. The validation of the analytical methodology

was carried out for cold infusions and tonic waters, obtaining recovery values in the range 71–

124% and limits of quantification of the method of 0.025–1.25 μg/L. Analyses of real samples

were carried out using ultra-high performance liquid chromatography coupled to tandem mass

spectrometry for a reliable identification and quantification.


54

Eutectic Mixtures as Promising Formulation Strategy for

Poorly Water-Soluble Drugs

Sarah El Masria,b, Sophie Fourmentina,*, Steven Ruellana, Maha Zakhourb and Lizette

Auezovab a Unité de Chimie Environnementale et Interactions sur le Vivant (UCEIV), EA 4492 SFR

Condorcet FR CNRS 3417, Université du Littoral-Côte d'Opale, Dunkerque, France

b Bioactive Molecules Research Laboratory, Doctoral School of Sciences and Technologies,

Faculty of Sciences, Lebanese University, Fanar, Lebanon.

*Corresponding author: [email protected]

Keywords: deep eutectic solvents, cyclodextrins, solubility.

According to the Biopharmaceutics Classification System (BCS), up to 70% of the new

chemical entities suffer from poor water solubility1. This represents a serious challenge to the

successful development of new therapeutics in the pharmaceutical industry2. Many approaches

have been employed to address the formulation challenges of poorly water-soluble drugs,

including drug delivery systems such as liposomes, cyclodextrins, solid lipid nanoparticles, …3.

In this context, deep eutectic solvents (DES), particularly those consisting of components from

natural origin, have emerged as solvents of great promise for pharmaceutical applications

because of their biodegradability, low toxicity and ability to dissolve chemically diverse

compounds, including water-insoluble ones4. In this study we have investigated, along with

classical DES, a new generation of DES called supramolecular deep eutectic solvents

(SUPRADES)5 based on cyclodextrins (CD), cage molecules able to encapsulate various guests

in their hydrophobic cavity and known for their use as functional pharmaceutical excipients to

enhance drug solubility3. We were interested in comparing the solubilizing potential of these

two classes and highlighting the benefit of combining the solubilization properties of a solvent

and a drug carrier. Our results showed a significant increase in solubility for the different active

pharmaceutical ingredients (API) studied, with factors ranging from 574 to 22440. For most of

the studied API, the solubility was either equally enhanced in both DES, or more enhanced with

the SUPRADES. Even upon water addition, the DES based on CD were more efficient in

retaining their solubilizing potential. We assumed that this is due to the formation of inclusion

complexes in the SUPRADES and their aqueous solutions; this hypothesis was validated by

NMR studies. We were also interested in eutectic mixtures based on API. Different mixtures

were prepared and investigated for their ability to maintain supersaturation in aqueous media.


55

Extraction and Stabilization of Bioactive Compounds

From Aromatic Plants Using Sustainable NADES

Sílvia Rebocho a,*, Rita Craveiro a, Alexandre Paiva a,b, Ana Rita C. Duarte a,b

a LAQV-REQUIMTE, Departamento de Química, Faculdade Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal b Des Solutio, Avenida Tenente Valadim nº 17 2º F, 2560-265 Torres Vedras, Portugal

* [email protected]

Keywords: Natural deep eutectic systems, antioxidants, extraction, Salvia officinalis.

This work describes an innovative sustainable approach for the extraction of individual

bioactive constituents from aromatic plants, particularly from sage (Salvia officinalis). This

plant is rich in unique and highly concentrated essential oils, with extremely attractive

properties. The most prevalent compounds in this plant are the phenolic compounds, as caffeic

acid and its derivatives as rosmarinic acid, and the diterpenes such as carnosic acid and

carnosol, and the triterpene ursolic acid. Properties such as antioxidant, anti-inflammatory,

antimicrobial, anti-cancer, antitumor and applications with health benefits are very interesting

to investigate, especially towards new oncology and neurodegenerative treatments, as

Alzheimer’s disease.

In this work, we use natural deep eutectic systems (NADES) to design more sustainable

extraction processes. Combinations of compounds such as glucose, trehalose, lactic acid,

glycerol, menthol or betaine, are used in adequate molar ratio to form our systems. The

screening of the most promising systems for extraction was carried out with two methods: heat

and stirring (HS) and ultrasound assisted extraction (UAE), under the same conditions of

temperature (40°C), time (1h) and solid/liquid ratio (1:20). In general, the most promising

results were reach using UAE. The results revealed that in the extracts of menthol based DES,

carnosic acid and carnosol are the predominant compounds, with the values of 14.27±0.81 mg

of carnosic acid/g sage and 1.73 ± 0.09 mg of carnosol/g sage for the system menthol: myristic

acid (8:1). On the other hand, rosmarinic acid was not detect in this extract, which revealed, for

this system, a selectivity for more nonpolar compounds. Lactic acid based systems revealed

more promising results for the extraction of rosmarinic acid, namely for lactic acid:glucose

(5:1) and lactic acid:proline (3:1), with concentrations of 1.76±0.21 and 2.91±0.13 mg of

rosmarinic acid/g sage, respectively. Thus, a simultaneous extraction of the compounds, with

different polarities is being explored, taking advantage of the selectivity of the systems.

Acknowledgements: This project has received funding from the European Union’s Horizon 2020 (European

Research Council) under the grant agreement No ERC-2016-CoG 725034. This work was also supported by the

Associate Laboratory for Green Chemistry - LAQV which is financed by national funds from FCT/MCTES

(UIDB/50006/2020 and UIDP/50006/2020).


56

Delivery of Deep Eutectic Solvents Comprising

Nonsteroidal Anti-inflammatory Drugs using Biopolymer-

Based Systems

Sónia N. Pedro a, *, Maria S. M. Mendes a, Bruno Miguel Neves b, Mara G. Freire a, Armando

J. D. Silvestre a and Carmen S. R. Freire a a CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro,

Aveiro, Portugal b Department of Medical Sciences and Institute of Biomedicine – iBiMED, University of

Aveiro, 3810-193 Aveiro, Portugal

* [email protected]

Keywords: Active pharmaceutical ingredients, nonsteroidal anti-inflammatory drugs, deep

eutectic solvents, drug delivery, controlled release.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in the treatment of pain

conditions, including arthritic ones. However, their usefulness is mainly limited by dose-

dependent adverse effects, such as gastrointestinal damage, cardiovascular risks and renal

toxicity. These effects can be minimized by appropriate topical delivery systems, which deliver

the active pharmaceutical ingredients (APIs) locally, further reducing the systemic

concentration. However, a main disadvantage of topical drug delivery systems comprising

NSAIDs, such as patches, is their difficulty to convey the API through the stratum corneum.

With this in mind, we have considered the use of deep eutectic solvents (DES) as alternative

solvents to increase the solubility, therapeutic efficacy and delivery of NSAIDs, such as

ibuprofen and ketoprofen. Aiming to unveil the DES influence on the NSAIDs efficacy, we

have studied the anti-inflammatory properties of these formulations in vivo in Raw 264.7

macrophages cell lines. Finally, we have successfully encapsulated these formulations in

alginate-based systems, obtaining good encapsulation efficiencies (>66%) for the NSAIDs

studied and controlled release profiles over a 2-hour period at body’s temperature. The DES-

based systems here developed sustain the promising ability of DES to improve not only the

APIs characteristics but also the biopolymer systems’ properties, enabling more effective drugs

delivery.


Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when

appropriate co-financed by FEDER under the PT2020 Partnership Agreement. S. N. Pedro acknowledges the PhD

grant SFRH/BD/132584/2017.


57

ATR-IR Spectroscopy for Rapid Quantification of Water

Content in Deep Eutectic Solvents Suha Elderderi a, b, Charlotte Leman-Loubière c, Laura Wils c, Hugh J. Byrne e, Igor Chourpa a,

Cécile Enguehard-Gueiffier c, Emilie Munnier a, Abdalla A. Elbashir f, Leslie Boudesocque-

Delaye c, Franck Bonnier a,*

a Université de Tours, Faculté de pharmacie, EA 6295 NMNS, Tours, France b University of Gezira, Faculty of Pharmacy, Gezira, Sudan.

c Université de Tours, EA 7502 SIMBA, Tours, France e FOCAS Research Institute, TUDublin, Dublin 8, Ireland

f University of Khartoum, Faculty of Science, Khartoum, Sudan

* [email protected]

Keywords: Infrared spectroscopy, Attenuated Total Reflectance, multivariate analysis, water

quantification, deep eutectic solvent

NADES have a wide range of applications, mainly as solvents for plant extractions,

biocatalysis, and nanoparticle synthesis. Water content is very critical, impacting significantly

on NADES properties and can lead to NADES disruption. NADES are hygroscopic; therefore

controlling H2O concentration appears essential for their optimal use after storage. In the

present study, Attenuated Total Reflectance–infrared spectroscopy (ATR-IR) coupled to

multivariate analysis, namely Partial Least Squares Regression (PLSR), was investigated as a

rapid, label free and cost-effective tool for measuring the water concentration of NADES. ATR-

IR enables direct molecular characterisation of samples without pre-analytical protocols. A

drop can be deposited on the ATR crystal to collect a spectral signature specific to NADES

chemical composition. Betaine_Glycerol, Choline Chloride_Glycerol and Glucose_Glycerol

were selected as NADES model systems. For the purpose of the study, a range of water

concentrations between 0% (w/w) and 40% (w/w) was prepared for each model. PLSR results

demonstrate the robustness of the analysis, yielding R2 values of 0.99 and Root Mean Square

Error of Cross Validation (RMSECV) of respectively 0.2602% w/w, 0.6883% w/w and

0.7034% w/w. Moreover, the percentage relative error achieved is below a 5% threshold. This

preliminary work shows the potential of ATR-IR spectroscopy as a tool for water quantification

in the 3 NADES systems studied. Such analytical protocols can support the development of

green chemistry, which currently represents a major focus of interest in both research and

industrial environments.

Reference: S. Elderderi et al. ATR-IR spectroscopy for rapid quantification of water content in deep eutectic

solvents, Journal of Molecular liquids. 311 (2020) 113361. https://doi.org/10.1016/j.molliq.2020.113361.


58

POSTER PRESENTATIONS


59

Determination of the Enthalpy of Fusion of Choline

Chloride Using Dissolution and Titration Calorimetry

Adriaan van den Bruinhorst*, Margarida Costa Gomes

École Normale Supérieure Lyon, Laboratoire de Chimie, 46 allée d’Italie, 69364 Lyon, FR

*[email protected]

Keywords: fusion properties, choline chloride, isothermal calorimetry, excess enthalpy

Deep eutectic systems (DESs) are mixtures with a eutectic temperature significantly below the

ideal eutectic point that can be used as alternative liquid media. The liquid window of a DES is

determined by the fusion properties of its pure constituents and by the intermolecular

interactions in the liquid phase. Choline chloride (ChCl) is one of the most commonly studied

DES constituents, but it decomposes before melting thus rendering the fusion properties

inaccessible by direct experimental measurement1. We therefore aim to determine the enthalpy

of fusion indirectly using isothermal dissolution and titration calorimetry.

To date, two enthalpies of fusion were reported for ChCl: 4.3 kJ mol−1 from solid–liquid

equilibria1 and 29.8 kJ mol−1 from the enthalpy of dissolution2. They differ significantly owing

to various factors. Non-idealities in the free energy of mixing were omitted1 or assumed to be

composition and solvent independent2, and solid–solid transition of ChCl was not considered2.

A re-evaluation of the ChCl mixing behaviour and the derived fusion properties is pertinent.

Using the thermodynamic cycle above, we explored the mixing behaviour of ChCl in a series

of diols via isothermal dissolution calorimetry and isothermal titration calorimetry. The

thermodynamic consistency was validated using solid–liquid equilibrium data, considering the

solid–solid transition of ChCl. Via this route, we could quantify the contributions of the

intermolecular interactions and the fusion properties to the (non-)ideality of the eutectic phase

behaviour for mixtures containing ChCl.

References:

1 L. Fernandez, L. P. Silva, M. A. R. Martins, O. Ferreira, J. Ortega, S. P. Pinho and J. A. P. Coutinho,

Fluid Phase Equilib., 2017, 448, 9–14.

2 P. López-Porfiri, J. F. Brennecke and M. Gonzalez-Miquel, J. Chem. Eng. Data, 2016, 61, 4245–4251.


60

Development of high barrier electrospun poly(3-

hydroxybutyrate-co-3-hydroxyvalerate) films using deep

eutectic solvents technology for food packaging

applications

Ahmet Ozan Basar, Cristina Prieto, Jose M. Lagaron*

Novel Materials and Nanotechnology Group, IATA-CSIC, Valencia, Spain

* [email protected]

Keywords: DES, PHBV, electrospinning, food packaging, barrier properties, active

properties

In the present study, high barrier electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate)

(PHBV) films will be developed with the use of novel deep eutectic solvents (DES) technology

for food packaging applications. PHBV is a biodegradable aliphatic polyester produced by

microorganisms. However, its application in food packaging sector has been also limited due

to several drawbacks, such as weak mechanical properties, poor thermal stability, and narrow

processing windows [1]. DES, on the other hand, are the new generation of solvents with several

unique properties, such as negligible volatility, broad range of polarity, high solubilization and

stabilization capacity for a wide range of compounds, and as well as biodegradability,

sustainability, plasticization ability, low cost, and simple preparation [2]. Hence, this study aims

to improve PHBV film properties with the addition of DES via electrospinning technique. For

this, different formulations of DES will be selected to plasticize PHBV in order to achieve films

that can withstand thermoforming. Furthermore, thermoformable active electrospun PHBV

films containing natural antioxidant, antimicrobial, and as well as nano-oxygen scavenger

particles will also be developed for novel use in the food packaging applications using DES as

solvents. After the production, the characterizations of the electrospun structures will be carried

out in terms of morphological by scanning electron microscopy (SEM); size and distribution of

the particles by transmission electron microscopy (TEM); composition and interactions by

attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR); thermal

properties by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC);

mechanical properties; water vapour permeability and water sorption by gravimetric methods;

oxygen scavenging properties by oxygen absorption assay based on fluorescence; antioxidant

capacity by DPPH and ABTS methods; and lastly the antimicrobial performance by the

bactericidal inhibitory method.

References:

[1] Yu, H. et al., RSC Advances, 2014, 4, 59792.

[2] Y. Dai et al., Food Chemistry, 2015, 1870 14–19.


61

Innovative Material for the Extraction of Alkylphenols

from Animal-based Milk Samples

Álvaro Santana-Mayor a,*, Ruth Rodríguez-Ramos a,

Bárbara Socas-Rodríguez b, and Miguel Ángel Rodríguez-Delgado a

a Departamento de Química, Unidad Departamental de Química Analítica, Facultad de

Ciencias, Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, s/n, 38206 San

Cristóbal de La Laguna, España b Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera

9, 28049 Madrid, Spain

* [email protected]

Keywords: alkylphenols, deep eutectic solvent, milk, liquid chromatography

Alkylphenols (APs) are commonly used as additives in the plastic industry as well as the

production of textiles, paper or utilised as surfactants in industrial or agricultural applications,

among others. The widespread use of these compounds, their persistence and their possible

effects on human health and the environment have alerted the scientific community and popular

society. APs represent an important group of endocrine disruptors that can mimic or induce

similar responses to the natural hormones of organisms and not only alter their reproductive

system, but also cause other serious damages at low concentration levels. Thus, the evaluation

of those matrices susceptible to suffer APs migration from the packaging that contains them is

of vital importance to guarantee public and environmental health. Milk is a product highly

consumed by the population due to it is an important source of proteins and sugars, as well as

other important nutrients. Therefore, guaranteeing its quality and safe consumption is crucial.

Migration of APs from plastic materials can occur throughout the entire food chain including

processing and storage, and even transportation. In this sense, and added to the complexity of

milk samples, the analysis of these compounds can be a real challenge. In this regard, deep

eutectic solvents (DESs) have emerged as promising solvents and replacement of toxic organic

solvents and have been applied in many fields including industry and medicine, but also have

demonstrated their potential as extraction agents in analytical chemistry procedures. With the

aim of improving extraction methods for the extraction of APs in milk matrices towards greener

and sustainable protocols, in this work a new method based on a DES-lab-made material has

been developed for the analysis of APs in animal-based milk samples. The separation and

quantification of the target analytes were carried out by ultra-high performance liquid

chromatography coupled to a tandem mass spectrometry system. The whole methodology was

thoroughly optimised and validated for the determination of APs in animal-based milk matrices.


62

NADES, a new class of cryoprotectant agents inspired by

nature

Ana Rita Jesus a, Alexandre Paiva a,*, and Ana Rita C. Duarte a

a LAQV@REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516, Caparica, Portugal

* [email protected]

Keywords: cryopreservation, natural products, eutectic systems

Cell cryopreservation with high rates of post-thawing survival remains a major challenge and

many environmental factors can seriously affect cellular function during the freezing process

such as the cryoprotectant agents (CPAs). [1] Natural Deep Eutectic Solvents (NADES have

emerged in the last decade as alternative solvents for many applications. [2] Some components

are found in animals living in extreme cold environments and are involved in the hibernation

process allowing them to survive during winter time,[3] which inspired us to develop NADES

as a new class of CPAs [4]. Herein, we present the successful cryopreservation of mammalian

cells. Cytotoxicity evaluation has showed that these NADES are non-toxic with IC50 values

ranging from 1.0-2.2 M. Differential Calorimetry Scanning (DSC) was used to evaluate the

thermal behavior of these eutectic systems, showing the strong effect on the water

crystallization/freezing and melting processes. Thus, NADES are able to reduce the formation

of ice crystals, and therefore reducing the cell damage during the freezing/thawing processes.

Post-thawing studies showed that some of these systems are in fact able to efficaciously

cryoprotect cells, resulting in high-rates of post-thawing cell survival.

References

[1] B. Stokich, Q. Osgood, D. Grimm, S. Moorthy, N. Chakraborty, M. A. Menze, Cryobiology 69 (2014) 281–

290

[2] A. Paiva, R. Craveiro, I. Aroso, M. Martins, R. L. Reis, A. R. C. Duarte, ACS Sustainable Chemical

Engineering. 2 (2014) 5, 1063–1071

[3] A. Gertrudes, R. Craveiro, Z. Eltayari, R. L. Reis, A. Paiva, A. R. C. Duarte, ACS Sustainable Chemistry

Engineering, 5 (2017) 9542−9553

[4] V. I.B. Castro, R. Craveiro, J. M. Silva, R. L. Reis, A. Paiva, A. R. C. Duarte, Cryobiology, 83 (2018) 15-26

Acknowledgements

This project has received funding from the European Research Council (ERC) under the European Union’s

Horizon 2020 Research and Innovation Programme, under grant agreement No ERC-2016-CoG 725034. This

work was also supported by the Associate Laboratory for Green Chemistry – LAQV, financed by national funds

from FCT/MCTES (UID/QUI/50006/2019) and by FCT/MCTES through the project CryoDES (PTDC/EQU-

EQU/29851/2017).


63

Kraft lignin solubility in aqueous solutions of deep eutectic

solvents

Filipe H. B. Sosaa,b, Andre M. da Costa Lopes a,c*, João A. P. Coutinhoa, Mariana C. Costab. aCICECO, Department of Chemistry, University of Aveiro, Campus Universitário de

Santiago, Aveiro, Portugal. bSchool of Chemical Engineering (FEQ), University of Campinas (UNICAMP), Campinas,

Brazil. cCECOLAB - Collaborative Laboratory Towards Circular Economy, R. Nossa Senhora da

Conceição, 3405-155 Oliveira do Hospital

*[email protected]

Keywords: deep eutectic solvents, Kraft lignin, solubility, hydrotropy, depolymerization, non-

derivatization

Pulp and paper companies have shown increasing interest in Kraft lignin valorization rather

than its combustion to enhance carbon source (wood) efficiency and process sustainability.

However, the low solubility of Kraft lignin and the lack of efficient and environmentally safe

solvents for its dissolution is hindering successful developments of new applications. A

promising approach for the dissolution of this macromolecule may rely on the use green

solvents, such as deep eutectic solvents (DES). In this study, the ability of eleven DES based

on cholinium chloride ([Ch]Cl) as hydrogen bond acceptor (HBA) combined with alcohols or

carboxylic acids as hydrogen bond donors (HBDs) to dissolve Kraft lignin and their potential

to chemically modify it was examined. The influence of the chemical structure of HBDs,

HBD:HBA molar ratio, and water content on Kraft lignin solubility were investigated (313.15

K). The obtained results showed that HBDs play an important role in Kraft lignin dissolution,

and the efficiency is governed by its chemical nature (alcohol or carboxylic), chain length, and

molar ratio to HBA. The Kraft lignin solubility was enhanced by increasing both the HBD’s

carbon chain length and the molar ratio. Among studied solvents, [Ch]Cl:HEXA (1,6-

hexanediol) and [Ch]Cl:MaleA (maleic acid) were the best solvents for kraft lignin dissolution,

allowing 32.99 and 34.97 wt % solubility at 313.15 K, respectively. Moreover, the addition of

water negatively affected the lignin solvation power of DES. Thermal treatments of Kraft lignin

at 393.15 K showed that carboxylic acid-based DESs promote chemical modifications to lignin,

especially the disruption of several C−O bonds (e.g. β-O-4), while alcohol-based DESs were

found to be non-derivatizing solvents by maintaining the lignin chemical structure. These

results show the versatility of DES, which, depending on the HBA and HBD combination, and

their chemical nature, may offer distinct scenarios for lignin valorization.

Acknowledgments: This work was financed in part by the CAPES, FAPESP, CNPq, and partially developed

within the scope of the project CICECO, FCT Ref. UIDB/50011/2020 & UIDP/50011/2020.


64

Deep Eutectic Systems as Potential Solubilization Vehicles

for Mometasone Furoate and Dexamethasone

Â. Rochaa, A. Paivaa,*, T. Alvesb, L. Godinhoc, F. Oliveiraa, I. Sá-Nogueirac, J. Martob, H.

Ribeirob, A. Duartea a LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology,

NOVA University of Lisbon, Campus de Caparica, 2829-516 Caparica, Portugal b Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of

Lisbon, Av. Prof. Gama Pinto,1649-003 Lisboa, Portugal c UCIBIO, Department of Life Sciences, NOVA School of Science and Technology, NOVA

University of Lisbon, Campus de Caparica 2829-516 Caparica, Portugal

* [email protected]

Keywords: Deep eutectic systems, Active pharmaceutical ingredients, Solubility, Emulsions

Mometasone furoate (MF) and dexamethasone (DEX) are corticosteroids commonly used in

the treatment of allergies, skin diseases and autoimmune diseases due to their anti-inflammatory

properties. Despite their widespread use these corticosteroids are hindered by their very low

water solubilities.

Deep eutectic systems (DES) are defined as a mixture of two or more compounds, which at a

specific molar ratio present a strong depression of the melting point when compared with those

of its individual components. DES which are liquid at room temperature can be used as solvents.

These systems are advantageous because they can be easily prepared in high purity at low cost,

and, when composed by natural compounds, are inherently biodegradable and have low

toxicity. DES have been successfully employed in the solubilization of several active

pharmaceutical ingredients (APIs) due to their high stabilization and solubilization power. In

addition, by changing the components of the eutectic system, the solubility, permeation and

absorption of APIs can be increased by several folds, when compared with water, or tuned to

suit the specific needs of each application.

Herein, we report the use of DES based on natural organic acids and terpenes for the

solubilization of MF and DEX. In some cases, DES are able to dissolve up to 2.3 times the

amount of drug observed for Transcutol® P, one of the most commonly used co-solvents in

pharmaceutical formulations. These systems also exhibit interesting antimicrobial activities and

can potentially be used as preservatives. As proof of concept, MF solubilized in DES was used

to prepare o/w emulsions for skin delivery. The study included optimization of the emulsions

and subsequent characterization, namely pH, droplet size, rheology and in vitro permeation

studies.


65

NADES as emerging sustainable systems for the

extraction and stabilization of bioactive compounds from

Rosemary

Vieira C.a,*, Craveiro R.a, Paiva, A.a,b, Duarte, A.R. a,b, Rebocho S.a a LAQV-REQUIMTE, Departamento de Química, Faculdade Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal b Des Solutio, Avenida Tenente Valadim nº 17 2ºF, 2560-265 Torres Vedras

*[email protected]

Keywords: Natural deep eutectic systems, extraction, Rosmarinus officinalis, antioxidant

activity.

Rosemary (Rosmarinus officinalis) is a natural source of bioactive compounds and essential oil

with high antioxidant activity. It has been used since ancient times as a medicinal herb and

currently is widely used due to its inherent pharmacological and therapeutic potential.

Regarding this, the demand for these compounds in pharmaceutical, food, and cosmetic

industries increased the value of this plant. The development of new promising and sustainable

techniques of extraction has received a lot of attention. Recently, a new class of green solvents,

known as natural deep eutectic systems (NADES) came to offer suitable systems, with high

solvent power, low toxicity, biodegradability and lower environmental impact. The present

work aims to extract the principal bio compounds from rosemary, such as rosmarinic acid,

carnosol, and carnosic acid using these alternative solvents. For that, a NADES screening was

made, using the same conditions of temperature, S/L molar ratio and time, under two different

methods, heat and stirring (HSE) and ultrasound-assisted extraction (UAE), to test the solvent

efficiency. In terms of total phenolic content, best results were achived with lactic acid:glucose

(5:1), reaching up to 2% mg GAE/mg rosemary. The quantification of the compounds was also

made, with the most promising results for rosmarinic acid 0.833 mg/g rosemary and carnosol

1.751 mg/g rosemary using menthol:myristic acid (8:1), and carnosic acid 6.722 mg/g rosemary

with menthol:lauric acid (2:1). It was demonstrated that the polarity of the systems interferes

with the selectivity of the extracted compounds, so a fractional extraction with opposite

character systems was performed. Preliminary results demonstrate that, in some cases, the

combined systems showed better capability of extraction, comparative to the individual

systems.

Acknowledgements: This project has received funding from the European Union’s Horizon 2020 (European

Research Council) under grant agreement No ERC-2016-CoG 725034; This work was also supported by the

Associate Laboratory for Green Chemistry - LAQV which is financed by national funds from FCT/MCTES

(UIDB/50006/2020 and UIDP/50006/2020).


66

Evaluation of deep eutectic systems as alternative solvents

in conservation and restoration

Cláudio Fernandesa, Ana Rita C. Duarte a,* a LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciência e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal

*[email protected]

Keywords: varnishes; Dammar; Mastic; NADES; Polarity; Solubility; Nile red; physical

properties; thermodynamic properties

Natural deep eutectic solvents (NADES) are considered as green solvents and due their

promising sustainability, they have been applied in many research fields. In this study the main

goal is to use some NADES systems to replace the traditional solvents commonly used

conservation and restoration in the removal of unwanted varnishes layers of a paint. The toxicity

potential of these traditional solvents, such as toluene or acetone is well known in chemistry

fields. For the replacement is hence important to have the knowledge about the intrinsic

physicochemical properties of a solvent that may act as substitute. Polarity and solubility are

then proposed as the best tools required for this study. Using Nile red as a dye, it may confirm

some similarity between the polarity of deep eutectic and traditional solvents. On another hand,

according to the polarity, it is possible to determine the best solvent to solubilize the natural

resin varnishes. Besides that, the use of some arithmetic models can also be applied to estimate

the critical or thermodynamic properties, as they are useful tools to predict the behaviour of

solvents, which can establish certain conditions for their application. We have further proven

that it is indeed possible to dissolve natural varnishes such as Dammar or Mastic in hydrophobic

DES, such as Menthol : Lauric acid, Menthol : Decanoic acid or Menthol : Thymol.

Acknowledgements:

This project has received funding from the European Union’s Horizon 2020 (European Research Council) under

grant agreement No ERC-2016-CoG 725034 and was supported by the Associate Laboratory for Green Chemistry-

LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020).


67

Strategies for the implementation of extractions using

Natural Deep Eutectic Systems at an industrial scale

Rente D.1, Paiva A.1,2 Duarte A.1,2,* 1LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal 2Des Solutio, Avenida Tenente Valadim, nº 17, 2ºF, 2560-275 Torres Vedras, Portugal

*[email protected]

Keywords: Extraction, NaDES, Residues, Scale-up

The potential of Natural Deep Eutectic Solvents (NaDES) for the extraction of a wide array of

phytochemicals has been thoroughly explored in literature. Nevertheless, their application at an

industrial scale is still far from being widespread. While problems associated with different

extraction methods exist, such as reactor geometry, type of mixing (ultrasounds, mechanical,

microwave) inside the reactor, energetic costs, during scale up, a large part has to do with the

choice of NaDES to be used. These problems arise mainly from the physicochemical properties

of NaDES such as its characteristic higher viscosity that may cause problems in handling or

mass transfer phenomena as well as production costs. Potential solutions to these problems

could be modulating the properties of the NaDES by controlling the ratio of the hydrogen bond

donor to the hydrogen bond acceptor or controlling properties inside the reactor by optimizing

extraction times, temperatures, solid to liquid ratios, or the amount of water added to enhance

the extraction yields. The aim of this work is to identify barriers to the scale up of extraction

using NaDES and offer potential solutions.

Acknowledgements:

This project has received funding from the European Union’s Horizon 2020 (European Research Council) under

grant agreement No ERC-2016-CoG 725034. This work was supported by the Associate Laboratory for Green

Chemistry- LAQV which is financed by national funds from FCT/MCTES (UID/QUI/50006/2019). Alexandre

Paiva would like to thank the financial support of FCT/MCTES under the project IF/01146/2015


68

The Liquid Structure Of Deep Eutectic Solvents Based On

Different Tartaric Acid Enantiomers From Neutron

Diffraction And Atomistic Modelling

Elly K. Bathke a*, Daniel T. Bowronb and Karen J. Edlerc

a* [email protected], Department of Chemistry, University of Bath, Claverton Down, Bath

BA2 7AY, UK, b [email protected] ISIS Neutron and Muon Source, Science and Technology

Facilities Council, Rutherford Appleton Laboratory, Didcot OX11 0QX, UK, c [email protected] Department of Chemistry, University of Bath, Claverton Down, Bath

BA2 7AY, UK

The structure of Deep Eutectic Solvents (DES) is dominated by H-bonds formed between the

component molecules. In this the structure of the components play an important role through

effects such as access to hydrogen bonding sites and steric hindrance, leading to changes in

physicochemical properties such as melting point and viscosity between DES consisting of

similar but slightly different precursors. Water has also been found to influence their properties

and has to be considered due to the hygroscopic nature of most DES, but which can

also be used to modify the DES properties for specific applications.

Here we present the structure of L-Tartaric Acid:Choline Chloride (molar ratio 1:2), DL-

Tartaric Acid:Choline Chloride (molar ratio 1:2) and L-Tartaric Acid:Choline Chloride:Water

(molar ratio 1:2:2) DES through total neutron scattering and EPSR modelling. We investigate

the influence of using either a single enantiomer of Tartaric Acid or the racemic mixture, both

of which are widely available, as well as the influence of the addition of 2 moles of water on

the structure.


69

Solid-liquid equilibrium of eutectic solvents composed by

choline chloride under high pressures.

Fernanda P Pelaquim a, Mariana C. Costa a,*, Irede A. L. Dalmolin b a University of Campinas, School of Chemical Engineering, Campinas, São Paulo, Brazil

b Universidade Tecnológica Federal do Paraná, UTFPR, Francisco Beltrão, Paraná, Brazil

* [email protected]

Keywords: Eutectic solvents, Solid-liquid equilibrium (SLE), high pressure, phase diagrams,

variable-volume view cell.

Greener technology is one of the most important topics to be developed by chemistry, since it

aims to reduce the negative influence of human being in the world, which acts to decrease the

environmental pollution mainly caused by our lifestyle. Deep eutectic solvents (DESs) have

appeared as an alternative to some current aggressive organic solvents [1] and they are receiving

great attention. According to Abbott et al. (2004) [2] DESs are mixtures of amides with

quaternary ammonium salts that had melting point much lower than their pure compounds. This

melting point lowering happens due to formation of a hydrogen bonding complex between a

hydrogen bonding donor (HBD) and a hydrogen bonding acceptor (HBA) at a well-defined

stoichiometric ratio close or equal to the eutectic composition of the mixture. In 2018, Martins

et al. [3] defined that DESs are not new compounds or pseudo-pure compounds, but just

mixtures. So, DES should be a mixture of pure compounds for which the temperature of the

eutectic point is many degrees below the temperature of the eutectic point of ideal liquid

mixture. Otherwise, they should be called just eutectic solvent (ESs). Considering this new

definition and ES uses, it is important to comprehend their phase equilibria at ambient pressure

[4] and also under high pressure. So, this work aimed to determine the solid-liquid equilibrium

of the eutectic solvent composed by choline chloride (1) + ethylene glycol (2) and choline

chloride (1) + 1,3 propanediol (2) at pressures between 60 and 250 bar, 1:2 molar ratio and 4%

water content. The pressure versus temperature diagrams were constructed from experimental

data determined using a high-pressure variable-volume view cell. It was possible to observe a

linearity behavior in both phase diagrams. The increase of pressure implied in a slight

temperature increase, getting around 22 °C, as expected for choline chloride (1) + ethylene

glycol (2).

References:

1. Dai, Y.; van Spronsen, J.; Witkamp, G.J.; Verpoorte, R.; Choi, Y.H. Natural deep

eutectic solvents as new potential media for green technology. Anal. Chim. Acta 2013.

2. Abbott, A.P.; Capper, G.; Davies, D.L.; Rasheed, R.K.; Tambyrajah, V. Novel solvent

properties of choline chloride / urea mixtures. R. Soc. Chem. 2003, 70–71.

3. Martins, M.A.R.; Pinho, S.P.; Coutinho, J.A.P. Insights into the Nature of Eutectic and

Deep Eutectic Mixtures. J. Solution Chem. 2018, 1–21.

4. Crespo, E.A.; Silva, L.P.; Martins, M.A.R.; Bülow, M.; Ferreira, O.; Sadowski, G.;

Held, C.; Pinho, S.P.; Coutinho, J.A.P. The Role of Polyfunctionality in the Formation of

[Ch]Cl-Carboxylic Acid-Based Deep Eutectic Solvents. Ind. Eng. Chem. Res. 2018, 57, 11195–

11209.


70

Solubility, stability and cytotoxic evaluation of different

anti-tuberculosis drugs combined in therapeutic liquid

mixtures

Filipa Santos a, Ana Rita C. Duarte a,*

a LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal

* [email protected]

Keywords: therapeutic liquid mixtures, tuberculosis

Tuberculosis continues to be one of the deathliest infectious diseases worldwide and, in 2019,

the average of deaths was 1.2 million. In spite, of this disease being considerable treatable the

treatment involves a prolonged regimen of various antibiotics, which may cause serious

adverse effects and leading to a low compliance of the treatment by the patient, contributing

for the ineffectiveness of the treatment and emergence of drug resistance. The approaches

used for preventing and treating tuberculosis infection and disease are the same, since their

development at around 50 years ago. Due to that and to the emergence of drug resistance to

the various antibiotics used it is surely needed a breakthrough investigation to find

alternatives able to rapidly reduce the incidence to tuberculosis, mainly in low-burden

countries.

In this work, we use green chemistry approaches such as preparation of therapeutic liquid

mixtures with anti-tuberculosis drugs currently used in therapy for the improvement of their

performance and therefore to reduce the dose administered and incidence of severe adverse

effects. Previously reported therapeutic liquid mixtures (with ethambutol and arginine) were

used, and combined with first-line drugs anti-tuberculosis to evaluate its solubility in

phosphate buffered saline, stability (by NMR and UV-vis), in vitro cytotoxicity and

permeability in human alveolar epithelial cells (A549).

Acknowledgements:

This project has received funding from the European Union’s Horizon 2020 (European

Research Council) under grant agreement No ERC-2016-CoG 725034 and was supported by

the Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES

(UIDB/50006/2020).


71

Deep eutectic systems: new methodologies for toxicity

assessment

Filipe Oliveira a, Inês João Ferreira a, Sara Valente a, Alexandre Paiva a, Mario Diniz a, Ana

Rita C. Duarte a* a LAQV@REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal, *[email protected]

Deep eutectic solvents (DES) are a mixture of two or more components, combining a hydrogen

bond acceptor (HBA) and a hydrogen bond donor (HBD), resulting in a mixture with a melting

point lower than those of its individual components. The deep melting point decrease lead to

the opportunity of having a mixture of solid compounds in the liquid form at room temperature

[1,2]. These systems have been emerging as a sustainable alternative to conventional organic

solvents in a wide range of applications [3].

The toxicology assessment of a system/compound is essential for the protection of human

health and the environment, however, currently there is a lack of studies concerning eutectics

biodegradability and biocompatibility. DES toxicity profile is depended on their concentration,

individual components, and interaction with living organisms. Therefore, the intuit of this work

is to establish innovative methodologies for the toxicity assessment of DES in two different

contexts: i) a pharmacological context where the system’s cytotoxic effect is tested at

concentrations that can be used in the pharmaceutical industry; ii) and also in an environmental

context where the system’s ecotoxicity is tested considering measured environmental

concentrations (MEC). The eutectic-promoted cytotoxic effect was quantitatively assessed via

cell viability assays in a mouse fibroblast continuous cell line (L929) and human keratinocytes

cell line (HaCat), here working as a preliminary safety indicator [4]. The ecotoxicity studies

were performed in two animal models: zebrafish and mussels, simple models recurrently used

in environmental toxicology assessment [5][6]. Furthermore, the activity of different key

enzymes involved in cell protection against toxic compounds, namely in antioxidant pathways,

oxidative stress, and against changes in cell membrane structure, were also considered. The

promising results herein reported revealed DES as systems with tailor-made toxic effect, were

the choice and fine-tuning of its individual components should be carefully considered in a

situation manner. Therefore, the main goal of this work was to establish methodologies for DES

toxicity assessment. Acknowledgments

The research leading to these results has received funding granted through the project Des.solve (ERC

consolidator), ERC-2016-COG 725034. This work was supported by the Associate Laboratory for Green

Chemistry- LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020)

References

1. Abbott AP, Capper G, Davies DL, Rasheed RK, Tambyrajah V. Novel solvent properties of choline

chloride/urea mixtures. Chem Commun. 2003;9(1):70–1.

2. Abbott AP, Boothby D, Capper G, Davies DL, Rasheed RK. Deep Eutectic Solvents formed between

choline chloride and carboxylic acids: Versatile alternatives to ionic liquids. J Am Chem Soc. 2004;126(29):9142–

7.

3. Paiva A, Craveiro R, Aroso I, Martins M, Reis RL, Duarte ARC. Natural deep eutectic solvents - Solvents

for the 21st century. ACS Sustain Chem Eng. 2014;2(5):1063–71.

4. ISO/EN10993-5. Biological Evaluation of Medical Devices - Part 5: Tests for in vitro cytotoxicity. Vol.

5. 2009. p. 1–34.

5. Valavanidis A, Vlachogianni T. Ecotoxicity Test Methods and Ecological Risk Assessment. Aquatic and

Terrestrial Ecotoxicology Tests under the Guidelines of International Organizations. www.chem-tox-ecotox.org.

2015;1:1–29.

6. Rubinstein AL. Zebrafish assays for drug toxicity screening. Vol. 2, Expert Opinion on Drug Metabolism

and Toxicology. Taylor & Francis; 2006. p. 231–40.


72

Understanding the molecular level behaviour of eutectic

systems

Hugo Monteiro1, Alexandre Paiva1 and Ana Rita C. Duarte1 1LAQV-REQUIMTE, Chemistry Department, NOVA SCHOOL OF SCIENCE AND

TECHNOLOGY, 2829-516 Caparica, Portugal

Keywords: DES, MD simulations, Green Chemistry, Force fields

With the needs of modern times, the world seeks new solutions to environmental problems and

science pursues to respond to these needs. Solvents play a very important role in multiple

industries such as the pharmaceutical industry. This industry, in order to decrease the

environmental impact, is replacing traditional solvents (e.g. organic solvents) for more

sustainable green solvents, such as ionic liquids or deep eutectic systems (DES) [1]. DES are

mixtures of compounds with very interesting characteristics. While the raw materials possess

high melting points in their pure state, they however, become liquid at room temperature, after

preparation at a particular composition. They also present low toxicity, low vapor pressure,

good solvation power and the process to obtain them is cheaper when compared to ionic liquids

as no chemical synthesis is required for their production [2,3,4]. DES have been used as a

greener alternative for many applications, such as alternative solvents, polymers production,

biodiesel treatment [2] Nonetheless, the full potential of DES will only be unravelled after the

understanding of the thermodynamic properties of DES. In this sense, molecular dynamics

(MD) have been applied to study DES systems in order to comprehend the behaviour at

molecular level. MD applications allied to experimental data can lead us to a better

understanding of this green system and avoid the application of harsh solvents. In this work

Force field calculations were done density and viscosity studies were applied in order to

compare with experimental data.

References:

1.Gutiérrez. A; Atilhan. M; Apricio. S ; A theoretical study on lidocaine solubility in deep eutectic solvents :

Phys.Chem.Chem.Phys., 2018, 20, 27464

2.García. G; Atilhan. M; Aparicio. S; The impact of charges in force field parameterization for molecular

Dynamics simulations of deep eutectic solvents : Journal of molecular liquids 211 (2015) 506-514

3.Paiva, A; Craveiro, R; Aroso, I. ; Martins. M; Reis, R. Duarte, R ; Natural Deep Eutectic Solvents –Solvents

for the 21st Century : ACS Sustainable Chem. Eng. 2014, 2, 5, 1063-1071

4.Kaur, S. ; Gupta, A. ; Kashyap, K.; Nanoscale Spatial Heterogeneity in Deep Eutectic Solvents : ACS J.Phys.

Chem. B 2016, 120, 6712-6720


73

Citrus-Processing Waste Valorisation: Extraction of Rutin

and Naringin from Orange Peels Using Deep Eutectic

Solvents

Inês S. Cardosoa,*, Armando J. D. Silvestrea, Mara G. Freirea aCICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro,

Campus Universitário de Santiago, 3810-193 Aveiro, Portugal

*[email protected]

Keywords: citrus-processing by-products, citrus peels, extraction, phenolic compounds,

naringin, rutin, deep eutectic solvents

Citrus-processing industries produce large amounts of by-products, among which citrus peels

represent a significant fraction. Given that citrus peel contains phenolic bioactive compounds

of high value (e.g., rutin and naringin) with economic relevance, the development of sustainable

extraction processes to isolate these fractions is a priority to valorise these by-products. Within

the circular economy context, this work intends to valorise orange peels through the isolation

of added-value phenolic compounds using sustainable extraction processes. For this purpose,

aqueous solutions of deep eutectic solvents (DES) have been studied. The results obtained show

that designed DES aqueous solutions are able to increase the solubility of rutin and naringin by

several orders of magnitude. Experimental design of experiments was then applied to optimize

extraction conditions using selected DES. Under the identified optimal conditions, the proposed

process resulted in the efficient extraction of rutin and naringin from orange peels, with

maximum extraction yields of 6.72 and 18.20 mg/g of biomass. This process is a competitive

and more sustainable alternative to replace conventional processes using volatile organic

solvents.


Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when

appropriate co-financed by FEDER under the PT2020 Partnership Agreement. Inês S. Cardoso acknowledges FCT

for the PhD grant SFRH/BD/139801/2018.


74

Deep Eutectic Solvent with Betaine: toxicological studies

towards applications in products for human consumption

Ferreira I.J. a, Paiva A. a, Diniz M.a and Duarte A.R. a* a LAQV@REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal,

* [email protected]

Keywords: Toxicity, Deep Eutectic Solvents, Green Solvents

Deep Eutectic Solvents (DES) are a mixture of two or more components where at least one is a

hydrogen bond acceptor (HBA) and other a hydrogen bond donor (HBD). These combinations

result in a decrease in the melting point of mixture in comparison with the melting point of any

of the individual components. DES appear as a “green alternative” to organic solvents, and

cheaper than ionic liquids. But, at the moment, the number of studies concerning the real

biodegradability and biocompatibility is reduced. It is within this context that this work was

carried out. With the intuit to study the toxicity of a DES and its individual components by

intraperitoneal injection, different concentrations that can be relevant were tested. These studies

were performed with zebrafish, a simple animal model recurrently used in pharmacological and

environmental tests. The preliminary results demonstrated very low toxicity in the

concentrations tested. For instance, up to 1000 µM when the system betaine: glycerol (1:2) and

their individual components were tested in an toxicity context by intraperitoneal injection. The

activity of different enzymes involved in antioxidant pathways, protection towards toxic

compounds, oxidative stress and changes in barrier structure, namely glutathione S-transferase

activity, catalase activity, total antioxidant capacity, lipoperoxidation and glutathione

peroxidase activity were tested and demonstrate the low toxicity of the system tested. The

promising results herein presented show that in fact DES can be in the future the new class of

green solvents, not only used in pharmaceutical industry but also in cosmetic and chemical

engineering processes.

Acknowledgements:

The research leading to these results has received funding granted through the project Des.solve (ERC

consolidator), ERC-2016-COG 725034. This work was supported by the Associate Laboratory for Green

Chemistry- LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020)


75

Fatty acid based eutectic systems to improve solubility and

sustained release of simvastatin

Isabel Teixeira*, João Baixinhob, Alexandre Paivaa, ARC. Duartea, Naiara Fernándezb, Rita

Craveiroa, a LAQV@REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal, b iBET-Instituto de Biologia Experimental e Tecnológica, Food & Health Division, 2781-901

Oeiras, Portugal,

* [email protected]

Keywords: Simvastatin, Fatty acids, Deep eutectic systems, PGSS

Simvastatin is a well-known lipid lowering drug, commonly used to treat hypercholesterolemia,

but that can also have effects in osteogenesis promoting bone regeneration. Although it is

effective, it has very limited water-solubility and is classified as a type II drug according to the

Biopharmaceuticals Classification System (BCS). It is then necessary to find methods to

improve simvastatin solubility and consequent bioavailability, allowing the reduction of drug

dosage, improving drug-patient compliance, and making the process more sustainable. Lipid-

base solvents and drug delivery systems have been reported to increase the solubility of poorly

water-soluble drugs, such as simvastatin, and a recent class of solvents, named deep eutectic

systems (DES), are reported to increase the solubility and bioavailability of several drugs. Fatty

acid-based DES can be obtained and have already been reported for biomedical applications.

In this work, DES based on fatty acids such as capric, lauric, myristic and stearic acids, are

prepared and characterized. Simvastatin solubility in these DES was studied and an increase of

90% was obtained, compared with solubility in water. Additionally, micronization techniques

are proposed to improve simvastatin solubility and bioavailability. A supercritical CO2 (scCO2)

assisted technique was carried out, Particles from Gas Saturated Solutions (PGSS). Operating

conditions such as temperature, pressure, among others, were studied and particle size and

shape, as well as simvastatin loading were optimized. The use of DES and scCO2 technologies

is proved valid for enhancement of simvastatin solubility and for the production of efficient

drug delivery systems.


76

Composition of Hydrophobic Deep Eutectic Solvents

controlling rate of polymerisation in the ATRP of styrene

Jake Hooton a,*, Dr. Antoine Buchard a, Prof. Gareth Price b and Prof. Karen Edler a a Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY,

UK b Khalifa University, Al Saada St, Zone 1, Abu Dhabi, United Arab Emirates

* [email protected]

Keywords: Hydrophobic Deep Eutectic Solvents, Polymerisation, Atom Transfer

Radical Polymerisation, Styrene, Rate Constant, Component Variation, Composition

Variation

The kinetics of Atom Transfer Radical Polymerisation (ATRP) have been examined for the

monomer styrene within a series of “Type V” hydrophobic deep eutectic solvents, composed

of L-menthol and members of the natural aliphatic carboxylic acid family, from chain length

C8 (caprylic acid) to chain length C18 (stearic acid). Each solvent was prepared at its eutectic

composition. The initiation system was based on the Activators Regenerated by Electron

Transfer (ARGET)-ATRP method, using copper(I) bromide, Me6TREN ligand, and tin(II)

ethyl hexanoate reducing agent. The apparent rate constant of propagation was found to be

higher, in a consistent trend, for eutectic mixtures composed of aliphatic carboxylic acids of

longer chain length (Figure 1). Concomitantly, these eutectic mixtures are also composed of

a higher composition of L-menthol. Further experimentation also revealed that the rate

constants increase with L-menthol composition in the mixture, in mixtures prepared from

consistent chemical species (lauric acid and L-menthol). These trends are rationalised through

comparison with a number of different physicochemical properties of the eutectic mixtures,

such as viscosity, surface tension, and solvent polarity, and a discussion of relative molecular

volume and localised concentration of the monomer, and eutectic mixture components.

Figure 1: Variation of the apparent rate

constant of the ATRP of styrene in eutectic

mixtures composed of an aliphatic carboxylic

acid and L-menthol (denoted CX:Menthol

where X is the number of carbon atoms in the

carboxylic acid). Polymerisation conditions

[Styrene] : [EBiB] : [CuBr] : [Me6TREN] :

[Sn(EH)2] = 96 : 1 : 0.096 : 0.48 : 0.96.

Styrene concentration 1.65 mol dm-3.

Reaction temperature 110°C.

10

8

6

4

2

0

6 8 10 12 14 16 18 20

X (Chain Length) in CX:Menthol

k ap

p (3

h)

/ 1

0-5

s-1

mailto:[email protected]


77

Sustainable valorisation of a by-product: Recovery of

polyphenols from out of caliber kiwifruits using deep

eutectic solvents

Jean-Baptiste Chagnoleau1, Nicolas Papaiconomou1*, João A. P. Coutinho2, and Xavier

Fernandez1 1Université Côte d'Azur, CNRS, Institut de Chimie de Nice, UMR 7272, Nice, France.

2CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro,

3810-193 Aveiro, Portugal.

*Corresponding author:

[email protected]

Keywords: Actinidia deliciosa Hayward, hydrophilic deep eutectic solvents, antioxidant

activity, solid−liquid extraction.

Kiwis are fruits with excellent bioactive properties1, but their production generates tons of

wastes every year. In particular, several tons of kiwis are discarded because out of caliber.2 In

this work, a sustainable valorisation of this by-product is proposed by extracting bioactive

compounds using sustainable solvents. Deep eutectic solvents (DES) have recently attracted

considerable attention due to the fact that they are eco-friendly, non-toxic and exhibit low

volatility3. In order to study the influence of DES on the extraction of polyphenols, a screening

of different DES and several conventional solvents was carried out. To that end, solid-liquid

extractions of kiwi peels were performed, and the performance of the extraction solvent was

assessed using a DPPH test. The latter is used worldwide and based on a simple and fast method

which was used to analyse the antioxidant activities of the kiwi peel extracts dissolved in DES4.

Using this strategy, several DES were found to yield extracts with high antioxidant activities

compared to reference systems. Finally, in cases where an extract separated from DES would

be required, a stripping step using liquid-liquid extraction with ethyl acetate was studied.

Acknowledgements:

This work was partly developed within the scope of the project CICECO-Aveiro Institute of Materials,

UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when

appropriate co-financed by FEDER under the PT2020 Partnership Agreement.

(1) Richardson, D. P.; Ansell, J.; Drummond, L. N. The Nutritional and Health Attributes of Kiwifruit: A

Review. Eur. J. Nutr. 2018, 57 (8), 2659–2676.

(2) Nunley, M. From Farm to Fork to Landfill: Food Waste and Consumption in America, 2013.

(3) Llorente, D. R.; Barcala, A. C.; Torrellas, S. Á.; Águeda, V. I.; García, J.; Larriba, M. A Review of the

Use of Eutectic Solvents , Terpenes and Terpenoids in Liquid – Liquid Extraction Processes. Processes 2020, 1–

54.

(4) Foti, M. C. Use and Abuse of the DPPH• Radical. J. Agric. Food Chem. 2015, 63 (40), 8765–8776.


78

Stabilisation of Aromas: Supercritical Carbon Dioxide

Extraction Coupled with Deep Eutectic Solvents

Jelena Vladić a*, Alexandre Paiva a, Ana Rita C. Duarte a a Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal

* [email protected]; [email protected]

Keywords: aroma, supercritical carbon dioxide, deep eutectic solvent

Due to their numerous pharmacological and sensory properties, the significance of natural

aromas has long been recognised. Moreover, their application in different industries is

constantly increasing including the pharmaceutical, cosmetics, beverage, and food industry.

Conventional methods of isolation of these mixtures of volatile compounds are time-consuming

and non-selective. Therefore, these shortcomings have been overcome with the development of

superior extraction approaches. Supercritical carbon dioxide extraction (ScCO2) is an

established green and highly efficient technology for isolation of aromas present in different

natural matrixes. Despite the efficiency of this process, the instability of aromas limits their

application. For these reasons and in addition to defining optimal extraction procedures for the

recovery of aromas, it is necessary to define an optimal procedure that will provide the stability

of aromatic volatile compounds and secure their properties in the long term. Deep eutectic

solvents (DES) are solvents of high absorption capacity in which various natural compounds

have high solubility. Additionally, these alternative solvents are affordable, biodegradable, and

easy for manipulation.

Therefore, the main goal of this study is to develop and optimize a procedure for isolation and

stabilisation of aromas. The extraction of aromas from different natural materials will be

performed using ScCO2. By varying process parameters and analyzing their impact on the

extraction efficacy and chemical composition of the extracts, the most optimal extraction

parameters will be established. The following step will be to stabilise aromas with DES by

dispersing the recovered aromas in DES. To achieve optimal stabilisation, characterization and

optimization of DES systems will be conducted. In addition, the chemical profile of stabilised

aromas will be monitored during storage under different conditions.

Acknowledgements: This project has received funding from the European Union’s Horizon 2020 research and

innovation programme under the Marie Sklodowska-Curie grant agreement No 101003396.


79

Simple and ecofriendly preparation of chin-glucan

complexes from white button mushroom using deep

eutectic solvents

Hireem Kim a, Seulgi Kang a, Ke Li a, Dasom Jung a, Keunbae Park a and Jeongmi Lee a,*

aSchool of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea

* [email protected]

Keywords: Chitin-glucan complex; mushroom; deep eutectic solvent; Agaricus bisporus

Deep eutectic solvents (DESs) have been used in various applications as ecofriendly and safe

solvents. In the present study, we applied DESs to prepare various kinds of chitin-glucan

complexes (CGCs) from Agaricus bisporus, commonly known as white button mushroom. A

conventional chemical method involving the treatment of mushroom with NaOH solution and

ultrasonic irradiation yielded one type of CGC, a residue that is NaOH-insoluble and thus,

called alkali-insoluble matter (AIM). In contrast, each DES yielded two types of CGCs, one

from the DES-insoluble residue (DES_P) and another from the DES-soluble extract (DES_S).

As a result, ten CGCs could be prepared from five different DESs, and they contained varying

chitin-to-glucan ratios that were also different from that of AIM. BU composed of betaine and

urea produced BU_S and BU_P at the highest yields among the ten CGCs, and their protein

and mineral contents were reasonably low. BU_S and BU_P had different acetylation degrees

(77.3% versus 57.3%), however, both degraded at 318 °C and had remarkably low

crystallinity (32.0−37.0%) compared to AIM, commercial chitin, and the reported CGCs.

Different from AIM, the surface of BU_S and BU_P was very porous and rough, and this is

probably because of reduced H-bonds and lowered crystallinity. This study is the first

presentation of a simple and ecofriendly method to prepare CGCs from mushroom, having no

concerns of allergenic proteins included in the chitinous materials.

The current presentation is based on our recent publication in International Journal of

Biological Macromolecules (2021,Vol. 169:122-129).


80

Overcoming the Colorectal Cancer Challenge With

Therapeutic Deep Eutectic Systems Pereira J. a,*, Castro M. a, Oliveira F. a, Duarte A. a

a LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e

Tecnologia,Universidade Nova de Lisboa, Caparica, Portugal

* [email protected]

Keywords: Colorectal cancer, THEDES, NSAID, Natural compounds, Terpenes

Cancer remains a major health problem worldwide, with colorectal cancer (CRC) being the

third most incident.1 Inflammation has been highly associated with cancer development and

maintenance,2 therefore, the reduction of the inflammatory microenvironment represents a

promising therapeutic strategy. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) to

reduce CRC risk has already been described.2

Deep eutectic systems (DES) are based on the combination of different components which

together present a deep decrease in their melting point. These systems are most widely in

compliance with the green chemistry metrics and have low production costs, thus presenting

an alternative to conventional solvents.3 When an active pharmaceutical ingredient is part of a

DES it is designated by therapeutic deep eutectic system (THEDES).3 To evaluate THEDES

potential therapeutic activity, seven new THEDES based on natural occurring molecules with

anticancer properties combined with NSAIDs were prepared: Safranal:Ibuprofen (3:1),

Safranal:Iburofen (4:1), Menthol:Ibuprofen (3:1), Menthol:Ketoprofen (4:1),

Menthol:Flurbirpofen (4:1), Linalool:Ketoprofen (4:1) and Linalool:Flurbiprofen (4:1). The

evaluation of these THEDES physico-chemical properties alongside with the assessment of its

bioavailability and bioactivity, were explored in this work as an integrative approach to

determine their anti-CRC activity. Our first results show that Safranal:Ibuprofen (3:1),

Safranal:Ibuprofen (4:1) and Menthol:Ibuprofen (3:1) present promising therapeutic activity

towards CRC cells due to a selective cytotoxic action towards cancer cells.

Refernces: (1) Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. Global Cancer Statistics 2018:

GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36Cancers in 185 Countries. CA. Cancer J.

Clin. 2018, 68 (6), 394–424.

(2) Terzić, J.; Grivennikov, S.; Karin, E.; Karin, M. Inflammation and Colon Cancer. Gastroenterology 2010, 138

(6), 2101–2114.

(3) Zainal-Abidin, M. H.; Hayyan, M.; Ngoh, G. C.; Wong, W. F.; Looi, C. Y. Emerging Frontiers of Deep Eutectic

Solvents in Drug Discovery and Drug Delivery Systems. J. Control. Release 2019, 316, 168–195.


81

Choline Chloride – based Deep Eutectic Solvents to obtain

phenolics from Rosmarinus officinalis L.

José Pedro Wojeicchowskia,b*, Ana M. Ferreiraa, Caroline Marquesb, Luciana Igarashi-Mafrab,

João A.P.Coutinhoa, Marcos R. Mafrab a CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro

(UA), 3810-193, Aveiro, Portugal. b Department of Chemical Engineering, Federal University of Paraná (UFPR), 81531-990,

Curitiba, Parana, Brazil.

* [email protected]

Keywords: COSMO-RS, rosemary, carnosic acid, and rosmarinic acid

In the last years, deep eutectic solvents (DES) have emerged as an alternative to the hazardous

organic solvents to extract natural bioactive compounds from natural matrices. In this study,

the most common hydrogen bond acceptor, choline chloride ([Ch]Cl), was combined with

different hydrogen bond donors (HBD). Solid-liquid extractions were carried out with these

solvents, at 30°C, 2.5h and 1:20 (solid-liquid ratio), in order to extract antioxidants compounds,

carnosic acid (CA) and rosmarinic acid (RA), from Rosmarinus officinalis L. An in silico

solubility study using the quantum thermodynamic model, Conductor-like Screening Model for

Real Solvents (COSMO-RS), was made. Results indicated good correspondence between

computational and experimental data, as observed by the high correlation (> 0.73) between total

phenolic contents and predicted solubility (log xsolute) of CA and RA, Fig.1. These results reveal

that the higher the solubility of a compound in a solvent, the greater the achieved extraction

efficiency. Chromatographic analyses supported it, once the lowest content of CA and RA, 4.12

and 6.21 mg/g respectively, was found by DES with zinc chloride as HBD. Thus, besides

showing the successful rosemary bioactive compounds extraction using DES, this work also

demonstrated that COSMO-RS is a useful tool for selecting solvents instead of the trial-and-

error methodology.

Fig.1. Relative solubility of carnosic acid ()

and rosmarinic acid () into different hydrated

DES (30 % of water, 30 ºC), and their

phenolic content in mg GAE/g (bars) obtained

by these solvents.

Acknowledgments: This work was developed within the scope of the project CICECO-Aveiro Institute

of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the

FCT/MCTES. J.P. Wojeicchowski acknowledges Coordenação de Aperfeiçoamento de Pessoal de Nível

Superior (CAPES, Brazil) for the scholarship, Finance Code 001.


82

Stability and Crystal Formation in Betaine-Urea-Water

NADES System

Lamya Al Fuhaida, Maria F. Nava-Ocampoa, Szilárd S. Bucsa, Robert Verpoorteb, Young Choib,

Geert J. Witkampa, Andreia S. F. Farinhaa*

a Water Desalination and Reuse Center, King Abdullah University of Science and


*[email protected]

Predicting compound combinations yielding a (NA)DES and its resulting properties is not yet

possible. Similarly, the stability of the obtained liquid cannot be predicted from molecular

considerations. After their preparation at elevated temperatures, we have observed that some

NADES exhibited crystal formation when transferred to room temperature or below. This study

addresses the effect of curing temperature and time on the stability and crystallization of

different molar ratios of betaine-urea-water (BUW) NADES. The samples were characterized

by Fourier-transform infrared spectroscopy and 1D and 2D nuclear magnetic resonance to

unravel the bonding and supramolecular organization, and the crystal structure was resolved by

single-crystal X-ray diffraction. Proton NMR analysis of the crystals’ mother liquor allowed

the extrapolation of the maximum ratios that can form stable BUW NADES. Moreover, to

investigate the role of water and the minimum moisture content that has to be present in the

system, thermogravimetric analysis was performed, and the enthalpies of vaporization were

calculated from isothermal microcalorimetry measurements. Our results revealed that more

extended curing periods at higher temperatures increased the (meta)stability of NADES.

Despite the variation in the crystals’ macro-morphology, all unstable BUW NADES created

hydrogen-bonded orthorhombic betaine hydrate crystals. Additionally, water loss upon drying

showed two different kinetics, an initial phase characterized by a fast decline of mass, followed

by a longer, slower one. This pattern indicates that part of the water molecules is trapped within

the supramolecular network through hydrogen bonding, whereas the rest is less tightly bound.


83

NADES-based formulations of Spirulina enriched in free

fatty acids: preparation, characterization and skin-impact

Laura Wils a,*, Charlotte Leman-Loubière a, b , Nicolas Bellin c, Barbara Clément-Larosière b,

Charles Bodet c and Leslie Boudesocque-Delaye a

a EA 7502 SIMBA, Faculté de Pharmacie, Université de Tours, 31 avenue Monge,

37200 Tours, France b Aqua Eco Culture, 7 rue d’Armor Maroué,

22403 Lamballe, France c EA 4331 LITEC, Pole Biologie Santé - Bât. B38 1 rue Georges Bonnet BP 633

86022 Poitiers Cedex

* [email protected]

Keywords: NADES, Spirulina, cytotoxicity, cutaneous microbiota, keratinocyte, free fatty

acids

Cosmetic industry was intensively involved in the green transition, especially by the

development of sustainable biocosmetic ingredient (renewable raw materials, sustainable

process). In this context, the use of microalgae as a source of ingredients has focused the interest

of cosmetic industry for some years now, as they represent a huge potential for innovation in

the field. In fact microalgae is a renewable resource of various biomolecules of cosmetic

interest: phycobiliproteins, polyunsaturated fatty acids (PUFA), and carotenoids.

Free fatty acids (FFA) as anti-inflammatory, microbiota regulator and moisturizing agents are

new cosmetic targets. FFA are commonly extracted by organic solvent (chloroform, hexane)

incompatible with a topical use and required purification and evaporation additional steps. In

this context, Natural Deep Eutectic Solvents (NADES) represent an exciting opportunity to

overcome current processes by developing a new green approach compatible with a topical use.

The first part of the work was focused on NADES development for FFA microalgal extraction,

using Arthrospira platensis (Spirulina) as a model. Resulting NADES formulations were

characterized by LC-MS, HPLC and spectrophotometric assays. A first screening of the

NADES was carried out on their selectivity for pigment (chlorophyll, carotenoid,

phycobiliprotein) and FFA. Six of them were intensified before biological evaluation. Then,

selected NADES and the resulting extracts were evaluated towards skin inflammation and

microbiota. The cytotoxicity of the solvents and associated extracts was evaluated on human

keratinocytes and on four bacterial strains (pathogens or commensals): Staphylococcus aureus,

Staphylococcus epidermidis, Cutibacterium acnes and Corynebacterium xerosis individually.

Our data demonstrated the good harmlessness of NADES and formulation on human

keratinocytes and highlighted the huge potential of some of them towards microbiota

regulation.


84

Use of COSMO-RS for design of THEDES

as improved formulation of chiral drug

Kristina Radoševića, Ivana Radojčić Redovnikovića,*, Manuela Panića, Mia Radovića, Marina

Cvjetko Bubaloa, Jasmina Lapića, Senka Djakovića, Marko Rogošićb a Faculty of food technology and biotechnology, Pierottijeva 6, 10 000 Zagreb, Croatia

b Faculty of Chemical Engineering and Technology, Marulićev trg 19, 10 000 Zagreb, Croatia

* [email protected]

Keywords: COSMO-RS, natural deep eutectic solvents, bioavailability, permeability,

therapeutic deep eutectic solvents

Designing new, environmentally-friendly, and tuneable solvents have been dramatically

expanding in popularity in order to overcome the flaws of organic solvents from technological,

environmental and economic aspects. Though it is sometimes relatively easy to find an

appropriate natural deep eutectic solvent (NADES) for certain process and application, this is

occasionally ungrateful procedure, meaning that sometimes is difficult to predict which

mixtures and in which molar ratios will originate as a NADES and also which solvent properties

will be exerted. Therefore, the composition of NADES and their physical, thermal, chemical or

biological properties should be characterized on case-by-case scenario. Abundance of possible

NADES formulations, especially when possible addition of certain amount of water is taken

into account, makes it impossible to prepare and characterize all of them, pointing out the need

for development of predictive NADES structure-activity mathematical models. Approaches

used so far for screening appropriate/ideal NADES (out of enormous pool of structural

possibilities) have been governed by time consuming empirical methods, while systematic

investigation in NADES structure-activity relationship, as a backbone for rational design of

these solvents, is still lacking. Current literature suggests COSMO-RS, software that can predict

thermodynamic properties and phase equilibrium which would help in designing the best

possible solvent for a certain application. COSMO-RS can design new solvent structures with

tailored properties and thus the trial-and-error method of NADES preparation can be avoided.

The aim of this work is to rationally design NADES for solubilisation of poorly-water soluble

active pharmaceutical ingredients (APIs) as well as the preparation of therapeutic deep eutectic

solvents (THEDES). It is expected that such approach will enable better solubility, permeability

and bioavailability of the APIs, with probably better stability of active compound with

preserved or maybe even enhanced activity.

Acknowledgements: The work was supported by the Croatian Science Foundation (Grant No. 7712)


85

Design and application of novel dihydrogen

phosphate cholinium-based DES

M.S. Álvareza,*, F.J. Deivea,, M.A. Longoa,, A. Rodrígueza a Department of Chemical Engineering, Campus Lagoas-Marcosende 36310, Vigo

Pontevedra, Spain

*E-mail: [email protected]

Keywords: Dihydrogen phosphate cholinium-based DES, synthesis, lipases, stability.

Deep eutectic solvents (DES) are presented as promising green and sustainable solvents with

numerous applications in biotechnology, environmental remediation, drug bioavailability or

chemical processes [1, 2]. Since the eutectic mixture named reline was reported by Abbot [3]

as a new class of solvent, choline chloride salt has been selected as a model hydrogen

bond acceptor (HBA) and combined with several hydrogen bond donor (HBD) promoting an

extensive library of tunable solvents. Among other fields, biocatalysis is one of the

prominent niches where these new solvents have arisen interest, especially in those catalytic

reactions where partial or total absence of water is essential [4].

In this study, we propose the quaternary ammonium salt, choline dihydrogen phosphate as HBA

combined with ethylene glycol (ChDHP:E (1:2)) and glycerol (ChDHP:G (1:2) or both

(ChDHP:E:G (1:1:1)) as HBD for evaluating the stability of the commercial lipase B

from Candida antarctica. After all DES were prepared following the literature methods,

density, viscosity, refractive index, NMR and DSC measurements were performed in order to

carry out a comprehensive physicochemical and structural characterization. Further, the effect

of DES in lipase stability was evaluated in terms of residual lipase activity after

thermal incubation for 1 hour at 40ºC in pure DES and in 2 M solutions. The results have shown

that the residual activity after incubation in pure DES and 2 M solutions was over 60% and

90%, respectively, observing a clear trend in the order (ChDHP:E> ChDHP:G> ChDHP:E:G).

In conclusion, these new DES could be an alternative as co-solvents in biocatalytic

reactions like biodiesel production.

References:

[1] A. Fernández, F.J. Deive, A. Rodríguez, M.S. Álvarez. J. Mol. Liq. 2020, 305, 112824- 112831.

[2] C.J. Clarke, W.C. Ti, O. Levers, A. Brohl, et al. Chem. Rev. 2018, 118, 747–800. [3] A.P. Abbott, G.

Capper, D.L. Davies, R. Rasheed, et al. Chem. Commun. 2003, 1, 70-71. [4] M. Pätzold, S. Siebenhaller, S.

Kara, A. Liese, et al. Trends Biotechnol 2019, 37, 943-959.

Acknowledgements: The authors thank Xunta de Galicia and Spanish Ministry of Science, Innovation and

Universities for funding through a postdoctoral grant (ED481D-2019/017) and the project RTI2018-094702-B-

I00.


86

Picolinium-based Deep Eutectic Systems (DESs) in the

Lubrication of Silicon Surfaces

Mariana Donatoa,b, Mónica Antunesa,c, Rogério Colaçoc, Luís C. Branco*b, Benilde Saramago*a a Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av.

Rovisco Pais, 1049-001 Lisboa, Portugal b LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, Campus da Caparica, 2829-516 Caparica, Portugal c IDMEC-Instituto de Engenharia Mecânica, Departamento de Engenharia Mecânica, Instituto

Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

* Corresponding authors: [email protected]; [email protected]

Keywords: deep eutectic systems, lubricants, silicon, friction coefficient.

Deep eutectic systems (DESs) have recently been proposed as “green” alternatives to mineral

oils and ionic liquids (ILs) in the lubrication of several surfaces.[1,2] DESs have similar physical

properties to ILs but have the advantage of being cheaper and easier to prepare. In a previous

work, we have synthesized sulphur-containing DESs that showed very interesting lubrication

properties.[3] Herein, new picolinium salts-based DESs were prepared and tested in the

lubrication of silicon surfaces which are relevant for nano/microelectromechanical systems

(NEMS/MEMS). All prepared DESs were characterized in terms of their water content,

viscosity, wettability and tribological properties. The friction coefficients were measured using

steel spheres against Si surfaces. The most promissory DESs showed a good tribological

performance, both in terms of friction and wear reduction comparing to commercial lubricants.

Figure 1. Schematic representation of the (nano)tribometer system and the interactions between

the DESs and the Si surface.

Acknowledgements

The authors thank the financial support by FCT – MCTES (UID/QUI/00100/2013, UID/QUI/50006/2013 and

IF/0041/2013/CP1161/CT00, SFRH/BD/140079/2018) and Solchemar company.

References

[1] M. T. Donato, R. Colaço, L. C. Branco, B. Saramago, J. Mol. Liq. 2021.

[2] A. Somers, P. Howlett, D. MacFarlane, M. Forsyth, Lubricants 2013, 1, 3–21.

[3] M. Antunes, M. T. Donato, V. Paz, F. Caetano, L. Santos, R. Colaço, L. C. Branco, B. Saramago,

Tribol. Lett. 2020, 68, 1–14.


87

NADES-assisted valorisation of orange peel waste by the

integrated biorefinery approach

Manuela Panića, Martina Andlara, Marina Tišmab, Tonči Rezića, Darijo Šibalicb, Marina

Cvjetko Bubaloa*, Ivana Radojčić Redovnikovića

aFaculty of Food Technology and Biotechnology, University of Zagreb, Pierotijeva 2, 10000

Zagreb, Croatia bJosip Juraj Strossmayer University of Osijek, Faculty of Food Technology Osijek, Franje

Kuhača 18, Osijek HR-31000, Croatia

* [email protected]

Keywords: Biorefinery, D-limonene, Natural deep eutectic solvents, Orange peel waste,

Pectin methylestrase, Polyphenols, (R)-1-phenylethanol, SWOT analysis

Orange peel waste obtained from orange juice and canned food production present one of the

most abounded wastes from the food industry. Yearly 70 Mt of the oranges is produced

worldwide among which the peel comprises about 40-50% of the total orange weight as a

leftover which needs to be disposed of as waste. Valorisation of orange peel waste by following

the biorefinery concept is usually carried out via several platforms: (1) direct application as

animal feed and fertilizer; (2) the use as a substrate for the production of biofuels, proteins,

industrially valuable enzymes, and other biotechnological products (e.g. citric and succinic

acid); (3) extraction of bioactive compounds (e.g. essential oils, and organic acids), pectin, and

enzymes (e.g. pectin methylesterase). Natural deep eutectic solvents (NADESs) – assisted

valorisation of orange peel waste fully fits the green biorefinery concept since these solvents

are of low cost and are prepared from natural raw materials with 100% atom economy.

This research investigates the use of seven NADESs for valorisation of orange peel waste, with

the final goal to propose a unique NADES for integrated biorefinery. Initial screening of

NADESs revealed the excellent ability of cholinium-based NADES with ethylene glycol as

hydrogen bond donor (ChEg50) to serve as a medium for orange peel-catalysed kinetic

resolution (hydrolysis) of (R,S)-1-phenylethyl acetate with high enantioselectivity, as well as

it’s stabilizing effect on the hydrolytic enzymes. The ChEg50 also showed a satisfactory

capacity to extract D-limonene, and excellent capacity to extract polyphenols, and proteins from

the peel. Based on the obtained results, the integrated biorefinery of orange peel waste using

ChEg50 in a multistep process was performed. Firstly, enantioselective kinetic resolution was

performed (step I; ee = 83.2%, X = 35%), followed by isolation of the product 1-phenylethanol

(step II; h = 82.2%) and extraction of polyphenols (step III; h = 86.8%) from impoverished

medium. Finally, the residual orange peel was analysed for sugar and lignin content, and results

revealed the potential of waste peel for the anaerobic co-digestion process. The main

bottlenecks and futures perspective of NADES-assisted integrated biorefinery of orange peel

waste were outlined through SWOT analysis

Acknowledgements: The work was supported by the Croatian Science Foundation (Grant No. 7712 and 9550)


88

Synthesis of PLLA/PCL Blends with Tunable Properties

Obtained Via Ring Opening Polymerization of Eutectic

Mixtures Composed of LLA y ε-CL

Castillo-Santillan M.a, Perez-Garcia M. G.b, Martinez-Richa A.b, Torres-Lubian J.R.b, Mota-

Morales J.D.a,*.

[email protected], [email protected], [email protected],

[email protected], [email protected],*.

Keywords: Blend PLLA/PCL, DES monomers, Biodegradable polyesters.

PCL and PLLA are among the most common biocompatible and biodegradable polyesters used

in areas such as packaging and 3D printing. Replacing the great quantities of volatile organic

solvents (VOCs) and organometallic compounds normally used in the process of ROP of ε-

caprolactone (CL) and L-lactide (L-LA) has been challenging.

It has been reported that the ROP of DESs composed of L-LA and CL (3:7 molar ratio,

respectively) proceed at low temperature (37ºC) with the use of organocatalysts and in

solventless conditions with full conversions, along with an unusual composition consisting of

a blend of homopolymers. (1,2)

Together with the absence of volatile organic solvents and metallic catalysts, controlling the

final polyesters' properties, such as mechanical properties and their profile degradation will

open the path for their use in biomedical and related areas. These properties depend upon

various parameters such as molecular weight, polymer architecture, and polymers’ crystallinity.

In this work, the ROP of DESs composed of L-LA and CL was studied at various temperatures

below and above the melting point of PCL. A blend of homopolymers were obtained composed

of PLLA and PCL. It is noteworthy that practically PCL's molecular weight was increased in

ca 35% of the final blend, and even open the possibility to modify the crystallinity in these final

polyesters.

References:

1. Perez-García M., et al., ACS Appl. Mater. Interfaces, 2016, 8, 16939-16949.

2. Coulembier O., et al., Chem. Sci., 2012, 3, 723.


89

Application of low-temperature eutectic solvents in the

extraction of ellagitannins and phenolic acids from

Alchemilla vulgaris

Martina Jakovljević and Maja Molnar,

Faculty of Food Technology Osijek, Josip Juraj Strossmayer University of Osijek, Franje

Kuhača 20, 31000 Osijek, Croatia,

* [email protected]

Keywords: deep eutectic solvents, extraction, ellagitannins, optimization, RSM

Due to the growing use of bioactive components in the food and in the pharmaceutical industry,

rapid development of various methods for their extraction and separation is required. In the last

few years, deep eutectic solvents (DESs), composed of a hydrogen bond acceptor (HBA) and

hydrogen bond donor (HBD) components, stand out as an appropriate substitution to

conventional solvents due to their properties, with emphasis on non-toxicity, thermal stability

and biodegradability, with easy preparation and low price of components. Alchemilla vulgaris L. is a plant that is often used in folk medicine as it possesses numerous

health-promoting benefits due to its specific chemical composition with emphasis on phenolic

acids and elagitannins. The most important components with antioxidant activity in sage are

phenolic acids, such as gallic and ellagic acid as well as elagitannins which can be extracted by

various extraction techniques, most commonly solid-liquid extraction.

The aim of this paper was to select the most suitable choline chloride based deep eutectic

solvent for the extraction of gallic and ellagic acid as well as elagitannins from lady's mantle

(Alchemilla vulgaris L.) and then optimize extraction conditions for extraction with stirring and

heating, ultrasound-assisted extraction and mechanoextraction. Seventeen different choline

chloride-based DESs with different volumes of water (10%, 30%, and 50% (v/v)) were used for

the extraction at different temperatures (30, 50, and 70 °C) to investigate the influence on this

extraction parameters on yield of desired components. The results obtained were compared with

the results obtained by extraction with conventional solvents. Gallic and ellagic acid content

was obtained by high-performance liquid chromatography with diode-array detector (HPLC-

DAD) and total ellagitannins were determined spectrophotometrically in the obtained extracts.

Screening revealed that among 17 different DESs, the most suitable solvent is choline chloride:

urea (1:2) and the most suitable extraction technique is extraction with stirring and heating.

According to the results, the prepared solvents prove to be a good substitute for organic solvents

in the extraction of bioactive components from lady's mantle plant.


90

A comprehensive study of CO2 absorption and desorption

by choline chloride levulinic acid-based deep eutectic

solvents

Mohaned Aboshatta ,Vitor Magueijo

Department of Chemical and Process Engineering, University of Strathclyde, Glasgow,

UK

[email protected]

Keywords: Deep eutectic solvents, Choline Chloride, Levulinic Acid, CO2 Absorption, DESs

Regeneration, Carbon Capture, Green Sorbent

Over the last six decades, the concentration of

CO2 in the atmosphere has increased

dramatically, reaching a value of 414 ppm in

January 2021. Amine absorption is currently

the most used and established method for CO2

capture; however, it has environmental

shortcomings and is energy intensive. Deep

eutectic solvents (DESs) are among the most

favourable alternatives to overcome

conventional amines for CO2 capture. DESs are

greener and more benign solvents for CO2

capture than ionic liquids due to their

biodegradability, nontoxicity, and low prices.

In this work, the solubility of CO2 in choline

chloride/levulinic acid-based deep eutectic

solvents (ChCl: LvAc DESs) was measured at

different temperatures, pressures and stirring speeds using a vapour liquid equilibrium rig.

DESs regeneration (CO2 desorption) was performed using a heat treatment method. FTIR

was used to verify the absorption and desorption of CO2 by ChCl: LvAc DESs at different

temperatures. The molar ratios of ChCl: LvAc were selected as (1:2) and (1:3) with different

water contents of 0%, 2.5% and 5%. Henry’s constants for CO2−DESs have been calculated

with values ranging between 4.6 to 14.2 MPa under these conditions. Thermodynamic

properties such as enthalpy, entropy and standard Gibbs free energy changes of CO2

dissolution were calculated from the solubility data correlations. Results showed that the

solubility of CO2 increases with increasing water content, pressure, stirring speed and molar

ratio of the HBD and decreases with increasing temperature. Statistical analysis of results

revealed significant second and third orders interactions among input variables along with

the optimal operating conditions these give the highest CO2 absorption by ChCl: LvAc

DESs. DESs regeneration was performed at different temperatures, the optimal regeneration

temperature of these compositions is estimated to be 353 K. In this work, DESs exhibited

good recyclability as samples have lost only 0.48% of their initial weight after five

consecutive cycles of CO2 absorption at 25 °C and desorption at 80 °C. Finally, ChCl: LvAc

DESs showed high selectivity towards CO2 over N2 with up to 5.63 at 50% mole CO2 and 25 °C which makes ChCl: LvAc DESs more viable for CO2 absorption processes.


91

Extraction of ellagic acid from defatted raspberry seeds

using NADES

Nemanja Teslića,*, Boško Marića, Branimir Pavlićb, Filipa Santosc, Filipe Oliveirac, Nadiia

Khakimovaa, Alena Stupara, Milica Pojića, Anamarija Mandića, Aleksandra Cvetanovićb, Ana

Rita C. Duartec, Aleksandra Mišana a Institute of Food Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad,

Serbia b Faculty of Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad, Serbia

c LAQV, REQUIMTE, Departamento de Química Nova School of Science and Technology,

2829-516 Caparica, Portugal

*[email protected]

Keywords: NADES, raspberry seed, ellagic acid, hydrolysis, extraction

Ellagic acid and its metabolites have several health beneficial effects due to their antioxidative,

hepatoprotective, antimicrobial, antiproliferative activities etc. Most of the ellagic acid in

raspberry seeds is present in form of ellagitannins which have low bioavailability. Therefore,

ellagic acid has to be hydrolysed from ellagitannins. Acid hydrolysis often requires use of

strong mineral acids which are hazardous for human health. Natural Deep Eutectic Systems

(NADES) composed of organic acids (citric, malic, lactic and tartaric acid) as hydrogen-bond

donors and betaine or sugars (fructose and glucose) as hydrogen-bond acceptors could serve as

alternative hydrolysis media which are edible and nontoxic for human health. Ten different

combinations of NADES where made and used for hydrolyzation and extraction of ellagic acid

from defatted raspberry seeds. In order to compare efficiency of the process, ellagic acid was

also recovered from raspberry seeds with aqueous ethanol (80% w/w) and 2M HCl in methanol.

Obtained extracts were analysed in terms of total polyphenol content (TPC), antioxidant activity

(AOA) measured with DPPH assay and ellagic acid content (EAC) determined by HPLC. All

NADES exhibited higher TPC, AOA and EAC comparing to aqueous ethanol extract. NADES

had significantly lower EAC comparing to 2M HCl in methanol extract, however, usage of

NADES allows us to produce non-hazardous and ready-to-use-extracts which could further be

used in food and cosmetic industry.

Acknowledgment/Funding

Authors would like to thank the Ministry of education, science and technological development

of the Republic of Serbia, Grant No. 451-03-9/2021-14/ 200222; the Science Fund of the

Republic of Serbia, PROMIS, Grant No. 6060592, DEStiny; and the European Union, Horizon

2020 (European Research Council), Grant no ERC-2016-CoG 72503 for the funding.


92

Phloroglucinol Solubility in Aqueous Mixtures Of Deep

Eutectic Solvents and water: Measurements And PC-

SAFT Modeling

Nicolás Gajardo-Parra a, Bruno Sepulveda-Orellanab, Hoang T. Do a, José Matías Garrido,c José

R. Pérez-Correa,b Gabriele Sadowski a, Roberto I. Canalesb and Christoph Held a,* a Laboratory of Thermodynamics, Department of Biochemical and Chemical

Engineering,Technische Universität Dortmund, Emil-Figge-Str. 70, 44227 Dortmund,

Germany, b Departamento de Ingeniería Química y Bioprocesos, Pontificia Universidad Católica de

Chile, Avenida Vicuña Mackenna 4860, Macul, Santiago 7820244, Chile c Departamento de Ingeniería Química, Universidad de Concepción, Concepción 4070386,

Chile

* E-mail: [email protected]

Keywords: Deep eutectic solvents, Phloroglucinol, PC-SAFT, Solubility.

Phlorotannins are phenolic compounds recognized as an essential source of antioxidants in

brown algae. They are mainly present in the seaweed cell-walls and represent between 5 and

30% of the algae dry weight. Phloroglucinol is the basic unit from which the phlorotannins

polymerize; thus, its thermodynamic behavior is essential for designing the extraction of this

solute. Deep eutectic solvents (DES) are emerging as extracting solvents in operations that

involve the recovery of natural compounds. DES are advantageous due to their

biodegradability, easy preparation, and adaptability. Several authors have studied the DES

capacity to enhance the extraction yields; however, aqueous mixtures of DES are usually

needed to reduce the viscosity of the extracting solution. In this work, the solubility of

phloroglucinol is measured in pure water; aqueous solutions of different hydrogen bond donors

as ethylene glycol, 1,3-propanediol, and glycerol; and aqueous mixtures of deep eutectic

solvents using choline chloride as the hydrogen bond acceptor, and ethylene glycol, 1,3-

propanediol, and glycerol as the hydrogen bond donors. All the measurements were performed

from 293.15 K to 313.15 K at different water concentrations at 101.3 kPa. As expected,

solubility increases with temperature and decreases with the increasing amount of water in the

mixture. The results show that the aqueous mixtures of DES perform better than the aqueous

solutions of pure hydrogen bond donors for all the temperatures and water concentrations. On

the other hand, the highest solubility was obtained in the ethylene glycol-based DES, followed

by 1,3 propanediol and glycerol, which suggests the importance of the molecular structure and

interactions on the solubility of phloroglucinol. Powder X-ray diffraction was measured for the

non-dissolved phloroglucinol after the equilibrium showing that the compound is dihydrated,

changing the structure from the pure crystal. All the solid-liquid equilibrium results were

accurately modeled with PC-SAFT using the solubility product approach for dihydrates.


93

The Influence of Urea Derivatives on Nonideal

Mixing Behavior of Choline-based Deep Eutectic

Solvents

Omid Shayestehpour a, Stefan Zahn a,* a Leibniz Institute of Surface Engineering, Permoserstraße 15, 04318 Leipzig,

Germany * [email protected]

Omid Shayestehpour, Stefan Zahn

Keywords: molecular dynamics simulations, physicochemical

properties,activity coefficients, computational studies

Recently, experimental activity coefficients for homologous DESs based on choline chloride

and urea were reported by Silva et al. [1] It was highlighted that urea is mainly responsible

for negative deviations from ideality while choline chloride shows overall small deviations

from ideal mixing behavior. Motivated by this seminal study, we have carried out

molecular dynamics simulations to identify the molecular impact of the urea derivative on the

liquid structure of these mixtures.

We observed a strong correlation between the experimentally obtained activity coefficients and

coordination numbers of the HBD sites around chloride anion (Fig. 1) [2]. Furthermore, the

interaction of the oxygen atom of urea with the cationic core facilitates displacement of the

chloride anion from the cationic center toward its hydroxyl group. The substitution of hydrogen

atoms by methyl groups forces the nonpolar alkyl chains to interact with the cationic center.

Additionally, indications for formation of nonpolar domains within the liquid and, thus,

nanoscale segregation is visible as soon as one hydrogen atom of urea is replaced by an alkyl

group.

Fig. 1 Plot of the activity coefficients of choline chloride in mixture with a series of urea derivatives, versus the number

of hydrogen bond donor sites close to the chloride anion. urea (U), thiourea (TU), 1-methylurea (MU), 1,3-

dimethylurea (13MU), 1,1-dimethylurea (11MU).

[1] Silva, L. P. et al., Phys. Chem. Chem. Phys. 2019, 21, 18278. [2]

Shayestehpour, O. and Zahn, S., J. Phys. Chem. B 2020, 124, 35, 7586.


94

Natural Deep Eutectic Solvents as sustainable solvent for

Suzuki-Miyaura cross-coupling reactions applied to

imidazo-fused heterocycles

Pierre-Olivier Delayea*, Mélanie Pénichon, Leslie Boudesocque-Delaye, Cécile Enguehard-

Gueiffier a University of Tours, EA 7502 SIMBA, Faculty of Pharmacy, 31

Avenue Monge, Tours, France. * [email protected]

Keywords: deep eutectic solvent, imidazopyridine, Suzuki–Miyaura coupling, sustainable

chemistry

Herein, we present the first Suzuki–Miyaura cross-coupling in a sustainable natural deep

eutectic solvent (NaDES) applied to biologically relevant imidazo-fused scaffolds imidazo[1,2-

a]pyridine and imidazo[1,2-b]pyridazine. The choline chloride/glycerol (1:2, mol/mol) NaDES

allowed the functionalisation of diverse positions on the heterocycles with various boronic

acids, by using 2.5 mol% of readily available Pd(OAc)2. Notably, the catalytic system proceeds

without any ligands or additives, without protection from the atmosphere. System recycling has

been carried out up to five times.

P.-O. Delaye et al, SynOpen 2018, 2, 306–311.


95

Density predictions of DESs by proposing novel group

contribution and atomic contribution models

Reza Haghbakhsh a,b, Sona Raeissi b, Ana Rita C. Duarte a,*

a LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e

Tecnologia,Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. b School of Chemical and Petroleum Engineering, Shiraz University, Mollasadra Ave., Shiraz

71348-51154, Iran.

* [email protected]

Keywords: DES; green solvent; physical property; modelling; density.

The necessity of taking green chemistry from the labs and computers into the industries is

urgent. The Deep Eutectic Solvents (DESs) are a promising family of green solvents that

possess the desired characteristics of liquids and solids simultaneously. In addition, they have

the potential to be designed or engineered to have the most adequate characteristics for the

application in mind. However, because they are novel, global density estimation models are

not available without requiring other DES properties as their input. This is limiting when one

requires screening for feasibility studies in DESs, especially since a large number of DESs will

be proposed in the future. This study presents, for the first time, a group contribution (GC)

model for densities of DESs. For even greater simplicity, an atomic contribution (AC) model

is also proposed. Both of these models are developed using the most up-to-date databank,

consisting of different types of DESs. The approach is to decompose the molecular structure

into a number of simple predefined groups or atoms. The resulting errors in densities were less

than 3% for both the GC and AC models. Since for a designer solvent, the predictive capability

is of significant importance, the errors of predictions were also checked and shown to be of

high reliability. In this manner, very simple, global, and highly accurate models are proposed

for DESs that do not require any physical property information. This will allow them to be used

as useful predictive models for novel types of green solvents with high potentials in green

technology.


96

Experimental investigation of viscosities for the

mixtures of Ethaline + methanol and Ethaline + ethanol

Reza Haghbakhsh a,b, Ana Rita C. Duarte a, Sona Raeissi b,* a LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e

Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. b School of Chemical and Petroleum Engineering, Shiraz University, Mollasadra Ave.,

Shiraz 71348-51154, Iran.

* [email protected]

Keywords: DES, Ethaline, Methanol, Ethanol, Viscosity, Experiment

Scientists and researchers are continually working on proposing green solvents as

alternatives to conventional solvents in order to minimize environmental pollution of the

chemical industries. This will also minimize health concerns for those whose work

environments involve toxic organic solvents. A new category of solvents, the Deep Eutectic

Solvents (DESs), have recently attracted researchers due to their unique physical and chemical

properties, including low volatility, nontoxicity, inflammability, ease of synthesis, and

biodegradability. However, since DESs are still rather new, their properties are mostly not yet

investigated. Viscosity is among the most important properties for a solvent, as it is required

for transport calculations (including mass, heat, or momentum transfer), as well as in

thermodynamic modelling. Industrial simulations also require information on viscosities. In

addition to pure DESs, the viscosities of DES mixtures with different substances must also be

known. Only a limited number of studies on the viscosities of DES mixtures are available in

literature, which themselves are mostly devoted to only aqueous mixture of DESs.

In this work, the dynamic viscosities of mixtures of Ethaline (1 choline chloride + 2

ethylene glycol) with methanol and ethanol are investigated experimentally. This deep eutectic

solvent is one the most commonly researched DESs in the literature. The novel experimental

viscosity data for Ethaline + methanol or ethanol cover the full composition range within a

temperature range of 283.15 to 333.15 K at atmospheric pressure.


97

Esterification of rac-menthol in Deep Eutectic

Systems Using Immobilized CRL.

Rita Craveiro a,*, Tânia Neto a, Ana Rita C. Duarte a, Alexandre Paiva a a

LAQV@REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia,

Universidade Nova de Lisboa, 2829-516 Caparica, Portugal,

* [email protected]

Secondary alcohols, such as rac-menthol have an undeniable importance in pharmaceutical

or food industries, given its therapeutic properties, characteristic flavor and aroma. Considering

rac-menthol, only the (-)-menthol presents the desired and valuable properties, so a

separation strategy is need for its resolution. Enzymatic kinetic resolution has proved as an

efficient strategy, as for example carrying out an esterification of rac-menthol, catalyzed by an

enzyme such as a lipase. This type of reactions is usually carried out in organic solvents, but

the use of deep eutectic systems (DES) as reaction medium has only recently began to be

explored, presenting several advantages. The use of DES, which are composed by the reaction

substrates, rac-menthol and a fatty acid (lauric acid) has been proposed and allows the

production of the menthyl ester of interest, allowing its posterior separation. In this work, rac-

menthol (M) and lauric acid (LA) DES was used simultaneously as reaction substrates and

reaction solvent. The esterification reaction was catalyzed by Candida Rugosa lipase producing

menthyl laurate (ML), and it was explored the effect of immobilizing the enzyme onto solid

supports to allow its reutilization. Three supports were used, porous acrylic resins XAD16N

and XAD7HP, as well as siliceous porous material Celite 577 fine, yielding an immobilization

efficiency >98%. Different amounts of CRL (13 and 25 mg/mL) were immobilized in the

supports. Celite 577 fine, loaded with 25 mg/mL of CRL, is the support that results in higher

specific activity of CRL, as well as higher ML yield. The effect of water activity was also

evaluated, and when the supported enzyme and DES were incubated in aw between 0.3-0.5.

reaction efficiency was higher. Enzyme reutilization was also evaluated and proved possible.

These results show that enzymatic immobilization is useful for rac-menthol esterification in

DES, and it envisages it is useful for the design of enzymatic packed-bed reactors, allowing this

reaction to occur continuously.

Acknowledgements: The research leading to these results has received funding from the European Union

Horizon 2020 Program under the agreement number ERC-2016-CoG 725034 (ERC Consolidator Grant

Des.solve). This work was supported also by the Associate Laboratory for Green Chemistry-LAQV which is

financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007265). A. Paiva

acknowledges the financial support from project IF/01146/2015 and CryoDES, PTDC/EQU-EQU/29851/2017.


98

Exploring the use of eutectic solvents in the extraction of

proanthocyanidins from by-products

Rodrigo T. Neto a,*, Sónia A. O. Santos a, Joana Oliveira b and Armando J. D. Silvestre a a CICECO - Aveiro Institute of Materials, Chemistry Department, University of Aveiro,

Campus de Santiago, 3810-193 Aveiro, Portugal, b REQUIMTE - Laboratório Associado para a Química Verde, Departamento de Química e

Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687,

4169-007 Porto, Portugal

* [email protected]

Keywords: Eutectic solvent, proanthocyanidin, microwave, degree of polymerization,

galloylation percentage

Proanthocyanidins, or condensed tannins, are natural polymers composed of catechin units and

its derivatives. These components have been increasingly used in the production of leather,

wood agglomerates and wine, and therefore, their global demand has also increased.

Proanthocyanidins rich extracts are generally obtained with pressurized hot aqueous sulfite

solution using as raw material dedicated crops such as quebracho or mimosa. This method has

low specificity and yield, yet with high cost, which limits their industrial application.

Consequently, the development of novel extraction methodologies and the use of more

sustainable biomass sources such as agroforestry by-products is of great importance. In this

vein, Eutectic Solvents (ESs) have been proposed has good alternatives for conventional

solvents due to their low price, easiness of preparation, biocompatibility, and ability of being

custom made to a specific application.

Herein, we report the use of ESs in the extraction of proanthocyanidins from white grape

pomace. Several hydrogen bond acceptor and donor combinations were tested from which

choline chloride and glycerol can be highlighted due to their high extraction yield. Furthermore,

these compounds synergize very well with the addition of water and ethanol further contributing

to the development of a cheap and sustainable extraction process. In addition, with this

quaternary solvent system it is possible to control the mean degree of polymerization and

galloylation percentage of the final extract, allowing for a customization of the extracts’

characteristics that no other extraction process offers.

Auxiliary extraction techniques such as microwave radiation was also explored from which a

similar yield was obtained by using a combination of choline chloride, lactic acid and water,

with the advantage of achieving it in a shorter period of time and with a higher mean degree of

polymerization reinforcing the potential that ESs have in the improvement of proanthocyanidin

extraction.


99

A Natural Hydrophobic Deep Eutectic Solvent-based

Analytical Method for the Extraction of Plastic migrants

from Edible Matrices

Ruth Rodríguez-Ramos a,*, Álvaro Santana-Mayor a, Bárbara Socas-Rodríguez b, Miguel

Ángel Rodríguez-Delgado a a Departamento de Química, Unidad Departamental de Química Analítica, Facultad de

Ciencias, Universidad de La Laguna (ULL). Avda. Astrofísico Fco. Sánchez, s/n. 38206 San

Cristóbal de La Laguna, España, b Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera


* [email protected]

Keywords: alkylphenol, phthalate, deep eutectic solvent, food, microextraction

Endocrine disrupting compounds have raised great concern in recent years since they can affect

the normal functioning of the hormonal system of humans and biota through different

mechanisms (mimicking or blocking the natural hormone, etc.), even at low concentrations.

Among them, alkylphenols and phthalates are important groups of this kind of contaminants

due to their wide use as additives in plastic industry, what makes them omnipresent in

environment and consumer goods, including foodstuff. This is why analytical methodologies

to determine these organic pollutants at trace levels in edible matrices are needed. In this way,

sustainable research trends have led to the development of a new generation of green solvents,

the so-called deep eutectic solvents (DESs). These neoteric materials have demonstrated several

advantages compared to volatile organic solvents, traditionally used in the extraction step of

sample preparation, such as low cost and easy synthesis, biodegradability, biocompatibility and

non- or low toxicity. Among them, hydrophobic deep eutectic solvents (HDESs) have emerged

as an ideal group of DESs to be applied for extraction in aqueous samples. Within HDESs,

mainly formed by poorly water-soluble compounds, ionic- and non-ionic solvents can be

distinguished, the latter being generally more hydrophobic. The aim of this work was to develop

a dispersive liquid-liquid microextraction based on HDESs formed by combinations of camphor

with menthol and thymol, for the extraction of a group of alkylphenols and phthalates from

vegetable-based milk samples. After the evaluation of HDESs extraction performance, the

methodology was optimised and validated obtaining results that showed its suitability for the

established analytical purpose with recovery values in the range 70-120%, for most analytes.

Separation and quantification were carried out by using ultra-high performance liquid

chromatography coupled to tandem mass spectrometry with low limits of quantification in the

range of µg/kg.


100

Enhanced Antibiofouling Paints Using Deep Eutectic

Solvents Based on Natural Compounds

Valente S.1, Oliveira F.1, Paiva A.1 Gaudêncio S.1,2, Duarte A. R.1

1LAQV-REQUIMTE, Chemistry Department, Faculty for Sciences and Technology,

NOVA University of Lisbon, 2829-516 Caparica, Portugal 2UCIBIO, Chemistry Department, Blue Biotechnology and Biomedicine Lab, Faculty

for Sciences and Technology, NOVA University of Lisbon, 2829-516 Caparica,

Portugal

Corresponding author email: [email protected]

Keywords: Marine biofouling, Napyradiomycines, Deep eutectic system, Antifouling

paints

Marine biofouling is one of the most challenging problems currently faced by marine

technology. This phenomenon is defined as the undesirable colonization of submerged

man-made surfaces by fouling organisms. Presently, this represents a great material and

economic loss in marine operations, while rising a series of environmental concerns. It is

estimated that antifouling coatings provide the shipping industry with annual fuel savings

of $60 billion, and reduced emissions of 384 million and 3.6 million tonnes per annum,

for carbon dioxide and sulphur dioxide, respectively. However, there is still absent a

universal and green antifouling system. Natural marine products are a potential source

for the discovery of antifouling compounds, representing a promising sustainable

alternative. In this study, the ability of napiradiomycins to inhibit micro and macrofouling

species was explored, with particular emphasis on developing sustainable antifouling

products, namely paints and coatings. Deep eutectic systems (DES) are a promising

alternative to organic solvents commonly used in conventional antifouling products and

they have emerged in the literature as an excellent option for this purpose. In this work,

the DES were based on natural occurring molecules with antifouling activity, such as fatty

acids (oleic acid and 3-hydroxybutyric acid) and terpenes (menthol), which prove to be

good candidates for preparing sustainable, effective and cheap antifouling painting

supplements. For this purpose, firstly DES was characterized by differential scanning

calorimetry (DSC) and nuclear magnetic resonance (NMR), followed by the evaluation

of DES antimicrobial potential towards microorganisms, namely, Staphylococcus aureus

(ATCC 25922), and the results demonstrate that these systems have antimicrobial activity.

The ecotoxicity assessment is currently ongoing in a marine representative animal model

– mussels - a simple model recurrently used in environmental toxicology evaluation. I

hope that my work will be an asset to improve the sustainability of the marine industry.

Acknowledgements: This project has received funding from the European Union’s Horizon

2020 (European Research Council) under grant agreement No ERC-2016-CoG 725034. This work

was also supported by the Associate Laboratory for Green Chemistry – LAQV – which is financed

by national funds from FCT/MCTES (UID/QUI/50006/2019)


101

Glycerol based NADES as green solvents for ultrasound-

assisted extraction of phycocyanin from Arthrospira

platensis-RSM optimization and ANN modeling

Soukaina Hilali a,*, Laura Wils a, Mervé Yagmur a, Barbara Clément-Larosière b, Franck Bonnier c and Leslie Boudesocque-Delaye a


Faculté de Pharmacie, 31 avenue Monge 37200 Tours, France b Aqua Eco Culture, 7 rue d'Armor Maroué, 22400 Lamballe, France

c NMNS EA 6295 Nanomédicaments et Nanosondes, Université de Tours,


* [email protected]

Keywords: Natural Deep Eutectic Solvent, Spirulina, Phycoprotein, Reponse surface

methodology, artificial neural network

The aim of this study was to investigate the eco-extraction of Arthrospira platensis

phycocyanin’s via ultrasound-assisted process using different naturel deep eutectic solvents

(NADES). Response surface methodology (RSM) and artificial neural network (ANN) were

adapted in this study for the generation of predictive models to simulate and optimize

phycocyanin extraction for each given NADES. Input parameters were extraction time (15–60

min), temperature (25–50°C), and water addition ratio (20–60%). Those variables were

investigated in order to study their influence on phycocyanin extraction efficiency using Box-

Behnken design. Additionally, correlation coefficients (R2) as well as errors analysis such as

the root mean square error (RMSE), standard error of prediction (SEP), relative percent

deviation (RPD) were calculated and further used to compare the prediction abilities of RSM

and ANN using the validation data set. The stability of phycocyanin in the extract was also

investigated and included in RSM and ANN setting leading to an innovative relevant approach

to design extraction process.


102

Biomass-derived itaconic acid-based polyelectrolytes

for synthesis of self-assembled nanocomposite hydrogels

Kacper Mielczareka, Sonia Bujokb, Samuel Wierzbicki, Hynek Benešb,*, Szczepan Bednarza,*

a Faculty of Chemical Engineering and Technology, Cracow University of Technology

Warszawska 24, 31-155 Cracow, Poland, b Institute of Macromolecular Chemistry CAS

Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic

* [email protected] (HB), [email protected] (SB)

Keywords: Deep Eutectic Solvents, photopolymerization, physical hydrogels, biomonomers

Itaconic acid (IA) is an important renewable monomer, considered as bio-based alternative to

petrochemical acrylic or methacrylic acid. Here, we summarise our very recent findings that

daylight-induced and initiator-free polymerization of Deep Eutectic Monomers (DEMs)

enables synthesis of IA-based polyelectrolytes with unexpected high-molecular weight, which

are suitable for fabrication of self-assembled nanocomposite hydrogels [1]. Relations between

kinetics of initiation and termination processes in DEMs and structure – properties of polymers

obtained will be discussed. The self-assembling behaviour of the polyelectrolytes in the

nanoparticle/dispersant aqueous systems will be also outlined.

References:

[1] K. Mielczarek, M. Łabanowska, M. Kurdziel, R. Konefał, H. Beneš, S. Bujok, G. Kowalski, S. Bednarz. High-

molecular-weight polyampholytes synthesized via daylight-induced, initiator-free radical polymerization of

renewable itaconic acid. Macromolecular Rapid Communications 41 (2020) 190061. DOI:

10.1002/marc.201900611


103

Thermal and rheological analysis of different natural deep

eutectic solvents (NADES). Application to the eco-

extraction of bioactive compounds from quinoa leaves

(Chenopodium quinoa Willd.)

Verónica Taco a.c*, Dennys Almachi b, Pablo Bonilla b, Samira Benali b, Jean-Marie Raquezb,

Pierre Duez c, Amandine Nachtergael c a Facultad de Ciencias Químicas, Universidad Central del Ecuador, Quito-Ecuador,

b Center of Innovation and Research in Materials, University of Mons, Mons-Belgium, c Unit of Therapeutic Chemistry and Pharmacognosy, Faculty of Medicine and Pharmacy,

University of Mons, Mons-Belgium

* [email protected]

Keywords: NADES, thermal and rheological behaviours, quinoa leaves, eco-extraction

Introduction: Natural deep eutectic solvents (NADES) have emerged as a recent generation of

green solvents. They can dissolve efficiently natural compounds with the major advantages of

biodegradability and biocompatibility; their physico-chemical properties can be fine-tuned by

modulating their composition and water content. Quinoa is one of the most important

pseudocereals of Andean origin, rich in bioactive compounds. The thermal and rheological

behaviours of different NADES were investigated and their suitability to extract bioactive

compounds from quinoa leaves was assessed.

Methods: Quinoa leaves, variety INIAP Tunkahuan, were collected in the Instituto Nacional

de Investigaciones Agropecuarias (INIAP), Quito-Ecuador. NADES were prepared by heating

method in the following molar ratios: malic acid-choline chloride (chcl)-water (w) (1:1:2, A),

chcl-glucose-w (5:2:5, B), proline-malic acid-w (1:1:3, C), glucose-fructose-sucrose-w

(1:1:1:11, D), 1,2-propanediol- chcl-w (1:1:1, E), lactic acid-glucose-w (5:1:3, F), glycerol-

chcl-w (2:1:1, G) and xylitol-chcl-w (1:2:3, H). Different amounts of water were added to

NADES A to D to decrease their viscosities; the effects of water addition on NADES thermal

stabilities and viscosities were studied by calorimetry (DSC) and rheometry (evaluation of shear

stress using a rheometer cone /plane), respectively. The flavonoids profiles of NADES-quinoa

leaves extracts were evaluated using HPTLC.

Results: The NADES viscosity significantly decreased after water addition; 17.5%, 20%, 10%

and 10% were the maximum amounts of water that could be added to NADES A, B, C and D,

respectively, to avoid the disruption of eutectic environment. The viscosities of all NADES

were highly dependent on time and shear stress. NADES E and G gave the best results in terms

of stability and extraction efficiency of flavonoids from quinoa leaves.

Conclusions and perspectives: Eco-extraction of quinoa leaves bioactive compounds is

possible using NADES; given their low toxicity, these solvents allow direct addition of extracts

to food formulations and pharmaceutical products thanks to a good understanding of thermal

and rheological behavior of NADES. The stability of NADES-quinoa leaves extracts is now

being investigated by chromatography and calorimetry.


104

Preparation of Thermo-responsive Hydrogels via

Polymerizable Deep Eutectic Monomer Solvents

Yeasmin Nahara,*, Stuart C. Thicketta, Alex C. Bissembera , James Horneb and Vinh Truongc a School of Natural Sciences (Chemistry), University of Tasmania, Hobart, TAS 7001,

Australia b Central Science Laboratory, University of Tasmania, Hobart, TAS 7001, Australia

cSchool of Chemistry and Physics, Queensland University of Technology, Brisbane, QLD

4000, Australia

*[email protected]

We report the preparation of thermoresponsive poly(N-isopropylacrylamide) (polyNIPAM)

hydrogels via the free radical polymerization of deep eutectic monomer solvents (DEMs) for

the first time, where NIPAM serves as a polymerizable hydrogen bond donor. DEMs were

prepared by a simple heating and stirring protocol using NIPAM and either choline chloride

(ChCl) or acetylcholine chloride (AcChCl) (as hydrogen bond acceptor) in various ratios to

yield low-melting point liquids (as low as 15 °C). 1D and 2D NMR spectroscopy supported the

association of the NIPAM and choline salts present within the DEM structure, in addition to

the low self-diffusion coefficients of the species present compared to when dissolved in water.

Thermogravimetric analysis demonstrated an enhanced thermal stability of the DEMs

compared to NIPAM. Hydrogels prepared by free-radical polymerization of the prepared DEMs

in the presence of N,N′-methylenebisacrylamide (BIS) as crosslinker showed a significant

increase in reaction rate compared to the equivalent reaction in water, which was attributed in

part to the high viscosity of the DEMs. These gels exhibited thermoresponsive swelling

behaviour when immersed in water. Specifically, gels prepared via DEMs featured reduced

swelling capacity and increased mechanical strength relative to those prepared by aqueous

polymerization, attributed to a significant increase in cross-linking density.

Figure 1. The formation of deep eutectic monomer solvents and Schematic diagram of thermo-responsive hydrogels

formation.


105

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BOOK OF A3BSTRACTS...Book of Abstracts - 2nd International Meeting on Deep Eutectic Systems 7 Bárbara Socas-Rodríguez, David M. Alonso García, José A. Mendiola, Alejandro Cifuentes