PAOLO CASU

PhD Graduate

PhD program:: XXXVII


supervisor: Paola D'Angelo

Thesis title: Deep Eutectic Solvents as Extraction Media for the Sustainable Recovery of Micronutrients from Food Waste: A Comprehensive Approach Integrating Computational Simulations and Practical Applications

The project focuses on tackling today’s challenges of reducing waste and minimizing pollution from the agricultural and food industries. This involves addressing the proper handling of waste byproducts and rethinking intensive production methods. One practical solution is to make better use of agricultural byproducts by recovering through solvents extraction the valuable bioactive compounds they contain. In recent years, the spotlight has shifted toward the use of environmentally friendly "green" solvents as alternatives to traditional organic ones. These innovative solvents are gaining attention for their potential to improve extraction processes from natural, complex materials while being safer and more sustainable. A class of alternative solvents is that of Deep eutectic solvents (DESs): they are mixtures made from two or more components with a melting point much lower than expected from the solid-liquid equilibrium phase diagram. This is due to a strong network of hydrogen bonds formed within the mixture. The components of DESs are typically categorized as hydrogen bond donors (HBDs) and acceptors (HBAs). In some cases, these mixtures do not have a clear melting point but instead show a glass transition, classifying them as low transition temperature mixtures (LTTMs).Thanks to their excellent solvating power, DESs and LTTMs have become popular for many applications, especially in extraction processes, where they improve efficiency, safety, and sustainability compared to traditional solvents. The approach taken in studying these solvents includes a comprehensive analysis of the mixture structures, their practical applications in extractions from real matrices, and, ultimately, an exploration of how they interact with the extracted analytes. Thermal characterization through DSC was performed on three systems formed by the three isomers of hydroxyphenol —catechol (Cate), resorcinol (Reso), and hydroquinone (Hydro)— which were mixed with choline chloride (ChCl) at a ChCl:HBD ratio of 1:x (x = 0.75, 1, 2, 3). The ChCl:Cate mixtures 1:0.75, 1:1, 1:2, and 1:3, ChCl:Reso 1:0.75, 1:1, and ChCl:Hydro 1:0.75, 1:1, and 1:2 were identified as DESs due to their lower melting points observed in DSC, compared to predictions from the ideal phase diagram, while the others either lacked a distinct melting point (ChCl:Reso 1:2, 1:3) or did not show a liquid phase of the mixture (ChCl:Hydro 1:3). Through combined ATR-FTIR analyses and molecular dynamics (MD) simulations, it was possible to understand how the bonds forming the mixture are stronger than those within the pure compounds. Specifically, these bonds involve hydrogen interactions between the chlorine atom in ChCl and the hydroxyl hydrogens of the two components. Additionally, it was observed that a deep eutectic mixture is more easily formed at a ChCl:HBD molar ratio of 1:1. Similar results were observed with the ChCl:4-methoxyphenol (4-MPh) 1:2 system, which, however, does not qualify as a DES but rather as an LTTM due to the glass transition seen in its DSC thermogram. This mixture was chosen based on preliminary tests as the most effective for quercetin extraction, particularly from red onion skins. ChCl:4-MPh with 10% of water was used in solid-liquid extractions enhanced by ultrasound (UAE), and subsequent quantitative analysis via HPLC-MS/MS revealed a quercetin concentration of 7.41 mg/g, with an extraction yield of approximately 98% from red onion peels. This not only outperformed the yield achieved with ethanol but also improved the analyte’s stability against oxidative degradation, as confirmed by oxidation tests. The ChCl:4-MPh 1:2 and ChCl:2-MPh 1:2 systems, along with the same mixtures supplemented with water at a ChCl:HBD 1:2:1.8 molar ratio, were compared with ethanol regarding their ability to solvate quercetin. In the case of ethanol, the primary interaction with quercetin involves hydrogen bonds formed between the hydrogen atoms of the solvent and the hydroxyl groups of quercetin. On the other hand, the eutectic solvents interact with hydroxyl groups of quercetin through hydrogen bonds with the chlorine atom, which is unique to these mixtures. Adding water to the eutectic systems did not result in significant changes in the structure surrounding quercetin. Particularly noteworthy is the interaction between the oxygen atom double bonded to quercetin’s central ring, which primarily binds with ethanol and 4-MPh. These observations were supported by results from MD simulations , which also allowed the calculation of the ΔGsolv of quercetin in the three pure solvents. Among the systems tested, ChCl:2-MPh (1:2) demonstrates the most favorable thermodynamic contribution to quercetin solvation, marginally surpassing the ChCl:4-MPh (1:2) system, while ethanol provides the least favorable contribution. Viscosity measurements conducted on the eutectic mixtures with water revealed that, over a temperature range from ambient to 50°C, the ChCl:4-MPh:H2O system is significantly less viscous than ChCl:2-MPh:H2O. This difference helps explain why, despite computational results, the system containing 4-MPh performed better in extraction tests. The study of quercetin solvation, therefore, cannot rely solely on computational data. Experimental measurements, combined with computational insights, provide a comprehensive understanding of the systems, offering a synergy that has been maintained throughout the project.

Research products

11573/1738029 - 2025 - Different impact of menthol chirality on ideal and deep eutectic solvents: Thermal and structural insights
Mannucci, Giorgia; Busato, Matteo; Pietropaoli, Eva; Palluzzi, Matteo; Casu, Paolo; Capocefalo, Angela; Fasolato, Claudia; Postorino, Paolo; D'angelo, Paola - 01a Articolo in rivista
paper: JOURNAL OF MOLECULAR LIQUIDS (Amsterdam, Netherlands: Elsevier BV) pp. 127676- - issn: 0167-7322 - wos: (0) - scopus: 2-s2.0-105004220424 (0)

11573/1721741 - 2024 - On the composition and isomerism effect in the thermal and structural properties of choline chloride/hydroxyphenol deep eutectic solvents
Casu, Paolo; Busato, Matteo; Palluzzi, Matteo; Spezia, Riccardo; D'angelo, Paola - 01a Articolo in rivista
paper: PHYSICAL CHEMISTRY CHEMICAL PHYSICS (Thomas Graham House, Science Park, Cambridge: Royal Society of Chemistry) pp. 23168-23176 - issn: 1463-9076 - wos: WOS:001298291100001 (0) - scopus: 2-s2.0-85202682235 (0)

11573/1691299 - 2023 - The complex story behind a deep eutectic solvent formation as revealed by L-menthol mixtures with butylated hydroxytoluene derivatives
Busato, M; Mannucci, G; Rocchi, La; Di Pietro, Me; Capocefalo, A; Zorzi, E; Casu, P; Veclani, D; Castiglione, F; Mele, A; Martinelli, A; Postorino, P; D'angelo, P - 01a Articolo in rivista
paper: ACS SUSTAINABLE CHEMISTRY & ENGINEERING (Washington DC: American Chemical Society, c2013-) pp. 8988-8999 - issn: 2168-0485 - wos: WOS:001008530200001 (9) - scopus: 2-s2.0-85162882234 (13)

11573/1629848 - 2022 - Sodium-conducting ionic liquid electrolytes: electrochemical stability investigation
Maresca, Giovanna; Casu, Paolo; Simonetti, Elisabetta; Brutti, Sergio; Battista Appetecchi, Giovanni - 01a Articolo in rivista
paper: APPLIED SCIENCES (Basel: MDPI AG, 2011-) pp. 4174- - issn: 2076-3417 - wos: WOS:000795281700001 (8) - scopus: 2-s2.0-85129203377 (8)

11573/1703893 - 2021 - Sodium-conducting, ionic liquid electrolytes for Na battery systems
Maresca, G.; Casu, P.; Bellusci, M.; Simonetti, E.; Brutti, S.; Appetecchi, G. B. - 04d Abstract in atti di convegno
conference: SCI 2021 - XXVII Congresso Nazionale della Società Chimica Italiana (online)
book: SCI 2021 - XXVII Congresso Nazionale della Società Chimica Italiana - ()

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma