{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:28:17Z","timestamp":1764332897301,"version":"3.46.0"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018811","name":"University of La Rioja","doi-asserted-by":"crossref","award":["REGI 22\/64"],"award-info":[{"award-number":["REGI 22\/64"]}],"id":[{"id":"10.13039\/501100018811","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FCT\/MCTES","award":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020"],"award-info":[{"award-number":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sustainable Chemistry"],"abstract":"<jats:p>Deep eutectic solvents (DES) were selected for the extraction of anthocyanins from red grape skins as an efficient and environmentally friendly solvent alternative to traditional mixtures based on methanol. In silico studies (COSMO-RS) were employed as screening tools to identify the most suitable options, significantly reducing the chemical space of potential DES to be studied. A total of 30,132 DES combinations were assessed. The DESs selected were polyalcohols (ethyleneglycol, glycerol, 1,2-propanediol, and 1,6-hexanediol) and carboxylic acids (citric, oxalic, malic, and lactic acid) as hydrogen bond donors (HBD) and choline chloride, betaine, or salts (potassium carbonate, sodium acetate, and propionate), as hydrogen bond acceptors (HBA). Choline chloride:glycerol and choline chloride:oxaclic acic were selected as solvents to optimize time, temperature, and water content in ultrasound- and microwave-assisted extraction of anthocyanins. In both cases, around 20 wt% of water was found to be the optimum to maximize the extractions, whereas extraction time and temperature depended on the type of anthocyanin. The amount of malvidin-3-O-glucoside extracted by microwave-assisted extraction with choline chloride: oxalic acid was 172 \u00b1 7 mg\/kg and 119.5 \u00b1 0.5 mg\/kg by ultrasound-assisted extraction with choline chloride: glycerol, which means an increase in performance of, respectively, 64 and a 13% compared to the traditional method.<\/jats:p>","DOI":"10.3390\/suschem6040047","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T13:09:25Z","timestamp":1763989765000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New Approaches for the Extraction of Anthocyanins from Grape Skins Using Deep Eutectic Solvents"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-334X","authenticated-orcid":false,"given":"Marta","family":"Jim\u00e9nez-Salcedo","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of La Rioja, C\/Madre de Dios 53, E-26006 Logro\u00f1o, La Rioja, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1649-4597","authenticated-orcid":false,"given":"Filipe H. B.","family":"Sosa","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3841-743X","authenticated-orcid":false,"given":"Jo\u00e3o A. P.","family":"Coutinho","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-2653","authenticated-orcid":false,"given":"Mar\u00eda Teresa","family":"Tena","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of La Rioja, C\/Madre de Dios 53, E-26006 Logro\u00f1o, La Rioja, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/ijfs.14118","article-title":"Valorisation of grape pomace: An approach that is increasingly reaching its maturity\u2014A review","volume":"54","author":"Bordiga","year":"2019","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1021\/jf051807j","article-title":"Commercial dietary ingredients from Vitis vinifera L. leaves and grape skins: Antioxidant and chemical characterization","volume":"54","author":"Monagas","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"130049","DOI":"10.1016\/j.foodchem.2021.130049","article-title":"Characterization of Tempranillo negro (VN21), a high phenolic content grapevine Tempranillo clone, through UHPLC-QqQ-MS\/MS polyphenol profiling","volume":"360","author":"Royo","year":"2021","journal-title":"Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.foodchem.2017.03.060","article-title":"Recovery of anthocyanins from residues of Rubus fruticosus, Vaccinium myrtillus and Eugenia brasiliensis by ultrasound assisted extraction, pressurized liquid extraction and their combination","volume":"231","author":"Machado","year":"2017","journal-title":"Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev-chembioeng-101121-085323","article-title":"Everything you wanted to know about deep eutectic solvents but were afraid to be told","volume":"14","author":"Abranches","year":"2023","journal-title":"Annu. Rev. Chem. Biomol. Eng."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhou, M., Fakayode, O.A., and Li, H. (2023). Green extraction of polyphenols via deep eutectic solvents and assisted technologies from agri-food by-products. Molecules, 28.","DOI":"10.3390\/molecules28196852"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"168716","DOI":"10.1016\/j.scitotenv.2023.168716","article-title":"Microwave-assisted extraction with natural deep eutectic solvents for polyphenol recovery from agri-food waste: Mature for scaling-up?","volume":"912","author":"Granados","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Coscarella, M., Nardi, M., Alipieva, K., Bonacci, S., Popova, M., Procopio, A., Scarpelli, R., and Simeonov, S. (2024). Alternative assisted extraction methods of phenolic compounds using NaDESs. Antioxidants, 13.","DOI":"10.3390\/antiox13010062"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Brunetti, L., Leuci, R., Colonna, M.A., Carrieri, R., Celentano, F.E., Bozzo, G., Loiodice, F., Selvaggi, M., Tufarelli, V., and Piemontese, L. (2022). Food industry byproducts as starting material for innovative, green feed formulation: A sustainable alternative for poultry feeding. Molecules, 27.","DOI":"10.3390\/molecules27154735"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100937","DOI":"10.1016\/j.scp.2022.100937","article-title":"Deep eutectic solvents as sustainable extraction media for plants and food samples: A review","volume":"31","author":"Kaoui","year":"2023","journal-title":"Sustain. Chem. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"135147","DOI":"10.1016\/j.jclepro.2022.135147","article-title":"Review of deep eutectic systems from laboratory to industry, taking the application in the cosmetics industry as an example","volume":"380","author":"Rente","year":"2022","journal-title":"J. Clean. Prod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105761","DOI":"10.1016\/j.supflu.2022.105761","article-title":"Modifiers based on deep eutectic mixtures: A case study for the extraction of anthocyanins from black bean hulls using high pressure fluid technology","volume":"191","author":"Kuasnei","year":"2022","journal-title":"J. Supercrit. Fluids"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1007\/s12272-015-0678-4","article-title":"Highly efficient extraction of anthocyanins from grape skin using deep eutectic solvents as green and tunable media","volume":"38","author":"Jeong","year":"2015","journal-title":"Arch. Pharmacal Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.lwt.2016.05.037","article-title":"Natural deep eutectic solvents as beneficial extractants for enhancement of plant extracts bioactivity","volume":"73","author":"Radosevic","year":"2016","journal-title":"LWT"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113761","DOI":"10.1016\/j.molliq.2020.113761","article-title":"NADES as potential solvents for anthocyanin and pectin extraction from Myrciaria cauliflora fruit by-product: In silico and experimental approaches for solvent selection","volume":"315","author":"Benvenutti","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.foodchem.2016.01.040","article-title":"Green extraction of grape skin phenolics by using deep eutectic solvents","volume":"200","author":"Bubalo","year":"2016","journal-title":"Food Chem."},{"key":"ref_17","first-page":"469","article-title":"Extraction of anthocyanins from grape (Vitis vinifera) skins employing natural deep eutectic solvents (NaDES)","volume":"87","author":"Iannone","year":"2021","journal-title":"Chem. Eng. Trans."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dabetic, N., Todorovic, V., Panic, M., Radojcic Redovnikovic, I., and \u0160obajic, S. (2020). Impact of Deep Eutectic Solvents on Extraction of Polyphenols from Grape Seeds and Skin. Appl. Sci., 10.","DOI":"10.3390\/app10144830"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dabetic, N., Todorovic, V., Malenovic, A., Sobajic, S., and Markovic, B. (2022). Optimization of extraction and HPLC\u2013MS\/MS profiling of phenolic compounds from red grape seed extracts using conventional and deep eutectic solvents. Antioxidants, 11.","DOI":"10.3390\/antiox11081595"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105773","DOI":"10.1016\/j.ultsonch.2021.105773","article-title":"Ultrasound-assisted extraction of phenolic acids, flavonols, and flavan-3-ols from muscadine grape skins and seeds using natural deep eutectic solvents and predictive modelling by artificial neural networking","volume":"79","author":"Alrugaibah","year":"2021","journal-title":"Ultrason. Sonochem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Punzo, A., Porru, E., Silla, A., Simoni, P., Galletti, P., Roda, A., Tagliavini, E., Samor\u00ec, C., and Caliceti, C. (2021). Grape pomace for topical application: Green NaDES sustainable extraction, skin permeation studies, antioxidant and anti-inflammatory activities characterization in 3D human keratinocytes. Biomolecules, 11.","DOI":"10.3390\/biom11081181"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Xue, H., Tan, J., Li, Q., Tang, J., and Cai, X. (2020). Ultrasound-assisted deep eutectic solvent extraction of anthocyanins from blueberry wine residues: Optimization, identification, and HepG2 antitumor activity. Molecules, 25.","DOI":"10.3390\/molecules25225456"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Grillo, G., Gunjevic, V., Rado\u0161evic, C., Redovnikovic, I.R., and Cravotto, G. (2020). Deep eutectic solvents and nonconventional technologies for blueberry-peel extraction: Kinetics, anthocyanin stability, and antiproliferative activity. Antioxidants, 9.","DOI":"10.3390\/antiox9111069"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103470","DOI":"10.1016\/j.jfca.2020.103470","article-title":"Natural deep eutectic solvents as a biocompatible tool for the extraction of blueberry anthocyanins","volume":"89","author":"Pauletto","year":"2020","journal-title":"J. Food Compos. Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111220","DOI":"10.1016\/j.lwt.2021.111220","article-title":"Natural deep eutectic solvent enhanced pulse-ultrasonication assisted extraction as a multi-stability protective and efficient green strategy to extract anthocyanin from blueberry pomace","volume":"144","author":"Fu","year":"2021","journal-title":"LWT"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115406","DOI":"10.1016\/j.molliq.2021.115406","article-title":"COSMO-SAC-supported evaluation of natural deep eutectic solvents for the extraction of tea polyphenols and process optimization","volume":"328","author":"Cui","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11057","DOI":"10.1007\/s13399-021-01821-2","article-title":"COSMO-SAC model approach for deep eutectic solvent selection to extract quercetin from macela (A. satureioides) and experimental process optimization","volume":"13","author":"Goltz","year":"2023","journal-title":"Biomass Convers. Biorefinery"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12132","DOI":"10.1021\/acssuschemeng.0c03553","article-title":"Using COSMO-RS in the Design of Deep Eutectic Solvents for the Extraction of Antioxidants from Rosemary","volume":"8","author":"Wojeicchowski","year":"2020","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117054","DOI":"10.1016\/j.seppur.2020.117054","article-title":"Design of natural deep eutectic solvents for the ultrasound-assisted extraction of hydroxytyrosol from olive leaves supported by COSMO-RS","volume":"248","author":"Zurob","year":"2020","journal-title":"Sep. Purif. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lazovic, M., Cvijetic, I., Jankov, M., Milojkovi\u0107-Opsenica, D., Trifkovic, J., and Ristivojevic, P. (2022). Efficiency of natural deep eutectic solvents to extract phenolic compounds from Agrimonia eupatoria: Experimental Study and In Silico Modelling. Plants, 11.","DOI":"10.3390\/plants11182346"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"135093","DOI":"10.1016\/j.foodchem.2022.135093","article-title":"Combining eutectic solvents and food-grade silica to recover and stabilize anthocyanins from grape pomace","volume":"406","author":"Mesquita","year":"2023","journal-title":"Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/aic.690480220","article-title":"Fast solvent screening via quantum chemistry: COSMO-RS approach","volume":"48","author":"Eckert","year":"2002","journal-title":"AIChE J."},{"key":"ref_33","first-page":"020011","article-title":"Vitamin E extraction from red palm biodiesel by using K2CO3 based deep eutectic solvent with glycerol as hydrogen bond donor","volume":"Volume 1977","author":"Manurung","year":"2018","journal-title":"Human-Dedicated Sustainable Product and Process Design: Materials, Resources, and Energy, Proceedings of the 4th International Conference on Engineering, Technology, and Industrial Application (ICETIA) 2017, Surakarta, Indonesia, 13\u201314 December 2017"},{"key":"ref_34","first-page":"020010","article-title":"Purification of red palm biodiesel by using K2CO3 based deep eutectic solvent (DES) with glycerol as hydrogen bond donor (HBD)","volume":"Volume 1977","author":"Manurung","year":"2018","journal-title":"Human-Dedicated Sustainable Product and Process Design: Materials, Resources, and Energy, Proceedings of the 4th International Conference on Engineering, Technology, and Industrial Application (ICETIA) 2017, Surakarta, Indonesia, 13\u201314 December 2017"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sander, A., Petracic, A., Vukovic, J.P., and Husinec, L. (2020). From coffee to biodiesel\u2014Deep eutectic solvents for feedstock and biodiesel purification. Separations, 7.","DOI":"10.3390\/separations7020022"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13847","DOI":"10.1007\/s13399-022-03569-9","article-title":"Deep eutectic solvents for the extraction of \u03b2-chitin from Loligo vulgaris squid pens: A sustainable way to valorize fishery by-products","volume":"14","author":"McReynolds","year":"2024","journal-title":"Biomass Convers. Biorefinery"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"118113","DOI":"10.1016\/j.carbpol.2021.118113","article-title":"Sequential natural deep eutectic solvent pretreatments of apple pomace: A novel way to promote water extraction of pectin and to tailor its main structural domains","volume":"266","author":"Chen","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Yang, T.-X., Qi, B.-K., Li, H., Zhao, Q.-S., and Zhao, B. (2023). Acidic and alkaline deep eutectic solvents (DESs) pretreatment of grapevine: Component analysis, characterization, lignin structural analysis, and antioxidant properties. Int. J. Biol. Macromol., 236.","DOI":"10.1016\/j.ijbiomac.2023.123977"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.procbio.2024.09.005","article-title":"Extraction of polyphenols from Apocynum venetum leaves using customized deep eutectic solvents: Process optimization and antioxidant evaluation","volume":"147","author":"Lv","year":"2024","journal-title":"Process Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1021\/j150487a027","article-title":"The solubility of nonelectrolytes. By Joel H. Hildebrand and Robert S. Scott","volume":"55","author":"Huggins","year":"1951","journal-title":"J. Phys. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.15376\/biores.15.1.1154-1170","article-title":"An alkaline deep eutectic solvent based on potassium carbonate and glycerol as pretreatment for the isolation of cellulose nanocrystalas from empty fruit bunch","volume":"15","author":"Gan","year":"2020","journal-title":"BioResources"},{"key":"ref_42","first-page":"97","article-title":"Optimization Studies of Coal Organic Sulfur Removal using Potassium Carbonate and Ethylene Glycol as a Deep Eutectic Solvent","volume":"25","author":"Ismail","year":"2023","journal-title":"Malays. J. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1007\/s10098-019-01727-8","article-title":"Development of sodium propionate-based deep eutectic solvents for polyphenol extraction from onion solid wastes","volume":"21","author":"Stefou","year":"2019","journal-title":"Clean. Technol. Environ. Policy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115232","DOI":"10.1016\/j.lwt.2023.115232","article-title":"Deep eutectic solvent-inspired solid alkali carbonate for highly efficient interesterification of lard","volume":"186","author":"Meng","year":"2023","journal-title":"LWT"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lv, J., Fang, Y., Wang, D., Wu, M., Zhang, W., Ou, X., Li, H., Shang, L., Li, Z., and Zhao, Y. (2023). Green preparation of \u03b2-chitins from squid pens by using alkaline deep eutectic solvents. Int. J. Biol. Macromol., 253.","DOI":"10.1016\/j.ijbiomac.2023.126767"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11695","DOI":"10.1039\/D4GC03707C","article-title":"Valorization of pomegranate waste through green solvent extraction and biochar production: A zerowaste biorefinery approach","volume":"26","author":"Mesquita","year":"2024","journal-title":"Green Chem."},{"key":"ref_47","first-page":"12485","article-title":"Hydrotropy and cosolvency in lignin solubilization with deep eutectic solvents","volume":"7","author":"Soares","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8930","DOI":"10.1021\/acssuschemeng.4c02529","article-title":"Role of deep eutectic solvent precursors as hydrotropes: Unveiling synergism\/antagonism for enhanced kraft lignin dissolution","volume":"12","author":"Sosa","year":"2024","journal-title":"ACS Sustain. Chem. Eng."}],"container-title":["Sustainable Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-4079\/6\/4\/47\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:15:51Z","timestamp":1764332151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-4079\/6\/4\/47"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["suschem6040047"],"URL":"https:\/\/doi.org\/10.3390\/suschem6040047","relation":{},"ISSN":["2673-4079"],"issn-type":[{"type":"electronic","value":"2673-4079"}],"subject":[],"published":{"date-parts":[[2025,11,24]]}}}