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Researchers have been looking for alternatives to develop safer and more sustainable alternative bioactive compound extraction processes. Besides, the investigation on deep eutectic solvents (DES), formed from hydrogen bonds between a hydrogen-bond acceptor (HBA) and a hydrogen-bond donor (HBD), is growing exponentially due to their characteristics as green solvents. Within this context, this research aimed to evaluate the phenolic compound extraction from olive leaves (Olea europaea L.), a residue obtained from the production of olive oil and rich in bioactive compounds, with DES formed by choline chloride ([Ch]Cl; GRAS), as HBA, and four organic carboxylic acids present in foods (acetic, malic, malonic and citric acids) as HBD. Initially, for comparative purposes, the response surface methodology (RSM) and central composite rotatable design (CCRD) was used for modeling the influence of temperature and water in ethanol on phenolic extraction. Quantification of phenolic compounds was carried out in UPLC-ESI-MS. After that, the screening with five DES was performed to analyze the best on phenolic extraction. As [Ch]Cl:acetic acid was the DES with the highest extraction potential of phenolic compounds, the same RSM and (CCRD) methodology was adopted to analyze the effect of temperature and water addition in DES on phenolic extraction. The maximum extraction assay with ethanol:water was under the experimental conditions of 40.0 °C and 0.5% water content, and for [Ch]Cl:acetic acid was 40.0 °C and 50.0% water content. The temperature within the studied range was not significant for phenolic extraction. With the increase of water addition in ethanol, a decrease in phenolic extraction was observed, but the opposite was observed with DES, in which the more water, the greater the phenolic compounds extraction. This new solvent extracted 75% more phenolic compounds (485.29 mg.kg-1) than ethanol (276.13 mg.kg-1), showing that they have potential to replace the commonly used organic solvents.
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