Prediction of pH Value of Aqueous Acidic and Basic Deep Eutectic Solvent Using COSMO-RS σ Profiles' Molecular Descriptors.

The aim of this work was to develop a simple and easy-to-apply model to predict the pH values of deep eutectic solvents (DESs) over a wide range of pH values that can be used in daily work. For this purpose, the pH values of 38 different DESs were measured (ranging from 0.36 to 9.31) and mathematically interpreted. To develop mathematical models, DESs were first numerically described using σ profiles generated with the COSMOtherm software. After the DESs' description, the following models were used: (i) multiple linear regression (MLR), (ii) piecewise linear regression (PLR), and (iii) artificial neural networks (ANNs) to link the experimental values with the descriptors. Both PLR and ANN were found to be applicable to predict the pH values of DESs with a very high goodness of fit (R2independent validation > 0.8600). Due to the good mathematical correlation of the experimental and predicted values, the σ profile generated with COSMOtherm could be used as a DES molecular descriptor for the prediction of their pH values.

COSMOtherm as an Effective Tool for Selection of Deep Eutectic Solvents Based Ready-To-Use Extracts from Grasevina Grape Pomace.

The aim of this work is to develop an industrially suitable process for the sustainable waste disposal in wine production. The proposed process involves the development of an environmentally friendly method for the isolation of biologically active compounds from Grasevina grape pomace according to the green extraction principles, in order to obtain a ready-to-use extract. In this process, deep eutectic solvents (DES) were used as extraction solvents. Aiming to save time in selecting the optimal DES that would provide the most efficient Grasevina pomace polyphenols extraction, the user-friendly software COSMOtherm was used and 45 DES were screened. Moreover, the prepared extracts were chemically and biologically characterized to confirm their safety for human application. Computational and experimental results proved the applicability of COSMOtherm in the selection of the optimal DES for the environmentally friendly preparation of the ready-to-use extract from Grasevina grape pomace with expected application in the cosmetic industry.

Development of ANN models based on combined UV-vis-NIR spectra for rapid quantification of physical and chemical properties of industrial hemp extracts.

OBJECTIVES: The aim of this study was to develop artificial neural network (ANNs) models for prediction of physical (total dissolved solids, extraction yield) and chemical (total polyphenolic content, antioxidant activity) properties of industrial hemp extracts, prepared by two different extraction methods (solid-liquid extraction and microwave-assisted extraction) based on combined UV-VIS-NIR spectra. Spectral data were gathered for 46 samples per extraction method. RESULTS: The PCA analysis ensured efficient separation of the samples based on the amount of ethanol in extraction solvent using NIR spectra for both conventional and microwave-assisted extraction. CONCLUSIONS: Results showed that reliable ANN models (R2 >0.7000) for describing physical, chemical, and simultaneously physical and chemical characteristics can be developed based on combined UV-VIS-NIR spectra of industrial hemp extracts without spectra pre-processing.

Natural deep eutectic solvent as a unique solvent for valorisation of orange peel waste by the integrated biorefinery approach.

This research investigates the use of seven natural deep eutectic solvents (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 (ee = 83.2%, X  = 35%), as well as it's stabilizing effect on the hydrolytic enzymes (hydrolytic enzymes within ChEg50 peel extract were stabile during 20 days at 4 °C). The ChEg50 also showed a satisfactory capacity to extract D-limonene (0.5 mg gFW-1), and excellent capacity to extract polyphenols (45.7 mg gFW-1), and proteins (7.7 mg gFW-1) 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.

Biological Potential of Flaxseed Protein Hydrolysates Obtained by Different Proteases.

Flaxseed meal, a byproduct of flaxseed oil extraction, was treated as low-value agrowaste for a long time despite its high protein content. Flaxseed meal has recently garnered increasing interest as a source of proteins and other bioactive compounds with positive impacts on human health. The aim of this study was to investigate the in vitro biological potential of flaxseed protein hydrolysates (FPH). Three FPHs were prepared using three hydrolytic enzymes: Alcalase, Neutrase and Protamex. The molecular weight profile of peptides contained in the hydrolysates was determined by size exclusion chromatography (SEC). The oxygen radical absorbance capacity (ORAC) assay was used to determine the peptide antioxidant capacity, while proliferative effects were studied in two cell lines: HeLa and HaCaT. The latter was also used to determine the protective effect of the FPH during induced oxidative stress. Alcalase showed the highest proteolytic activity, while the produced flaxseed protein hydrolysate (FPH-A) exhibited the strongest antioxidant potential. FPH-A had cytotoxic effects at 10 mg/mL in HeLa cells, but it stimulated HaCaT cell growth. Moreover, a mild protective effect of FPH-A was detected in HaCaT cells after induction of oxidative stress. Flaxseed protein hydrolysates obtained by Neutrase (FPH-N) and Protamex (FPH-P) have less pronounced or no potential at all, with respect to their antioxidative or antiproliferative activity. Therefore, to increase value-added utilization of flaxseed meal we suggest further research on hydrolysate obtained by Alcalase.

Enabling technologies for the extraction of grape-pomace anthocyanins using natural deep eutectic solvents in up-to-half-litre batches extraction of grape-pomace anthocyanins using NADES.

Bioactive compounds should be extracted using alternative solvents and enabling technologies, in accordance with green extraction principles. The aim of this study is to develop an eco-friendly extraction method for grape-pomace anthocyanins on a larger scale. From a preliminary screening of 8 different natural deep eutectic solvents (NADES), a combination of choline chloride:citric acid was selected because of its price, physicochemical properties, and anthocyanin recovery and stability. The effects of multimode-microwave (MW), and low-frequency-ultrasound (US) irradiation (used alone or simultaneously), as well as that of process parameters on extraction efficiency have been investigated in order to maximise anthocyanin extraction yield. The best conditions were found to be: simultaneous ultrasound/microwave-assisted extraction (UMAE) (MW power at 300 W, US power 50 W), for 10 min with 30% (v/v) of water. This gave 1.77 mg gdw-1 of anthocyanins. Anthocyanins were efficiently recovered from NADES, which were recycled. The optimised procedure was scaled up to a half-litre batch.

Ready-to-use green polyphenolic extracts from food by-products.

To establish environmentally friendly polyphenolic extracts from grape and olive pomace, natural deep eutectic solvents (NADES) were used coupled with alternative energy sources - ultrasound and microwave irradiation. Obtained extracts were characterized by HPLC analysis, while antioxidant capacity was determined by ORAC method. Furthermore, in vitro cytotoxicity of prepared extracts was assessed by antiproliferation assay on two tumour cell lines, whereas for investigation of type of cell death or cell cycle arrest a flow cytometric analysis was applied. In addition, a detection of compounds with DNA/RNA-bindingaffinity in extracts was investigated by UV/Vis and circular dichroism spectroscopy. Grape pomace extract in NADES showed to be the best of all extracts tested, with regard to extraction of total polyphenolic compounds (p < 0.05) and related biological activities such as antioxidant and antiproliferative activity. Prepared polyphenolic extracts in NADES could be considered as ready-to-use in food and pharmaceutical industry without demanding and expensive downstream purification steps.

Green asymmetric reduction of acetophenone derivatives: Saccharomyces cerevisiae and aqueous natural deep eutectic solvent.

OBJECTIVE: Chiral building blocks [(S)-1-(3-methylphenyl)ethanol, (S)-1-(3,4-dimethylphenyl)ethanol and (S)-1-(2,4,6-trimethylphenyl)ethanol] for drug synthesis were prepared using two green approaches: (1) the yeast Saccharomyces cerevisiae as the biocatalyst and (2) the natural deep eutectic solvents (NADES) as the alternative solvents. Three different NADES with different water contents were prepared and screened for the highest conversion and enantiomeric excess of reduction of 1-(3-methylphenyl)ethanone, 1-(3,4-dimethylphenyl)ethanone (DMPA) and 1-(2,4,6-trimethyphenyl)ethanone by S. cerevisiae. The results were used in the development of eco-friendly procedures on a preparative scale. RESULTS: The highest enantioselectivity of baker´s yeast was for the bioconversion of DMPA in choline chloride:glycerol with 30% (v/v) of water (ChGly30). This reaction was used for further studies. Parameters such as pre-treatment of biocatalysts and recyclation of solvent were tested for a possible scale-up of this reaction system. Conversion was improved with the ultrasound pre-treatment of the biocatalysts in ChGly30. Moreover, the biocatalytic asymmetric reduction of DMPA in ChGly30 was successfully performed on a preparative scale with the efficient recyclation of NADES in two cycles, in which the reduction of DMPA was also successfully performed. CONCLUSION: Three enantioselective reductions in NADES with baker's yeast were successfully conducted. According to the highest enantioselectivity of the biocatalyst, the asymmetric reduction of 1-(3,4-dimethylphenyl)ethanone in ChGly30 was also performed on a preparative scale with efficient recyclation and reuse of NADES as a first step towards the implementation of this method on the industrial scale.

Antimicrobial, cytotoxic and antioxidative evaluation of natural deep eutectic solvents.

Natural deep eutectic solvents (NADES) are a new generation of green solvents. They are mixtures of two or three compounds such as choline chloride as a cationic salt and alcohols, acids, amides, amines or sugars as hydrogen-bond donors. Although the majority of NADES' components are of natural origin and therefore NADES are often presumed to be non-toxic, the evaluation of their toxicity and biodegradability must accompany the research on their synthesis and application. Therefore, the aim of this work was to investigate the effect of ten synthesised NADES towards bacteria (i.e., Escherichia coli, Proteus mirabilis, Salmonella typhimurium, Pseudomonas aeruginosa, Staphylococcus aureus), yeast (i.e., Candida albicans) and human cell lines (i.e., HeLa, MCF-7 and HEK293T). In addition, oxygen radical absorbance capacity (ORAC) method was used to determine the antioxidative activity of the tested NADES. Differences in toxicity response between microorganisms and cell lines were observed, and only NADES that contained organic acid showed toxicity towards the test systems. Furthermore, the NADES containing compounds that possess antioxidative activity also showed antioxidative activity. However, research whose primary purpose is the synthesis and application of NADES must be followed by an evaluation of their biological properties (e.g., antimicrobial activity, toxicity towards animal cells and antioxidative or other biological activity) to find the solvent with the best profile for wider industrial applications.