Eco-friendly solvents in liquid-liquid microextraction techniques for biological and environmental analysis: a critical review.

In recent years, green solvents have emerged as promising alternatives in the field of analytical chemistry, replacing conventional organic solvents known for their toxicity, volatility, and flammability. The combination of these solvents with liquid-liquid microextraction techniques has facilitated the development of simpler, faster, more economical, and environment-friendly methodologies for the analysis of samples of varying complexity. This review discusses the fundamental physicochemical properties and advantages of using deep eutectic solvents, ionic liquids, switchable-hydrophilicity solvents, supramolecular solvents, and surfactants as extractants. Furthermore, analytical methods based on liquid-liquid microextraction techniques developed in the last 5 years for the determination of organic compounds and metals in biological and environmental samples are presented and discussed, highlighting their applications and benefits to improve analytical performance and sustainability.

Alternative green solvents associated with ultrasound-assisted extraction: A green chemistry approach for the extraction of carotenoids and chlorophylls from microalgae.

This study proposes a method for the ultrasonic extraction of carotenoids and chlorophyll from Scenedesmus obliquus and Arthrospira platensis microalgae with green solvents. Ethanol and ethanolic solutions of ionic liquids were tested with a variety of extraction parameters, including number of extractions, time of extraction, and solid-liquid ratio R(S/L), to determine the optimal conditions. After selecting the most effective green solvent (ethanol), the process conditions were established: R(S/L) of 1:10, three extraction cycles at 3 min each), giving an extraction yield of 2602.36 and 764.21 µgcarotenoids.gdried biomass-1; and 22.01 and 5.81 mgchlorophyll.gdried biomass-1 in S. obliquus and A. platensis, respectively. The carotenoid and chlorophyll extracts obtained using ethanol were shown to be potent scavengers of peroxyl radical, being 5.94 to 26.08 times more potent α-tocopherol. These findings pave the way for a green strategy for valorizing microalgal biocompounds through efficient and environmentally friendly technological processes.

A New Single-Step Approach Based on Supramolecular Solvents (SUPRAS) to Extract Bioactive Compounds with Different Polarities from Eugenia pyriformis Cambess (Uvaia) Pulp.

This work employed supramolecular solvents (SUPRAS) made up of octanoic acid, ethanol, and acidified water (pH ~ 3) to extract and concentrate bioactive compounds from Eugenia pyriformis Cambess (uvaia) pulp. At first, the SUPRAS phase characterization demonstrated the spherical aggregates' formation with an internal hydrophobic structure and an external hydrophilic media. Subsequently, the simultaneous production and extraction (SUPRAS-SPE) method was employed in the solid-liquid extraction (SLE) of uvaia pulp. The extracts were evaluated through Folin-Ciocalteu reducing capacity, antioxidant activity (DPPH assay), total carotenoid content (TCC), and total flavonoid content (TFC). The results showed that reducing the ethanol concentration in the SUPRAS composition boosted the TCC extraction while increasing the ethanol presence, promoting a high TFC yield. Moreover, the SUPRAS-SPE method was compared with the ex situ method (SUPRAS-ES), where the solvent was previously produced and then applied to the SLE. Both methods were evaluated concerning their EE% and thermal degradation. The SUPRAS-SPE method increased the EE% of uvaia pulp bioactive compounds compared to the SUPRAS-SE method, providing a suitable microenvironment to extract, concentrate, and stabilize carotenoids from uvaia pulp, offering a sustainable alternative to obtain valuable compounds.

Exploring a Sustainable Process for Polyphenol Extraction from Olive Leaves.

Olive leaves are residues from pruning and harvesting and are considered an environmental management problems. Interestingly, these residues contain high polyphenol concentrations, which can be used to treat chronic diseases. However, these compounds are a technological challenge due to their thermolability and reactivity during extraction. Thus, this study assessed the use of pressurized liquid extraction (PLE) with green solvents like water-ethanol and water-glycerol mixtures (0-15%) at 50 °C and 70 °C to yield polyphenol-rich antioxidant extracts with reduced glucose and fructose content. The use of 30% ethanol at 70°C presented the highest polyphenol content (15.29 mg gallic acid equivalent/g dry weight) and antioxidant capacity, which was expressed as IC50 (half maximal inhibitory concentration): 5.49 mg/mL and oxygen radical absorbance capacity (ORAC): 1259 µmol Trolox equivalent/g dry weight, as well as lower sugar content (glucose: 3.75 mg/g dry weight, fructose: 5.68 mg/g dry weight) compared to water-glycerol mixtures. Interestingly, ethanol exhibits a higher degree of effectiveness in recovering flavanols, stilbenes and secoiridoids, while glycerol improves the extraction of phenolic acids and flavonols. Therefore, to enhance the efficiency of polyphenol recovery during the PLE process, it is necessary to consider its solvent composition and chemical structure.

From Nature to Innovation: The Uncharted Potential of Natural Deep Eutectic Solvents.

This review discusses the significance of natural deep eutectic solvents (NaDESs) as a promising green extraction technology. It employs the consolidated meta-analytic approach theory methodology, using the Web of Science and Scopus databases to analyze 2091 articles as the basis of the review. This review explores NaDESs by examining their properties, challenges, and limitations. It underscores the broad applications of NaDESs, some of which remain unexplored, with a focus on their roles as solvents and preservatives. NaDESs' connections with nanocarriers and their use in the food, cosmetics, and pharmaceutical sectors are highlighted. This article suggests that biomimicry could inspire researchers to develop technologies that are less harmful to the human body by emulating natural processes. This approach challenges the notion that green science is inferior. This review presents numerous successful studies and applications of NaDESs, concluding that they represent a viable and promising avenue for research in the field of green chemistry.

Sequential Process of Subcritical Water Hydrolysis and Hydrothermal Liquefaction of Butia Capitata Endocarp to Obtain Fermentable Sugars, Platform Chemicals, Bio-oil, and Biochar.

Butia capitata endocarp (BCE) is a biomass residue with the potential to produce a wide variety of bio-products. The processing of BCE in a sequential process of subcritical water hydrolysis (SWH) and hydrothermal liquefaction (HTL) was investigated to obtain fermentable sugars, platform chemicals, bio-oil, and biochar. The SWH was evaluated at 230 and 260 °C and solvent: feed mass ratios (R) of 10 and 20 for the production of fermentable sugars and platform chemicals. The solid residue from SWH was sequentially submitted to the HTL at 330 and 360 °C for bio-oil and biochar production. The results were analyzed by comparing the sequential (SWH/HTL) and individual (HTL only) processes. The highest yields of fermentable sugars (5.26 g/ 100 g BCE) were obtained for SWH at 260 °C and R-20 with higher contents of xylose (2.64 g/100 g BCE) and cellobiose (1.75 g/100 g BCE). The highest yields of platform chemicals (2.44 g/100 g BCE) were obtained for SWH at 260 °C and R-10 with higher contents of acetic acid (1.78 g/100 g BCE) and furfural (0.54 g/100 g BCE). The highest yield of bio-oil (25.30 g/100 g BCE) occurred in HTL individual process at 360 °C and R-20. Sequential process SWH/HTL showed a decrease in bio-oil yield but maintained a similar biochar yield compared to HTL, in addition to the production of fermentable sugars and platform chemicals.

Morphological Characterization of Nicotiana tabacum Inflorescences and Chemical-Functional Analysis of Extracts Obtained from Its Powder by Using Green Solvents (NaDESs).

The production of smokeable tobacco for use in cigarettes is characterized by the production of pre-harvest and post-harvest waste, with ensuing undesirable effects on the environment. The inflorescences of tobacco after blunting, deflowering, or topping are considered pre-harvest waste and left in the field. Using green and ecofriendly solvents such as Natural deep eutectic solvents (NaDESs), these wastes could be used to obtain antioxidant molecules of interest in cosmetics. Taking into account its potential as plant matrix to obtain metabolites of commercial interest, tobacco inflorescences and inflorescence powders of different particle sizes were characterized by optic and electronic microscopy. Thus, the powdered inflorescences were extracted with four conventional solvents, i.e., distilled water (DW), acetone: distilled water (AW), ethanol 70° (EW), methanol (Me), and five NaDESs, i.e., lactic acid: sucrose (LAS), lactic acid: sucrose: distilled water (SALA), fructose: glucose: sucrose: distilled water (FGS), choline chloride: urea: distilled water (CU), and citric acid: propylene glycol (CAP). Among the tested NADESs, SALA was the most promising solvent; higher extraction yields of total phenolic compound (3420.0 ± 9.4 µg GAE/mL) than conventional solvents were attained and it was the only selective solvent to phenolics. CU was the best solvent for flavonoids and alkaloids extraction (215.3 ± 3.2 µg QE/mL and 392.3 ± 8.0 µg ACE/mL, respectively). All extracts showed antioxidant activity. A heatmap with dendrogram and main component analysis showed that acid-based NaDESs are grouped together, this group being the one with the best performance in H2O2 scavenging. The extracts obtained with green solvents could be used directly in cosmetic formulations as antioxidant ingredients because both tobacco flower oil and flower extracts are listed in the cosmetic ingredients database as non-toxic products. Additionally, the demand for sustainable ecological cosmetics is growing. In this sense, NaDESs represent an opportunity to develop innovative extracts with unique phytochemical fingerprints and biological activities.

Nicotiana tabacum Leaf Waste: Morphological Characterization and Chemical-Functional Analysis of Extracts Obtained from Powder Leaves by Using Green Solvents.

Tobacco cultivation and industrialization are characterized by the production of trillions of pre-harvest and post-harvest waste biomasses each year with the resulting negative effects on the environment. The leaves of blunt, pre-harvest waste, could be further used to obtain bioactive metabolites, i.e., polyphenols and alkaloids, for its potential cosmetic use. This study was conducted to obtain bio-compounds from pre-harvest tobacco leaf waste (var. Virginia) by applying conventional and green solvents (NaDES). Leaves and ground leaf waste were characterized based on their microscopic features. Conventional solvents, such as water, acetone, ethanol, and non-conventional solvents, such as Natural Deep Eutectic Solvents (NaDES), i.e., sucrose:lactic acid (LAS), frutose:glucose:sucrose (FGS), lactic acid:sucrose:water (SALA), choline chloride:urea (CU), and citric acid: propylene glycol (CAP) were used for bioactive extraction from tobacco waste powder. CU, FGS, and acetone/ethanol had similar behavior for the best extraction of alkaloids (6.37-11.23 mg ACE/g tobacco powder). LAS, FGS, SALA, and CU were more effective in phenolic compound extraction than conventional solvents (18.13-21.98 mg AGE/g tobacco powder). Because of this, LAS and SALA could be used to obtain phenolic-enriched extracts with lower alkaloid content rather than CU and FGS. Extracts of the powder obtained with conventional solvent or CU showed a high level of sugars (47 mg/g tobacco powder) The ABTS antioxidant capacity of tobacco leaf powder was higher in the extracts obtained with CU, FGS, and acetone (SC50 1.6-5 µg GAE/mL) while H2O2 scavenging activity was better in the extracts obtained with LAS, CAP and SALA (SC50 3.8-8.7 µg GAE/mL). Due to the biocompatibility of the NaDES with the components of tobacco leaf waste, the opportunity to apply these extracts directly in antioxidant formulations, such as cosmetics, phytotherapic, and other formulations of topic use seems promising. Furthermore, NaDES constituents, i.e., urea and organic acid can also have beneficial effects on the skin.

Pressurized aqueous solutions of deep eutectic solvent (DES): A green emergent extraction of anthocyanins from a Brazilian berry processing by-product.

Deep eutectic solvents (DES) are emergent solvents with high extractability of bioactive compounds. Therefore, anthocyanin rich-fractions were recovered from jaboticaba peels by combining aqueous solutions of DES and pressurized liquid extraction (PLE). The extraction occurred at 10 MPa, 12 min, with conditions optimized through response surface methodology: 47% DES concentration, 90 °C, and 5.3 mL/min flow rate. PLE with different DES (choline chloride combined with propylene glycol or malic acid) solutions were compared to conventional solvents (water and acidified water) concerning yield, thermostability, antioxidant, anti-diabetic, and anti-obesity activities. DES solutions presented anthocyanin yields up to 50% higher than conventional solvents. ChCl:Ma, with the highest anthocyanin stability ( E a  = 77.5 kJ.mol-1), was a promising solvent concerning color, anti-diabetic and anti-obesity potential. Environmental analysis by Green Certificate and EcoScale indicated PLE with DES solutions is a green and efficient approach to recover anthocyanin from jaboticaba peel, providing useful extracts.

Evaluation of Techniques for Intensifying the Process of the Alcoholic Extraction of Coffee Ground Oil Using Ultrasound and a Pressurized Solvent.

Ultrasound-assisted extraction (UAE) and pressurized liquid extraction (PLE) techniques were evaluated and compared with conventional extraction for obtaining spent coffee ground oil (SCGO). The use of absolute ethanol (ET0) and hydrated ethanol (ET6) as solvents, two levels of SCG mass ratio:solvent, 1:4 (U4) and 1:15 (U15), and ultrasound powers of 0, 200, 400, and 600 W were tested. ET0 and U15 resulted in higher extraction yields of SCGO (YSCGO, 82%). A positive effect of sonication on YSCGO was observed only for condition U4. UAE resulted in defatted solids (DS) with higher apparent density values, corroborating the increase in the amount of smaller diameter particles due to sonication. The micrographs showed changes in the surfaces of the solids from the UAE and PLE, although the crystalline structures of the DS were not altered. UAE and PLE, compared to conventional extraction, did not allow significant gains in terms of YSCGO and, consequently, in the number of contact stages in an extractor configured in cross-currents.

Vegetable oils as green solvents for carotenoid extraction from pumpkin (Cucurbita argyrosperma Huber) byproducts: Optimization of extraction parameters.

Pumpkin pulp is the main waste generated by pumpkin seed growers. This agro-industrial waste is a valuable source of bioactive compounds, especially carotenoids (ß-carotene, α-carotene, and lutein), which exhibit a broad spectrum of health-promoting effects. In this study, vegetable oils (canola, corn, and soybean oil) were used as green solvent alternatives to conventional organic solvents for carotenoid extraction from dried pumpkin pulp (DPP) waste. The highest carotenoid extraction yield (CEY) was obtained with canola oil, at a 1:10 DPP/oil ratio. Response surface methodology (RSM) was used to optimize the extraction process parameters (temperature, time, and stirring rate) through a Box-Behnken design (BBD) maximizing CEY in canola oil. The extraction temperature and stirring rate were found to have a significant linear and quadratic effect, respectively, on CEY. Optimum conditions were achieved at 21.8 min, 250 rpm, and 60°C. Under these optimized conditions, the estimated value for CEY was 378.1 µg ß-carotene equivalents/g of DPP, corresponding to 61.6% of the total carotenoid content present in the DPP. In contrast, the observed experimental value was 373.2 µg ß-carotene equivalents/g of DPP (61.2%). The experimental value was very close to the estimated value, which verifies the model's adequacy and fit. This study shows an alternative method to extract carotenoids from DPP with canola oil, obtaining an oil naturally enriched with carotenoids that could be used as a potential functional ingredient in the development of food, cosmetics, and medicinal products. PRACTICAL APPLICATION: Pumpkin by-products are a potential carotenoid source. Vegetable oil can be used as an alternative solvent for carotenoid extraction from pumpkin residues to obtain an enriched carotenoid oil that can be used to formulate food products.

Metabolomics of Pigmented Rice Coproducts Applying Conventional or Deep Eutectic Extraction Solvents Reveal a Potential Antioxidant Source for Human Nutrition.

Rice bran (RB) corresponds to the outer layers of whole grain rice and contains several phenolic compounds (PCs) that make it an interesting functional food ingredient. PC richness is enhanced in pigmented RB varieties and requires effective ways of extraction of these compounds. Therefore, we investigated conventional and deep eutectic solvents (DES) extraction methods to recover a wide array of PCs from red and black RB. The RB were extracted with ethanol/water (60:40, v/v) and two DES (choline chloride/1.2-propanediol/water, 1:1:1 and choline chloride/lactic acid, 1:10, mole ratios), based on Generally Recognized as Safe (GRAS) components. Besides the quantification of the most typical phenolic acids of cereals, nontargeted metabolomic approaches were applied to PCs profiling in the extracts. Globally, metabolomics revealed 89 PCs belonging to flavonoids (52%), phenolic acids (33%), other polyphenols (8%), lignans (6%) and stilbenes (1%) classes. All extracts, whatever the solvents, were highly concentrated in the main phenolic acids found in cereals (37-66 mg/100 g in black RB extracts vs. 6-20 mg/100 g in red RB extracts). However, the PC profile was highly dependent on the extraction solvent and specific PCs were extracted using the acidic DES. The PC-enriched DES extracts demonstrated interesting DPPH scavenging activity, which makes them candidates for novel antioxidant formulations.

Natural deep eutectic solvent (NADES)-based blueberry extracts protect against ethanol-induced gastric ulcer in rats.

Blueberry is a polyphenol-rich fruit bearing great bioactive potential. Natural deep eutectic solvents (NADES) emerged as putatively biocompatible solvents that could substitute for toxic organic solvents in the extraction of fruit phenolic compounds for developing nutraceuticals or functional foods. Therefore, the aim of this study was to investigate the gastroprotective effects and the biocompatibility of a blueberry crude extract (CE) obtained using NADES and of the extract fractions (anthocyanin-rich fraction - ARF; non-anthocyanin phenolic fraction - NAPF) in a model of ethanol-induced gastric ulcer in rats. CE was the NADES-containing, ready-to-use extract that was obtained using choline chloride:glycerol:citric acid NADES (0.5:2:0.5 M ratio). ARF and NAPF were the NADES-free fractions obtained by solid phase purification of CE and were investigated to identify the bioactive fraction responsible for the effects of CE. Animals were treated for 14 days with water, NADES vehicle, CE, ARF, NAPF or lansoprazole (intragastric) and then received ethanol to induce gastric ulcer. CE decreased ulcer index and preserved the integrity of gastric mucosa. The pretreatment with CE or ARF reduced glutathione depletion and the inflammatory response. All treatments, including NADES vehicle reduced protein oxidation and nitric oxide overproduction in ethanol-treated rats. Additionally, ARF increased short-chain fatty acids in feces. These findings suggest that NADES can be used to obtain biocompatible extracts of blueberry that exhibit gastroprotective effects with no need of solvent removal. The gastroprotective effects were mainly associated to ARF but NAPF and even NADES vehicle also contributed to some protective effects.

Eco-friendly and Enantiospecific Biginelli Synthesis Using (+)-Myrtenal as the Substrate - An Impeccable and Unequivocal Analysis of the Product.

BACKGROUND: We found in the literature, an excellent review of the Biginelli reaction that addresses the methodologies for obtaining enantiopure dihydropyrimidinones (DHPMs). In 1992, optically pure DHPMs were obtained by fractional crystallization of the diastereomeric ammonium salt derivative with (S)-(-) and (R)- (+)-α-methyl benzylamine and by other chiral resolution techniques, such as chiral high-performance liquid chromatography (HPLC). Asymmetric syntheses of these compounds are also explained in the literature. The main strategy is to use acid catalysts such as organophosphates, organometallic complexes, amines and diamines, nanocomposites, and chiral ionic liquids, e.g., L-prolinium sulfate (Pro2SO4). OBJECTIVE: The objective was to study the Biginelli reaction with a chiral aldehyde. METHODS: A mixture of ethyl acetoacetate (0.26 g, 3 mmol), urea (0.18 g, 3 mmol) and ethyl lactate (EL) (1 mL) was left under heating at 70°C and stirring for 1 h. Next, (-)-(1R)-myrtenal (0.45 g, 3 mmol) was added, and the medium was heated for 5 h more until the formation of a white solid. Ten millilitres of distilled water was added, and the product was extracted with CH2Cl2 (3 x 4 mL). The solvent was evaporated, and the product was recrystallized from ethanol-water. RESULTS AND DISCUSSION: (+)-Myrtenal was used as a chiral substrate for a study that led to ethyl (R)-4-((1R,5S)- 6,6-dimethylbicyclo [3.1.1]hept-2-en-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate by the Biginelli synthesis using EL as a green solvent. The result is the first example of the enantiospecific Biginelli reaction. The product was exhaustively characterized by several physical analysis methods, i.e., 1H, 13C and 2D nuclear magnetic resonance (NMR) spectroscopies, infrared (IR) spectroscopy, mass spectrometry (MS), and high-resolution MS (HRMS), and its structure was unequivocally elucidated by X-ray crystallography. CONCLUSION: Compound (4R)-4-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-6-methyl-2-oxo-1,2,3,4- tetrahydropyrimidine- 5-ethyl carboxylate is the first example of the enantiospecific Biginelli reaction. In addition, the process has the advantage of using EL as a green solvent. The product was characterized by 1H, 13C, and 2D NMR and IR spectroscopy, MS, HRMS, and X-ray crystallography.

Natural deep eutectic solvents for sample preparation prior to elemental analysis by plasma-based techniques.

Natural deep eutectic solvents (NADES) based on xylitol, citric acid, and malic acid were synthesized and were then characterized using infrared spectroscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), also density and viscosity were measurements. The deep eutectic solvents were used as solvent in ultrasound-assisted extraction (DES-UAE) of plant samples prior to elemental analysis. Inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectrometry (ICP OES) were employed for the determination of As, Ca, Cd, Cu, Fe, K, Mg, Mn, Na, P, and Zn in the extracts. The infrared analyses of the NADES revealed bands characteristic of the initial reagents, with the presence of hydrogen bonds, which confirmed the formation of a NADES. The thermal analyses showed decomposition temperatures of around 170 °C and endothermic events related to degradation of the NADES. The viscosity and density parameters were found to be related to the presence of hydrogen bonds. The extraction recoveries ranged from 80% to 120%, with some analytes presenting poor recoveries. There were no significant differences between the NADES, in terms of the concentrations of the analytes found in the extracts. However, there were differences between the analyte concentrations obtained using the NADES extraction method and the concentrations obtained using microwave-assisted acid digestion (MW-AD), possibly due to the different types of interactions between the solvents and the analytes. Plant tissues are complex matrices containing substantial amounts of silica, so some elements may be tightly bound and consequently difficult to release. The results indicated that UAE using NADES is a promising technique for the elemental extraction of plant samples.