Natural Deep Eutectic Solvents and Their Applications in Biotechnology.

Natural deep eutectic solvents (NADES) have gained significant attention as green solvents due to their unique properties, such as high solubility, low volatility, low toxicity, and tunability. Liquid phase microextraction (LPME) is a sample preparation technique that plays a crucial role in analytical chemistry, and the use of NADES as extraction solvents in LPME offers numerous benefits compared to traditional solvents. NADES can effectively extract bioactive compounds from natural sources without damaging their structure and activity. They can also serve as solvents and catalysts in organic reactions, enhancing the bioavailability of natural compounds. In addition, NADES can be utilized as mobile or stationary phases in chromatographic techniques for separating and analyzing natural compounds. The review highlights the efficiency of NADES in terms of extraction ability, analyte stabilization capacity, and detection compatibility. Moreover, the availability of their components, ease of preparation, low toxicity, cost-effectiveness, and biodegradability make NADES attractive for researchers in the field of analytical chemistry. The applications of NADES in LPME contribute to the principles of green analytical chemistry and green sample preparation by providing a sustainable and environmentally friendly approach to sample preparation. A comprehensive overview of the applications of NADES in liquid phase microextraction is provided, emphasizing their potential for advancing green practices in analytical chemistry.

Shale instability is a significant problem, accounting for approximately 70% of wellbore challenges during drilling operations. To address this issue, shale inhibitors are commonly added to drilling mud to stabilize the encountered shale formations. Ionic liquids and deep eutectic solvents have been recognized as effective shale inhibitors due to their environmental friendliness and effectiveness. However, despite their advantages, these solutions still lack full environmental sustainability, leading researchers to explore more natural alternatives like Natural Deep Eutectic Solvents (NADES). This study focuses on the synthesis and application of a NADES composed of Potassium Chloride (KCl) and glycerine, aiming to enhance the environmental profile and efficacy of shale inhibitors. The NADES was prepared with a 1:8 molar ratio at a temperature of 60 °C. Characterization analyses, including Fourier Transform Infrared and Thermogravimetric Analysis, confirmed the formation of bonds between –(OH) and Cl− and demonstrated the NADES's thermal stability up to 200 °C. Incorporating 3% NADES into water-based mud, prepared following API 13B-1 standards, resulted in significant improvements in mud rheology. Specifically, the addition of 3% NADES reduced filtrate volume by 14.2% and mud cake thickness by 19.2%. Furthermore, the 3% NADES exhibited remarkable inhibition of clay swelling by 69.23% and demonstrated a shale recovery rate of 58%. When compared with 3% KCl and 3% 1-ethyl-3-methylimidazolium chloride (EMIM-Cl), the NADES-based mud outperformed both in terms of efficacy. These findings were further supported by additional analyses, including d-spacing measurements (XRD), Zeta Potential, Surface tension, and Field Emission Scanning Electron Microscopy. Additionally, the rheological behavior of the NADES-based mud aligned with the Yield Power Law at both 25 °C and 100 °C. The study's findings contribute to the advancement of greener drilling practices and highlight the applicability of KCl-based NADES as a potential drilling fluid additive.

Currently, biorefinery process from cellulosic biomass is complex and energy-intensive where biomass fractionation, a key step for production of biomass-derived chemicals, demands conventional organic solvents. Since there is a clear and an unmet need for a robust and affordable biomass conversion technology, researchers are constantly developing novel, cost-effective green solvents that are eco-friendly, benign, renewable, and biodegradable in nature. In this perspective, natural deep eutectic solvents, commonly referred as NADES, have been evolved as the most advanced green solvents entirely made up of natural compounds to combat and deconstruct the recalcitrance of lignocellulosic biomass into the extraction of potential renewable chemicals. Although NADES are characteristically similar to deep eutectic solvents (DESs) and ionic liquids, NADES have shown advantages to combat the challenges associated with ionic liquids and DES by being highly specific and green in nature. Moreover, NADES could be recovered and recycled without losing their efficiency, making these solvents highly economical and sustainable. In this chapter, we have comprehensively described the applicability of NADES in biorefinery and bioprocessing as an effective tool of lignocellulosic biomass pretreatment for bioconversion processes.

During drilling, almost 70% of wellbore instability issues result from the encountering of shale formations. Various additives such as salts, silicates, and polymers are used in water-based mud to enhance its shale-inhibition capability; however, such additives have certain limitations. Lately, ionic liquids and deep eutectic solvents (DES) have been used by various research groups as shale inhibitors in drilling fluid due to their biodegradability and efficacy. However, their popularity faded when a natural derivative of DES, i.e., Natural Deep Eutectic solvent (NADES), came into the picture. This research utilizes the in-house-prepared Ascorbic acid and Glycerine (AA:Gly)-based NADES as a drilling fluid additive for shale inhibition and compares its efficacy with counterpart inhibitors such as KCl, imidazolium-based ionic liquid, and Choline Chloride-based DES. The results show that 3% NADES improved the overall Yield point to Plastic viscosity ratio, with a 39.69% decline in mud cake thickness and a 28% decline in the filtrate volume of drilling mud. Along with improved drilling fluid properties, 3% NADES resulted in 77.77% shale inhibition and 87% shale recovery. Surface tension, d-spacing, zeta potential, and FESEM have been conducted to justify and elucidate the inherent mechanism behind the working of NADES as a drilling fluid additive and clay stabilizer. Thus, Ascorbic acid-based NADES is recommended as a potential non-toxic and cheap drilling fluid additive to improve drilling fluid properties and clay stability.

Shale rock swelling poses a significant challenge during drilling a well, leading to issues related to wellbore instability. Water-based mud with specific shale inhibitors is preferred over oil-based drilling mud due to its lower environmental impact. Recently, ionic liquids (ILs) have emerged as potential shale inhibitors due to their adjustable properties and strong electrostatic attraction. However, research has shown that the most commonly used class of ILs (imidazolium) in drilling mud are toxic, non-biodegradable, and expensive. Deep Eutectic Solvents (DESs), the fourth generation of ionic liquids, have been proposed as a cheaper and non-toxic alternative to ILs. However, ammonium salt-based DESs are not truly environmentally friendly. This research explores the utilization of Natural Deep Eutectic Solvent (NADES) based on Epsom salt (a naturally occurring salt) and glycerine as a drilling fluid additive. The drilling mud is prepared according to API 13B-1 standards. Various concentrations of NADES-based mud are tested for yield point, plastic viscosity, and filtration properties for both aged and non-aged samples. The linear swell meter is used to determine the percentage swelling of the NADES-based mud, and the results are compared with the swelling caused by KCl- and EMIM-Cl-based mud. FTIR analysis is conducted to understand the interaction between NADES and clay, while surface tension, d-spacing (XRD), and zeta potential are measured to comprehend the mechanism of swelling inhibition by NADES. The findings reveal that NADES improves the yield point and plastic viscosity of the mud, resulting in a 26% reduction in mudcake thickness and a 30.1% decrease in filtrate volume at a concentration of 1%. NADES achieves a significant 49.14% inhibition of swelling at the optimal concentration of 1%, attributed to its ability to modify surface activity, zeta potential of clay surfaces, and d-spacing of clay layers. Consequently, NADES emerges as a non-toxic, cost-effective, and efficient shale inhibitor that can replace ILs and DESs.

Green solvents are intended to provide more sustainable alternatives in chemical synthesis, yet they often come with a trade-off in reaction efficiency. Natural Deep Eutectic Solvents (NADES) have recently attracted significant interest due to their intrinsic advantages-namely, biocompatibility, low toxicity, and readiness to biocompatibility, low toxicity, and readiness to biocompatibility, low toxicity, and readiness to biodegrade. Despite these benefits, several practical limitations remain, including their notably high viscosities (50-10,000 cP) , susceptibility to thermal degradation above 80°C , and compositional changes that occur during recycling, all of which restrict their broader applicability. This review critically examines the progress made from (2025 to 2025) in using NADES as a mediator for multicomponent reactions (MCRs) leading to nitrogen- based heterocyclic rings. Using rigorous inclusion criteria relevant to NADES- assisted MCRs within the specified timeframe, a total of 127 articles were found through systematic searches of Web of Science, Scopus, and PubMed. Many NADES- mediated transformations demonstrated remarkable efficiencies throughout these investigations; several reports indicated yields of 85 – 98 % and substantial increases in E- factor values of 40 – 70 % . The environmental benefits are somewhat offest by higher energy requirements, primarily because some protocols require higher temperatures and longer reaction times. NADES technology is still a feasible alternative to the conventional hazardous flow synthesis technique , and its promise is especially pertinent to sectors that largely depend on heterocyclic scaffolds, like fine chemicals, agrochemicals, and medicines. Moving forward, research should prioritize the development of task- specific NADES, optimization of reaction conditions for scale-up, and the establishment of standardized experimental procedures to enhance reproducibility across different laboratories. In addition to identifying important research gaps that need to be filled, this study advances the field by offering a fundamental framework for assessing (NADES) performance in industrial settings and setting reasonable standards for upcoming advancements in sustainable synthetic techniques.

Extraction of natural compounds generally uses organic solvents, which have a high risk to human health. Green solvents based on the natural deep eutectic solvents (NADES) have been used for the extraction of active compounds from coffee cherry waste. This research has formulated eight NADES based on choline chloride by combining fructose, citric acid, glycerol, proline, glucose, xylose, propylene glycol, and lactic acid with a mole ratio of 1:2. The FTIR analysis of NADES showed that there was a hydrogen bond interaction with OH group peaks in the wave number range 3012-3357 cm-1. NADES application was used for phenolic and tannin extraction from coffee cherry waste. The extraction efficiency of phenolic was combined of choline chloride with HBD of proline>xylose>glucose>glycerol>lactic acid >fructose>propylene glycol>citric acid. The maximum phenolic content in the extract using choline chloride-proline was 11.81 mg GAE/g. The ability of NADES to extract tannins using choline chloride with the combination of glucose>proline>lactic acid>propylene glycol>glycerol>citric acid> fructose. The maximum tannin content was obtained at 1.58% using NADES based on choline chloride with glucose. NADES has been successfully used as an environmentally friendly to replace organic solvents to extract phenolic and tannin in coffee cherry waste.

Eutectic mixture (EM) is as a mixture of more than one substance that does not interact individually to create a new entity but in a particular ratio that exhibits a lower range of melting point than it had in individual. EM should be formulated in such a way that it should have major advantages in pharmaceutical industries. EM can be a mixture of Active Pharmaceutical Ingredients (APIs), or different ratios of APIs and excipients, or various excipients. Deep eutectic solvents containing APIs (API-DES) considered as an innovative approach to form different APIs in the liquid state. This new approach of liquid form is versatile and plays an important role in drug delivery. The selection of ideal hydrogen bond-donor (HBD) and hydrogen bond-acceptor (HBA) is an essential parameter. Ionic liquids (IL), derivatives of deep eutectic solvents (DES) have got much attention since it can replace harmful organic solvent by their extraordinary properties. Therapeutic deep eutectic solvents (THEDESs) are considered to be an exceptional option in the advancement of biomedicine. This can be utilized for improvising drug solubility, bioavailability as well as drug permeation through the skin. Natural deep eutectic solvent (NADES) can be considered as an alternate option, replacing harsh solvents. It has special characteristics of better biodegradability and biocompatibility. These NADES mainly used to separate and purification of natural compounds. This review focuses on the eutectic mixture and its application in the area of drug delivery systems, and pharmaceutical and pharmacological fields.

In the past decade, natural deep eutectic solvents (NADESs) as green and sustainable extraction solvents with great potential for the efficient extraction of bioactive compounds from the plants are emerging. In this study, a microwave-assisted technology is used to prepare natural deep eutectic solvents. And natural deep eutectic solvents as pretreatment solvents coupled with microwave-assisted hydrodistillation (MAHD) for isolating essential oil (EO) derived from turmeric (Curcuma longa L.) is investigated. To improve the essential oil yield of turmeric (Curcuma longa L.) as a target, various factors affecting extraction efficiency including the type and amount of natural deep eutectic solvents, pretreatment time, pretreatment temperature and hydrodistillation (HD) time are discussed and optimized through central composite design (CCD) of the response surface methodology (RSM). The optimal conditions are as follows: natural deep eutectic solvent composed of choline chloride and oxalic acid (molar ratio with 1:1) as a pretreatment solvent, an amount of 60 g, a pretreatment time of 5 min, a pretreatment temperature of 84 ºC, a hydrodistillation time of 76 min. Under the optimum conditions, the highest essential oil yield of 0.85% is achieved. Additionally, the essential oil is analyzed by using gas chromatography-mass spectrometry (GC-MS), with a total of 49 compounds being identified. Through combining natural deep eutectic solvents with a microwave-assisted hydrodistillation technique, this work provides an eco-friendly extraction way of isolating essential oil, which boosts development in the monitoring other spice quality field.

The extraction of bioactive compounds from food wastes or by‐products with natural deep eutectic solvents (NADES) could be an attractive alternative to traditional hydroalcoholic extraction but needs to be optimized taking advantage of modeling. This work aims to propose, develop, and discuss a new model for the extraction of phenolic compounds from spent coffee grounds (SCGs) using NADES to overcome some gaps related to the kinetic extraction models and the surface response methodology. The model presented is based on the same assumption as the kinetic model, but improving it to be able to predict phenolic extraction changing different process parameters (e.g., water content, time of extraction, temperature, etc.) using betaine: triethylene glycol (molar ratio 1:2). The model was validated on the extraction of total phenolic compounds from SCG as a function of water content of NADES ranging from 30 to 60% v/v. There was good agreement between experimental and simulated data and even, in some cases, better than with the second‐order kinetic models. In addition, the new model needs fewer parameters to be regressed concerning the specific case investigated in this work. This model and methodology can be the basis for further modeling applicable to other bioactives, and/or other NADES and feedstocks.Practical ApplicationsNatural deep eutectic solvents (NADES) can be a potential sustainable solvent for the valorization of food by‐products as they can be used to extract bioactive compounds with high added value. This extraction process needs to be optimized depending on several factors like water content in NADES solution, solids ratio, extraction time, and temperature. The model validated in this work on spent coffee ground (SCG) could be used for this purpose, improving the gaps related to the kinetic extraction models and the surface response methodology (RSM). The new model enables predicting the behavior of the process as a function of the parameters previously mentioned and reduces the number of experimental trials required compared with RSM. In particular, the new model was validated on the variation of water content in NADES solution. Certainly, this model will need to be further validated, but, once further studies are conducted, this model could be used for scale‐up calculation and design optimization of the industrial process.

The effects of a hydrogen bond acceptor and hydrogen bond donor on carbon dioxide absorption via natural deep eutectic solvents were studied in this work. Naturally occurring non-toxic deep eutectic solvent constituents were considered; choline chloride, b-alanine, and betaine were selected as hydrogen bond acceptors; lactic acid, malic acid, and fructose were selected as hydrogen bond donors. Experimental gas absorption data were collected via experimental methods that uses gravimetric principles. Carbon dioxide capture data for an isolated hydrogen bond donor and hydrogen bond acceptor, as well as natural deep eutectic solvents, were collected. In addition to experimental data, a theoretical study using Density Functional Theory was carried out to analyze the properties of these fluids from the nanoscopic viewpoint and their relationship with the macroscopic behavior of the system, and its ability for carbon dioxide absorption. The combined experimental and theoretical reported approach work leads to valuable discussions on what is the effect of each hydrogen bond donor or acceptor, as well as how they influence the strength and stability of the carbon dioxide absorption in deep eutectic solvents. Theoretical calculations explained the experimental findings, and combined results showed the superiority of the hydrogen bond acceptor role in the gas absorption process, with deep eutectic solvents. Specifically, the cases in which choline chloride was used as hydrogen bond acceptor showed the highest absorption performance. Furthermore, it was observed that when malic acid was used as a hydrogen bond donor, it led to low carbon dioxide solubility performance in comparison to other studied deep eutectic solvents. The cases in which lactic acid was used as a hydrogen bond donor showed great absorption performance. In light of this work, more targeted, specific, deep eutectic solvents can be designed for effective and alternative carbon dioxide capture and management.

Application of green solvents as sorbent modifiers in sorptive-based extraction techniques for extraction of environmental pollutants

The soap content in biodiesel is an important challenge during the production and purification processing of biodiesel. Natural deep eutectic solvents (NADES) have recently attracted considerable interest as an environmentally suitable substitute for traditional solvents in the biodiesel industry. This work investigates the soap removal from the contaminated biodiesel using NADES. Eight choline chloride‐based deep eutectic solvents (DESs) were screened using the conductor‐like screening model for real solvents (COSMO‐RS) to identify the most suitable solvent for soap removal and were validated experimentally. The effect of NADES molar ratio, NADES:biodiesel ratio, mixing speed and extraction time on the extraction efficiency were investigated. COSMO‐RS screening revealed that the malonic acid‐based NADES possess higher soap elimination, and this is compatible with the experimental screening. The higher extraction efficiency of 99.18% was achieved under the optimum conditions of 1:3 of NADES molar ratio, 1:1 DES:biodiesel, 150 rpm and 15 min of extraction time. The soap removal followed the first‐order kinetic equation with a rate constant of 0.183 min−1. This technique offers innovative and environmentally friendly routes for downstream processing of contaminated biodiesel.

Deep eutectic and natural deep eutectic solvent in sample preparation

Interest in bioactive phytochemicals and sustainable processes is the driving force behind this study on two novel green extraction methods for the recovery of anthocyanins from the residues of blueberry processing. Five natural deep eutectic solvents (NADES) have been tested for anthocyanin extraction. Acidified hydroalcoholic solutions were used as benchmarks and the shelf life of eutectic systems was monitored. The most promising NADES was tested in microwave (MAE)- and ultrasound-assisted extractions (UAEs), and Peleg’s kinetic model was used. Both the enabling technologies provided performance that was superior to that of conventional extraction. MAE and UAE yielded up to 25.83 and 21.18 mg/gmatrix of total anthocyanin content, respectively, after 15 and 30 min. Moreover, a preliminary test for extract concentration and NADES recycling was performed using resin adsorption. Finally, the antiproliferative activity of the extracts was determined by a CellTiter 96® AQueous One Solution Cell Proliferation Assay, the so-called MTS assay, on human tumour HeLa cells and human skin HaCaT cells. Nonconventional extracts exhibited strong antiproliferative activity that was much greater than that of their conventionally extracted analogues. Flow cytometry was used to evaluate cell-death type, and apoptosis was found to be the primary cause of tumour cell death. The presented study demonstrates that the implementation of enabling extraction technologies and green solvents can produce an antiproliferative agent from a food industry byproduct.