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Theoretical insights into the cineole-based deep eutectic solvents
Abstract
Deep eutectic solvents based on cineole as hydrogen bond acceptors and organic acids (succinic, malic, and lactic) as hydrogen bond donors are studied using a theoretical approach. The nature, strength, and extension of hydrogen bonding are analyzed, thus quantifying this prevailing interaction and its role in the fluid properties. Density functional theory was used to study small molecular clusters, and the topological characterization of the intermolecular forces was carried out using atoms in a molecule theory. Classical molecular dynamics simulations were considered to study nanoscopic bulk liquid properties and their relationship with relevant macroscopic properties such as density or thermal expansion. The reported results provide the characterization of environmentally friendly deep eutectic solvents and show the suitability of cineole for developing these sustainable materials.
... Aparicio's group has used a combination of QM and MD to investigate the properties of a number of DESs, including ones based on ChCl [52][53][54][55], ammonium [149], arginine [150][151][152], betaine [153], and cineole [154] for applications such as gas capture, drug delivery, oil desulfurization, and the development of task-specific solvents. In particular, the strength and localization of H-bonds, the binding energy of the ionic pairs, as well as energetically favored positions of solvated molecules with respect to DES molecules were obtained from DFT. ...
... It is important to note that the viscosity of DESs based on formic acid is two times lower due to its smaller size and faster movement in the liquid structure. The importance of the size of HBD was also shown by Rozas et al. [154] who used MD simulations and revealed the mechanism of H-bond network formation in salt-free cineole-based DES based on different acid HBDs: the interaction between cineole and HBD are highly dependent on the size of the HBD. Access to the ester group of cineole is sterically hindered, and only small molecules can form the most favorable interactions with it. ...
Deep eutectic solvents (DESs) are one of the most rapidly evolving types of solvents, appearing in a broad range of applications, such as nanotechnology, electrochemistry, biomass transformation, pharmaceuticals, membrane technology, biocomposite development, modern 3D-printing, and many others. The range of their applicability continues to expand, which demands the development of new DESs with improved properties. To do so requires an understanding of the fundamental relationship between the structure and properties of DESs. Computer simulation and machine learning techniques provide a fruitful approach as they can predict and reveal physical mechanisms and readily be linked to experiments. This review is devoted to the computational research of DESs and describes technical features of DES simulations and the corresponding perspectives on various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.
... Aparicio's group has used a combination of QM and MD to investigate the properties of a number of DESs, including ones based on ChCl [35][36][37][38], ammonium [133], arginine [134][135][136], betaine [137], and cineole [138] for applications such as gas capture, drug delivery, oil desulfurization, and the development of task-specific solvents. In particular, the strength and localization of H-bonds, the binding energy of the ionic pairs, as well as energetically favored positions of solvated molecules with respect to DES molecules were obtained from DFT. ...
... It is important to note that the viscosity of DESs based on formic acid is two times lower due to its smaller size and faster movement in the liquid structure. The importance of the size of HBD was also shown by Rozas et al. [138] who used MD simulations and revealed the mechanism of H-bond network formation in saltfree cineole-based DES based on different acid HBDs: the interaction between cineole and HBD are highly dependent on the size of the HBD. Access to the ester group of cineole is sterically hindered, and only small molecules can form the most favorable interactions with it. ...
Deep eutectic solvents (DESs) are one of the most rapidly evolving types of solvents, appearing in a broad range of applications such as nanotechnology, electrochemistry, biomass transformation, pharmaceuticals, membrane technology, biocomposite development, modern 3D-printing, and many others. The range of their applicability continues to expand, which demands the development of new DESs with improved properties. To do so requires an understanding of the fundamental relationship between the structure and properties of DESs. Computer simulation and machine learning techniques provide a fruitful approach as they can provide predictions, reveal physical mechanisms and readily be linked to experiments. This review is devoted to the computational research of DESs and describes technical features of DES simulations and the corresponding perspectives on various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.
... Using natural compounds in their formulation has been considered to develop more sustainable processes by reducing toxicity and price and increasing biodegradability [48][49][50][51]. Among them, terpenes have been used to form hydrophobic eutectic solvents [52][53][54][55][56][57][58][59][60] due to the asymmetric polarity of many of them, giving rise to type V eutectic solvents [61,62]. ...
The presence of pharmaceuticals in wastewater, mainly in hospital wastewater, is a serious environmental concern, as they are not removed by conventional processes in wastewater treatment plants and are discharged into the natural environment. This work proposes extracting drugs from hospital wastewater using natural, renewable, and non-toxic solvents such as terpenes and eutectic solvents. First, molecular simulation has been used with the COSMO-RS method performing a massive screening of 43 terpenes, 11 eutectic solvents, and 5 conventional solvents with 31 common pharmaceuticals. The most promising solvents in the screening have been chosen to extract 11 pharmaceuticals simultaneously. Experimental tests with ultrapure water and real hospital wastewater matrices showed a strong influence of pH and matrix on extraction. Under the optimal conditions, global pharmaceutical extraction yields with carvacrol of 94.16 % and the eutectic solvent thymol+dodecanoic acid of 96.86 % were obtained. The regeneration and reuse of both solvents were studied in 5 consecutive stages, showing the carvacrol's high stability and regenerability. Using carvacrol, countercurrent extraction tests showed a fast mass transfer of pharmaceuticals and high extraction yields using low solvent-to-feed (S/F) ratios. The predictions obtained with COSMO-RS were similar to the experimental results, confirming the reliability of this method for selecting alternative solvents for the extraction of pharmaceuticals. Finally, the drug removal process was simulated in a countercurrent extraction. The complete removal of pharmaceuticals from hospital wastewater could be achieved using carvacrol with an S/F of 2.00 at pH 4.00 in an extractor with six equilibrium stages.
... NADES have been considered in various different applications in the recent years such as pharmaceutical applications, as liquid catalysts, solvent extraction agents [9] and gas capture agents [12,13,14,15,16]. In a recently study we have shown the potential of cineole-based HBA combined with and set of organic acids as HBD (malic acid, succinic acid, and lactic acid) on CO 2 solubility through theoretical study [17]. These NADES systems were scrutinized through density functional theory (DFT) and molecular dynamics (MD) simulations to establish and characterize the intermolecular forces using atoms in a molecule theory and to analyze the nanoscopic behavior of bulk phase properties through MD. ...
Terpene based natural deep eutectic solvents (NADES) formed by using carvone as hydrogen bond acceptor and series of organic acids including tartaric, succinic, malic, and lactic acids as hydrogen bond donors are studied using a combination molecular simulation methods. Density functional theory (DFT) was used to study small molecular clusters, and the topological characterization of the intermolecular forces by using atoms-in-a-molecule theory (AIM). Close-range interactions between the optimized carvone (CARV) bases eutectic solvents between carbon dioxide (CO2) have been studied for potential utilization of these solvents for gas capture purposes. Furthermore, COSMO-RS calculations have been carried out for CO2 solubilization performance of NADES compounds, and to obtain s-profiles in order to infer on the polarity and H-bond forming ability of the studied solvents. On the other hand, molecular dynamics (MD) simulations were carried out to analyze the bulk liquid properties and their relationship with relevant macroscopic properties (e.g., density or thermal expansion). Last but not least, relevant toxicity properties of the studied systems were predicted and reported in this work. The reported results provide the characterization of environmentally friendly NADES and show the suitability of CARV for advanced applications as CO2 solubilizers.
... In a similar vein, the mesoscale structure in ChCl-based DESs at the Pd interface is also modulated by the hydrogen bond donor. 16 Rozas et al. 17 showed using quantum chemical and molecular dynamics simulations that natural DES (NADES) formed between cineole and various organic acids all exhibit highly localized hydrogen bonding networks via the cineole ether moiety, which persist at elevated temperatures. It is suggested that such cineole-based DES may have utility as acid-gas capture solvents (e.g., for CO 2 sequestration). ...
When selecting a solvent for a given solute, the strongly held idiom “like dissolves like”, meaning that polar solvents are used for polar solutes, is often used. This idea has resulted from the concept that most molecular solvents are homogeneous. In a deep eutectic solvent (DES), however, both components can be ionic or non-ionic, polar or non-polar. By tuning the components, DESs can solubilize a wide variety of solutes, often mixing hydrophobic and hydrophilic components, and the mixture can be designed to control phase behavior. The liquids often contain significant short-length order, and preferential solvation of one component often occurs. The addition of small polar molecules such as water or alcohols results in non-homogeneous liquids, which have significantly decreased viscosity and increased ionic conductivity. Accordingly, the areas covered in this special issue focus on structure and dynamics, solvation, the mobility of charged species, and the ability to obtain controllable phase behavior by adding polar diluents or using hydrophobic DESs.
Olive oil production leads to the generation of olive mill wastewater (OMWW). Due to the presence of phenolic compounds, they are difficult to process, but they represent a source of high-added value chemicals since they have antioxidant and therapeutic properties. This work has studied the extraction of phenolic compounds from a type of OMWW, olive vegetation water, which presents these compounds in a more diluted dosage than in other studied to date, to revalue this waste stream. A real olive vegetation water from a Spanish olive oil producer was used, and liquid-liquid extraction was applied. Terpenoids and terpene-based hydrophobic eutectic solvents were systematically used to extract phenolic compounds following the concentrations of tyrosol, catechol, caffeic acid, and total phenolic content. By molecular simulation with the COSMO-RS method, 4 terpenoids, and 2 eutectic solvents were selected and compared with 2 conventional solvents. The Solvent/Feed ratio in the extraction of phenolic compounds was studied, showing that the solvents with the highest extraction results were geraniol, eucalyptol, and eutectic solvent menthol + camphor, which outperformed conventional solvents methyl isobutyl ketone and diisopropyl ether. Menthol + camphor gave total phenol extraction yields of 88.73% at a Solvent/Feed ratio in volume of 0.50, surpassing all solvents tested. A solvent reuse and regeneration process was applied by back-extraction of the 4 solvents: FTIR results showed the stability of the solvents while maintaining yields in the solvent reuse process. The phenolic compounds could be concentrated in the alkaline phase to factors up to 49.3 to the initial concentration in olive vegetation water. The alkaline phases were neutralized to obtain a precipitate with a caffeic acid content of up to 26 % wt%, and a tyrosol-rich supernatant with a concentration of up to 6.54 g/L. This work proposes a process using natural solvents to extract phenolic compounds from olive vegetation water.
Novel solvents and their applications are experiencing an increasing interest by the scientific community. Imidazole has been utilized as a major component in many successful ionic liquids. However, very limited studies were reported for using it as a hydrogen bond acceptor in the synthesis of eutectic solvents. In this work, a novel eutectic solvent composed of Imidazole and Monoethanolamine (MEA) is synthesized at different molar ratios. The basic physicochemical properties such as melting point, density, viscosity, and refractive index were measured at different temperatures and modeled as a function of molar composition and temperature. FTIR and ¹H NMR analyses were conducted and, the nature and strength of the molecular interaction between the two solvent molecules were investigated by conducting combined molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The study revealed the electrostatic H-bonding nature of interaction with strength related to their bond distances. The binding energy between the two DES ingredients is proportional to the amount of MEA in the DES due to increasing the H-bonding interactions between Imidazole and MEA molecules. These findings suggest that DES might be used in a variety of chemical and industrial applications.
A theoretical study considering classical molecular dynamics simulations on Natural Deep Eutectic Solvents based on cineole and organic acids (malic, succinic, or lactic acid) and their behavior as a solvent for CO2 capture are reported. The nanoscopic properties of eutectic + CO2 mixtures in a wide composition range are studied, considering intermolecular forces, solvation, and the changes in the solvent properties upon CO2 absorption. Likewise, interfacial properties of the solvent in contact with vacuum and pure CO2 and flue gas–like gas phases were considered. The results on solvent–gas interfaces allowed the characterization of the mechanism of CO2 capture, considered as a two stages procedure started with the gas adsorption at the interphase followed by an interface to bulk solvent diffusion leading to the gas solvation in the fluid. The study probes the suitability of terpenoid–based natural eutectics for carbon capture operations, thus allowing green, low cost, and sustainable solvents.
Therapeutic deep eutectic systems (THEDES) emerged as alternative therapeutic agents that can enhance the bioavailability of the currently used active pharmaceutical ingredients. The use of THEDES in combination with supercritical CO2 has started to be explored to formulate drug delivery systems through green technology. This work aimed to develop THEDES-delivery systems for tuberculosis therapy, by encapsulating L-arginine-based THEDES in a lipidic matrix, through supercritical CO2 technology. From the phase equilibrium study of THEDES and CO2, PGSS was selected for THEDES encapsulation. Herein, THEDES encapsulation through PGSS was accomplished for the first time, with an average encapsulation efficiency of 75%. The influence of the THEDES water-content in PGSS processing was also studied, suggesting no interference of the THEDES-water content in the formulation of the THEDES particles. Furthermore, the cell viability of the THEDES and the particles with THEDES encapsulated was measured in L929 fibroblasts and the systems prepared were non-cytotoxic.
Skin penetration/permeation enhancers are compounds that improve (trans)dermal drug delivery. We designed hybrid terpene-amino acid enhancers by conjugating natural terpenes (citronellol, geraniol, nerol, farnesol, linalool, perillyl alcohol, menthol, borneol, carveol) or cinnamyl alcohol with 6-(dimethylamino)hexanoic acid through a biodegradable ester linker. The compounds were screened for their ability to increase the delivery of theophylline and hydrocortisone through and into human skin ex vivo. The citronellyl, bornyl and cinnamyl esters showed exceptional permeation-enhancing properties (enhancement ratios up to 82) while having low cellular toxicities. The barrier function of enhancer-treated skin (assessed by transepidermal water loss and electrical impedance) recovered within 24 h. Infrared spectroscopy suggested that these esters fluidized the stratum corneum lipids. Furthermore, the citronellyl ester increased the epidermal concentration of topically applied cidofovir, which is a potent antiviral and anticancer drug, by 15-fold. In conclusion, citronellyl 6-(dimethylamino)hexanoate is an outstanding enhancer with an advantageous combination of properties, which may improve the delivery of drugs that have a limited ability to cross biological barriers.
In this paper, we report high pressure experimental measurements and detailed density functional theory (DFT) as well as molecular dynamic (MD) simulations of methane (CH4) solubility in natural deep eutectic solvents (NADES) that were prepared by using alanine (Al), betaine (Be), choline chloride (ChCl) used as hydrogen bond acceptors (HBA) and lactic acid (La), malic acid (Ma), phyenlyaceticacid (Paa) as hydrogen bond donors (HBD). Al:La, Be:La, ChCl:La, ChCl:Ma and ChCl:Paa systems were experimented up to 50 bars at 298.15 K. Meanwhile, this work includes the quantum theory of atoms in molecules (QTAIM) calculations that allow quantifying and characterizing the short-range interactions of studied systems, which is reported first time for NADESs and CH4 interactions. Furthermore, MD simulations shed light into the characteristics of intermolecular forces, particularly for hydrogen bonding, molecular arrangements in the liquid phases and their role on fluid’s properties. Presented results showed that the studied NADESs can be used for selective CO2/CH4 separation in gas processing applications.
Deep eutectic solvents (DESs) based on terpenes are identified and characterized. 507 combinations of solid components are tested, which results in the identification of 17 new hydrophobic DESs. Four criteria are introduced to assess the sustainability from a chemical engineering point of view of these hydrophobic DESs. These criteria include a viscosity smaller than 100 mPa s, a density difference between DES and water of at least 50 kg m-3 upon mixing of the DES and water, low transfer of the DES to the water phase and minor to no pH change. The results show that five new hydrophobic DESs based on natural components satisfy these; thymol and coumarin (2:1), thymol and menthol (1:1), thymol and coumarin (1:1), thymol and menthol (1:2) and 1-tetradecanol and menthol (1:2), satisfy these criteria and thus are promising DESs. These new DESs can be considered as natural deep eutectic solvents, which have the potential to be environmentally friendly. A selected group of the hydrophobic DESs were used for the extraction of riboflavin from water. They all show higher removal of riboflavin in comparison to decanoic acid:tetraoctylammonium bromide (2:1). The highest extraction efficiency of Riboflavin from water, 81.1 %, was achieved with the hydrophobic DES DecA:Lid (2:1).
A stricter definition of a deep eutectic solvent (DES) is urgent, so that it may become a sound basis for further developments in this field. This communication aims at contributing to deepening the understanding of eutectic and deep eutectic mixtures concerning their definition, thermodynamic nature and modelling. The glut of literature on DES applications should be followed by a similar effort to address the fundamental questions on their nature. This hopefully would contribute to correct some widespread misconceptions, and help to establish a stringent definition of what a DES is. DES are eutectic mixtures for which the eutectic point temperature should be lower to that of an ideal liquid mixture. To identify and characterize them, their phase diagrams should be known, in order to compare the real temperature depression to that predicted if ideality is assumed, and to define composition ranges for which they are in the liquid state at operating temperatures. It is also shown that hydrogen bonding between the DES components should not be used to define or characterize a DES, since this would describe many ideal mixtures. The future of deep eutectic solvents is quite promising, and we expect that this work will contribute to the efficient design and selection of the best DES for a given application, and to model properties and phase equilibria without which the process design is impractical.
Recently some works reported claims that hydrophobic deep eutectic solvents could be prepared based on menthol and monocarboxylic acids. Despite of some promising potential applications these systems were poorly understood and this work addresses this issue. Here the characterization of eutectic solvents composed by the terpenes thymol or L(–)-menthol and monocarboxylic acids is studied aiming the design of these solvents. Their solid-liquid phase diagrams were measured by differential scanning calorimetry in the whole composition range, showing that a broader composition range, and not only fixed stoichiometric proportions can be used as solvents at low temperatures. Additionally, solvent densities and viscosities close to the eutectic compositions were measured, showing low viscosity and that are less dense than water. The solvatochromic parameters at the eutectic composition were also investigated aiming at better understanding their polarity. The high acidity is mainly provided by the presence of thymol in the mixture, while L(–)-menthol plays the major role on the hydrogen-bond basicity. The measured mutual solubilities with water attest the hydrophobic character of the mixtures investigated. The experimental solid-liquid phase diagrams were described using the PC-SAFT EoS that is shown to accurately describe the experimental data and quantify the small deviations from ideality.
Natural deep eutectic solvents (NADESs) are defined as mixtures of certain molar ratios of natural compounds such as sugars, organic acids, amino acids, and organic bases that are abundant in organisms. The melting points of these mixtures are considerably lower than those of their individual ingredients and far below ambient temperature. The first publications on the NADES concept in 2011 created a great expectation regarding their potential as green solvents that could replace conventional organic solvents in a wide range of applications. This was largely because many of the drawbacks of conventional synthetic ionic liquids (ILs) and deep eutectic solvents (DESs), particularly their toxicity and environmental hazards, could be solved using NADESs. Throughout the last 7 years, the interest in NADESs has increased enormously as reflected by the exponential growth of the number of related publications. The research on NADESs has rapidly expanded particularly into the evaluation of the feasibility of their application in diverse fields such as the extraction of (targeted) bioactive compounds from natural sources, as media for enzymatic or chemical reactions, preservatives of labile compounds, or as vehicles of non–water-soluble compounds for pharmaceutical purposes. Along with the exploration of these potential applications, there have been a large number of other studies related to their physicochemical features, the search for new NADESs, the research into the interactions between NADES components or with solutes, the recovery of solutes from NADES solutions, and the ways of circumventing inherent problems of NADESs such as their high viscosity and the consequent difficulties in handling them. This article contains a review of the applications of NADESs as extraction solvents, reaction media, and preservative, providing also a perspective of their future.
In recent years, a new type of solvents, natural deep eutectic solvents (NADES), have been developed and are gaining popularity as an alternative “green solvent” to conventional organic solvents. The traditional extraction of flavor or fragrance from plant materials such as vanillin is a tedious procedure that involves the use of organic solvents. In this case the solubility of vanillin and its extractability from vanilla pods in 14 NADES was evaluated. The solubility in some NADES such as lactic acid: propanediol (620 mg/mL) and lactic acid: fructose (320 mg/mL) was found to be almost similar to that of organic solvents e.g. methanol (632.94 mg/mL) or ethanol (375.81 mg/mL). Interestingly, the extractability of vanillin from vanilla pods did not reflect the results observed for the solubility tests. Some NADES with constituents that are suitable as food ingredients such as citric acid-fructose-glucose (CAFG), fructose-glucose (FG), malic acid-glucose (MAG), and malic acid-fructose-glucose (MAFG), showed a higher extraction power (7.6, 10.1, 16.7, and 16.3 mg/g DW, respectively) than ethanol (4.4 mg/g DW). The discrepancy between solubility and extractability might be due to differences in the interaction with the matrix depending on the NADES. The effect of water content in some NADES on the extractability of vanillin was also studied. With the high extraction capacity and the absence of toxicity of their components, NADES are very suitable for extraction of flavours and fragrances used in food and cosmetics.
Being considered greener alternatives to ionic liquids (IL), deep eutectic solvents (DES) and natural deep eutectic solvents (NADES) have currently attracted broad interests from academics and industry. In this study, the transformation of isoeugenol to vanillin catalyzed by Lysinibacillus fusiformis CGMCC1347 cells was taken as the model reaction to examine the impacts of 24 DESs and 21 NADESs as co-solvents on whole-cell biocatalysis. Both types of co-solvents showed the ability of improving the production yields up to 142% and 132% of the ones obtained in (NA)DES-free aqueous systems, respectively. The data obtained by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) tests and measurements of OD260 and OD280 agreed well with the bioconversion data, suggesting that addition of these co-solvents may be beneficial to whole-cell biocatalysis in enhancing the cellular membrane permeability. Interaction of DES with bacterial cell wall was discussed. The cells immobilized in PVA-alginate beads granted an augmented production yield in the presence of DES and NADES, up to 181% of the one obtained in pure water system, and their catalytic activity was well maintained after being used for at least 13 cycles.
To establish environmentally friendly extraction methods for the anthocyanins in wine lees, natural deep eutectic solvents (NADES) were investigated as a green alternative to conventional solvents, coupled with high-efficiency ultrasound-assisted extraction. Screening for the optimal NADES for this extraction was initially performed. A choline-chloride-based NADES with malic acid as the hydrogen bond donor was selected as the most promising, which provided more effective extraction of wine lees anthocyanins compared to a conventional solvent. To optimise this extraction of wine lees anthocyanins using the NADES and ultrasound-assisted extraction, response surface methodology was successfully applied. Considering the maximum amount of extracted compounds, the optimal conditions were: extraction time, 30.6 min; ultrasound power, 341.5 W; and water content in NADES, 35.4% (w/w). This approach using NADES as a green solvent and ultrasound as an alternative energy source represents a good choice for designing eco-friendly extraction methods for phenolic compounds from various sources.
The high level density functional theory, B3LYP, was proposed for the derivatives of energetic molecule Trinitrophenyl Nitramide [TNPN]; MTNPN, ETNPN and NETNPN respectively, in order to understand its explosive characteristics. The geometrical analysis has been studied from both the polarized, 6-311g∗∗ and augmented, aug-cc-pVDZ basis sets, and found consistency between the structural parameters. The bond strength of each molecule has been characterized from bader’s AIM analysis, thereby correlating the bond topological properties with the impact sensitivity, which predicts that C-NO2 bonds were the weakest and found more sensitive among the rest of the bonds in all three molecules. The impact sensitivity of the molecules were measured in terms of ΔELUMO-HOMO, OB100, QNO2, h50% and Vmid, revealed the high sensitive nature of NETNPN towards the external shock. The reaction surface of all the three molecules has been located from the isosurface of electrostatic potential.
Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria.
This research considers the application of Natural Deep Eutectic Solvents (NADES) as green solvents for the extraction of bioactive compounds, mainly α-mangostin, from the pericarp of mangosteen (Garcinia mangostana L.). Extractions were carried out using NADES consisting of choline chloride, a quarternary ammonium salt, and four hydrogen bond donors: 1,2-propanediol, citric acid, glycerol, and glucose. The highest α-mangostin extraction yield of 2.6 % (w/w) in dried pericarp was obtained using a mixture of choline chloride and 1,2-propanediol in 1:3 mole ratio. The presence of hydrogen bonding was indicated by the broadening of the OH peak in the infra-red spectra of the NADES used. The polarity and viscosity data of NADES were determined to describe the solubility of -mangostin. The decomposition and glass transition temperatures were determined in order to study their thermal behavior and stability. The results of this study suggest that NADES made of choline chloride and diol-based hydrogen bond donors are effective for the extraction of bioactive compounds from the mangosteen pericarp.
The present investigation demonstrated pretreatment of lignocellulosic biomass rice straw using natural deep eutectic solvents (NADESs), and separation of high-quality lignin and holocellulose in a single step. Qualitative analysis of the NADES extract showed that the extracted lignin was of high purity (>90 %), and quantitative analysis showed that nearly 60 ± 5 % (w/w) of total lignin was separated from the lignocellulosic biomass. Addition of 5.0 % (v/v) water during pretreatment significantly enhanced the total lignin extraction, and nearly 22 ± 3 % more lignin was released from the residual biomass into the NADES extract. X-ray diffraction studies of the untreated and pretreated rice straw biomass showed that the crystallinity index ratio was marginally decreased from 46.4 to 44.3 %, indicating subtle structural alterations in the crystalline and amorphous regions of the cellulosic fractions. Thermogravimetric analysis of the pretreated biomass residue revealed a slightly higher T dcp (295 °C) compared to the T dcp (285 °C) of untreated biomass. Among the tested NADES reagents, lactic acid/choline chloride at molar ratio of 5:1 extracted maximum lignin of 68 ± 4 mg g(-1) from the rice straw biomass, and subsequent enzymatic hydrolysis of the residual holocellulose enriched biomass showed maximum reducing sugars of 333 ± 11 mg g(-1) with a saccharification efficiency of 36.0 ± 3.2 % in 24 h at 10 % solids loading.
Previously it was demonstrated that natural deep eutectic solvents (NADES) are promising green solvents for the extraction of natural products. However, despite their potential, an obvious disadvantage of NADES is the high viscosity. Here we explored the dilution effect on the structures and physicochemical properties of NADES and their improvements of applications using quercetin and carthamin. The results of FT-IR and (1)H NMR experiments demonstrated that there are intensive H-bonding interactions between the two components of NADES and dilution with water caused the interactions weaken gradually and even disappeared completely at around 50% (v/v) water addition. A small amount of water could reduce the viscosity of NADES to the range of water and increase the conductivity by up to 100 times for some NADES. This study provides the basis for modulating NADES in a controllable way for their applications in food processing, enzyme reactions, pharmaceuticals and cosmetics.
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Green technology actively seeks new solvents to replace common organic solvents that present inherent toxicity and have high volatility, leading to evaporation of volatile organic compounds to the atmosphere. Over the past two decades, ionic liquids (ILs) have gained enormous attention from the scientific community, and the number of reported articles in the literature has grown exponentially. Nevertheless, IL “greenness” is often challenged, mainly due to their poor biodegradability, biocompatibility, and sustainability. An alternative to ILs are deep eutectic solvents (DES). Deep eutectic solvents are defined as a mixture of two or more components, which may be solid or liquid and that at a particular composition present a high melting point depression becoming liquids at room temperature. When the compounds that constitute the DES are primary metabolites, namely, aminoacids, organic acids, sugars, or choline derivatives, the DES are so called natural deep eutectic solvents (NADES). NADES fully represent green chemistry principles. Can natural deep eutectic solvents be foreseen as the next generation solvents and can a similar path to ionic liquids be outlined? The current state of the art concerning the advances made on these solvents in the past few years is reviewed in this paper, which is more than an overview on the different applications for which they have been suggested, particularly, biocatalysis, electrochemistry, and extraction of new data. Citotoxicity of different NADES was evaluated and compared to conventional imidazolium-based ionic liquids, and hints at the extraction of phenolic compounds from green coffee beans and on the foaming effect of NADES are revealed. Future perspectives on the major directions toward which the research on NADES is envisaged are here discussed, and these comprised undoubtedly a wide range of chemically related subjects.
A general purpose, scalable parallel molecular dynamics package for simulations of arbitrary mixtures of flexible or rigid molecules is presented. It allows use of most types of conventional molecular-mechanical force fields and contains a variety of auxiliary terms for inter- and intramolecular interactions, including an harmonic bond-stretchings. It can handle both isotropic or ordered systems. Besides an NVE MD ensemble, the simulations can also be carried out in either NVT or NPT ensembles, by employing the Nosé–Hoover thermostats and barostats, respectively. If required, the NPT ensemble can be generated by maintaining anisotropic pressures. The simulation cell can be either cubic, rectangular, hexagonal or a truncated octahedron, with corresponding periodic boundary conditions and minimum images. In all cases, the optimized Ewald method can be used to treat the Coulombic interactions. Double time-step or constrained dynamics schemes are included. An external electric field can be applied across the simulation cell. The whole program is highly modular and is written in standard Fortran 77. It can be compiled to run efficiently both on parallel and sequential computers. The inherent complexity of the studied system does not affect the scalability of the program. The scaling is good with the size of the system and with the number of processors. The portability of the program is good, it runs regularly on several common single- and multiprocessor platforms, both scalar and vector architectures included.
Developing green solvents with low toxicity and cost is an important issue for the biochemical industry. Synthetic ionic liquids and deep eutectic solvents have received considerable attention due to their negligible volatility at room temperature, high solubilization ability, and tunable selectivity. However, the potential toxicity of the synthetic ionic liquids and the solid state at room temperature of most deep eutectic solvents hamper their application as extraction solvents. In this study, a wide range of recently discovered natural ionic liquids and deep eutectic solvents (NADES) composed of natural compounds were investigated for the extraction of phenolic compounds of diverse polarity. Safflower was selected as a case study because its aromatic pigments cover a wide range of polarities. Many advantageous features of NADES (such as their sustainability, biodegradability combined with acceptable pharmaceutical toxicity profiles, and their high solubilization power of both polar and non-polar compounds) suggest their potential as green solvents for extraction. Experiments with different NADES and multivariate data analysis demonstrated that the extractability of both polar and less polar metabolites was greater with NADES than conventional solvents. The water content in NADES proved to have the biggest effect on the yield of phenolic compounds. Most major phenolic compounds were recovered from NADES with a yield between 75%-97%. This study reveals the potential of NADES for applications involving the extraction of bioactive compounds from natural sources.
We describe a simple method to automate the geometric optimization of molecular orbital calculations of supermolecules on potential surfaces that are corrected for basis set superposition error using the counterpoise (CP) method. This method is applied to the H‐bonding complexes HF/HCN, HF/H2O, and HCCH/H2O using the 6‐31G(d,p) and D95++(d,p) basis sets at both the Hartree–Fock and second‐order Møller–Plesset levels. We report the interaction energies, geometries, and vibrational frequencies of these complexes on the CP‐optimized surfaces; and compare them with similar values calculated using traditional methods, including the (more traditional) single point CP correction. Upon optimization on the CP‐corrected surface, the interaction energies become more negative (before vibrational corrections) and the H‐bonding stretching vibrations decrease in all cases. The extent of the effects vary from extremely small to quite large depending on the complex and the calculational method. The relative magnitudes of the vibrational corrections cannot be predicted from the H‐bond stretching frequencies alone. © 1996 American Institute of Physics.
Adequate initial configurations for molecular dynamics simulations consist of arrangements of molecules distributed in space in such a way to approximately represent the system's overall structure. In order that the simulations are not disrupted by large van der Waals repulsive interactions, atoms from different molecules must keep safe pairwise distances. Obtaining such a molecular arrangement can be considered a packing problem: Each type molecule must satisfy spatial constraints related to the geometry of the system, and the distance between atoms of different molecules must be greater than some specified tolerance. We have developed a code able to pack millions of atoms, grouped in arbitrarily complex molecules, inside a variety of three-dimensional regions. The regions may be intersections of spheres, ellipses, cylinders, planes, or boxes. The user must provide only the structure of one molecule of each type and the geometrical constraints that each type of molecule must satisfy. Building complex mixtures, interfaces, solvating biomolecules in water, other solvents, or mixtures of solvents, is straightforward. In addition, different atoms belonging to the same molecule may also be restricted to different spatial regions, in such a way that more ordered molecular arrangements can be built, as micelles, lipid double-layers, etc. The packing time for state-of-the-art molecular dynamics systems varies from a few seconds to a few minutes in a personal computer. The input files are simple and currently compatible with PDB, Tinker, Molden, or Moldy coordinate files. The package is distributed as free software and can be downloaded from http://www.ime.unicamp.br/~martinez/packmol/.
The previously developed particle mesh Ewald method is reformulated in terms of efficient B‐spline interpolation of the structure factors. This reformulation allows a natural extension of the method to potentials of the form 1/r p with p≥1. Furthermore, efficient calculation of the virial tensor follows. Use of B‐splines in place of Lagrange interpolation leads to analytic gradients as well as a significant improvement in the accuracy. We demonstrate that arbitrary accuracy can be achieved, independent of system size N, at a cost that scales as N log(N). For biomolecular systems with many thousands of atoms this method permits the use of Ewald summation at a computational cost comparable to that of a simple truncation method of 10 Å or less.
The Trotter factorization of the Liouville propagator is used to generate new reversible molecular dynamics integrators. This strategy is applied to derive reversible reference system propagator algorithms (RESPA) that greatly accelerate simulations of systems with a separation of time scales or with long range forces. The new algorithms have all of the advantages of previous RESPA integrators but are reversible, and more stable than those methods. These methods are applied to a set of paradigmatic systems and are shown to be superior to earlier methods. It is shown how the new RESPA methods are related to predictor–corrector integrators. Finally, we show how these methods can be used to accelerate the integration of the equations of motion of systems with Nosé thermostats.
Deep eutectic solvents (DESs) are an emerging class of mixtures characterized by significant depressions in melting points compared to those of the neat constituent components. These materials are promising for applications as inexpensive "designer" solvents exhibiting a host of tunable physicochemical properties. A detailed review of the current literature reveals the lack of predictive understanding of the microscopic mechanisms that govern the structure-property relationships in this class of solvents. Complex hydrogen bonding is postulated as the root cause of their melting point depressions and physicochemical properties; to understand these hydrogen bonded networks, it is imperative to study these systems as dynamic entities using both simulations and experiments. This review emphasizes recent research efforts in order to elucidate the next steps needed to develop a fundamental framework needed for a deeper understanding of DESs. It covers recent developments in DES research, frames outstanding scientific questions, and identifies promising research thrusts aligned with the advancement of the field toward predictive models and fundamental understanding of these solvents.
In the design of greener chemicals, deep eutectic solvents (DESs) are considered as one of the most versatile alternative media with widespread applications. DESs have the advantages of being nonflammable with negligible vapor pressure compared to the traditional solvents. They share many characteristics of ionic liquids, but DESs are cheaper to formulate, typically nontoxic, highly pure, recyclable, biodegradable, and are suitable for use with biological systems. In this article, the two emerging and unconventional types of DESs, therapeutic DES (THEDES) and amino acid-based DES (AADES) are reviewed. Based on the published literature, choline chloride and menthol are the two most common constituents to formulate THEDESs, while proline is the most common component to formulate AADESs. THEDESs have primarily been developed to enhance the efficacy of drugs, whereas AADESs have been explored for pharmaceuticals as well as for the extraction of phytochemicals, radioactive iodine capture, oil separation from ores, and to synthesize bioactive compounds. Since detailed knowledge of their structures, nonbonding interactions, formulations, and applications are yet to be explored, the aim of this review is to compile these details and provide a solid background for the future research.
The solvation of two different antibiotics (ampicillin and piperacillin) in three newly designed arginine-based deep eutectic solvents (DESs) is studied using computational chemistry methods: molecular dynamics simulations and quantum chemistry calculations. The main features of intermolecular forces and structural characteristics between the antibiotics and the solvents are characterized in order to justify the large affinity of ampicillin and piperacillin molecules for selected DESs, with the emphasis on the hydrogen bonding, with respect to strength, deviations of ideality, topological properties, interaction patterns and how they occur, structuring of the solvation shells and their analysis regarding dynamic properties. Arginine (Ar) is combined with glutamic acid (Ga), oxalic acid (Oa), and tartaric acid (Ta) to form DESs (ArGa, ArOa, ArTa), and they are coupled with ampicillin (Ap) and piperacillin (Pp). Results shared in this work allow to deduce on the effective solvation of antibiotics in DESs because of strong solute-solvent intermolecular interactions accompanied by a slight volume expansion and minor solvent structural changes, thus, confirming these solvents as suitable materials for antibiotic drug delivery in the liquid phase.
Bio-based organic acids constitute an important group of building block chemicals that can be produced from renewable resources, becoming a sustainable alternative to conventional petrochemical-derived commodities. However, due to the growing number of green solvents emerging as extraction media, the proper solvent selection for biomolecule separation from fermentation broths has become a key challenge in the bio-refinery industry. The overall aim of this work is to develop a roadmap to select and design green solvents for sustainable downstream processing of bio-based organic acids. To this end, a wide range of neoteric solvents (ionic liquids, eutectic solvents and bio-based solvents) were systematically evaluated for the recovery of relevant bio-organic acids through combination of experimental and COSMO-RS molecular simulation methods. Comprehensive thermodynamic analyses evaluating the organic acid partition coefficients, excess enthalpy contributions, solvent-water affinity, and process spontaneity were performed to elucidate the main mechanism driving the separation process and to provide essential guidelines for further solvent development. Based on these findings, a rational screening approach was established to identify suitable solvents for the recovery of structurally different bio-organic acids. Ultimately, this paper provides a green solvent selection guide to design sustainable separation processes of bio-based organic acids, as valuable platform chemicals transitioning towards a bio-based economy.
Natural deep eutectic solvent that is formed by choline chloride and lactic acid is studied as a function of various molar mixing ratios at different temperatures. The focus of the investigation is dynamic properties (viscosity, electrical conductivity and thermal conductivity) as well as microscopic features from theoretical studies. The effect of water is analyzed considering the large hydrophilicity of this fluid and as an approach for tailoring its physicochemical properties, which in pure state are not favorable for industrial applications. The reported results reveal a complete description of fluid's characteristics and show how hydrogen bond donor and hydrogen bond acceptor clusters are diluted in water with increasing water absorption while hydrogen bonding is maintained upon dilution.
The solvation of lidocaine in three newly designed deep eutectic solvents is studied using combined experimental and theoretical methods that include density functional theory and molecular dynamics methods. The intermolecular forces between lidocaine and the hydrogen bond acceptor and hydrogen bond donor of the deep eutectic solvents were analysed regarding to type and the strength of inter- and intro-molecular bonding. The structure, composition and properties of the lidocaine solvation shells are analysed together with the possible lidocaine clustering around the studied deep eutectic solvents and their constituent molecules. Furthermore, the changes in the solvent structures upon lidocaine solution are also studied. Natural product based eutectic solvents showed considerably high solvation of lidocaine in all three deep eutectics based on the strong solute-solvent intermolecular interactions accompanied by a slight volume expansion and minor solvent structural changes. These non-toxic and almost null-volatility therapeutic deep eutectic solvents can be considered as suitable solubilization medium for developing pharmaceutical applications and they can be considered as effective drug delivery vehicles for active pharmaceutical ingredients.
The nanomicelles have recently drawn a great deal of attention for drug delivery into the skin. However, these carriers have only deposited in hair follicles and furrows, and drug in the micelles may not therapeutically reach into viable skin layers. The aim of this study was to formulate a combination of nanomicelles with terpenes to overcome this challenge and evaluate their potential for topical drug delivery into the skin. The nanomicelles were characterised with respect to size, size distribution (PDI), zeta potential, morphology and encapsulation efficiency (%). The drug accumulation and penetration were examined by tape stripping method in the skin. The colloidal stability of nanomicelles was followed with respect to size and PDI values. The nanomicelles were about 25-30 nm in size with narrow distribution. All of them had slightly negative surface charge, spherical shapes and high encapsulation efficiency (%). The tape stripping data revealed that nanomicelles consisting of terpinolene led to accumulation of more drug in the stripped skin as compared with commercial product and nanomicelles without terpene. Also, micelle formulations consisting of terpinolene (2.0 %) had the highest colloidal stability. Consequently, combination of nanomicelles with terpinolene could be a feasible approach for enhancement of skin drug delivery.
Investigation of the binding affinity gases on porous adsorbents are important for establishing understanding of effective carbon dioxide adsorption and design target specific sorbents for capturing hazardous gases for environmental protection and fuel upgrading. A density functional theory (DFT) study that highlights the impact of benzimidazole‐linked polymer structure design has been conducted to explain the molecular and electronic structure, investigate the interaction sites and elucidate the experimental results on carbon dioxide and nitrogen sorption on these porous structures. DFT calculations were used to infer the strength of the polymer – gas interaction modes as well as to quantify short‐range interactions between the polymer – gas via topological characteristics analysis of intermolecular forces. Obtained results shed light on the carbon dioxide and nitrogen affinity as well as the selectivity during the adsorption process, and yet conclusions were attained on the characteristics of the adsorption type and mechanism in this study.
Fragrance ingredients are extensively used in perfumes and other cosmetics, providing us with a pleasant scent. However, different fragrance chemicals and other chemicals present in perfume composition have been shown to cause undesirable side effects. The EC Regulation prohibits and limits the contents of some of them in cosmetics. Other international organizations, such as the International Fragrance Association and the Research Institute for Fragrance Materials, work on the safety of fragrance chemicals and release reports on the convenience or not of using certain fragrance chemicals in cosmetics, depending on their toxicity.
This chapter is focussed on the determination of fragrance chemicals in cosmetic products. The analytical literature shows the interest in developing new methods to control those fragrance chemicals that have been shown to pose a safety hazard.
As functional liquid media, natural deep eutectic solvent (NADES) species can dissolve natural or synthetic chemicals of low water solubility. Moreover, the special properties of NADES, such as biodegradability and biocompatibility, suggest that they are alternative candidates for concepts and applications involving some organic solvents and ionic liquids. Owing to the growing comprehension of the eutectic mechanisms and the advancing interest in the natural eutectic phenomenon, many NADES applications have been developed in the past several years. However, unlike organic solvents, the basic structural unit of NADES media primarily depends on the intermolecular interactions among their components. This makes NADES matrices readily influenced by various factors, such as water content, temperature, and component ratio and, thus, extends the metabolomic challenge of natural products (NPs). To enhance the understanding of the importance of NADES in biological systems, this review focuses on NADES properties and applications in NP research. The present thorough chronological and statistical analysis of existing report adds to the recognition of the distinctiveness of (NA)DES, involves a discussion of NADES-related observations in NP research, and reportes applications of these eutectic mixtures. The work identifies potential areas for future studies of (NA)DES by evaluating relevant applications, including their use as extraction and chromatographic media as well as their biomedical relevance. The chemical diversity of natural metabolites that generate or participate in NADES formation highlights the growing insight that biosynthetically primordial metabolites (PRIMs) are as essential to the biological function and bioactivity of unrefined natural products as the biosynthetically more highly evolutionary metabolites (HEVOs) that can be isolated from crude mixtures.
Natural deep eutectic solvents (NADES) play a role as alternative media to water in living organisms. They are formed by mixing two or more natural compounds in certain ratios producing a liquid having a lower melting point than those of the individual NADES components. Although, the eutectics medium bring several advantages as enhanced solubility of non-polar substrates and/or products, however, these advantages would often be limited by a lower stability of biocatalysts in these systems. To examine this matter, biochemical characterization, thermal stability and tertiary structure of laccase from Bacillus HR03 was investigated as a model in betaine and choline based NADES. In eutectics containing choline, a sudden drop in enzyme activity and stability was observed. Betaine based eutectics exhibited a better media for the laccase stability in comparison with the aqueous buffer and choline chloride eutectics. The enzyme highest activity was observed in 20% (v/v) glycerol:betaine (2:1). Among betaine based eutectics, the enzyme exhibited its highest stability in sorbitol:betaine:water (1:1:1) and glycerol:betaine (2:1) compared to the aqueous buffer at 80 and 90°C. Associated conformational changes caused by solvents were monitored using fluorescence technique. Finally, the effects of NADES on the enzyme activity and stability were discussed.
A lignite monomer of organic oxygen (LMO) and a lignite monomer of organic nitrogen (LMN) were constructed based on the occurrence forms of organic oxygen/nitrogen in lignites, then their intermolecular hydrogen bonding interactions (HBIs) with water molecules were investigated using the density functional theory (DFT) and the quantum theory of atoms in molecules (AIM). The results show that a variety of LMO-(H2O)n (n = 1–16) and LMN-(H2O)n (n = 1–12) complexes were formed. A water cage cluster containing 16 water molecules and a water film cluster containing 10 water molecules were observed in LMO-(H2O)16 and LMN-(H2O)12 complexes, respectively, and cyclic water tetramers were the dominated existing form of water clusters. The ratio of hydrogen bonding energy (HBE) among water molecules to the total HBE in lignite ⋯ water complexes gradually increases with the number of water molecules increasing, and the ratios are 84% and 44% in LMO-(H2O)16 and LMN-(H2O)12 complexes, respectively. The intermolecular HBIs in LMO-(H2O)12 and LMN-(H2O)12 complexes can be divided into purely weak and medium closed-shell non-covalent interactions. Molecular electrostatic potential analyses imply that the most formation sites of hydrogen bonds are transferred to the O atoms of water molecules from the O and N atoms in LMO and LMN with the number of water molecules increasing in LMO-(H2O)n and LMN-(H2O)n complexes.
Natural deep eutectic solvents (NADES) are a third class of liquids, separate from water and lipids. Some NADES, especially those containing organic acids, have been suggested to possess antimicrobial properties. Such properties may be advantageous when NADES are used as solvents in e.g. antimicrobial photodynamic therapy. However, to control the toxicity of acid-containing NADES, they must retain their specific qualities upon dilution. Hence, the aims of this study were to investigate the effect of dilution on the acid-containing NADES network, their antimicrobial activity on different planktonic microorganisms, and their influence on phototoxicity when used as solvents for a photosensitiser. Four bacteria and one fungus were exposed to the NADES, CS (citric acid:sucrose) and MFG (malic acid:fructose:glucose) (molar ratios 1:1 and 1:1:1, respectively), at ≤ 1:200 dilution. Additionally, the antimicrobial properties of the NADES were studied in Escherichia coli in terms of pH and chelating effects. In investigations of phototoxicity, the microorganisms were exposed to the photosensitiser meso-tetra(p-hydroxyphenyl)porphine (THPP; 1 nM) dissolved in diluted NADES combined with blue light (27 J/cm²). The eutectic network appeared to remain upon dilution ≤ 1:200. CS (1:200) was less toxic than an equal concentration of citric acid in the Gram-negative bacteria Klebsiella pneumoniae and E. coli (p < 0.05). A higher degree of phototoxicity was induced in E. coli (~ 1% survival) when THPP was dissolved in CS or MFG than in phosphate buffer (~ 61% survival; p < 0.05). No conclusion could be drawn as to whether the observed toxicity in E. coli exposed to NADES was due to the pH of the solutions or chelation of outer membrane-bound cations.
As part of our ongoing efforts to apply deep eutectic solvents (DESs) as green versatile solvents, we investigated DESs as multi-functioning solvents using green tea as a model. Green tea (Camellia sinensis) is a valuable source of catechins such as epigallocatechin-3-gallate (EGCG), a potent antioxidant. We screened DESs composed of cosmetics-compatible components, selected effective components, and recombined these components to produce a series of ternary DESs. Examination of the solvents' physicochemical properties suggested that catechin extraction efficiency was partially associated with solvent pH. Among the many solvents with high yields, BGG-4 (betaine, glycerol, and D-(+)-glucose, 4:20:1) was selected as the final solvent after considering usage limits in cosmetic products and production cost. The extraction conditions optimized by response surface methodology were ultrasound-assisted extraction using 81% BGG-4 at room temperature for 6.5 min, resulting in significantly higher extraction yields than alternative methods involving high temperature and/or long extraction times. Scanning electron microscopy analysis of green tea powder before and after extraction under different conditions supported that our optimized method caused rapid exudation of catechins during rupture process and subsequent efficient dissolution of catechins, leading to superior extraction efficiency. Stability of EGCG, which is prone to undesirable alterations, was monitored at 60 °C after extraction. Over a three-week storage period, the fastest destabilization was observed in 70% MeOH, leaving 27% of EGCG intact. In contrast, almost 60% of EGCG remained unchanged in BGG-4. These suggest that BGG-4 could serve as a multi-functioning medium to produce a beneficial catechin-rich tea extract in which catechins remain relatively stable. Moreover, the solvent itself could function as an active ingredient, and the extract could be readily applicable to cosmetic or pharmaceutical formulations for skin.
In this study, an efficient extraction technique using a combination of ultrasound and natural deep eutectic solvents (NADESs) was developed. Some basic physical properties, including viscosity, polarity, and solubility, of thirteen NADESs prepared from natural components were investigated systematically. Results show that the solubility of rutin increased in choline chloride- and glycerol-based NADESs by 660-1577 times compared to water. NADESs with high rutin extractability can be designed by combining NADESs components. A maximum of 9.5 mg/g rutin was extracted from tartary buckwheat hull with extraction efficiencies of 95%. NADESs can be recovered and recycled. In addition, the biocompatibility and biodegradability of the tested NADESs were also evaluated. The results demonstrated that these NADESs were excellent solvents with extremely low toxicities and favorable biodegradabilities. Our findings suggest that NADESs can be used as green solvents for the extraction of bioactive ingredients.
Using ultrasonic technology, Trans-Cinnamaldehyde as a natural antibacterial compound was used to prepare nano size emulsions to increase its bioavailability and therefore bactericidal action. Nanoemulsions containing Trans-Cinnamaldehyde as an active agent and 1,8 cineol as co additive oil (Ostwald ripening inhibitor) were formulated using probe sonicator. Three different determining factors, namely time of sonication, surfactant to oil ratio and type of emulsifier (Tween 80 and Tween 20) were investigated to enhance the stability profile. In addition, the effect of changes in the particle size and emulsifier on the antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were examined using agar dilution method. Then, the effect of optimized formulation on the membrane fluidity and cell constituent release, were investigated by analysis of membrane lipids using GC-MS and IR spectrometry, respectively. The data showed that a 15 min sonication of the formulation containing Tween 80 as emulsifier with surfactant to oil ratio of 2:1 (w/w) resulted in a significant stability for 6 months with considerably small particle size of 27.76 ± 0.37 nm. Furthermore, the nanoemulsion showed great antibacterial activity and could reduce the minimum inhibitory concentration (MIC) from 8 to 1 mg/mL against E. coli and S. aureus, and from 16 to 2 mg/mL against P. aeruginosa. Interestingly, E. coli’s membrane fluidity increased dramatically after treatment with the optimum nanoemulsion (T804). This study revealed that nanoemulsion of Trans-Cinnamaldehyde and 1,8 cineol has substantial antibacterial activity against selected microorganisms.
The determination of phenolic compounds in extra virgin olive oils (EVOO) by means of rapid, low-cost, environment-free methods would be a desirable achievement. A natural deep eutectic solvent (DES) based on glucose and lactic acid was considered as extraction solvent for phenolic compounds in EVOO. DESs are green solvents characterized by high availability, biodegradability, safety, and low cost. The spectrophotometric characteristics of DES extracts of 65 EVOO samples were related to the total phenolic content of the oils, assessed by methanol-water extraction coupled to the Folin-Ciocalteu assay. A regression model (ncalibration = 45, nvalidation = 20), including the absorbance at two wavelengths (257, 324 nm), was obtained, with an adjusted R2 = 0.762. Therefore the DES could provide a promising and viable approach for a green screening method of phenolic compounds in EVOO, by means of simple spectrophotometric measurements of extracts, even for on-field analysis (for example in olive mills).
Selected native Greek medicinal plants, including dittany, fennel, marjoram, mint and sage, were used to test the efficiency of some novel lactic acid-based natural deep eutectic solvents (NADES) to extract polyphenolic compounds. Extractions were performed under ultrasonication and the eutectic mixtures, tested as 80% (v/v) aqueous solutions, were lactic acid:choline chloride, lactic acid:sodium acetate, lactic acid:ammonium acetate and lactic acid:glycine:water, with corresponding molar ratios of 3:1, 3:1, 3:1 and 3:1:3. The three latter NADES are reported for the first time. Water and 60% (v/v) aqueous ethanol were also used as control solvents. The results obtained evidenced that lactic acid:glycine:water exhibited high efficiency, but in some instances lactic acid:sodium acetate and lactic acid:ammonium acetate were equally efficient. The data also suggested that extracts with high polyphenol concentration may also possess higher antiradical activity and reducing power. The NADES tested are non-toxic, renewable and exceptionally efficient solvents for polyphenol recovery from medicinal plants. The findings of this study were interpreted on the ground of assumptions regarding the polarity of the NADES tested.
Liquid eutectic system of menthol and camphor has been reported as solvent and co-solvent for some drug delivery systems. However, surprisingly, the phase diagram of menthol-camphor eutectic has not been reported previously. The evaporation behavior, physicochemical, and thermal properties of this liquid eutectic and ibuprofen eutectic solution were characterized in this study. Differential scanning calorimetry (DSC) analysis indicated that a eutectic point of this system was near to 1:1 menthol/camphor and its eutectic temperature was -1°C. The solubility of ibuprofen in this eutectic was 282.11 ± 6.67 mg mL(-1) and increased the drug aqueous solubility fourfold. The shift of wave number from Fourier transform infrared spectroscopy (FTIR) indicated the hydrogen bonding of each compound in eutectic mixture. The weight loss from thermogravimetric analysis of menthol and camphor related to the evaporation and sublimation, respectively. Menthol demonstrated a lower apparent sublimation rate than camphor, and the evaporation rate of eutectic solvent was lower than the sublimation rate of camphor but higher than the evaporation of menthol. The evaporation rate of the ibuprofen eutectic solution was lower than that of the eutectic solvent because ibuprofen did not sublimate. This eutectic solvent prolonged the ibuprofen release with diffusion control. Thus, the beneficial information for thermal behavior and related properties of eutectic solvent comprising menthol-camphor and ibuprofen eutectic solution was attained successfully. The rather low evaporation of eutectic mixture will be beneficial for investigation and tracking the mechanism of transformation from nanoemulsion into nanosuspension in the further study using eutectic as oil phase.
Sustainable technologies applied to energy related applications should develop a pivotal role along the next decades. In particular, carbon dioxide capture from flue gases emitted by fossil fuelled power plants would develop a pivotal role for controlling and reducing greenhouse effect. Therefore, the development of new materials for carbon capture purposes has merged as central research line for which many alternatives have been proposed. ILs have emerged as one of the most promising choices for carbon capture but in spite of their promising properties some serious drawbacks have also appeared. Deep eutectic solvents (DES) have been recently considered as alternatives to ILs that maintain most of their relevant properties, such as task-specific character, and at the same time avoid some of their problems, mainly from economic and environmental viewpoints. DES production from low cost and natural sources, together with their almost null toxicity and total biodegradability, makes these solvents as a suitable platform for developing gas separation agents within the green chemistry framework. Therefore, considering the promising characteristics of DES as CO2 absorbents, and in general as gas separating agents, the state-of-the-art on physicochemical properties of DES, in relationship with their influence on gas separation mechanisms, and on the studies of gas solubility in DES are discussed. The objective of this review work is to analyse the current knowledge on gas separation using DES, comparing the capturing abilities and properties of DES with those for ILs, inferring the weaknesses and strengths of DES and proposing future research directions on this subject.
The chemical industry has flourished in the 20th century due to the massive supply of cheap crude oil. However, growing concerns about the dependence on imported oil and the awareness that the world's oil supplies are limited have prompted interest in exploring nature's richness of plant sources. Plants offer enormous potential as cost-effective, unlimited, environmentally friendly production systems that make efficient use of light energy and supply raw materials for the production of fuels, bulk, and fine chemicals. Terpenes are one of the largest and most diverse classes of organic compounds produced by all plants. They are derived biosynthetically from isoprene units, which consist of five carbon atoms. Due to their high abundance they have attracted attention as a class of natural products that can be converted into novel and valuable compounds commercially important for the industrial production of fragrances, perfumes, flavors, and pharmaceuticals as well as useful synthetic intermediates and chiral building blocks. The review focuses on the use of terpenes available from renewable resources in the fine chemicals industry. Chemical and biotechnological approaches are highlighted.
In recent years, researchers have focused on finding green alternative media to organic solvents for enzyme-catalyzed reactions. Thereby, ionic liquids (IL) have emerged as fascinating media for enzymatic reactions. One drawback to the wider development of these solvents in biocatalysis is their cost and the difficulty of product recovery. Recently, a novel medium with similar properties to IL but with additional advantages regarding cost, environmental impact and synthesis has been created: Deep Eutectic Solvents (DESs). These DESs result from the association of an ammonium salt and a hydrogen-bond donor. This study aimed at analyzing the advantages and limitations of several DESs as ‘green solvents’ for biotransformation using immobilized Candida antarctica lipase B as catalyst. The transesterification of vinyl laurate was chosen as model reaction and the influence of substrate polarity was assessed using alcohols of various chain lengths. Results showed that grinding of immobilized lipase was essential parameters for good lipase activity and some DESs cannot be used as media for iCALB-catalyzed reaction, especially DESs based on dicarboxylic acids and ethylene glycol. Finally, the best DES’s specific activity - and stability up to five days incubation time - were analyzed and compared with conventional organic solvents. Experiments revealed that iCALB is less influenced by the chain length of alcohol in DES than organic solvents and it is preserves its activity with minimally destructive to protein structure.
The structure, stability and proton transfer in H-bonded complexes formed from interaction between uracil (U) and NH2NO (NA) have been investigated using B3LYP, B3PW91 and MP2 methods with a wide range of basis sets. With four preferential interaction sites in the vicinity of the uracil, eight cyclic complexes (UN1–8) with two intermolecular hydrogen bonds N(C)HU⋯O(N)NA and HNA⋯OU were found on the potential energy surface. RAHB mechanism is exhibited in all the complexes. Four 8- and four 7-membered ring complexes have electronic interaction energies (IEs) in the range of −44.0 to −63.2kJ/mol and −42.5 to −60.9kJ/mol at MP2/6-311++G(2d,2p) levels, respectively. The most stable complex is formed via NH bond of U with highest acidity and CO group of U with lowest proton affinity. Our results show that intermolecular interactions are affected more by acidity of proton donor group in U than by proton affinity of proton acceptor group. We found a relationship between H-bond distances and the corresponding frequency shifts. Thermodynamic properties correspond to the process of proton transfer between monomers have been calculated at various levels of theory. NBO and AIM analyses confirm that the charge transfer takes place from NA to U in UN1–6 and vice versa in UN7–8 which CH is a proton donor group in U. There is a correlation between intermolecular charge transfer energies and interaction energies and electron densities at H-bond critical points. AIM analysis shows that H-bond contacts are electrostatic in nature and covalent nature of proton donor groups decreases upon complex formation.
A rapid, reliable and sensitive method has been developed to determine malic and citric acid in fruits and vegetables. The
methodology is based on simple extraction with an aqueous solution of ethanol (80% v/v) and subsequent chromatographic analysis by liquid chromatography coupled to mass spectrometry. Electrospray ionization in
negative mode was used. The best response for citric and malic acid was provided by molecular ions [M−H]− at m/z 191 and 133 respectively. These ions were used for quantification, whereas other fragments were used as confirmation ions.
Different variables involved in the separation and detection process, such as mobile phase, gradient profile and flow rate
have been optimised. Linearity, repeatability, recovery and limits of quantification were evaluated. Good linearity was obtained
up to 5,000 mg kg−1. Recovery ranged from 90.0 to 104.6%, repeatability (expressed as RSD) was
ORCA is a general-purpose quantum chemistry program package that features virtually all modern electronic structure methods (density functional theory, many-body perturbation and coupled cluster theories, and multireference and semiempirical methods). It is designed with the aim of generality, extendibility, efficiency, and user friendliness. Its main field of application is larger molecules, transition metal complexes, and their spectroscopic properties. ORCA uses standard Gaussian basis functions and is fully parallelized. The article provides an overview of its current possibilities and documents its efficiency. © 2011 John Wiley & Sons, Ltd.