Enhanced Antimalarial Activity of Extracts of Artemisia annua L. Achieved with Aqueous Solutions of Salicylate Salts and Ionic Liquids.

Artemisinin, a drug used to treat malaria, can be chemically synthesized or extracted from Artemisia annua L. However, the extraction method for artemisinin from biomass needs to be more sustainable while maintaining or enhancing its bioactivity. This work investigates the use of aqueous solutions of salts and ionic liquids with hydrotropic properties as alternative solvents for artemisinin extraction from Artemisia annua L. Among the investigated solvents, aqueous solutions of cholinium salicylate and sodium salicylate were found to be the most promising. To optimize the extraction process, a response surface method was further applied, in which the extraction time, hydrotrope concentration, and temperature were optimized. The optimized conditions resulted in extraction yields of up to 6.50 and 6.44 mg·g-1, obtained with aqueous solutions of sodium salicylate and cholinium salicylate, respectively. The extracts obtained were tested for their antimalarial activity, showing a higher efficacy against the Plasmodium falciparum strain compared with pure (synthetic) artemisinin or extracts obtained with conventional organic solvents. Characterization of the extracts revealed the presence of artemisinin together with other compounds, such as artemitin, chrysosplenol D, arteannuin B, and arteannuin J. These compounds act synergistically with artemisinin and enhance the antimalarial activity of the obtained extracts. Given the growing concern about artemisinin resistance, the results here obtained pave the way for the development of sustainable and biobased antimalarial drugs.

Repurposing Kraft black Liquor as Reductant for Enhanced Lithium-Ion Battery Leaching.

The economic advantages of H2 SO4 make it the acid of choice for the hydrometallurgical treatment of waste lithium-ion batteries (LIBs). However, to facilitate the full dissolution of the higher valency metal oxides present in the cathode black mass, a suitable reducing agent is required. Herein, the application of industrial black liquor (BL) obtained from the Kraft pulping for papermaking is investigated as a renewable reducing agent for the enhanced leaching of transition metals from LIB powder with H2 SO4 . The addition of acidified BL to H2 SO4 significantly improved the leaching efficiency for a range of LIB cathode chemistries, with the strongest effect observed for manganese-rich active material. Focusing on NMC111 (LiMnx Coy Niz O2 ) material, a linear correlation between the BL concentration and the leaching yield of Mn was obtained, with the best overall leaching efficiencies being achieved for 2.0 mol L-1 H2 SO4 and 50 vol % of BL at 353 K. A quasi-total degradation of oxygenated and aromatic groups from the BL during NMC111 dissolution was observed after leaching, suggesting that these chemical groups are essential for LIB reduction. Finally, the leached transition metals could be easily recovered by pH adjustment and oxalic acid addition, closing the resource loop and fostering resource efficiency.

Unravelling the molecular interactions behind the formation of PEG/PPG aqueous two-phase systems.

The understanding of molecular interactions that control phase separation in polymer/polymer aqueous two-phase systems (ATPS) has been a subject of debate up to this day. In light of this, we set out to investigate the molecular interactions occurring in ternary mixtures composed of polyethylene glycol (PEG600), polypropylene glycol (PPG400) and water. The ternary phase diagram was plotted at two temperatures (298 K and 323 K), revealing a transition from a type 0 to a type I diagram. Molecular dynamics (MD) simulations were performed to elucidate the polymer-polymer and polymer-water interactions occurring at different temperatures and water concentrations. COnductor-like Screening Model for Realistic Solvents (COSMO-RS) was used to assess the thermodynamic properties of the polymer-water binary mixtures and their correlation with ATPS formation. The MD simulations clearly demonstrate the effect of segregation/separation with increasing water content and temperature, highlighting a significant reduction in PPG-water interactions compared to PEG-water counterparts. Polymer-water interactions were identified as those controlling the phase separation mechanism, and the thermodynamic properties determined with COSMO-RS for the polymer-water binary systems further support this view.

Improved accuracy in pentraxin-3 quantification assisted by aqueous biphasic systems as serum pretreatment strategies.

Although pentraxin-3 holds promise as a diagnosis/prognosis biomarker of microbial infections and lung cancer, its analysis in human serum can be constrained by matrix effects caused by high abundance proteins - human serum albumin and immunoglobulin G. Aqueous biphasic systems composed of polymers and citrate buffer are here proposed as a serum pretreatment step to improve the accuracy of pentraxin-3 analysis. Binodal curves were determined to identify the compositions required to form two phases and to correlate the polymers' properties and performance in serum pretreatment and biomarker extraction. Aqueous biphasic systems were evaluated regarding their ability to deplete human serum albumin and immunoglobulin G at the interphase. Polymers of relatively high to intermediate hydrophobicity were unveiled as efficient components to deplete high abundance serum proteins. Considering the possibility to extract pentraxin-3 from human serum into the polymer-rich phase, the system composed of polyethylene glycol with a molecular weight of 1000 g·mol-1 simultaneously achieved >93 % of human serum albumin and immunoglobulin G depletion and complete biomarker extraction. The accuracy of analysis of pretreated human serum by enzyme-linked immunosorbent assays outperformed that of a non-pretreated sample, with a relative error of 0.8 % compared to 14.6 %, contributing to boost pentraxin-3 usefulness as a biomarker.

Exploring the impact of sodium salts on hydrotropic solubilization.

Some ionic liquids (ILs) were shown to display a strong ability to enhance the solubility of phenolic compounds through hydrotropy. However, evidence shows that salt ions in hydrotropic aqueous solutions may change the behavior of molecules by promoting possible interactions between the components of the system, thus causing changes in solubility. Herein, we study the impact of sodium salt anions on the hydrotropic dissolution of syringic acid using 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) as a hydrotrope, with a focus on dicyanamide Na[N(CN)2] and thiocyanate Na[SCN] salts. Dynamic light scattering, Raman spectroscopy, and nuclear magnetic resonance spectroscopy were used to investigate how the mixture of IL-salts affects the solvation. The results obtained show that [C4mim]Cl is able to increase the solubility of syringic acid 80-fold. Despite their structural similarities, the presence of Na[N(CN)2] or Na[SCN] in an aqueous solution of [C4mim]Cl induced opposite solubility trends. The addition of Na[N(CN)2] promotes a higher ability to solubilize syringic acid than in the corresponding IL system due to a pH buffering effect, resulting in the deprotonation of the solute. The addition of Na[SCN], on the other hand, induces a relative decrease in syringic acid solubilization at higher concentrations of ILs due to the negative contribution of the NaCl formed by anion-exchange. These results emphasise the often overlooked pH contribution provided by ILs for biomolecule solubilisation whilst providing experimental insights into the structure of aqueous solutions of ionic liquids and the role it plays in the formation of IL-salt aggregates.

Enhanced Dissolution of Metal Oxides in Hydroxylated Solvents - Towards Application in Lithium-Ion Battery Leaching.

The recovery of critical metals from spent lithium-ion batteries (LIBs) is rapidly growing. Current methods are energy-intensive and hazardous, while alternative solvent-based strategies require more studies on their 'green' character, metal dissolution mechanism and industrial applicability. Herein, we bridged this gap by studying the effect of dilute HCl solutions in hydroxylated solvents to dissolve Co, Ni and Mn oxides. Ethylene glycol emerged consistently as the most effective solvent, dissolving up to four times more Co and Ni oxides than using aqueous acidic media, attributed to improved chloro-complex formation and solvent effects. These effects had a significant contribution compared to acid type and concentration. The highest Co dissolution (0.27 M) was achieved in 0.5 M HCl in 25 % (v/v) glycerol in water, using less acid and a significant amount of water compared to other solvent systems, as well as mild temperatures (40 °C). This solvent was applied to dissolve battery cathode material, achieving 100 % dissolution of Co and Mn and 94 % dissolution of Ni, following what was concluded to be a mixed mechanism. These results offer a simple alternative to current leaching processes, reducing acid consumption, enhancing atomic efficiency, and paving the way for optimized industrial hydrometallurgical processes leaning to 'greener' strategies.

Modeling the Solubility of Monoterpenoids with Hybrid and Predictive Thermodynamic Tools.

The Abraham and NRTL-SAC semipredictive models were employed to represent the solubility of (-)-borneol, (1R)-(+)-camphor, l-(-)-menthol, and thymol in water and organic solvents, using data measured in this work and collected from the literature. A reduced set of solubility data was used to estimate the model parameters of the solutes, and global average relative deviations (ARDs) of 27% for the Abraham model and 15% for the NRTL-SAC model were obtained. The predictive capability of these models was tested by estimating the solubilities in solvents not included in the correlation step. Global ARDs of 8% (Abraham model) and 14% (NRTL-SAC model) were obtained. Finally, the predictive COSMO-RS model was used to describe the solubility data in organic solvents, with ARD of 16%. These results show the overall better performance of NRTL-SAC in a hybrid correlation/prediction approach, while COSMO-RS can produce very satisfactory predictions even in the absence of any experimental data.

The path towards type V deep eutectic solvents: inductive effects and steric hindrance in the system tert-butanol + perfluoro tert-butanol.

The solid-liquid phase behaviour of two tertiary alcohols, perfluoro-tert-butanol and tert-butanol, was studied here using experimental (ITC, DSC and density measurements) and theoretical (MD simulations) approaches. The phase diagram of the binary mixture reveals highly negative deviations from ideality at low concentrations, as well as the formation of co-crystals and is characterized by two eutectic points, a congruent melting point and a peritectic reaction corresponding to TBH : TBF stoichiometries of 2 : 1 and 1 : 1 respectively. Excess molar enthalpies and volumes were calculated, showing negative and positive deviations from ideality, respectively. The effect of acidity, stereochemical hindrance and phobic effects and how they affect intermolecular interactions in these binary mixtures is discussed, with the aim of designing and fine-tuning type V deep eutectic solvents. The results showed that the fluorination of tertiary alcohols can be used for the tuning of the mixing properties and solid-liquid phase diagrams.

Everything You Wanted to Know about Deep Eutectic Solvents but Were Afraid to Be Told.

Are deep eutectic solvents (DESs) a promising alternative to conventional solvents? Perhaps, but their development is hindered by a plethora of misconceptions. These are carefully analyzed here, beginning with the very meaning of DESs, which has strayed far beyond its original scope of eutectic mixtures of Lewis or Brønsted acids and bases. Instead, a definition that is grounded on thermodynamic principles and distinguishes between eutectic and deep eutectic is encouraged, and the types of precursors that can be used to prepare DESs are reviewed. Landmark works surrounding the sustainability, stability, toxicity, and biodegradability of these solvents are also discussed, revealing piling evidence that numerous DESs reported thus far, particularly those that are choline based, lack sufficient sustainability-related traits to be considered green solvents. Finally, emerging DES applications are reviewed, emphasizing their most remarkable feature: the ability to liquefy a solid compound with a target property, allowing its use as a liquid solvent.

Juçara Fruit (Euterpe Edulis Martius) Valorization Combining Emergent Extraction Technologies and Aqueous Solutions of Alkanediols.

Anthocyanins from juçara fruits were extracted by pressurized liquid extraction (PLE) or ultrasound-assisted extraction (UAE), using aqueous solutions of 1,2-alkanediols and glycerol ethers as biobased solvents. The PLE (100 bar, 13 min, 1 mL/min flow rate) in the optimal extraction conditions originated 23.1 mganthocyanins·gdry biomass-1. On the other hand, the UAE was 10 min long, and the optimal conditions using 1,2-propanediol were 42.6 wt%, 160 W, and pH 7.0, leading to 50 mganthocyanins·gdry biomass-1. Extractions at the UAE optimized conditions, with aqueous solutions of five different 1,2-alkanediols and three glycerol ethers were performed, and compared to water and ethanolic extracts. The biobased solvent solutions presented anthocyanin yields up to 33% higher than water, and were shown to be as efficient as ethanol/water, but generated extracts with higher antioxidant capacity. The anthocyanin-rich extract of juçara, obtained with 1,2-propanediol, was used in the production of a natural soap and incorporated into a cream, showing that the addition of the juçara extract resulted in an antioxidant capacity in both products.

Rationalizing the Design of Pluronics-Surfactant Mixed Micelles through Molecular Simulations and Experiments.

Aqueous systems comprising polymers and surfactants are technologically important complex fluids with tunable features dependent on the chemical nature of each constituent, overall composition in mixed systems, and solution conditions. The phase behavior and self-assembly of amphiphilic polymers can be changed drastically in the presence of conventional ionic surfactants and need to be clearly understood. Here, the self-aggregation dynamics of a triblock copolymer (Pluronics L81, EO3PO43EO3) in the presence of three cationic surfactants (with a 12C long alkyl chain but with different structural features), viz., dodecyltrimethylammonium bromide (DTAB), didodecyldimethylammonium bromide (DDAB), and ethanediyl-1,2-bis(dimethyldodecylammonium bromide) (12-2-12), were investigated in an aqueous solution environment. The nanoscale micellar size expressed as hydrodynamic diameter (Dh) of copolymer-surfactant mixed aggregates was evaluated using dynamic light scattering, while the presence of a varied micellar geometry of L81-cationic surfactant mixed micelles were probed using small-angle neutron scattering. The obtained findings were further validated from molecular dynamics (MD) simulations, employing a simple and transferable coarse-grained molecular model based on the MARTINI force field. L81 remained molecularly dissolved up to ∼20 °C but phase separated, forming turbid/translucent dispersion, close to its cloud point (CP) and existed as unstable vesicles. However, it exhibited interesting solution behavior expressed in terms of the blue point (BP) and the double CP in the presence of different surfactants, leading to mixed micellar systems with a triggered morphology transition from unstable vesicles to polymer-rich micelles and cationic surfactant-rich micelles. Such an amendment in the morphology of copolymer nanoaggregates in the presence of cationic surfactants has been well observed from scattering data. This is further rationalized employing the MD approach, which validated the effective interactions between Pluronics-cationic surfactant mixed micelles. Thus, our experimental results integrated with MD yield a deep insight into the nanoscale interactions controlling the micellar aggregation (Pluronics-rich micelles and surfactant-rich micelles) in the investigated mixed system.

The role of biomass elemental composition and ion-exchange in metal sorption by algae.

The use of macroalgae, microalgae and cyanobacteria for metal sorption has been widely reported. Still, there are no studies allowing a direct comparison of the performance of these biomasses, especially while evaluating metal competition. The simultaneous sorption of Co2+, Cu2+, Ni2+ and Zn2+ present in a multi-elemental solution by six macroalgae, two microalgae and three cyanobacteria was evaluated. Brown macroalgae were shown to be the most promising biosorbent, with Undaria pinnatifida having a total metal sorption capacity of 0.6 mmol g-1. Overall, macroalgae performed better than microalgae, followed by cyanobacteria. Carboxyl groups were identified as being the main functional groups involved in metal sorption, and all biomass samples were found to be selective to Cu2+. This was linked not only to its higher complexation constant value with relevant functional groups when compared to the remaining metals, but also the Irving-Williams series. The release of K+ and Ca2+ to the aqueous solution during the metal sorption was followed. The obtained results suggest they are readily exchanged with metals in the solution, indicating the occurrence of an ion-exchange mechanism in metal sorption by most biomass. Red macroalgae are an exception to the reported trends, suggesting that their metal sorption mechanism may differ from the other biomass types.

Combining eutectic solvents and food-grade silica to recover and stabilize anthocyanins from grape pomace.

Concentrated in the skins of red grapes are the anthocyanins, the primary colorants responsible for the fruits' reddish-purple color. These colorants are recognized for their significant antioxidant properties and potent nutraceutical and pharmaceutical ingredients. Nevertheless, their widespread use is compromised by the (i) need for more efficient yet sustainable downstream processes for their recovery and (ii) by the challenges imposed by their poor stability. In this work, these drawbacks were overcome by applying eutectic solvents and stabilizing agents. Besides, the anthocyanins were successfully loaded into a solid host material (approved in both food and pharmaceutical sectors) based on silicon dioxide (SiO2, loading capacity: 1extract:7silica m/m). Summing up, with the process developed, the extraction yield (21 mganthocyanins.gbiomass-1) and the stability (under 55, 75, and 95 °C) of the recovered anthocyanins were over three times better than with the conventional process. Finally, the raw materials and solvents were recycled, allowing an economical and environmentally friendly downstream process.

Sustainable extraction of antioxidants from out-of-caliber kiwifruits.

Valorisation of discarded kiwifruits is proposed by extracting bioactive compounds using sustainable solvents namely deep eutectic solvents (DES). A screening of fifteen DES and several hydrogen bonding donor solvents was carried out. Extraction efficiency was measured in terms of antioxidant activity using DPPH and FRAP tests. The influence of solvents characteristics in particular DES structure, presence of ethanol or water, and pH of DES/water mixture on the antioxidant properties of the extracts was studied. Results show that kiwi peels extracts obtained with DES based on carboxylic acids exhibit enhanced antioxidant activity compared to conventional solvents and alcohol-based DES with a maximum DPPH scavenging activity of 42.0 mg TE/g DW. Glycerol or ethylene glycol are also efficient at extracting antioxidant compounds with DPPH scavenging activity of 33.1 and 36.7 mg TE/g DW. Finally, a chemical analysis of extracts using HPTLC revealed that most active compounds extracted are polyphenolic compounds, presumably tannins.

Integrated Approach to Extract and Purify Proteins from Honey by Ionic Liquid-Based Three-Phase Partitioning.

The purification of value-added compounds by three-phase partitioning (TPP) is a promising alternative to conventional processes since the target compound can be easily recovered from the liquid-liquid interphase. Although this technique has been successfully applied to the recovery of proteins, the minimization of the use of salts and solvents must be pursued to improve the overall process sustainability. Accordingly, we have here investigated the use of biobased glycine-betaine ionic liquids (IL) directly with honey, a carbohydrate-rich matrix, as phase-forming components of TPP systems. These ILTPP systems were applied in the purification of major royal jelly proteins (MRJPs) from honey. The results obtained show that MRJPs mostly precipitate in the ILTPP interphase, with a recovery yield ranging between 82.8% and 97.3%. In particular, MRJP1 can be obtained with a purity level up to 90.1%. Furthermore, these systems allow the simultaneous separation of antioxidants and carbohydrates to different liquid phases. The proposed approach allows the separation of proteins, antioxidants, and carbohydrates from honey in a single step, while using only ILs and a real carbohydrate-rich matrix, thus being sustainable TPP processes.

Preconcentration of Superbase Ionic Liquid from Aqueous Solution by Membrane Filtration.

Certain organic superbase ionic liquids (ILs) have shown good cellulose dissolution and fiber regeneration performance, allowing us to obtain high-quality textile fibers. However, there is a lack regarding the IL recovery from the spinning bath and its purification, which is essential for the economic viability of the process. Aiming to understand methods to separate ILs from water for reuse/recycle, the use of pressure-driven membrane processes to recycle ionic liquids from aqueous solution was investigated. The recovery of two superbase ILs, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-enium acetate, [mTBDH][OAc], and 5-methyl-1,5,7-triaza-bicyclo[4.3.0]non-6-enium acetate, [mTBNH][OAc], were studied using different types of membranes (microfiltration, ultrafiltration, nanofiltration, and reverse osmosis, RO). Additionally, pressure, IL concentration, temperature, and multicycle effect were evaluated. Significant retentions (>45%) were obtained for the nanofiltration and RO membranes (NF270-NF and BW30LE-RO). The increase in pressure and temperature resulted in an increase in volumetric flux and a decrease in IL retention. On the other hand, IL concentration decreased the volumetric flow and rejection. For the serial filtration tests, a three-fold ionic liquid concentration was achieved, for a maximum concentration of 14 wt % of the ionic liquid. The membrane filtration methodology proved to be an efficient technique for carrying out the preconcentration of the IL from dilute solutions.

Solubilities of Amino Acids in Aqueous Solutions of Chloride or Nitrate Salts of Divalent (Mg2+ or Ca2+) Cations.

The solubilities of glycine, l-leucine, l-phenylalanine, and l-aspartic acid were measured in aqueous MgCl2, Mg(NO3)2, CaCl2,, and Ca(NO3)2 solutions with concentrations ranging from 0 to 2 mol/kg at 298.2 K. The isothermal analytical method was used combined with the refractive index measurements for composition analysis guaranteeing good accuracy. All salts induced a salting-in effect with a higher magnitude for those containing the Ca2+ cation. The nitrate anions also showed stronger binding with the amino acids, thus increasing their relative solubility more than the chloride anions. In particular, calcium nitrate induces an increase in the amino acid solubility from 2.4 (glycine) to 4.6 fold (l-aspartic acid) compared to the corresponding value in water. Amino acid solubility data in aqueous MgCl2 and CaCl2 solutions collected from the open literature were combined with that from this work, allowing us to analyze the relations between the amino acid structure and the salting-in magnitude.

Imidazolium Chloride Ionic Liquid Mixtures as Separating Agents: Fuel Processing and Azeotrope Breaking.

Relevant chemical separations for the petrochemical and chemical industries include the removal of aromatic hydrocarbons from aliphatics, the desulfurization and denitrification of fuels, and the separation of azeotropic mixtures containing alkanols. In an attempt to contribute to the development of novel technologies, the potentialities of imidazolium chloride ionic liquid (IL) mixtures as separation agents were investigated. Selectivities, capacities, and solvent performance indices were calculated through the activity coefficients at infinite dilution of organic solutes and water in the imidazolium chloride IL: [C8mim]Cl, [C12mim]Cl, and the equimolar mixture of [C4mim]Cl and [C12mim]Cl. Results show that the imidazolium chloride IL might be appropriately tailored for specific purposes, in which an increase in the proportion of cations containing larger alkyl chains tends to increase the overall affinity with organic solutes. The IL designer solvent concept was explored by comparing the IL equimolar mixture results with the intermediary [C8mim]Cl. The COSMO-RS thermodynamic model was also applied, showing it to be a promising tool for a fast qualitative screening of potential separation agents for specific separation processes.

Selective Separation of Vanillic Acid from Other Lignin-Derived Monomers Using Centrifugal Partition Chromatography: The Effect of pH.

In this work, centrifugal partition chromatography (CPC) assisted by a polyethylene glycol (PEG)/sodium polyacrylate (NaPA) aqueous biphasic system (ABS) was applied in the separation of five lignin-derived monomers (vanillin, vanillic acid, syringaldehyde, acetovanillone, and p-hydroxybenzaldehyde). The influence of the system pH (unbuffered, pH 5, and pH 12) and added electrolytes (inorganic salts or ionic liquids (ILs)) on the compound partition was initially evaluated. The obtained data revealed that ILs induced more adequate partition coefficients (K < 5) than inorganic salts (K > 5) to enable separation performance in CPC, while alkaline conditions (pH 12) demonstrated a positive impact on the partition of vanillic acid. CPC runs, with buffered ABS at pH 12, enabled a selective separation of vanillic acid from other lignin monomers. Under these conditions, a distinct interaction between the top (PEG-rich) and bottom (NaPA-rich) phases of the ABS with the double deprotonated form of vanillic acid is expected when compared to the remaining lignin monomers (single deprotonated). This is an impactful result that shows the pH to be a crucial factor in the separation of lignin monomer compounds by CPC, while only unbuffered systems have been previously studied in the literature. Finally, the recovery of vanillic acid up to 96% purity and further recycling of ABS phase-forming components were approached as a proof of concept through the combination of ultrafiltration and solid-phase extraction steps.