Valorization of olive tree leaves: Extraction of oleanolic acid using aqueous solutions of surface-active ionic liquids.

The global olive oil industry annually generates approximately 750,000-1,500,000 tons of Olea europaea leaves as waste that are typically burned for energy production. Yet, this agricultural by-product is a rich source of oleanolic acid, a high value triterpenic acid with outstanding pharmaceutical and nutraceutical activities. The present study focuses on the extraction of oleanolic acid from dried O. europaea leaves using aqueous solutions of surface-active ionic liquids as alternative solvents. A number of imidazolium-based ionic liquids with variable chain length, different anions and optional side-chain functionalization was synthesized and employed in the extraction of oleanolic acid. Ionic liquids with long alkyl chains remarkably enhance the solubility of oleanolic acid in water, thus being able to compete with the solubilities afforded by molecular organic solvents, such as chloroform. Consequently, they are suitable alternatives for the solid-liquid extraction of triterpenic acids from natural matrices and provide improved extraction yields of up to 2.5 wt% oleanolic acid extracted from olive tree leaves.

Hydrogen bond basicity of ionic liquids and molar entropy of hydration of salts as major descriptors in the formation of aqueous biphasic systems.

Aqueous biphasic systems (ABS) composed of ionic liquids (ILs) and conventional salts have been largely investigated and successfully used in separation processes, for which the determination of the corresponding ternary phase diagrams is a prerequisite. However, due the large number of ILs that can be prepared and their high structural versatility, it is impossible to experimentally cover and characterize all possible combinations of ILs and salts that may form ABS. The development of tools for the prediction and design of IL-based ABS is thus a crucial requirement. Based on a large compilation of experimental data, a correlation describing the formation of IL-based ABS is shown here, based on the hydrogen-bonding interaction energies of ILs (EHB) obtained by the COnductor-like Screening MOdel for Real Solvents (COSMO-RS) and the molar entropy of hydration of the salt ions. The ability of the proposed model to predict the formation of novel IL-based ABS is further ascertained.

Extraction and recovery processes for cynaropicrin from Cynara cardunculus L. using aqueous solutions of surface-active ionic liquids.

Due to the wide range of relevant biological activities and high commercial value of cynaropicrin, and aiming at developing cost-effective processes, aqueous solutions of ionic liquids (ILs) were investigated for the extraction and recovery of cynaropicrin from the leaves of Cynara cardunculus L. Both cationic (1-alkyl-3-methylimidazolium chloride) and anionic (cholinium carboxylate) surface-active ILs were investigated, as well as a wide range of conventional surfactants and molecular organic solvents, allowing us to conclude that aqueous solutions of cationic surface-active ILs display a better performance for the extraction of cynaropicrin. Operational conditions were optimized, leading to a cynaropicrin extraction yield of 3.73 wt%. The recycling of both the biomass and the solvent were further investigated to appraise the extraction media saturation and to achieve a higher cynaropicrin extraction yield (6.47 wt%). Finally, it was demonstrated that 65 wt% of the extracted cynaropicrin can be efficiently recovered by precipitation from the IL aqueous extract through the addition of water as anti-solvent, allowing us to put forward both the extraction and recovery processes of the target value-added compound from biomass followed by solvent recycling. This approach opens the door to the development of more sustainable processes using aqueous solutions of ILs instead of the volatile organic solvents commonly used in biomass processing.

Deep Eutectic Solvents as Efficient Media for the Extraction and Recovery of Cynaropicrin from Cynara cardunculus L. Leaves.

In recent years a high demand for natural ingredients with nutraceutical properties has been witnessed, for which the development of more environmentally-friendly and cost-efficient extraction solvents and methods play a primary role. In this perspective, in this work, the application of deep eutectic solvents (DES), composed of quaternary ammonium salts and organic acids, as alternative solvents for the extraction of cynaropicrin from Cynara cardunculus L. leaves was studied. After selecting the most promising DES, their aqueous solutions were investigated, allowing to obtain a maximum cynaropicrin extraction yield of 6.20 wt %, using 70 wt % of water. The sustainability of the extraction process was further optimized by carrying out several extraction cycles, reusing either the biomass or the aqueous solutions of DES. A maximum cynaropicrin extraction yield of 7.76 wt % by reusing the solvent, and of 8.96 wt % by reusing the biomass, have been obtained. Taking advantage of the cynaropicrin solubility limit in aqueous solutions, water was added as an anti-solvent, allowing to recover 73.6 wt % of the extracted cynaropicrin. This work demonstrates the potential of aqueous solutions of DES for the extraction of value-added compounds from biomass and the possible recovery of both the target compounds and solvents.

Switchable (pH-Driven) Aqueous Biphasic Systems formed by Ionic Liquids as Integrated Production-Separation Platforms.

The ability to induce reversible transitions between homogeneous solutions and biphasic systems is of paramount relevance in separation processes. In this context, pH-triggered aqueous biphasic systems composed of ionic liquids and salts are here disclosed as switchable mono/biphasic systems, and their potential application further demonstrated through an intregated aproach comprising both the production and separation of hydroxymethylfurfural from fructose.

Aqueous solutions of surface-active ionic liquids: remarkable alternative solvents to improve the solubility of triterpenic acids and their extraction from biomass.

Triterpenic acids (TTAs) are well known for their relevant biological properties and have been facing an increasing interest for nutraceutical and pharmaceutical applications. To overcome the concerns associated to the commonly used volatile organic solvents for their extraction from biomass, here we investigate the potential of aqueous solutions of ionic liquids (ILs) as alternative solvents. The solubility of ursolic acid (UA) was firstly determined in several aqueous solutions of ILs (hydrotropes or surface-active) at 30°C to appraise the dissolution phenomenon. Conventional surfactants were also investigated for comparison purposes. The collected data reveal a remarkable enhancement in the solubility of UA (8 orders of magnitude) in surface-active ILs aqueous solutions when compared to pure water. Afterwards, the potential of these ILs aqueous solutions was confirmed by their use in the extraction of TTAs from apple peels. Total extractions yield of TTAs of 2.62 wt.% were obtained using aqueous solutions of surface-active ILs at moderate conditions, overwhelming the extraction yields of 2.48 wt.% obtained with chloroform and 1.37 wt.% with acetone using similar conditions.

A critical assessment of the mechanisms governing the formation of aqueous biphasic systems composed of protic ionic liquids and polyethylene glycol.

An extensive study on the formation of aqueous biphasic systems (ABS) using aqueous solutions of protic ionic liquids (PILs) and polyethylene glycol (PEG) was performed in order to understand the mechanisms underlying the phase separation. Aqueous solutions of PEG polymers with different molecular weights (600, 1000, 2000, and 3400 g mol-1) and several N-alkyl-, dialkyl-, and trialkyl-ammonium salts of acetate, propanoate, butanoate, hexanoate and octanoate were prepared and their ability to form ABS at several temperatures assessed. The ternary liquid-liquid phase diagrams were determined at several temperatures, as well as binary PIL (or salt)-PEG-1000 and salt-water solubility data to better clarify the mechanisms responsible for the phase separation. All data gathered indicate that the formation of PEG-PIL-based ABS is mainly governed by the PIL-PEG mutual interactions, where PILs with a higher solubility in the polymer exhibit a lower aptitude to form ABS displaying thus a smaller biphasic region, for which a direct correlation was identified. The effects of the molecular weight and temperature of the polymer were also addressed. The increase of the PEG hydrophobicity or molecular weight favours the phase separation, whereas the effect of temperature was found to be more complex and dependent on the nature of the PIL, with an increase or decrease of the biphasic regime with an increase in temperature.

The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropes.

Hydrotropes are compounds able to enhance the solubility of hydrophobic substances in aqueous media and therefore are widely used in the formulation of drugs, cleaning and personal care products. In this work, it is shown that ionic liquids are a new class of powerful catanionic hydrotropes where both the cation and the anion synergistically contribute to increase the solubility of biomolecules in water. The effects of the ionic liquid chemical structures, their concentration and the temperature on the solubility of two model biomolecules, vanillin and gallic acid were evaluated and compared with the performance of conventional hydrotropes. The solubility of these two biomolecules was studied in the entire composition range, from pure water to pure ionic liquids, and an increase in the solubility of up to 40-fold was observed, confirming the potential of ionic liquids to act as hydrotropes. Using dynamic light scattering, NMR and molecular dynamics simulations, it was possible to infer that the enhanced solubility of the biomolecule in the IL aqueous solutions is related to the formation of ionic-liquid-biomolecules aggregates. Finally, it was demonstrated that hydrotropy induced by ionic liquids can be used to recover solutes from aqueous media by precipitation, simply by using water as an anti-solvent. The results reported here have a significant impact on the understanding of the role of ionic liquid aqueous solutions in the extraction of value-added compounds from biomass as well as in the design of novel processes for their recovery from aqueous media.

Hydrogen-bond acidity of ionic liquids: an extended scale.

One of the main drawbacks comprising an appropriate selection of ionic liquids (ILs) for a target application is related to the lack of an extended and well-established polarity scale for these neoteric fluids. Albeit considerable progress has been made on identifying chemical structures and factors that influence the polarity of ILs, there still exists a high inconsistency in the experimental values reported by different authors. Furthermore, due to the extremely large number of possible ILs that can be synthesized, the experimental characterization of their polarity is a major limitation when envisaging the choice of an IL with a desired polarity. Therefore, it is of crucial relevance to develop correlation schemes and a priori predictive methods able to forecast the polarity of new (or not yet synthesized) fluids. In this context, and aiming at broadening the experimental polarity scale available for ILs, the solvatochromic Kamlet-Taft parameters of a broad range of bis(trifluoromethylsulfonyl)imide-([NTf2](-))-based fluids were determined. The impact of the IL cation structure on the hydrogen-bond donating ability of the fluid was comprehensively addressed. Based on the large amount of novel experimental values obtained, we then evaluated COSMO-RS, COnductor-like Screening MOdel for Real Solvents, as an alternative tool to estimate the hydrogen-bond acidity of ILs. A three-parameter model based on the cation-anion interaction energies was found to adequately describe the experimental hydrogen-bond acidity or hydrogen-bond donating ability of ILs. The proposed three-parameter model is also shown to present a predictive capacity and to provide novel molecular-level insights into the chemical structure characteristics that influence the acidity of a given IL. It is shown that although the equimolar cation-anion hydrogen-bonding energies (EHB) play the major role, the electrostatic-misfit interactions (EMF) and van der Waals forces (EvdW) also contribute, admittedly in a lower extent, towards the hydrogen-bond acidity of ILs. The new extended scale provided for the hydrogen-bond acidity of ILs is of high value for the design of new ILs for task-specific applications.

Extended scale for the hydrogen-bond basicity of ionic liquids.

In the past decade, ionic liquids (ILs) have been the focus of intensive research regarding their use as potential and alternative solvents in many chemical applications. Targeting their effectiveness, recent investigations have attempted to establish polarity scales capable of ranking ILs according to their chemical behaviours. However, some major drawbacks have been found since polarity scales only report relative ranks because they depend on the set of probe dyes used, and they are sensitive to measurement conditions, such as purity levels of the ILs and procedures employed. Due to all these difficulties it is of crucial importance to find alternative and/or predictive methods and to evaluate them as a priori approaches capable of providing the chemical properties of ILs. Furthermore, the large number of ILs available makes their experimental characterization, usually achieved by a trial and error methodology, burdensome. In this context, we firstly evaluated COSMO-RS, COnductor-like Screening MOdel for Real Solvents, as an alternative tool to estimate the hydrogen-bond basicity of ILs. After demonstrating a straight-line correlation between the experimental hydrogen-bond basicity values and the COSMO-RS hydrogen-bonding energies in equimolar cation-anion pairs, an extended scale for the hydrogen-bond accepting ability of IL anions is proposed here. This new ranking of the ILs' chemical properties opens the possibility to pre-screen appropriate ILs (even those not yet synthesized) for a given task or application.

Aqueous biphasic systems: a boost brought about by using ionic liquids.

During the past decade, ionic-liquid-based Aqueous Biphasic Systems (ABS) have been the focus of a significant amount of research. Based on a compilation and analysis of the data hitherto reported, this critical review provides a judicious assessment of the available literature on the subject. We evaluate the quality of the data and establish the main drawbacks found in the literature. We discuss the main issues which govern the phase behaviour of ionic-liquid-based ABS, and we highlight future challenges to the field. In particular, the effect of the ionic liquid structure and the various types of salting-out agents (inorganic or organic salts, amino acids and carbohydrates) on the phase equilibria of ABS is discussed, as well as the influence of secondary parameters such as temperature and pH. More recent approaches using ionic liquids as additives or as replacements for common salts in polymer-based ABS are also presented and discussed to emphasize the expanding number of aqueous two-phase systems that can actually be obtained. Finally, we address two of the main applications of ionic liquid-based ABS: extraction of biomolecules and other added-value compounds, and their use as alternative approaches for removing and recovering ionic liquids from aqueous media.

Critical assessment of the formation of ionic-liquid-based aqueous two-phase systems in acidic media.

In this work, the ability of Na(2)SO(4) and ionic liquids to induce the formation of acidic aqueous two-phase systems (ATPS) is investigated. Ternary phase diagrams, tie lines, and tie-line lengths for several systems were determined and reported at 298 K and atmospheric pressure. It is here shown that among the ionic liquids studied only those containing long alkyl side chains at the ions and/or anions with low hydrogen bond basicity are capable of undergoing liquid-liquid demixing in the presence of Na(2)SO(4) aqueous solutions. The results obtained indicate that, besides the salting-out ability of the inorganic salt, the pH of the aqueous solution plays a crucial role toward the formation of ionic-liquid-based ATPS. In acidic media the range of ionic liquids that are able to undergo ATPS formation is substantially reduced when compared to alkaline aqueous salt solutions. The use of inorganic salts and ionic liquids to promote acidic ATPS is envisaged as particularly valuable in the extraction of compounds that exhibit low acid dissociation constants.

Extraction of biomolecules using phosphonium-based ionic liquids + K(3)PO(4) aqueous biphasic systems.

Aqueous biphasic systems (ABS) provide an alternative and efficient approach for the extraction, recovery and purification of biomolecules through their partitioning between two liquid aqueous phases. In this work, the ability of hydrophilic phosphonium-based ionic liquids (ILs) to form ABS with aqueous K(3)PO(4) solutions was evaluated for the first time. Ternary phase diagrams, and respective tie-lines and tie-lines length, formed by distinct phosphonium-based ILs, water, and K(3)PO(4) at 298 K, were measured and are reported. The studied phosphonium-based ILs have shown to be more effective in promoting ABS compared to the imidazolium-based counterparts with similar anions. Moreover, the extractive capability of such systems was assessed for distinct biomolecules (including amino acids, food colourants and alkaloids). Densities and viscosities of both aqueous phases, at the mass fraction compositions used for the biomolecules extraction, were also determined. The evaluated IL-based ABS have been shown to be prospective extraction media, particularly for hydrophobic biomolecules, with several advantages over conventional polymer-inorganic salt ABS.

On the interactions between amino acids and ionic liquids in aqueous media.

The understanding of the molecular-level interactions between biomolecules and ionic liquids (ILs) in aqueous media is crucial for the optimization of a number of relevant biotechnological processes. In this work, the influence of a series of amino acids on the liquid-liquid equilibria between 1-butyl-3-methylimidazolium tricyanomethane and water was studied to evaluate the preferential interactions between these three compounds. The solubility effects observed are dependent on the polarity, size, and charge distribution of the amino acid side chains and are explained in terms of a refined version of the model proposed earlier (Freire et al. J. Phys. Chem. B 2009, 113, 202; Tome et al. J. Phys. Chem. B 2009, 113, 2815) for ion specific effects on aqueous solutions of imidazolium-based ILs. Although acting through different mechanisms, salting-in and salting-out phenomena possess a common basis which is the competition between water-amino acid side chain, IL-amino acid side chain, and water-IL interactions. The delicate balance between these interactions is dependent on the relative affinities of the biomolecules to water molecules or to IL cation and anion and determines the trend and magnitude of the solubility effect observed.