Ionic liquids (ILs) are a novel class of solvents with interesting physicochemical properties. Many different applications have been reported for ILs as alternatives to organic solvents in chemical and bioprocesses. Despite the argued advantage of having low vapor pressure, even the most hydrophobic ILs show some degree of solubility in water, allowing their dispersion into aquatic systems and raising concerns on its pollutant potential. Moreover, nowadays most widespread notion concerning the ILs toxicity is that there is a direct relationship with their hydrophobicity/lipophilicity. This work aims at enlarging the currently limited knowledge on ILs toxicity by addressing negative impacts in aquatic ecosystems and investigating the possibility of designing hydrophobic ILs of low ecotoxicity, by the manipulation of their chemical structures. The impact of aromaticity on the toxicity of different cations (pyridinium, piperidinium, pyrrolidinium and imidazolium) and hydrophobic anions (bis(trifluoromethylsulfonyl)imide [NTf(2)] and hexafluorophosphate [PF(6)]) was analysed. Concomitantly, several imidazolium-based ILs of the type [C( n )C( m )C( j )im][NTf(2)] were also studied to evaluate the effects of the position of the alkyl chain on the ILs' toxicity. For that purpose, standard assays were performed using organisms of different trophic levels, Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna, allowing to evaluate the consistency of the structure-activity relationships across different biological targets. The results here reported suggest the possibility of designing ILs with an enhanced hydrophobic character and lower toxicity, by elimination of their aromatic nature.

The therapeutic effectiveness of a drug largely depends on its bioavailability, and thus ultimately on its aqueous solubility. Hydrotropes are compounds able to enhance the solubility of hydrophobic substances in aqueous media and therefore are extensively used in the formulation of drugs and personal care products. Recently, some ionic liquids were shown to display a strong ability to enhance the solubility of biomolecules through hydrotropy. In this work, the impact of the ionic liquid chemical structures and their concentration on the solubility of ibuprofen was evaluated and compared with the performance of conventional hydrotropes. The results obtained clearly evidence the exceptional capacity of ionic liquids to enhance the solubility of ibuprofen. [CCim][SCN] and [CCim][N(CN)] seem to be the most promising ionic liquids for ibuprofen solubilisation, where an increase in the solubility of 60- and 120-fold was observed with ionic liquid concentrations of circa 1 mol kg, respectively. Dynamic light scattering and molecular dynamics simulations were used to investigate the mechanism of the IL-mediated drug solubility and the results obtained indicate that the structure of aqueous solutions of ionic liquids and the role it plays in the formation of ionic liquid-drug aggregates is the mechanism driving the hydrotropic dissolution.

The design of ionic liquids has been focused on the cation-anion combinations but other more subtle approaches can be used. In this work the effect of the branching of the cation alkyl chain on the design of ionic liquids (ILs) is evaluated. The mutual solubilities with water and toxicities of a series of bis(trifluoromethylsulfonyl)-based ILs, combined with imidazolium, pyridinium, pyrrolidinium, and piperidinium cations with linear or branched alkyl chains, are reported. The mutual solubility measurements were carried out in the temperature range from (288.15 to 323.15) K. From the obtained experimental data, the thermodynamic properties of the solution (in the water-rich phase) were determined and discussed. The COnductor like Screening MOdel for Real Solvents (COSMO-RS) was used to predict the liquid-liquid equilibrium. Furthermore, molecular dynamic simulations were also carried out aiming to get a deeper understanding of these fluids at the molecular level. The results show that the increase in the number of atoms at the cation ring (from five to six) leads to a decrease in the mutual solubilities with water while increasing their toxicity, and as expected from the well-established relationship between toxicities and hydrophobicities of ILs. The branching of the alkyl chain was observed to decrease the water solubility in ILs, while increasing the ILs solubility in water. The inability of COSMO-RS to correctly predict the effect of branching alkyl chains toward water solubility on them was confirmed using molecular dynamic simulations to be due to the formation of nano-segregated structures of the ILs that are not taken into account by the COSMO-RS model. In addition, the impact of branched alkyl chains on the toxicity is shown to be not trivial and to depend on the aromatic nature of the ILs.This journal is

A new range of Good's buffer ionic liquids (GB-ILs), displaying simultaneously the properties of ionic liquids and Good's buffers, were synthesized by combination of Good's buffers anions (MOPSO, BES, TAPSO and CAPSO) and tetrabutylammonium, tetrabutylphosphonium and cholinium cations via an acid-base neutralization reaction. The activity and stability of a lipolytic enzyme from Pseudomonas cepacia in aqueous solutions of these buffers were evaluated and the results show their advantage as media for enzymatic reactions when compared to conventional phosphate buffers. Moreover aqueous biphasic systems (ABS) composed by these GB-ILs and potassium citrate were investigated and shown to be highly effective and selective for the partitioning of the lipolytic enzyme into the GB-IL-rich phase. The results allow the development of an efficient and biocompatible process combining the self-buffering and enzyme-stabilizing properties of the GB-ILs in the reaction step, with the advantages of GB-ILs as extraction solvents in ABS.

The use of glycerol ethers (with alkyl side chain ranging from one to six methyl groups) as hydrotropes to enhance the solubility of gallic and syringic acids in water was here studied. These compounds were selected due to their biological and industrial applications and for serving as model molecules for lignin solubilization. The results obtained were compared against traditional co-solvents, demonstrating the exceptional hydrotropic ability of glycerol ethers. Setschenow constants show that the hydrophobicities of both solute and hydrotrope play an important role in the solubility enhancement by hydrotropy, shedding light into its molecular mechanism.The solubility curves of gallic acid and syringic acid in the aqueous glycerol ether solutions were fitted using a recently proposed statistical thermodynamics-based model. This allowed the estimation of solute recovery from hydrotropic solution by using water as antisolvent.Unlike what is usually claimed it is here shown that in some conditions it is impossible to recover the solute by simply adding water. This analysis paves the way for a rational design and selection of hydrotropes, in which both solubility enhancement and solute recovery are critical parameters to be taken into account.