Exploring asymmetry induced entropy in tetraalkylammonium-urea DES systems: what can be learned from inelastic neutron scattering?

In this work, inelastic neutron scattering (INS) spectroscopy is used to investigate the impact of entropic factors on the behaviour of deep eutectic solvents (DES). Periodic density functional theory calculations (DFT) provide a reliable assignment of the vibrational modes of pure compounds. This assignment guides the analysis of INS spectra of binary mixtures - with particular attention to methyl torsional modes. Deviations from ideality in the mixtures of tetraalkylammonium salts with urea are readily determined through a simplified thermodynamic approach. This study reports and discusses the relationship between the cation's asymmetry, the INS spectra of the eutectic mixture and its deviation from ideality. Contrary to the majority of systems studied so far, the deep eutectic system comprised of [N2,2,2,1]Cl and urea appears to owe its deviation from ideality to entropic rather than enthalpic factors.

Cytotoxicity profiling of deep eutectic solvents to human skin cells.

The tailor-made character of deep eutectic solvents (DES) turns them very attractive to be used in several applications, including in health-related areas such as pharmaceutical, nutraceutical, and cosmetic industries. However, although DES has been touted as "green" solvents, several works proved that their potential toxicity should not be neglected. Using the premise of DES applicability in the cosmetic and pharmaceutical sectors, we chose two cell lines to work as a skin model (keratinocytes HaCaT and tumor melanocytes MNT-1), to assess DES cytotoxicity. The effect of three different hydrogen bond acceptors (HBA) ([Chol]Cl, [N1111]Cl and [N4444]Cl) and three different hydrogen bond donors (HBD) (hexanoic and butanoic acid, ethylene glycol, 1-propanol and urea) were evaluated through a common viability assay (MTT assay). Results were promising since [Chol]Cl and [N1111]Cl- based DES showed good biocompatibility for the tested cells. [N4444]Cl-based DES, however, showed cytotoxicity for both cell lines, with the HBA being the driver of the toxicity. Interestingly, some compounds increased cell viability in the HaCaT cell line, namely [Chol]Cl, ethylene glycol, hexanoic acid, urea, and all [Chol]Cl and [N1111]Cl-based DES and should be considered as targets for future studies. These results highlight their possible use in cosmetic or pharmaceutical formulations.

Enhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropes.

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. [C4C1im][SCN] and [C4C1im][N(CN)2] 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-1, 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.

Inelastic neutron scattering study of reline: shedding light on the hydrogen bonding network of deep eutectic solvents.

The solids choline chloride and urea, mixed in a 1 : 2 molar proportion, form the iconic deep eutectic solvent "Reline". A combination of computational and vibrational spectroscopy tools, including inelastic neutron scattering (INS), have been used to probe intermolecular interactions in the eutectic mixture. Reline's experimental spectra were estimated using discrete and periodic ab initio calculations of a molecular aggregate with two choline chloride and four urea units. This is the minimum size required to achieve satisfactory agreement with experiment, as smaller clusters cannot represent all of reline's significant intermolecular interactions. The INS spectrum of reline, compared with that of pure choline chloride, reveals a displacement of chloride anions away from their preferred positions on top of choline's methyl groups, whose torsional movement becomes less hindered in the mixture. Urea, which adopts a planar (sp2) shape in the crystal, becomes non-planar (sp3) in reline, a feature herein discussed for the first time. In reline, urea molecules form a wide range of hydrogen bonds, from soft contacts to stronger associations, the latter being responsible for the deviation from ideality. The chloride's interactions with choline are largely conserved at the hydroxyl end while becoming weaker at the cationic headgroup. The interplay of soft and strong interactions confers flexibility to the newly formed hydrogen-bond network and allows the ensemble to remain liquid at room temperature.

Long-term protein packaging in bio-ionic liquids: Improved catalytic activity and enhanced stability of cytochrome C against multiple stresses.

There is a considerable interest in the use of structurally stable and catalytically active enzymes, such as cytochrome C (Cyt C), in the pharmaceutical and fine chemical industries. However, harsh process conditions, such as temperature, pH, and presence of organic solvents, are the major barriers to the effective use of enzymes in biocatalysis. Herein, we demonstrate the suitability of bio-based ionic liquids (ILs) formed by the cholinium cation and dicarboxylate-based anions as potential media for enzymes, in which remarkable enhanced activity and improved stability of Cyt C against multiple stresses were obtained. Among the several bio-ILs studied, an exceptionally high catalytic activity (> 50-fold) of Cyt C was observed in aqueous solutions of cholinium glutarate ([Ch][Glu]; 1g/mL) as compared to the commonly used phosphate buffer solutions (pH 7.2), and > 25-fold as compared to aqueous solutions of cholinium dihydrogen phosphate ([Ch][Dhp]; 0.5g/mL) -the best known IL for long term stability of Cyt C. The catalytic activity of the enzyme in presence of bio-ILs was retained against several external stimulus, such as chemical denaturants (H2O2 and GuHCl), and temperatures up to 120 °C. The observed enzyme activity is in agreement with its structural stability, as confirmed by UV-Vis, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopies. Taking advantage of the multi-ionization states of di/tri-carboxylic acids, the pH was switched from acidic to basic by the addition of the corresponding carboxylic acid and choline hydroxide, respectively. The activity was found to be maximum at a 1:1 ratio of [Ch][carboxylate], with a pH in the range from 3 to 5.5. Moreover, it was found that the bio-ILs studied herein protect the enzyme against protease digestion and allow long-term storage (at least for 21 weeks) at room temperature. An attempt by molecular docking was also made to better understand the efficacy of the investigated bio-ILs towards the enhanced activity and long term stability of Cyt C. The results showed that dicarboxylates anions interact with the active site's amino acids of the enzyme through H-bonding and electrostatic interactions, which are responsible for the observed enhancement of the catalytic activity. Finally, it is demonstrated that Cyt C can be successfully recovered from the aqueous solution of bio-ILs and reused without compromising its yield, structural integrity and catalytic activity, thereby overcoming the major limitations in the use of IL-protein systems in biocatalysis.

Dispelling some myths about the CO2 solubility in ionic liquids.

Ionic liquids have been objects of extensive research for physical sorption of CO2 and a number of myths have been perpetuated in the literature, for lack of a critical analysis, concerning their potential for CO2 capture. This study carries a critical analysis of a number of widely accepted ideas and others not so well accepted that have been repeatedly expressed in the literature concerning the CO2 physical sorption in ionic liquids. Using the CO2 solubility in eicosane as benchmark, it will be shown that there is no evidence that ILs display a physical sorption of CO2 larger than n-alkanes when analyzed in adequate concentration units; the fluorination of the ions has no impact on the CO2 solubility and the oxygenation will marginally contribute to a decrease of the solubility. Ionic liquid-based deep eutectic systems are also shown to have a poor CO2 solubility. Although these widely used approaches to physically enhance the CO2 solubility in ILs do not seem to have any positive influence, this does not mean that other types of interaction cannot provide enhanced CO2 solubility as in the case of the anion [B(CN)4] confirmed here by a critical analysis of the published data. The mechanism of CO2 physical sorption in ionic liquids is discussed based on the results analyzed, supported by spectroscopic measurements and molecular simulations previously reported and further suggestions of possibilities for enhanced physical sorption based on fluorinated aromatic rings, other cyano based anions, mixtures with other ILs or solvents or the use of porous liquids are proposed.

DFT Study of the Reaction Mechanisms of Carbon Dioxide and its Isoelectronic Molecules CS2 and OCS Dissolved in Pyrrolidinium and Imidazolium Acetate Ionic Liquids.

The reaction mechanisms of CO2 and its isoelectronic molecules OCS and CS2 dissolved in N-butyl-N-methylpyrrolidinium acetate and in 1-butyl-3-methylimidazolium acetate were investigated by DFT calculations in "gas phase". The analysis of predicted multistep pathways allowed calculating energies of reaction and energy barriers of the processes. The major role played by the acetate anion in the degradation of the solutes CS2 and OCS as well as in the capture of OCS and CO2 by the imidazolium ring is highlighted. In both ionic liquids, this anion governs the conversion of CS2 into OCS and of OCS into CO2 through interatomic S-O exchanges between the anion and the solutes with formation of thioacetate anions. In imidazolium acetate, the selective capture of CS2 and OCS by the imidazolium ring competes with the S-O exchanges. From the calculated values of the energy barriers a basicity scale of the anions is proposed. The (13)C NMR chemical shifts of the predicted adducts were calculated and agree well with the experimental observations. It is argued that the scenario issued from the calculated pathways is shown qualitatively to be independent from the functionals and basis set used, constitute a valuable tool in the understanding of chemical reactions taking place in liquid phase.

Assessing the non-ideality of the CO2-CS2 system at molecular level: a Raman scattering study.

The dense phase of CO2-CS2 mixtures has been analysed by Raman spectroscopy as a function of the CO2 concentration (0.02-0.95 mole fractions) by varying the pressure (0.5 MPa up to 7.7 MPa) at constant temperature (313 K). The polarised and depolarised spectra of the induced (ν2, ν3) modes of CS2 and of the ν1-2ν2 Fermi resonance dyad of both CO2 and CS2 have been measured. Upon dilution with CO2, the evolution of the spectroscopic observables of all these modes displays a "plateau-like" region in the CO2 mole fraction 0.3-0.7 never previously observed in CO2-organic liquids mixtures. The bandshape and intensity of the induced modes of CS2 are similar to those of pure CS2 up to equimolar concentration, after which variations occur. The preservation of the local ordering from pure CS2 to equimolar concentration together with the non-linear evolution of the spectroscopic observables allows inferring that two solvation regimes exist with a transition occurring in the plateau domain. In the first regime, corresponding to CS2 concentrated mixtures, the liquid phase is segregated with dominant CS2 clusters, whereas, in the second one, CO2 monomers and dimers and CO2-CS2 hetero-dimers coexist dynamically on a picosecond time-scale. It is demonstrated that the subtle interplay between attractive and repulsive interactions which provides a molecular interpretation of the non-ideality of the CO2-CS2 mixture allows rationalizing the volume expansion and the existence of the plateau-like region observed in the pressure-composition diagram previously ascribed to the proximity of an upper critical solution temperature at lower temperatures.

Surface tension of binary mixtures of 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids: experimental measurements and soft-SAFT modeling.

Ionic liquids have attracted a large amount of interest in the past few years. One approach to better understand their peculiar nature and characteristics is through the analysis of their surface properties. Some research has provided novel information on the organization of pure ionic liquids at the vapor-liquid interface; yet, a systematic study on the surface properties of mixtures of ionic liquids and their organization at the surface has not previously been carried out in the literature. This work reports, for the first time, a comprehensive analysis of the surface organization of mixtures of ionic liquids constituted by 1-alkyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ionic liquids, [C(n)mim][NTf(2)]. The surface tension of mixtures composed of [C(4)mim][NTf(2)] + [C(n)mim][NTf(2)] (n = 1, 2, 5, 6, 8, and 10) was experimentally determined, at 298.2 K and atmospheric pressure, in the whole composition range. From the experimental data, the surface tension deviations and the relative Gibbs adsorption isotherms were estimated showing how the surface composition of an ionic liquid mixture differs from that of the liquid bulk and that the surface is enriched by the ionic liquid with the longest alkyl chain length. Finally, the soft-SAFT equation of state coupled with the density gradient theory (DGT) was used, for the first time, to successfully reproduce the surface tension experimental data of binary mixtures of ionic liquids using a molecular-based approach. In addition, the DGT was used to compute the density profiles of the two components across the interface, confirming the experimental results for the components distribution at the bulk and at the vapor-liquid interface.

Modeling the [NTf2] pyridinium ionic liquids family and their mixtures with the soft statistical associating fluid theory equation of state.

In this work, the soft statistical associating fluid theory (soft-SAFT) equation of state (EoS) has been used to provide an accurate thermodynamic characterization of the pyridinium-based family of ionic liquids (ILs) with the bis(trifluoromethylsulfonyl)imide anion [NTf(2)](-). On the basis of recent molecular simulation studies for this family, a simple molecular model was proposed within the soft-SAFT EoS framework. The chain length value was transferred from the equivalent imidazolium-based ILs family, while the dispersive energy and the molecular parameters describing the cation-anion interactions were set to constant values for all of the compounds. With these assumptions, an appropriate set of molecular parameters was found for each compound fitting to experimental temperature-density data at atmospheric pressure. Correlations for the nonconstant parameters (describing the volume of the IL) with the molecular weight were established, allowing the prediction of the parameters for other pyridiniums not included in the fitting. Then, the suitability of the proposed model and its optimized parameters were tested by predicting high-pressure densities and second-order thermodynamic derivative properties such as isothermal compressibilities of selected [NTf(2)] pyridinium ILs, in a large range of thermodynamic conditions. The surface tension was also provided using the density gradient theory coupled to the soft-SAFT equation. Finally, the soft-SAFT EoS was applied to describe the phase behavior of several binary mixtures of [NTf(2)] pyridinium ILs with carbon dioxide, sulfur dioxide, and water. In all cases, a temperature-independent binary parameter was enough to reach quantitative agreement with the experimental data. The description of the solubility of CO(2) in these ILs also allowed identification of a relation between the binary parameter and the molecular weight of the ionic liquid, allowing the prediction of the CO(2) + C(12)py[NTf(2)] mixture. The good agreement with the experimental data shows the excellent ability of the soft-SAFT EoS to describe the thermophysical properties of ILs as well as their phase behavior. Results prove that this equation of state can be a valuable tool to assist the design of ILs (in what concerns cation and anion selection) in order to obtain ILs with the desired properties and, consequently, enhancing their potential industrial applications.

Carbon dioxide in 1-butyl-3-methylimidazolium acetate. I. Unusual solubility investigated by Raman spectroscopy and DFT calculations.

The unusual solubility of carbon dioxide in 1-butyl-3-methylimidazolium acetate (Bmim Ac) has been studied by Raman spectroscopy and DFT calculations. It is shown that the solubility results from the existence of two distinct solvation regimes. In the first one (CO(2) mole fraction ≤ 0.35), the usual Fermi dyad is not observed, a fact never reported before for binary mixtures with organic liquids or ionic liquids (IL). Strong experimental evidence complemented by effective DFT modeling shows that this regime is dominated by a chemical reaction leading to the carboxylation of the imidazolium ring accompanied by acetic acid formation. The reactive scheme proposed involves two concerted mechanisms, which are a proton exchange process between the imidazolium cation and the acetate anion and the carboxylation process itself initiated from the formation of "transient" CO(2)-1-butyl-3-methylimidazole 2-ylidene carbene species. In that sense, CO(2) triggers the carboxylation reaction. Moreover, this dynamic picture circumvents consideration of a long-lived carbene formation in dense phase. The second regime is characterized by the detection of the CO(2) Fermi dyad showing that the carboxylation reaction has been strongly moderated. This finding has been interpreted as due to the interaction of the acetic acid molecules with the COO group of acetate anions involved in monodentate forms with the cation. The observation of the Fermi doublet allows us to infer that CO(2) essentially preserves its linear geometry and that the nature and strength of the interactions with its environment should be comparable to those existing in organic liquids and other IL as well. These results have been supported by DFT calculations showing that the CO(2) molecule interacts with energetically equivalent coexisting structures and that its geometry departs only slightly from the linearity. Finally, we find that the CO(2) solvation in Bmim Ac and 1-butyl-3-methylimidazolium trifluoroacetate (Bmim TFA) cannot be straightforwardly compared neither in the first regime due to the existence of a chemical reaction nor in the second regime because CO(2) interacts with a variety of environments not only consisting of ions pairs like in Bmim TFA but also with carboxylate and acetic acid molecule.

Solubility of CO2 in 1-butyl-3-methyl-imidazolium-trifluoro acetate ionic liquid studied by Raman spectroscopy and DFT investigations.

The polarized and depolarized Raman spectra of 1-butyl-3-methyl-imidazolium-trifluoro acetate (Bmim TFA) ionic liquid and of the dense phase obtained after introduction of supercritical carbon dioxide (313K) under pressure (from 0.1 MPa up to 9 MPa) in the ionic liquid have been recorded. The spectrum of the pure ionic liquid has been assigned by comparison with the spectra of ionic liquids sharing the same cation and using literature data concerning the vibrational modes of the TFA anion. It was found that the spectra of the ionic liquid is almost unaffected by the CO(2) dilution. The only noticeable perturbation concerns a weak enhancement of the mode assigned here to the symmetric stretch vibration of the COO group of the TFA anion. The band shape analysis of the ν(CC) band in pure Bmim TFA shows that the carboxylate groups probe a variety of environments which are almost not affected by the dilution in carbon dioxide. The analysis of the Fermi dyad of carbon dioxide shows that this molecule is perturbed upon dilution in the ionic liquid. The spectra suggest the presence of carbon dioxide in two different environments. In the first one, carbon dioxide molecules interact with themselves, whereas in the second environment, this molecule interacts with the COO group of the TFA anion. This is supported by B3LYP-DFT calculations aimed at assessing the interaction between an ion pair dimer and a carbon dioxide molecule. It is shown that dissolved CO(2) molecules preferentially interact with the TFA anion through a weak charge transfer interaction taking place between the carbon atom of CO(2) (acting as a Lewis acid) and a oxygen atom of the COO group of TFA (as a Lewis base). The results show that Bmim TFA is able to accommodate a large amount of carbon dioxide without having its short-range local structure significantly perturbed. Most CO(2) is hosted in the voids existing among the ion pairs, while some also weakly interact with the anion. It is finally argued that the evolution of the local organization of the IL upon carbon dioxide dilution presents similarities with the microsegregation phenomena reported for IL upon increasing the alkyl chains lengths.

Cell surface characterization of Yarrowia lipolytica IMUFRJ 50682.

In the present work, the surface characteristics of a wild-type strain of Yarrowia lipolytica (IMUFRJ50682) were investigated. Six different methods to characterize cell surfaces--adhesion to polystyrene; hydrophobic interaction chromatography (HIC); microbial adhesion to solvents (MATS) test; zeta potential; microbial adhesion to hydrocarbons (MATH) test; and contact angle measurement (CAM)--were employed to explain the cell surface behaviour of Y. lipolytica (IMUFRJ50682). This Y. lipolytica strain presents significant differences at the cell surface compared with another Y. lipolytica strain (W29) previously reported in the literature. The main difference is related to the higher cell adhesion to non-polar solvents. The proteins present on the cell wall of Y. lipolytica IMUFRJ50682 seem to play an important role in these particular surface characteristics because of the consistent reduction of this yeast hydrophobic character after the action of pronase on its cell wall.

Optimization and modeling of laccase production by Trametes versicolor in a bioreactor using statistical experimental design.

Experimental design and response surface methodologies were applied to optimize laccase production by Trametes versicolor in a bioreactor. The effects of three factors, initial glucose concentration (0 and 9 g/L), agitation (100 and 180 rpm), and pH (3.0 and 5.0), were evaluated to identify the significant effects and its interactions in the laccase production. The pH of the medium was found to be the most important factor, followed by initial glucose concentration and the interaction of both factors. Agitation did not seem to play an important role in laccase production, nor did the interaction agitation x medium pH and agitation x initial glucose concentration. Response surface analysis showed that an initial glucose concentration of 11 g/L and pH controlled at 5.2 were the optimal conditions for laccase production by T. versicolor. Under these conditions, the predicted value for laccase activity was >10,000 U/L, which is in good agreement with the laccase activity obtained experimentally (11,403 U/L). In addition, a mathematical model for the bioprocess was developed. It is shown that it provides a good description of the experimental profile observed, and that it is capable of predicting biomass growth based on secondary process variables.

How does beta-cyclodextrin affect oxygen solubility in aqueous solutions of sodium perfluoroheptanoate?

The solubility of oxygen in aqueous solutions of sodium perfluoroheptanoate (NaPFHept) at different concentrations was measured at 310.15 K with an apparatus based on the saturation method. The effect of adding beta-cyclodextrin (betaCD) on the solubility of oxygen was also studied. Conductimetry measurements showed that the presence of betaCD in aqueous solutions of NaPFHept increases its critical micellar concentration (CMC). In the presence of betaCD (15 mM), the characteristic minimum of oxygen solubility observed at the CMC is shifted from 83 to 114 mM, and the curvature at the minimum is reduced to 64% of the value in the absence of betaCD. Chemical shift changes for the H5 protons of betaCD, recorded as functions of the initial concentration of NaPFHept, point to the formation of a relatively strong 1:1 inclusion in betaCD of the perfluoroheptanoate anion. Hence, it is suggest that the effect of adding betaCD on the solubility of oxygen cannot be accounted for only by the perfluoroheptanoate anion inclusion in betaCD, but has to be ascribed to the direct influence of this inclusion complex on disrupting the aggregation process reducing the increase of oxygen solubility after the CMC value.

Decolorization of dyes from textile wastewater by Trametes versicolor.

The white rot fungus Trametes versicolor was applied to the decolourisation of three synthetic textile dyes in the presence and absence of glucose. Different initial dye concentrations were tested and approximately 97% decolourisation was achieved. It was found that fungal metabolism induced by the glucose as well as the pH play an important role in the decolourisation process. This treatment was also applied to a real wastewater from a textile industry-dyeing sector leading to 92% decolourisation.

Effect of hyperbaric stress on yeast morphology: study by automated image analysis.

The effects of hyperbaric stress on the morphology of Saccharomyces cerevisiae were studied in batch cultures under pressures between 0.1 MPa and 0.6 MPa and different gas compositions (air, oxygen, nitrogen or carbon dioxide), covering aerobic and anaerobic conditions. A method using automatic image analysis for classification of S. cerevisiae cells based on their morphology was developed and applied to experimental data. Information on cell size distribution and bud formation throughout the cell cycle is reported. The results show that the effect of pressure on cell activity strongly depends on the nature of the gas used for pressurization. While nitrogen and air to a maximum of 0.6 MPa of pressure were innocuous to yeast, oxygen and carbon dioxide pressure caused cell inactivation, which was confirmed by the reduction of bud cells with time. Moreover, a decrease in the average cell size was found for cells exposed for 7.5 h to 0.6 MPa CO2.