Physicochemical Properties of 20 Ionic Liquids Prepared by the Carbonate-Based IL (CBILS) Process.

Ionic liquids (ILs) are an emerging materials' class with applications in areas such as energy storage, catalysis, and biomass dissolution and processing. Their physicochemical properties including surface tension, viscosity, density and their interplay between cation and anion chemistry are decisive in these applications. For many commercially available ILs, a full set of physicochemical data is not available. Here, we extend the knowledge base by providing physicochemical properties such as density (20 and 25 °C), refractive index (20 and 25 °C), surface tension (23 °C, including polar and dispersive components), and shear viscosity (ambient atmosphere, shear rate 1-200 s-1), for 20 commercial ILs. A correlation between the crystal volume, dispersive surface tension, and shear viscosity is introduced as a predictive tool, allowing for viscosity estimation. Systematic exploration of cation/anion alkyl side chain lengths reveals the impact on the IL's physicochemical attributes. Increasing the anion's headgroup decreases surface tension up to 35.7% and consequently shear viscosity. We further demonstrate that the dispersive part of the surface tension linearly correlates with the refractive index of the ionic liquid. While we provide additional physicochemical data, the screening and modeling efforts will contribute to better structure property predictions enabling faster progress in design and applications of ILs.

Evidence of a reverse side-chain effect of tris(pentafluoroethyl)trifluorophosphate [FAP]-based ionic liquids against pathogenic bacteria.

Increased interest in ionic liquids (ILs) is due to their designable and tunable unique physicochemical properties, which are utilized for a wide variety of chemical and biotechnological applications. ILs containing the tris(pentafluoroethyl)trifluorophosphate ([FAP]) anion have been shown to have excellent hydrolytic, electrochemical and thermal stability and have been successfully used in various applications. In the present study the influence of the cation on the toxicity of the [FAP] anion was investigated. Due to the properties of [FAP] ILs, the IL-toxicity of seven cations with [FAP] compared to [Cl] was examined by determination of minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) on six Gram-positive and six Gram-negative clinically-relevant bacteria. For the first time, to our knowledge, the results provide evidence for a decrease in toxicity with increasing alkyl side-chain length, indicating that the combination of both ions is responsible for this 'reverse side-chain effect'. These findings could portend development of new non-toxic ILs as green alternatives to conventional organic solvents.

Virucidal or Not Virucidal? That Is the Question-Predictability of Ionic Liquid's Virucidal Potential in Biological Test Systems.

For three decades now, ionic liquids (ILs), organic salts comprising only ions, have emerged as a new class of pharmaceuticals. Although recognition of the antimicrobial effects of ILs is growing rapidly, there is almost nothing known about their possible virucidal activities. This probably reflects the paucity of understanding virus inactivation. In this study, we performed a systematic analysis to determine the effect of specific structural motifs of ILs on three different biological test systems (viruses, bacteria and enzymes). Overall, the effects of 27 different ILs on two non-enveloped and one enveloped virus (P100, MS2 and Phi6), two Gram negative and one Gram positive bacteria (E. coli, P. syringae and L. monocytogenes) and one enzyme (Taq DNA polymerase) were investigated. Results show that while some ILs were virucidal, no clear structure activity relationships (SARs) could be identified for the non-enveloped viruses P100 and MS2. However, for the first time, a correlation has been demonstrated between the effects of ILs on enveloped viruses, bacteria and enzyme inhibition. These identified SARs serve as a sound starting point for further studies.

Predictability of ionic liquid toxicity from a SAR study on different systematic levels of pathogenic bacteria.

Ionic liquids (ILs), a new class of solvents with unique and tunable physicochemical properties, were initially envisioned as working alternatives to traditional organic solvents. However, they have now proven to have a wide range of alternative chemical and biochemical applications. Due to their increasing use, environmental and toxicity concerns are growing, but resolutions are hindered by the sheer number of possible variants. In order to assess and possibly predict IL-toxicity, a structure-activity relationship (SAR) approach was adopted using defined structural motifs. These included varied cationic alkyl side-chain lengths, cation lipophilicity and diverse anion effects. The predictive powers of such SARs in respect of antibacterial effects were compared using a total of 28 ILs on six Gram-negative and six Gram-positive pathogenic bacteria. Endpoints were minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC). Results indicate that while certain limited IL-toxicity responses in bacteria can be predicted from SARs, they caution that predictions cannot be generalized across species. This study demonstrates the complex species-specific nature of IL-toxicity and the current limitations of SAR predictability.

Carbonate based ionic liquid synthesis (CBILS®): thermodynamic analysis.

Within the last decade the Carbonate Based Ionic liquid Synthesis (CBILS®) has developed towards a widely applicable, greener and halogen free process for the industrial production of ionic liquids. A large number of diverse starting materials have been screened experimentally, to explore the structural limits of the core reaction step, which is the quaternization of nitrogen, phosphor or sulfur based nucleophiles with carbonic acid dialkyl or diaryl esters to the corresponding quaternary alkyl- or arylcarbonates. In order to overcome the large experimental effort of empirical screening, a practical method based on quantum-chemical calculation has been developed for an assessment of feasibility of chemical reactions. This method has been successfully tested with 16 typical CBILS® reactions by calculation of their thermodynamic functions. Thermodynamic equilibrium constants as a measure for the practical yield of the CBILS® reactions at 298 K and 393 K have been determined for both the gaseous state and the liquid state. The method has been evaluated by comparison of the theoretical results with experimental data and it can be considered as the powerful tool to reduce "trial and failure" for the industrial application of the CBILS® process.

High bulk modulus of ionic liquid and effects on performance of hydraulic system.

Over recent years ionic liquids have gained in importance, causing a growing number of scientists and engineers to investigate possible applications for these liquids because of their unique physical and chemical properties. Their outstanding advantages such as nonflammable liquid within a broad liquid range, high thermal, mechanical, and chemical stabilities, low solubility for gases, attractive tribological properties (lubrication), and very low compressibility, and so forth, make them more interesting for applications in mechanical engineering, offering great potential for new innovative processes, and also as a novel hydraulic fluid. This paper focuses on the outstanding compressibility properties of ionic liquid EMIM-EtSO4, a very important physical chemically property when IL is used as a hydraulic fluid. This very low compressibility (respectively, very high Bulk modulus), compared to the classical hydraulic mineral oils or the non-flammable HFDU type of hydraulic fluids, opens up new possibilities regarding its usage within hydraulic systems with increased dynamics, respectively, systems' dynamic responses.

Bacterial Resistance Toward Antimicrobial Ionic Liquids Mediated by Multidrug Efflux Pumps.

The effective elimination of foodborne pathogens through cleaning and disinfection measures is of great importance to the food processing industry. As food producers rely heavily on disinfectants to control pathogenic bacteria in their facilities, the increasing spread of tolerant, often even multidrug resistant, strains is of particular concern. In addition to efforts to prevent or at least reduce development and spread of strains resistant to disinfectants and sanitizers, there is an urgent need for new and effective antimicrobials. One new class of promising antimicrobials is ionic liquids (ILs), which have been reported to be effective against resistant strains as they interact with bacterial cells in multiple ways, but investigations of their effectivity against MDR bacteria or specific defense mechanisms are still limited. This study investigates the role of multidrug efflux pumps of the Resistance Nodulation-Division family (RND) on the resistance of bacterial pathogens Escherichia coli and Salmonella enterica serovar Typhimurium toward 10 antimicrobial active ILs. Results reveal that, while known structure-activity relationships (SARs), such as the side-chain effect, were found for all strains, antimicrobial ILs with one elongated alkyl side chain were significantly affected by the RND efflux pump, highlighting the importance of efflux pumps for future IL toxicity studies. In case of antimicrobial ILs with multiple side chains and different cationic head groups, two ILs were identified that were highly active against all investigated strains with little to no effect of the efflux pump. The results obtained in this study for RND efflux pumps can serve as a starting point for identifying and designing antimicrobial ILs as effective biocides against MDR bacteria.

Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease.

BACKGROUND: Shortened telomere length has been observed in a variety of diseases. Our objective was to analyze mean telomere length of patients with major depressive disorder. A key question was whether telomere length varies in different groups of depressive patients. METHODS: We obtained blood samples from patients with major depressive disorder (n = 54) and healthy subjects (n = 20). We isolated genomic DNA and measured mean telomere length using telomere restriction fragments and Southern blotting. We grouped patients according to the therapy they received including total antidepressant dose. RESULTS: Mean telomere length of the entire patient group (7.20 ± 0.61 kb) was significantly shorter than in the control group (7.55 ± 0.54 kb). We observed no significant difference in telomere length among the different patient groups, but each of these patient groups had significantly shorter telomeres than the healthy subjects. Further analysis revealed no significant association between telomere length and illness duration and between telomere length and the severity of depression, as determined by the Hamilton score. CONCLUSION: These results provide further evidence that major depressive disorder is associated with shortened telomeres. However, differences in the applied therapy, the duration of illness, or the severity of depression do not seem to have any influence on telomere length.

FTIR Spectroscopy Suggests a Revised Mode of Action for the Cationic Side-Chain Effect of Ionic Liquids.

Over the past decades, ionic liquids (ILs) have gained considerable attention from the scientific community because of their versatile and designable properties. As a result, there are numerous IL applications, not only in organic synthesis, catalysis, or extraction but also as active pharmaceutical ingredients or novel antimicrobials. While considerable effort has been put into developing quantitative structure-activity relationship (QSAR) models for IL toxicity prediction, little is known about their actual mode of action. In this study, Fourier transform infrared (FTIR) spectroscopy is used to monitor IL induced molecular responses directly at the cellular level. Investigation of the well-known cationic alkyl side-chain effect (increasing side-chain length leads to increasing toxicity) of imidazolium- and ammonium-based ILs on two bacterial pathogens, enteropathogenic  Escherichia coli (EPEC) and methicillin-resistant Staphylococcus aureus (MRSA), surprisingly revealed two distinct modes of action. Contrary to prior models, it was only for [TMC16A][Cl], where a molecular response in the membrane was found, while ILs with shorter side-chain lengths predominantly affected bacterial proteins. The results of this study highlight the importance of further direct investigations of the impact of ILs at the cellular level to improve toxicity prediction and assess the usefulness of spectroscopic methods, such as FTIR spectroscopy at achieving this goal.

Virucidal Influence of Ionic Liquids on Phages P100 and MS2.

An increasing number of publications describe the potential of ionic liquids (ILs) as novel antimicrobials, antibacterial coatings and even as active pharmaceutical ingredients. Nevertheless, a major research area, notably their impact on viruses, has so far been neglected. Consequently the aim of this study was to examine the effects of ILs on the infectivity of viruses. A systematic analysis to investigate the effects of defined structural elements of ILs on virus activity was performed using 55 ILs. All structure activity relationships (SARs) were tested on the human norovirus surrogate phage MS2 and phage P100 representing non-enveloped DNA viruses. Results demonstrate that IL SAR conclusions, established for prokaryotes and eukaryotes, are not readily applicable to the examined phages. A virus-type-dependent IL influence was also apparent. Overall, four ILs, covering different structural elements, were found to reduce phage P100 infectivity by ≥4 log10 units, indicating a virucidal effect, whereas the highest reduction for phage MS2 was about 3 log10 units. Results indicate that future applications of ILs as virucidal agents will require development of novel SARs and the obtained results serve as a good starting point for future studies.

Opposite effects of depression and antidepressants on processing speed and error rate.

Depressions increase reaction times and antidepressant treatment decreases them. Is it possible to get information, how these two conditions affect the stimulus-response pathway? Therefore, auditory and visual, left-hand and right-hand, simple and choice reaction times were measured in 38 patients with depression and 30 healthy control subjects. From these data, the minimal reaction times and the error rates were calculated. In the first study, the reaction times and error rates of patients with depression were correlated with the antidepressant doses. In the second study, the differences between medicated, depressive patients and healthy control subjects were investigated. The result of the first study was that antidepressant doses correlated negatively with reaction times but positively with error rates. In the second study, the patients with depression showed increased reaction times but reduced error rates compared to healthy control subjects. The auditory tasks were more affected than the visual tasks and the minimal reaction times more than the median reaction times. Therefore, we concluded that depression and antidepressant treatment had opposite effects on reaction times and error rates. The findings in minimal reaction times and auditory tasks suggest a special involvement of early cortical auditory processing in depression and antidepressant treatment.

Improvement in response times for simple and complex tasks after electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) has gone through fundamental changes since its introduction in 1938 and has developed from a frightening and distrusted procedure into an effective and safe treatment for people with severe psychiatric disorders. This study suggests that ECT has an effect on the response times of simple and complex tasks. METHODS: We had two groups. The first group consisted of eight patients suffering from severe therapy-resistant depression. They were treated with ECT. The second group consisted of eight sex- and age-matched persons who were treated conventionally with antidepressive medication. The authors measured auditory and visual response times of both simple and complex tasks in run A and run B on two different days. In the ECT group, the first measurement took place 1 day before a session of ECT, the second 3 h following a session of ECT. In the depressive control group, the two measurements were performed on two different days but at most within 4 days. RESULTS: The response times of the depressive subjects treated with ECT are prolonged in both run A and run B compared to those of the depressive control group. The response times in run B are reduced compared to run A on the whole. However the reduction is stronger in the ECT group than the one taking place in the depressive control group between the two runs. CONCLUSIONS: The considerable decrease of the response times from run A to run B in the ECT group compared to the depressive control group gives further evidence that ECT has a positive effect on important information processing parameters.

Sex differences in simple reaction tasks.

Many anatomical and brain mapping studies show a higher bilateral symmetry of female brains and a higher asymmetry of male brains so correlations between simple visual and auditory, left- and right-hand reaction times were examined for such sex differences. 20 healthy women and 20 men were tested in two sessions. For women all six response times correlated with each other significantly in Session A, but in Session B there were only two significant interhemispheric correlations. This represented different changes in visual and auditory reaction times between Sessions A and B. Men showed the same pattern in both sessions: a significant correlation between the interhemispheric visual reaction times and one between auditory reaction times. Women showed a total correlation pattern in Session A and an interhemispheric correlation pattern in Session B. This was interpreted as a transition between a holistic information-processing strategy in Session A and an analytic strategy in Session B. Men showed an analytic strategy in both sessions.

Making sense of enthalpy of vaporization trends for ionic liquids: new experimental and simulation data show a simple linear relationship and help reconcile previous data.

Vaporization enthalpy of an ionic liquid (IL) is a key physical property for applications of ILs as thermofluids and also is useful in developing liquid state theories and validating intermolecular potential functions used in molecular modeling of these liquids. Compilation of the data for a homologous series of 1-alkyl-3-methylimidazolium bis(trifluoromethane-sulfonyl)imide ([C(n)mim][NTf2]) ILs has revealed an embarrassing disarray of literature results. New experimental data, based on the concurring results from quartz crystal microbalance, thermogravimetric analyses, and molecular dynamics simulation have revealed a clear linear dependence of IL vaporization enthalpies on the chain length of the alkyl group on the cation. Ambiguity of the procedure for extrapolation of vaporization enthalpies to the reference temperature 298 K was found to be a major source of the discrepancies among previous data sets. Two simple methods for temperature adjustment of vaporization enthalpies have been suggested. Resulting vaporization enthalpies obey group additivity, although the values of the additivity parameters for ILs are different from those for molecular compounds.

Symmetry reversal in schizophrenia.

Schizophrenia is associated with cortical asymmetries concentrated in the left fronto-temporal hemisphere. In order to look for functional asymmetries between the two hemispheres, the stimulus-response times of patients were split into smaller periods and the interhemispheric and intrahemispheric correlations between these periods were investigated. Three groups were compared to each other: 22 patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 4th edn; DSM-IV) treated with neuroleptics; 24 psychiatric neuroleptic-treated patients without schizophrenia; and 30 healthy subjects. All subjects were investigated by simple (one stimulus-one response) and complex (two stimuli-two responses), auditory and visual, right-hemispheric and left-hemispheric stimulus-response tasks. There were no intrahemispheric but significant interhemispheric correlations between the two auditory and between the two visual time fragments in both the healthy and the neuroleptic control group. In contrast there was a significant intrahemispheric correlation between the auditory and visual time fragment in the left hemisphere of patients with schizophrenia and no interhemispheric correlation between the auditory times. The reduction of the interhemispheric auditory correlation is interpreted as an auditory disintegration, the appearance of the left-hemispheric audiovisual correlation as an audiovisual 'hyperintegration' in patients with schizophrenia. It is questionable as to whether these findings are due to schizophrenia or to the neuroleptic treatment.

Cuticular hydrocarbons of Tetramorium ants from central Europe: analysis of GC-MS data with self-organizing maps (SOM) and implications for systematics.

Cuticular hydrocarbons were extracted from workers of 63 different nests of five species of Tetramorium ants (Hymenoptera: Formicidae) from Austria, Hungary, and Spain. The GC-MS data were classified (data mining) by self-organizing maps (SOM). SOM neurons derived from primary neuron separation were subjected to hierarchical SOM (HSOM) and were grouped to neuron areas on the basis of vicinity in the hexagonal output grid. While primary neuron separation and HSOM resulted in classifications on a level more sensitive than species differences, neuron areas resulted in chemical phenotypes apparently of the order of species. These chemical phenotypes have implications for systematics: while the chemical phenotypes for T. ferox and T. moravicum correspond to morphological determination, in T. caespitum and T. impurum a total of six chemical phenotypes is found. Three hypotheses are discussed to explain this disparity between morphological and chemical classifications, including in particular the possibility of hybridization and the existence of cryptic species. Overall, the GC-MS profiles classified by SOM prove to be a practical alternative to morphological determination (T. ferox, T. moravicum) and indicate the need to revisit systematics (T. caespitum, T. impurum).