Toxicity Of Ionic Liquids Research Articles

The effect of imidazolium based ionic liquids on wheat and barley germination and growth: Influence of length and oxygen functionalization of alkyl side chain

In this work five different imidazolium based ionic liquids, namely: 1-(2-oxybutyl)-3-methylimidazolium chloride, [C2OC2mIm][Cl]; 1-(2-oxypropyl)-3-methylimidazolium chloride, [C1OC2mIm][Cl]; 1-(3-hydroxypropyl)-3-ethylimidazolium chloride, [OHC3eIm][Cl]; 1-(3-hydroxypropyl)-3-methylimidazolium chloride, [OHC3mIm][Cl]; 1-(2-hydroxyethyl)-3-methylimidazolium chloride, [OHC2mIm][Cl], together with commercial 1-butyl-3-methylimidazolium chloride, [bmim][Cl] and synthesized protic imidazolium chloride, [Im][Cl], were prepared and their toxicity examined towards wheat and barley germination and growth. Introduction of the polar groups (in the form of hydroxyde and/or ether group) in the alkyl side chain of the imidazolium cation and their influence on the reduction of the ionic liquid's toxicity is demonstrated. The results indicate that toxicity of oxygen functionalized ILs is significantly lower against wheat comparing to non-functionalized analogues. In the case of barley, influence on germination follow the same trend as in the case of wheat, but for seedlings growth different trend is observed with more pronounced toxicity of ether functionalized ILs. From these results it was also shown that alkylation in the position N-3 atom of the imidazole significantly reduces toxicity of cation.

Toxicity of Selected Imidazolium-based Ionic Liquids on Caenorhabditis elegans: a Quantitative Structure-Activity Relationship Study

Due to the large number of ionic liquids (ILs) and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure-activity relationship (QSAR) has been proven to be a quick and effective method to estimate the viscosity, melting points, and even toxicity of ILs. In this work, the LC50 values of 30 imidazolium-based ILs were determined with Caenorhabditis elegans as a model animal. Four suitable molecular descriptors were selected on the basis of genetic function approximation algorithm to construct a QSAR model with an R2 value of 0.938. The predicted lgLC50 in this work are in agreement with the experimental values, indicating that the model has good stability and predictive ability. Our study provides a valuable model to predict the potential toxicity of ILs with different sub-structures to the environment and human health.

Evaluation of risk assessment of new industrial pollutant, ionic liquids on environmental living systems

Ionic liquids (ILs) are much known for their promising alternative for volatile solvents in industries and gained popularity as a greener solvent, however industrial effluent discharge containing ILs are also increasing. There is a scarcity of information on the toxicity of ILs; the present study will explore different facts about their harmfulness. The toxic effects of five different ILs: [C4MIM]Br, [Hx3PC14]N(CN)2, [C10MIM]BF4, [BTDA]Cl and [C4MPY]Cl were analysed on bacteria, fungi, plant and animal cells. Both Gram positive and negative bacteria were found to be more susceptible to [C10MIM]BF4 and [BTDA]Cl than [C4MIM]Br, [Hx3PC14]N(CN)2 and [C4MPY]Cl, whereas fungi revealed quite a resistance to all ILs. All ILs were toxic towards Triticum aestivum affecting their roots and shoots, however [C10MIM]BF4 and [BTDA]Cl were more toxic amongst them. Studies on Allium cepa described their toxic behaviour at the genetic level by altering cell division and nuclear material. Furthermore, studies on human red blood cells described by % haemolysis in which [Hx3PC14]N(CN)2 and [BTDA]Cl exhibited higher toxicity at very lower concentrations. While the genotoxic effect on blood lymphocytes exerted by [Hx3PC14]N(CN)2, [C10MIM]BF4 and [BTDA]Cl confirmed their toxic effects on human cells.

Assessment and prediction of joint algal toxicity of binary mixtures of graphene and ionic liquids

Graphene and ionic liquids (ILs) released into the environment will interact with each other. So far however, the risks associated with the concurrent exposure of biota to graphene and ILs in the environment have received little attention. The research reported here focused on observing and predicting the joint toxicity effects in the green alga Scenedesmus obliquus exposed to binary mixtures of intrinsic graphene (iG)/graphene oxide (GO) and five ILs of varying anionic and cationic types. The isolated ILs in the binary mixtures were the main contributors to toxicity. The binary GO-IL mixtures resulted in more severe joint toxicity than the binary iG-IL mixtures, irrespective of mixture ratios. The mechanism of the joint toxicity may be associated with the adsorption capability of the graphenes for the ILs, the dispersion stability of the graphenes in aquatic media, and modulation of the binary mixtures-induced oxidative stress. A toxic unit assessment showed that the graphene and IL toxicities were additive at low concentration of the mixtures but antagonistic at high concentration of the mixtures. Predictions made using the concentration addition and independent action models were close to the observed joint toxicities regardless of mixture types and mixture ratios. These findings provide new insights that are of use in the risk assessment of mixtures of engineered nanoparticles and other environmentally relevant contaminants.

Growth and physiological responses of a marine diatom (Phaeodactylum tricornutum) against two imidazolium-based ionic liquids ([C4mim]BF4 and [C8mim]BF4)

Ionic liquids (ILs) have been considered as “green” substitutes for traditional organic solvents in many existing biological and chemical areas. However, they have high solubility and poor biodegradability in water, suggesting that they could become persistent chemical pollutants in aquatic environment. The ability of two widely used imidazolium-based ILs to affect the growth and physiological characteristics of a marine diatom (Phaeodactylum tricornutum) was investigated in this study. The diatom was exposed to different concentrations of 1-butyl-3-methylimidazolium tetrafluoroborate ([C4mim]BF4) and 1-octyl-3-methylimidazolium tetrafluoroborate ([C8mim]BF4) for 96h within a batch-culture system. Results showed that [C4mim]BF4 and [C8mim]BF4 were very stable in seawater during 96h of exposure, and the compounds significantly inhibited the growth of P. tricornutum with 24, 48, 72 and 96h EC50 values of 30.81, 28.53, 39.92, 45.88mgL−1 and 30.17, 23.36, 28.62, 31.37mgL−1, respectively. In addition, the photosynthetic activity and chlorophyll a synthesis of P. tricornutum were inhibited by [C4mim]BF4 and [C8mim]BF4, indicating that the structural integrity of chloroplasts of the diatom may be disrupted or damaged by the two ILs. Compared with that of the controls, reactive oxygen species (ROS) level was increased by 0.65, 1.17, 1.85, 3.13, 2.94 times and 0.55, 1.77, 2.42, 3.45, 3.47 times in 5, 10, 20, 40 and 60mgL−1 [C4mim]BF4 and [C8mim]BF4 treatments, respectively. The excessive ROS may cause lipid peroxidation, shortage of metabolic energy and decline of photosynthetic efficiency, which may be the main reason for toxicity of the two ILs to marine diatoms. To withstand the damaging effects of excessive ROS, remarkable physiological and biochemical responses occurred in treatments with the two ILs to protect the cells of P. tricornutum. Parameters such as soluble protein content, soluble sugar content, and superoxide dismutase (SOD) and peroxidase (POD) activities of the diatom increased significantly with increasing concentrations of the two ILs at 96h of exposure relative to the controls. These findings not only provide strong background for evaluating the ecological risks and toxicity of ILs in marine environment, but also help to unravel the toxic mechanism of the two ILs to marine diatoms.

Membrane partitioning of ionic liquid cations, anions and ion pairs – Estimating the bioconcentration potential of organic ions

Recent efforts have been directed towards better understanding the persistency and toxicity of ionic liquids (ILs) in the context of the “benign-by-design” approach, but the assessment of their bioaccumulation potential remains neglected. This paper reports the experimental membrane partitioning of IL cations (imidazolium, pyridinium, pyrrolidinium, phosphonium), anions ([C(CN)3]−, [B(CN)4]−, [FSO2)2N]−, [(C2F5)3PF3]−, [(CF3SO2)2N]−) and their combinations as a measure for estimating the bioconcentration factor (BCF). Both cations and anions can have a strong affinity for phosphatidylcholine bilayers, which is mainly driven by the hydrophobicity of the ions. This affinity is often reflected in the ecotoxicological impact. Our data revealed that the bioconcentration potential of IL cations and anions is much higher than expected from octanol-water-partitioning based estimations that have recently been presented. For some ILs, the membrane-water partition coefficient reached levels corresponding to BCFs that might become relevant in terms of the “B” (bioaccumulation potential) classification under REACH. However, this preliminary estimation need to be confirmed by in vivo bioconcentration studies.

Environmental Impact of Ionic Liquids: Recent Advances in (Eco)toxicology and (Bio)degradability.

This Review aims to integrate the most recent and pertinent data available on the (bio)degradability and toxicity of ionic liquids for global and critical analysis and on the conscious use of these compounds on a large scale thereafter. The integrated data will enable focus on the recognition of toxicophores and on the way the community has been dealing with them, with the aim to obtain greener and safer ionic liquids. Also, an update of the most recent biotic and abiotic methods developed to overcome some of these challenging issues will be presented. The review structure aims to present a potential sequence of events that can occur upon discharging ionic liquids into the environment and the potential long-term consequences.

Assessing the toxicity of ionic liquids – Application of the critical membrane concentration approach

Charged organic chemicals are a prevailing challenge for toxicity modelling. In this contribution we strive to recapitulate the lessons learned from the well-known modelling of narcosis (or baseline toxicity) of neutral chemicals and apply the concept to charged chemicals. First we reevaluate the organism- and chemical independent critical membrane concentration causing 50% mortality,.cmemtox, based on a critical revision of a previously published toxicity dataset for neutral chemicals. In accordance to values reported in the literature we find a mean value for cmemtox of roughly 100 mmol/kg (membrane lipid) for a broad variety of 42 aquatic organisms (333 different chemicals), albeit with a considerable scatter. Then we apply this concept to permanently charged ionic liquids (ILs). Using COSMOmic, a quantum mechanically based mechanistic model that makes use of the COSMO-RS theory, we predict membrane-water partition coefficients (Kmem/w) of the anionic and cationic IL components. Doing so, cmemtox(total) for permanently charged ILs can be estimated assuming independent, concentration additive contributions of the cationic and its respective anionic species. The resulting values for some of the toxicity data for ionic liquids are consistent with the expected range for baseline toxicity for neutral chemicals while other values are consistently greater or smaller. Based on the calculation of toxic ratios we identify ILs that exert a specific mode of toxic action. Limitations of the modelling approach especially but not exclusively due to the use of nominal concentrations instead of freely-dissolved concentrations in the published literature are critically discussed.

Acute Toxicity of Imidazole Nitrate Ionic Liquids with Varying Chain Lengths to Earthworms (Eisenia foetida).

When ionic liquids (ILs) first came into use, we thought that they were safe. However, upon further investigation, researchers found that ILs are not harmless. In this study, the model soil organism, earthworms (Eisenia foetida), were used to study the acute toxicity of imidazole nitrate ionic liquids with varying chain lengths from 2 to 12. The experiment used two different methods, a filter paper contact test (48h) and an artificial soil test (14 days), to determine the toxicity. These results demonstrated that the toxicity increased with the length of carbon chains until C8 and that the cut-off effect occurred at 1-octyl-3-methyl imidazole nitrates.Then, the toxicity began to increase again. At the same time, the concentrations of [C10mim]NO3 and [C12mim]NO3 were determined by high performance liquid chromatography and demonstrated that ILs were stable throughout the experiment. The present study revealed the acute toxicity of ILs with varying chain lengths.

The acute toxic effects of imidazolium-based ionic liquids with different alkyl-chain lengths and anions on zebrafish (Danio rerio)

With the increasing applications of ionic liquids (ILs), the toxicity of ILs has drawn increasing attention in recent years, especially the influences of different anions and alkyl-chain lengths on the acute toxicity to aquatic organisms. We performed a study on the acute toxicity of 1-alkyl-3-methylimidazolium nitrate ([Cnmim]NO3 (n=2, 4, 6, 8, 10, 12)), 1-hexyl-3-methylimidazolium ILs ([C6mim]R (R=Cl–, Br–, BF4–, PF6–)) to zebrafish (Danio rerio). We also evaluated the sensibility of the investigated animals and the stability of ILs in water via high performance liquid chromatography (HPLC, Agilent 1260, Agilent Technologies Inc., USA) to prove the reliability of the present study. The results illustrated that the test zebrafish (Danio rerio) were sensitive to the reference toxicant and that the investigated ILs in water were stable. The 50% lethal concentration (LC50) was used to represent the acute toxicity to zebrafish (Danio rerio). The present study showed that the highest toxic IL is [C12mim]NO3 and the lowest toxic IL is [C2mim]NO3 on Danio rerio. The LC50s for ILs with different anions had similar values. Accordingly, we believe that ILs with different alkyl-chain lengths cause greater effects than other anions on acute toxicity to aquatic organisms. Furthermore, the present study can also provide scientific methods for future studies to select and assess ILs.

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.

Potential toxicity of ionic liquid ([C12mim]BF4) on the growth and biochemical characteristics of a marine diatom Phaeodactylum tricornutum

Recently, some researchers have pointed out that the threats of ionic liquids (ILs) to aquatic environment cannot be ignored. Thus, this study investigated the potential toxicity of 1-dodecyl-3-methylimidazolium tetrafluoroborate ([C12mim]BF4) on a marine diatom Phaeodactylum tricornutum at population, biochemical and physiological levels using 96h growth tests with a batch-culture system. Results showed that [C12mim]BF4 was very stable in aquatic environment during 96h of exposure. The growth of P. tricornutum was significantly inhibited by [C12mim]BF4 with 24, 48, 72 and 96h EC50 values of 0.63, 0.61, 0.68 and 0.72mgL−1, respectively. Although there were no significant differences between the controls and treatments with 0.1 and 0.5mgL−1 [C12mim]BF4, the effective quantum yields (ΦPSII) of the diatom in 1, 2.5, 5 and 10mgL−1 [C12mim]BF4 treatments were 61.48, 17.04, 2.96 and 0.74% of that in the controls at 96h of exposure, respectively. Chl a content of the diatom was decreased by 34.86, 47.79, 49.81, 59.21, 79.82 and 86.98% compared with that of the controls at 96h of exposure in 0.1, 0.5, 1, 2.5, 5 and 10mgL−1 [C12mim]BF4 treatments, respectively. Relative to the controls, soluble sugar content, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, superoxide dismutase (SOD) and peroxidase (POD) activities of the diatom increased with increasing [C12mim]BF4 concentrations at 96h of exposure, and reached their maxima (1.46μg106cell−1, 7.48FU107cell−1, 3.35nmol108cell−1, 33.41 and 7.23Umg−1 proteins, respectively) in 5mgL−1 [C12mim]BF4 treatments. While the maximum soluble protein content (1.56μg106cell−1) of the diatom was obtained in 0.5mgL−1 [C12mim]BF4 treatments, and then decreased with increasing [C12mim]BF4 concentrations from 0.5 to 10mgL−1. These findings provide strong evidence for the potential toxicity of ILs to marine diatoms.

Global versus local QSAR models for predicting ionic liquids toxicity against IPC-81 leukemia rat cell line: The predictive ability

Abstract The unlimited possibility of modifying the structure of the cation and anion of a given ionic liquid (IL) delivers a countless number of potential derivatives having different toxicological activities. The experimental measurements for such huge set of compounds are impossible due to time and costs limitations. In the absence of experimental data, computational methods such as quantitative structure–activity relationship (QSAR) method can be applied to characterize those species for which experimental data is not available. However, two different ways of QSAR modeling could be applied: local modeling - dedicating to one specific group and more complex global models. The aim of this study was to investigate how local/global QSAR modeling works for the ionic liquids. Which of these two approaches is more suitable in ILs' modeling? We have developed six local models and a global one for predicting the toxicity against the leukemia rat cell line IPC-81. Based on the obtained results, we conclude that local models are useful to solve specific mechanistic problems among one group of ILs, but in case of predicting the toxicity for a new designed compound the global model, whenever fulfills all quality recommendations, is recommended.

Asymmetric whole-cell bioreduction of sterically bulky 2-benzoylpyridine derivatives in aqueous hydrophilic ionic liquid media

The asymmetric reduction of 2-benzoylpyridine derivatives for enantiopure alcohols with excellent enantioselectivity and atom economy is still a challenging synthetic problem due to the coordination effects of 2-pyridine and substituents. In this study, we investigated an alternative cost-effective and green route for the enantioselective bioreduction of prochiral 2-benzoylpyridine derivatives employing a novel biocatalyst Cryptococcus sp. whole-cell to corresponding (S)-alcohols. This biocatalyst was more enantioselective toward the reduction of 2-benzoylpyridine derivatives with a para-substituent on the phenyl group, rather than those with an ortho- or meta-substituent. This property was quite contrary to the cases of known chemical catalysts. Moreover, Cryptococcus sp. whole-cell-catalyzed reduction of (4-chlorophenyl)-(pyridin-2-yl) methanone (CPMK) could proceed with perfect enantioselectivity in aqueous hydrophilic ionic liquid (IL) media, affording the product (S)-(4-chlorophenyl)-(pyridin-2-yl)methanol [(S)-CPMA] with excellent enantioselectivity (99% ee) and good conversion (89%), which is a crucial chiral synthon of new antiallergic drug, Betahistine. To overcome the known toxicity of hydrophilic ILs to cells, a high IL-tolerant mutant of Cryptococcus sp. (M9-3) was adopted in the reaction. The excellent tolerance of the biocatalyst to various hydrophilic ILs enabled the exploration of the positive effects of ILs on the biocatalytic efficiency and enantio-selectivity. In addition, the enzymatic hydrolyzate of bagasse was firstly used as the co-substrate during the asymmetric bioreduction of CPMK, with a higher conversion achieved (92%) than using pure glucose. This is a novel and economical route for the green synthesis of chiral diarylmethanols.

Antifungal activity of ionic liquids based on (−)-menthol: a mechanism study

The mechanism of toxicity of chiral ionic liquids with (1R,2S,5R)-(−)-menthol [Cn-Am-Men][Cl] (n=10, 11 or 12) in the fungus Candida albicans is reported here. Ionic liquids were more toxic towards Candida strain lacking all identified multidrug resistance efflux pumps. Moreover, the compounds tested inhibited C. albicans filamentation at the concentration at which detached fungal cells also adhered to the plastic surface. Our results showed the high activity of all the tested chiral ionic liquids in the permeabilization of C. albicans’ membranes and in the digestion and interruption of the cell wall. The investigated ionic liquids thus have potential as disinfectants because besides their antifungal and antiadhesive action these compounds do not cause hemolysis.

Investigation of dermal toxicity of ionic liquids

Investigation of dermal toxicity of ionic liquids

Mechanistic insights into the effect of imidazolium ionic liquid on lipid production by Geotrichum fermentans.

BackgroundIonic liquid (IL) pretreatment has emerged as a promising technique that enables complete utilization of lignocellulosic biomass for biofuel production. However, imidazolium IL has recently been shown to exhibit inhibitory effect on cell growth and product formation of industrial microbes, such as oleaginous microorganisms. To date, the mechanism of this inhibition remains largely unknown.ResultsIn this study, the feasibility of [Bmim][OAc]-pretreated rice straw hydrolysate as a substrate for microbial lipid production by Geotrichum fermentans, also known as Trichosporon fermentans, was evaluated. The residual [Bmim][OAc] present in the hydrolysate caused a reduction in biomass and lipid content (43.6 and 28.1%, respectively) of G. fermentans, compared with those of the control (7.8 g/L and 52.6%, respectively). Seven imidazolium ILs, [Emim][DEP], [Emim]Cl, [Amim]Cl, [Bmim]Cl, [Bzmim]Cl, [Emim][OAc], and [Bmim][OAc], capable of efficient pretreatment of lignocellulosic biomass were tested for their effects on the cell growth and lipid accumulation of G. fermentans to better understand the impact of imidazolium IL on the lipid production. All the ILs tested inhibited the cell growth and lipid accumulation. In addition, both the cation and the anion of IL contributed to IL toxicity. The side chain of IL cations showed a clear impact on toxicity. On examining IL anions, [OAc]− was found to be more toxic than those of [DEP]− and Cl−. IL exhibited its toxicity by inhibiting sugar consumption and key enzyme (malic enzyme and ATP-citrate lyase) activities of G. fermentans. Cell membrane permeability was also altered to different extents in the presence of various ILs. Scanning electron microscopy revealed that IL induces fibrous structure on the surface of G. fermentans cell, which might represent an adaptive mechanism of the yeast to IL.ConclusionsThis work gives some mechanistic insights into the impact of imidazolium IL on the cell growth and lipid accumulation of oleaginous yeast, which is important for IL integration in lignocellulosic biofuel production, especially for microbial lipid production.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-016-0682-z) contains supplementary material, which is available to authorized users.

The European Young Chemists Award 2016

The future is in good hands! The European Young Chemist Award for 2016 was awarded at the 6th EuCheMS Chemistry Congress in Seville. Reflections on the participants and their chemistry from the Convener of the event, Professor Bruno Pignataro, are given in the Guest Editorial.

Enhancement of anaerobic digestion of grass by pretreatment with imidazolium-based ionic liquids

ABSTRACTIn this work, the toxicity of imidazolium-based ionic liquids (ILs) and the enhancement of high-solid anaerobic digestion by pretreatment were studied. Compared with [Bmim]Cl, [Bmim]OAc and [Bmim]BF4, [Bmim]PF6 had the highest toxicity. When the mass ratio of [Bmim]PF6 to grass was higher than 1:10, biogas was not produced within 30 days. The ability to remove lignin and hemicellulose followed the sequence of [Bmim]OAc, [Bmim]Cl, [Bmim]BF4 and [Bmim]PF6. The crystallinity index of grass pretreated with [Bmim]OAc, [Bmim]Cl, [Bmim]BF4 and [Bmim]PF6 reduced by 73.83%, 54.44%, 17.52% and 7.47%, respectively. The pretreatment with ILs enhanced the methane yield of grass by reducing crystallinity and particle size. The grass pretreated with [Bmim]OAc had the highest methane yield, about 221 mL/g volatile solids, due to its good lignin removal ability and relative low toxicity. After 10 times recycling, the cumulative methane yield of grass pretreated by recycled [Bmim]OAc decreased by 11.95%.

Structural feature based computational approach of toxicity prediction of ionic liquids: Cationic and anionic effects on ionic liquids toxicity

The density functional theory (DFT) based a unique model has been developed to predict the toxicity of ionic liquids using structural-feature based quantum chemical reactivity descriptors. Electrophilic indices (ω), the energy of highest occupied (EHOMO) and lowest unoccupied molecular orbital, (ELUMO) and energy gap (∆E) were selected as the best toxicity descriptors of ILs via Pearson correlation and multiple linear regression analyses. The principle components analysis (PCA) demonstrated the distribution and inter-relation of descriptors of the model. A multiple linear regression (MLR) analysis on selected descriptors derived the model equation for toxicity prediction of ionic liquids. The model predicted toxicity values and mechanism are very consistent with observed toxicity. Cationic and side chains length effect are pronounced to the toxicity of ILs. The model will provide an economic screening method to predict the toxicity of a wide range of ionic liquids and their toxicity mechanism.