Ionic liquids in green analytical chemistry-are they that good and green enough?

The widespread use of ionic liquids (ILs) as greener solvents in analytical sciences, especially in sample pretreatment, has focused attention on exploiting their enormous potential, not only on eliminating and improving the drawbacks faced by scientists. These ionic compounds with unique physicochemical properties can be tuned through smart synthesis, combining cations and anions, so that the compound exhibits excellent properties for its intended purpose. Ionic liquids are rightly referred to as designer solvents. Validation of a newly proposed analytical methods using ionic liquids, either in sample preparation or in further analysis, is a critical process to demonstrate that a particular analytical method is fit for purpose and provides reliable and accurate results. In addition, this article specially addressed the potential toxicity of ionic liquids with the modest goal of assisting researchers in this field by expanding their target areas.

Application of biodegradable cholinium ionic liquids for the extraction of 5-hydroxymethylfurfural (HMF) from honey.

5-Hydroxymethylfurfural (HMF), a Maillard reaction product, can be formed when honey is subjected to heat treatment or a long storage time, becoming volatile and toxic depending on its concentration. The fact that, until today, there is no literature data on the extraction of 5-hydroxymethylfurfural (HMF) from honey using ionic liquids directed the investigation of the influence of biodegradable cholinium ionic liquids on the formation of aqueous biphasic systems and the application of these systems for the extraction of HMF from honey. The influence of anions of synthesised ionic liquids on the construction of biphasic systems in which an inorganic salt was used as a salting agent was investigated. Then, the extraction of HMF in these systems was examined, and the mechanisms of HMF extraction using ionic liquids were explained using computer simulations. Examining the effect of cholinium ionic liquids (choline chloride ([Ch][Cl]), cholinium nicotinate ([Ch][Nic]), cholinium propionate ([Ch][Prop]), and cholinium butyrate ([Ch][But])) on the formation of aqueous biphasic systems by comparing the phase diagrams, it was concluded that the ability of ionic liquids to form an aqueous biphasic system with tripotassium phosphate (K3PO4) decreases in the following order: [Ch][But] ≈ [Ch][Prop] > [Ch][Nic] > [Ch][Cl]. By applying all tested aqueous biphasic systems for the extraction of HMF from honey, an extraction efficiency of more than 89% was achieved. Complete extraction was achieved using the extraction system with [Ch][But], while the weakest ability to extract HMF was exhibited by the system with [Ch][Cl]. The mechanisms of HMF extraction using ionic liquids are explained on the basis of the optimised structures of the ionic liquid systems with HMF, together with the visualisation of non-covalent interactions, and on the basis of the calculated binding energies ΔGbin, which can be used as a good predictor of the extraction potential of newly synthesised ionic liquids.

Greener chemistry in analytical sciences: from green solvents to applications in complex matrices. Current challenges and future perspectives: a critical review.

More environment-friendly solvents in analytical chemistry are almost inevitable in both sample preparation and analysis to meet the high standards of sustainable chemistry and human welfare. In this review paper, a critical look at the advantages and still unsolved problems of most potential classes of green solvents is presented to give an overview of the current state-of-the-art in this field. Replacing volatile organic compounds (VOCs) by ecofriendly and benign solvents in extractions/separations in sample preparation, as the most tedious and demanding step in analysis, is one of roads toward sustainable chemistry. Water under sub- and supercritical conditions, carbon-dioxide, ionic liquids (ILs), deep eutectic solvents (DESs), and those of natural origin (NADES) belong to the most promising classes of solvents in green analytical chemistry. Basic theory and mechanisms of their use illustrated by representative but not exhaustive list of examples related to complex matrices (environmental and natural food products) from analytical practice are presented in this review. Perspectives of QuEChERS, in line with GAC principles, are highlighted, in line with current trends of "going green" for quick, easy, cheap, effective, rugged, and safe analytical methods. Compliance with green chemistry (GC), especially green analytical chemistry (GAC) principles, is not a fashionable issue but, more the trend toward a sustainable future with greener chemistry; thus, green metrics are an unavoidable tool to measure how green the applied method or procedure is. Herein, the most common tools will be presented and discussed, such as national environmental method index (NEMI), analytical ecoscale, green analytical procedure index (GAPI), analytical greenness calculator (AGREE), complementary green analytical procedure index (ComplexGAPI), and analytical greenness metric for sample preparation (AGREEprep). The future trends for research and development in this still expanding field are presented in a critical view of advantages and disadvantages as well as improvement of the validation of analytical procedures. The creation of new certified reference materials (CRMs) and validated methods for specified analytes in complex matrices is a demanding task in the coming years. Tailor-made solvents with physicochemical properties for intended use are required for the selective extraction and separation and open numerous possibilities and huge potential for future research and industrial applications.

On the Geochemistry of the Danube River Sediments (Serbian Sector).

To determine the nature and origin of the unconsolidated bottom sediments, as well as to demonstrate and quantify the presence of Presumably Contaminating Elements (PCE) in the Serbian Danube River, as a novelty, the mass fractions on nine major elements as oxides-SiO2, TiO2, Al2O3, FeO, MnO, MgO, CaO, Na2O, and K2O, as well as Sc, V, Cr, Co, Ni, Cu, Zn, As, Rb, Sr, Zr, Sb, Cs, Ba, La, Hf, Ta, W, Th, and U were determined by Instrumental Neutron Activation Analysis (INAA) in 13 sediment samples collected between Belgrade and Iron Gate 2 dam. INAA was chosen for its ability to perform elemental analysis without any preliminary sample treatment that could introduce systematic errors. The distribution of major elements was relatively uniform, with the sampling locations having less influence. Concerning the trace elements, excepting the PCE Cr, Ni, Cu, Zn, As, and Sb, their distributions presented the same remarkable similarity to the Upper Continental Crust (UCC), North American Shale Composite (NASC), Average Bottom Load (ABL), and Average Dobrogea Loess (AVL), and were in good concordance with the location of the Serbian Danube River in the Pannonian Plain. In the case of considered PCE, both Enrichment Factor and Pollution Load Index showed values higher than the pollution threshold, which pointed towards a significant anthropogenic contamination, and rising concern to what extent the water quality and biota could be affected.

Spatial distribution of multielements including lanthanides in sediments of Iron Gate I Reservoir in the Danube River.

Recent studies show that lanthanides (Ln) are becoming emerging pollutants due to their wide application in new technologies, but their environmental fate, transport, and possible accumulation are still relatively unknown. This study aims to determine major and trace elements including Ln in the Danube River sediment which either belong or close to the Iron Gate Reservoir. The Iron Gate Reservoir is characterized by accumulation of sediments as an effect of building hydropower dam Iron Gate I. The surface sediments were collected on the Danube River-1141 to 864 km and three tributaries along this waterway. Two samples of deep sediments were used for comparison. The results indicate the significant upward enrichment of Zn, Sb, Cr, Nd, and Dy in sediments belongs to the Iron Gate Reservoir. The sample 4-Smed is labelled as a hot spot of contamination with Zn, Cr, As, Sb, Nd, and Dy. Also, a trend of increasing concentration in the time period from 1995 to 2016 was found for elements Zn, Cr, and Ni in sediment samples in the Iron Gate Reservoir. Chemometric analysis shows the grouping of sample sites into clusters characterized by the following properties: (i) increased concentration of all measured elements (samples within the Iron Gate Reservoir); (ii) increased Cu concentration (11-Pek); and (iii) lower concentrations of the measured elements (deep sediments). The data presented hereby contribute to the monitoring of pollution of the River Danube sediments and give the first view of Ln profile in the studied sediments.

The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro.

Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either mAChE or hAChE, to predict the listed pesticides' binding modes. Calculated energies of global minima (Eglob_min) and free energies of binding (∆Gbinding) were correlated with the pesticides' acute toxicities (i.e., the LD50 values) against mice, as well to generate the model that could predict the LD50s against humans. Although for most of the pesticides the low Eglob_min correlates with the high acute toxicity, it is the ∆Gbinding that conditions the LD50 values for all the evaluated pesticides. Derived pLD50 = f(∆Gbinding) mAChE model may predict the pLD50 against hAChE, too. The hAChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.

New sample preparation method based on task-specific ionic liquids for extraction and determination of copper in urine and wastewater.

In this study, four hydrophilic ionic liquids (ILs) containing 1-alkyl-3-methylimidazolim cation and either salicylate or chloride anions were synthetized and studied as new task-specific ionic liquids (TSILs) suitable for aqueous biphasic system (ABS) formation and selective one-step extraction of copper(II). TSILs are designed so that the anion is responsible for forming the complex with metal(II) and preventing hydrolysis of metal cations at very strong alkaline pH, whereas the cation is responsible for selective extraction of metal(II)-salicylate complexes. It was found that 1-butyl-3-methylimidazolium salicylate could be used for selective extraction of Cu(II) in the presence of Zn(II), Cd(II), and Pb(II) at very alkaline solution without metal hydroxide formation. It was assumed that formation of metal(II)-salicylate complexes prevents the hydrolysis of the metal ions in alkaline solutions. The determined stability constants for Cu(II)-salicylate complexes, where salicylate was derived from different ionic liquids, indicated that there was no significant influence of the cation of the ionic liquid on the stability of the complexes. The ABS based on 1-butyl-3-methylimidazolium salicylate has been applied as the sample preparation step prior to voltammetric determination of Cu(II). The effect of volume of aqueous sample and IL and extraction time were investigated and optimum extraction conditions were determined. The obtained detection limits were 8 ng dm-3. The optimized method was applied for the determination of Cu(II) in tap water, wastewater, and urine. The study indicated that application of the ABS based on 1-butyl-3-methylimidazolium salicylate ionic liquid could be successfully applied as the sample preparation method for the determination of Cu(II) from various environmental samples. Graphical abstract Aqueous biphasic system based on task-specific ionic liquid as a sample pretreatment for selective determination of Cu(II) in biological and environmental sample.

Solid-phase extraction disk based on multiwalled carbon nanotubes for the enrichment of targeted pesticides from aqueous samples.

A sensitive method for the determination of six varying polarity pesticides (imidacloprid, acetamiprid, carbendazim, simazine, linuron, and tebufenozide) based on a solid-phase extraction disk with multiwalled nanotubes is proposed.A dispersion of multiwalled nanotubes in a surfactant aqueous solution (Triton X-100) was used for the preparation of the solid-phase extraction disk. The effect of surfactant on the functional groups of multiwalled nanotubes was examined by applying temperature-programmed desorption. It was found that this treatment increased the amount of oxygen groups of treated multiwalled nanotubes comparing with untreated ones. The factors that may influence the adsorption and recovery such as the kind and volume of eluent, volume, flow rate and pH of sample were investigated and optimized. Under the optimized conditions, the maximal enrichment factors for low polar pesticides are ranging from 4000 to 4985 and for more polar are 2250 and 2750. The linear range of calibration curves was 10-500 ng/L with correlation coefficient higher than 0.9960, and the detection limit was 6.2-23.7 ng/L. Finally optimized method was applied for determination trace level of five out of six pesticides in tap and river water samples with good recovery.

Liquid-phase membrane extraction of targeted pesticides from manufacturing wastewaters in a hollow fibre contactor with feed-stream recycle.

A two-phase membrane extraction in a hollow fibre contactor with feed-stream recycle was applied to remove selected pesticides (tebufenozide, linuron, imidacloprid, acetamiprid and dimethoate) from their mixed aqueous solutions. The contactor consisted of 50 polypropylene hollow fibres impregnated with 5% tri-n-octylphosphine oxide in di-n-hexyl ether. For low-polar pesticides with log P ≥ 2 (tebufenozide and linuron), the maximum removal efficiency increased linearly from 85% to 96% with increasing the feed flow rate. The maximum removal efficiencies of more polar pesticides were significantly higher under feed recirculation (86%) than in a continuous single-pass operation (30%). It was found from the Wilson's plot that the mass transfer resistance of the liquid membrane can be neglected for low-polar pesticides. The pesticide removals from commercial formulations were similar to those from pure pesticide solutions, indicating that built-in adjuvants did not affect the extraction process.

Mass transfer resistance in a liquid-phase microextraction employing a single hollow fiber under unsteady-state conditions.

In this study, the mass transport resistance in liquid-phase microextraction (LPME) in a single hollow fiber was investigated. A mathematical model has been developed for the determination of the overall mass transfer coefficient based on the acceptor phase in an unsteady state. The overall mass transfer coefficient in LPME in a single hollow fiber has been estimated from time-dependent concentration of extracted analyte in the acceptor phase while maintaining a constant analyte concentration in the donor phase. It can be achieved either using a high volume of donor to acceptor phase ratio or tuning the extraction conditions to obtain a low-enrichment factor, so that the analyte concentration in the sample is not significantly influenced by the mass transfer. Two extraction systems have been used to test experimentally the developed model: the extraction of Lu(III) from a buffer solution and the extraction of three local anesthetics from a buffer or plasma solution. The mass transfer resistance, defined as a reciprocal values of the mass transfer coefficient, was found to be 1.2 × 10(3) cm(-1) min for Lu(III) under optimal conditions and from 1.96 to 3.3 × 10(3) cm(-1) min for the local anesthetics depending on the acceptor pH and the hydrophobicity of the drug.

Voltammetric determination of the herbicide Linuron using a tricresyl phosphate-based carbon paste electrode.

This paper summarises the results of voltammetric studies on the herbicide 3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea (Linuron), using a carbon paste electrode containing tricresyl phosphate (TCP-CPE) as liquid binder. The principal experimental conditions, such as the pH effect, investigated in Britton-Robinson buffer solutions (pH 2.0-7.0), the peak characteristics for the analyte of interest, or instrumental parameters for the differential pulse voltammetric mode were optimized for the method. As found out, the best electroanalytical performance of the TCP-CPE was achieved at pH 2.0, whereby the oxidation peak of Linuron appeared at ca. +1.3 V vs. SCE. The analytical procedure developed offers good linearity in the concentration range of 1.25-44.20 µg mL(-1) (1.77 × 10(-4)-5.05 × 10(-6) mol L(-1)), showing-for the first time-the applicability of the TCP-CPE for anodic oxidations in direct voltammetry (without accumulation). The method was then verified by determining Linuron in a spiked river water sample and a commercial formulation and the results obtained agreed well with those obtained by the reference HPLC/UV determination.

Determination of selected pesticides in environmental water by employing liquid-phase microextraction and liquid chromatography-tandem mass spectrometry.

An optimised extraction and cleanup method for the analysis of pesticide in natural water samples is presented. Sixteen pesticides of different polarity and from the different chemical classes (organophosphates, triazines, benzimidazoles, carbamates, carbamides, neonicotinoides, methylureas, phenylureas and benzohydrazides), most frequently used in Serbia, were selected for the analysis. Liquid-phase microextraction in a single hollow fibre (HF-LPME) has been applied for sample preparation. The concentrations of pesticides were determined using HPLC-MS/MS method with electrospray ionisation. The extraction behaviour and selection of the experimental conditions was predicted based on log D and pK(a) values of targeted pesticides, which were calculated applying the computer software ACD/Labs PhysChem Suite v12. The influence of the donor pH and concentration of pesticides, organic phase composition as well as the extraction time on the extraction efficiency was investigated. Optimum extraction conditions were evaluated with respect to the investigated parameters of the extraction. The extraction method was validated for 10 out of 16 studied pesticides. Linear range of the pesticides was 0.1-5 microg L(-1) with the correlation coefficient from 0.991 to 0.9998, and the relative standard deviation for three standard measurements was between 0.2 and 11.8%. The limits of detections ranged from 0.026 to 0.237 microg L(-1) and the limits of quantifications from 0.094 to 0.793 microg L(-1). The optimised two-phase HF-LPME method was successfully applied for determination of moderately polar as well low-polar pesticides in the environmental water samples.

Extraction of lutetium(III) from aqueous solutions by employing a single fibre-supported liquid membrane.

Transport behaviour of Lu(III) across a polypropylene hollow fibre-supported liquid membrane containing di(2-ethylhexyl)phosphoric acid (DEHPA) in dihexyl ether as a carrier has been studied. The donor phase was LuCl(3) in the buffer solution consisting of 0.2 M sodium acetate at pH 2.5-5.0. A miniaturised system with a single hollow fibre has been operated in a batch mode. The concentration of Lu(III) was determined by indirect voltammetric method using Zn-EDTA complex. The effect of pH and volume of the donor phase, DEHPA concentration in the organic (liquid membrane) phase, the time of extraction and the content of the acceptor phase on the Lu(III) extraction and stripping behaviour was investigated. The results were discussed in terms of the pertraction and removal efficiency, the memory effect and the mean flux of Lu(III). The optimal conditions for the removal of (177)Lu(III) from labelled (177)Lu-radiopharmaceuticals were discussed and identified. The removal efficiency of Lu(III) greater than 99% was achieved at pH of the donor phase between 3.5 and 5.0 using DEHPA concentration in the organic phase of 0.47 M and the ratio of the donor to the acceptor phase of 182.

Characterization of drug-protein binding process by employing equilibrium sampling through hollow-fiber supported liquid membrane and Bjerrum and Scatchard plots.

The technique equilibrium sampling through membrane (ESTM) was extended to measuring the free drug concentration in solutions of drug and protein. Bjerrum and Scatchard plots were employed for characterizing individual drug binding to pure human blood proteins. Four drugs were investigated as a model system: fluvoxamine and ropivacaine which dominantly bind to alpha-acid glycoprotein (AGP), and R,S-ibuprofen and S-ketoprofen which highly bind to human serum albumin (HSA). The level of drug binding to AGP and HSA relied on drug and protein concentrations. Bjerrum and Scatchard plots revealed high affinity constants (Ka) at low protein concentration. Both Bjerrum and Scatchard plots of fluvoxamine and ropivacaine binding to AGP showed one specific binding site (n1=1) with ropivacaine Ka value close to 5 times higher than the Ka of fluvoxamine at 22.9 microM AGP concentration. Bjerrum plots of ketoprofen and ibuprofen gave total number of binding sites or bound molecules of 6-7, which did not depend on the drug or protein concentration. Scatchard plots of ketoprofen and ibuprofen exhibited two binding sites (n1 and n2) at 0.15 microM and 0.75 microM HSA concentrations. On one hand, at 0.15 microM HSA, ketoprofen and ibuprofen were bound to site I at n1=1.2 and n1=1.0, respectively. However, at 0.75 microM HSA, ketoprofen and ibuprofen were bound to site I at n1=1.2 and n1=1.9, respectively. On the other hand, site II, at 0.15 microM HSA, interacted with ketoprofen and ibuprofen at n2=5.6 and 6.7, respectively. However, at 0.75 microM HSA, site II interacted with ketoprofen at n2=7.4 and ibuprofen at n2=6.2. It would be concluded that, upon mixing ketoprofen and ibuprofen in a HSA solution, a ketoprofen-ibuprofen interaction would most likely occur at site II in HSA.

Equilibrium sampling through membrane based on a single hollow fibre for determination of drug-protein binding and free drug concentration in plasma.

The determination of drug-protein binding and free drug concentration in plasma applying the equilibrium sampling through membrane (ESTM) technique has been studied using supported liquid membrane extraction in a single hollow fibre without any membrane carrier. In the extraction setup, the donor phase (plasma or buffer) was placed in the vial, into which was immersed the hollow fibre with the acceptor phase situated in the lumen. This proposed technique was applied to study the drug-protein binding of five local anaesthetics and two antidepressants as model substances, and the influence of the total drug concentration on the drug-protein binding was investigated. The brief theoretical background for determination of the drug-protein binding under equilibrium conditions is described. The developed method shows a new, improved and simple procedure for determination of free drug concentration in plasma and extent of drug-protein binding.

Determination of drug-protein binding using supported liquid membrane extraction under equilibrium conditions.

A technique for determination of drug-protein binding based on a membrane extraction technique termed "equilibrium sampling through membrane (ESTM)" is presented. It involves the establishment of an equilibrium between an aqueous buffer and either a blood plasma sample or a matched buffer, both containing the drug. Analysis of the aqueous buffer in the two cases gives the drug-protein binding. The principle bypasses some sources of systematic error found with common techniques for this measurement based on e.g. ultrafiltration, as it senses the equilibrium conditions without disturbing the sample. The technique is applied to some local anesthetic drugs as model substances and two alternative ways for the evaluation are presented. Results with these evaluation methods are compared with literature values for the drug-protein binding of these compounds. It is found that the drug-protein binding values obtained are lower than literature values, which is attributed to reduced systematic error.