An investigation on the toxicological assessment of 10 choline chloride (ChCl)-based deep eutectic solvents (DESs) towards four fungi strains and Cyprinus carpio fish was conducted. ChCl was combined with materials from different chemical groups such as alcohols, sugars, acids and others to form DESs. The study was carried out on the individual DES components, their aqueous mixture before DES formation and their formed DESs. The agar disc diffusion method was followed to investigate their toxicity on four fungi strains selected as a model of eukaryotic microorganisms (Phanerochaete chrysosporium, Aspergillus niger, Lentinus tigrinus and Candida cylindracea). Among these DESs, ChCl:ZnCl2 exhibited the highest inhibition zone diameter towards the tested fungi growth in vitro, followed by the acidic group (malonic acid and p-toluenesulfonic acid). Another study was conducted to test the acute toxicity and determine the lethal concentration at 50 % (LC50) of the same DESs on C. carpio fish. The inhibition range and LC50 of DESs were found to be different from their individual components. DESs were found to be less toxic than their mixture or individual components. The LC50 of ChCl:MADES is much higher than that of ChCl:MAMix. Moreover, the DESs acidic group showed a lower inhibition zone on fungi growth. Thus, DESs should be considered as new components with different physicochemical properties and toxicological profiles, and not merely compositions of compounds.
The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes.
Global deterioration of water, soil, and atmosphere by the release of toxic chemicals from the ongoing anthropogenic activities is becoming a serious problem throughout the world. This poses numerous issues relevant to ecosystem and human health that intensify the application challenges of conventional treatment technologies. Therefore, this review sheds the light on the recent progresses in nanotechnology and its vital role to encompass the imperative demand to monitor and treat the emerging hazardous wastes with lower cost, less energy, as well as higher efficiency. Essentially, the key aspects of this account are to briefly outline the advantages of nanotechnology over conventional treatment technologies and to relevantly highlight the treatment applications of some nanomaterials (e.g., carbon-based nanoparticles, antibacterial nanoparticles, and metal oxide nanoparticles) in the following environments: (1) air (treatment of greenhouse gases, volatile organic compounds, and bioaerosols via adsorption, photocatalytic degradation, thermal decomposition, and air filtration processes), (2) soil (application of nanomaterials as amendment agents for phytoremediation processes and utilization of stabilizers to enhance their performance), and (3) water (removal of organic pollutants, heavy metals, pathogens through adsorption, membrane processes, photocatalysis, and disinfection processes).
Deep eutectic solvents (DESs) have received attention in various applications because of their distinctive properties. In this work, DESs were used as functionalizing agents for graphene due to their potential to introduce new functional groups and cause other surface modifications. Eighteen different types of ammonium- and phosphonium-salt-based DESs were prepared and characterized by FTIR. The graphene was characterized by FTIR, STA, Raman spectroscopy, XRD, SEM, and TEM. Additional experiments were performed to study the dispersion behavior of the functionalized graphene in different solvents. The DESs exhibited both reduction and functionalization effects on DES-treated graphene. Dispersion stability was investigated and then characterized by UV-vis spectroscopy and zeta potential. DES-modified graphene can be used in many applications, such as drug delivery, wastewater treatment, catalysts, composite materials, nanofluids, and biosensors. To the best of our knowledge, this is the first investigation on the use of DESs for graphene functionalization.
Deep eutectic solvents (DESs) are novel solvent media that are currently under investigation as an alternative to ionic liquids and conventional solvents. The physical properties of DESs as well as their mild environmental footprint and potentially critical industrial application necessitate understanding the interaction of functional groups on both the salt and hydrogen bond donor (HBD). In this study, four DESs were prepared by mixing triethylenglycol, diethylenglycol, ethylenglycol, and glycerol as HBDs with methyltriphenylphosphonium bromide as a salt at a molar ratio of 1:4. Fourier transform infrared spectroscopy was conducted to highlight the chemical structure and mechanism of the combination of the four DESs. New spectra illustrating the combination of the functional groups of the HBDs and salt were observed and interpreted. This study is the first to investigate the properties of neoteric phosphonium-based DESs.
With the rapid development of ionic liquid analogues, termed 'deep eutectic solvents' (DESs), and their application in a wide range of chemical and biochemical processes in the past decade, the extraction of bioactive compounds has attracted significant interest. Recently, numerous studies have explored the extraction of bioactive compounds using DESs from diverse groups of natural sources, including animal and plant sources. This review summarizes the-state-of-the-art effort dedicated to the application of DESs in the extraction of bioactive compounds. The aim of this review also was to introduce conventional and recently-developed extraction techniques, with emphasis on the use of DESs as potential extractants for various bioactive compounds, such as phenolic acid, flavonoids, tanshinone, keratin, tocols, terpenoids, carrageenans, xanthones, isoflavones, α-mangostin, genistin, apigenin, and others. In the near future, DESs are expected to be used extensively for the extraction of bioactive compounds from various sources.
Climate engineering solutions with emphasis on CO2 removal remain a global open challenge to balancing atmospheric CO2 equilibrium levels. As a result, warnings of impending climate disasters are growing every day in urgency. Beyond ordinary CO2 removal through natural CO2 sinks such as oceans and forest vegetation, direct CO2 conversion into valuable intermediaries is necessary. Here, a direct electrosynthesis of the peroxydicarbonate anion (C2O62-) was investigated by the reaction of CO2 with the superoxide ion (O2·-), electrochemically generated from O2 reduction in bis(trifluoromethylsulfonyl)imide [TFSI-] anion derived ionic liquid (IL) media. This is the first time that the IL media were employed successfully for CO2 conversion into C2O62-. Moreover, the charge transfer coefficient for the O2·- generation process in the ILs was less than 0.5, indicating that the process was irreversible. Voltammetry experiments coupled with global electrophilicity index analysis revealed that, when CO2/O2 was contacted simultaneously in the IL medium, O2·- was generated in situ first at a potential of approximately -1.0 V. Also, CO2 was more susceptible to attack by O2·- before any possible interaction with the IL except for [PMIm+][TFSI-]. This was because CO2 has a higher global electrophilicity index (ωCO2 = 0.489 eV) than those for the [EDMPAmm+][TFSI-] and [MOEMMor+][TFSI-]. By further COSMO-RS modeling, CO2 absorption was proven feasible at the COSMO-surface of the [TFSI-] IL-anion where the charge densities were σ = -1.100 and 1.1097 e/nm2. Therefore, the susceptible competitiveness of either IL cations or CO2 to the nucleophilic effects of O2·- was a function of their positive character as estimated by their electrophilicity indices. As determined by experimental attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and DFT-FTIR computation, the reaction yielded C2O62- in the ILs. Consequently, the presence of O=O symmetric stretching FTIR vibrational mode at ∼844 cm-1 coupled with the disappearance of the oxidative cyclic voltammetry waves when sparging CO2 and O2 confirmed the presence of C2O62-. Moreover, based on DFT/B3LYP/6-31G, pure C2O62- has symmetric O=O stretching at ∼805 and ∼844 cm-1 when it is in association with the IL-cation. This was the first spectroscopic observation of C2O62- in ILs, and the O=O symmetric stretching vibration has peculiarity for identifying C2O62- in ILs. This will open new doors to utilize CO2 in industrial applications with the aid of reactive oxygen species.
The application of graphene in the field of drug delivery has attracted massive interest among researchers. However, the high toxicity of graphene has been a drawback for its use in drug delivery. Therefore, to enhance the biocompatibility of graphene, a new route was developed using ternary natural deep eutectic solvents (DESs) as functionalizing agents, which have the capability to incorporate various functional groups and surface modifications. Physicochemical characterization analyses, including field emission scanning electron microscope, fourier-transform infrared spectroscopy, Raman spectroscopy, Brunauer-Emmett-Teller, X-ray diffraction, and energy dispersive X-ray, were used to verify the surface modifications introduced by the functionalization process. Doxorubicin was loaded onto the DES-functionalized graphene. The results exhibited significantly improved drug entrapment efficiency (EE) and drug loading capacity (DLC) compared with pristine graphene and oxidized graphene. Compared with unfunctionalized graphene, functionalization with DES choline chloride (ChCl):sucrose:water (4:1:4) resulted in the highest drug loading capacity (EE of 51.84% and DLC of 25.92%) followed by DES ChCl:glycerol:water (1:2:1) (EE of 51.04% and DLC of 25.52%). Following doxorubicin loading, graphene damaged human breast cancer cell line (MCF-7) through the generation of intracellular reactive oxygen species (>95%) and cell cycle disruption by increase in the cell population at S phase and G2/M phase. Thus, DESs represent promising green functionalizing agents for nanodrug carriers. To the best of our knowledge, this is the first time that DES-functionalized graphene has been used as a nanocarrier for doxorubicin, illustrating the potential application of DESs as functionalizing agents in drug delivery systems.
Understanding the reaction mechanism that controls the one-electron electrochemical reduction of oxygen is essential for sustainable use of the superoxide ion (O2˙-) during CO2 conversion. Here, stable generation of O2˙- in butyltrimethylammonium bis(trifluoromethylsulfonyl)imide [BMAmm+][TFSI-] ionic liquid (IL) was first detected at -0.823 V vs. Ag/AgCl using cyclic voltammetry (CV). The charge transfer coefficient associated with the process was ∼0.503. It was determined that [BMAmm+][TFSI-] is a task-specific IL with a large negative isovalue surface density accrued from the [BMAmm+] cation with negatively charged C(sp2) and C(sp3). Consequently, [BMAmm+][TFSI-] is less susceptible to the nucleophilic effect of O2˙- because only 8.4% O2˙- decay was recorded from 3 h long-term stability analysis. The CV analysis also detected that O2˙- mediated CO2 conversion in [BMAmm+][TFSI-] at -0.806 V vs. Ag/AgCl as seen by the disappearance of the oxidative faradaic current of O2˙-. Electrochemical impedance spectroscopy (EIS) detected the mechanism of O2˙- generation and CO2 conversion in [BMAmm+][TFSI-] for the first time. The EIS parameters in O2 saturated [BMAmm+][TFSI-] were different from those detected in O2/CO2 saturated [BMAmm+][TFSI-] or CO2 saturated [BMAmm+][TFSI-]. This was rationalized to be due to the formation of a [BMAmm+][TFSI-] film on the GC electrode, creating a 2.031 × 10-9 μF cm-2 double-layer capacitance (CDL). Therefore, during the O2˙- generation and CO2 utilization in [BMAmm+][TFSI-], the CDL increased to 5.897 μF cm-2 and 7.763 μF cm-2, respectively. The CO2 in [BMAmm+][TFSI-] was found to be highly unlikely to be electrochemically converted due to the high charge transfer resistance of 6.86 × 1018 kΩ. Subsequently, O2˙- directly mediated the CO2 conversion through a nucleophilic addition reaction pathway. These results offer new and sustainable opportunities for utilizing CO2 by reactive oxygen species in ionic liquid media.
In this work, the cytotoxicity and toxicity of phosphonium-based deep eutectic solvents (DESs) with three hydrogen bond donors, namely glycerine, ethylene glycol, and triethylene glycol were investigated. The cytotoxicity effect was tested using brine shrimp (Artemia salina). The toxicity was investigated using the two Gram positive bacteria Bacillus subtilis and Staphylococcus aureus, and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The cytotoxicity of tested DESs was much higher than that of their individual components, indicating their toxicological behavior was different. It was also found that there was toxic effect on the studied bacteria, indicating their potential application as anti-bacterial agents. To the best of our knowledge, this is the first time the cytotoxicity and toxicity of phosphonium-based DESs were studied.
An industrial grade acidic crude palm oil (ACPO) pre-treatment process was carried out using ethanesulfonic acid (ESA) as a catalyst in the esterification reaction. ESA was used in different dosages to reduce free fatty acid (FFA) to a minimum level for the second stage of biodiesel production via alkaline transesterification reaction. Different process operating conditions were optimized such as ESA dosage (0.25-3.5% wt/wt), methanol to ACPO molar ratio (1:1-20:1), reaction temperature (40-70 °C), and reaction time (3-150 min). This study revealed the potential use of abundant quantities of ACPO from oil palm mills for biodiesel production. The lab scale results showed the effectiveness of the pre-treatment process using ESA catalyst. Three consecutive catalyst recycling runs were achieved without significant degradation in its performance. Second and third reuse runs needed more reaction time to achieve the target level of FFA content. Esterification and transesterification using ESA and KOH respectively is proposed for biodiesel industrial scale production. The produced biodiesel meets the international standards specifications for biodiesel fuel (EN 14214 and ASTM D6751).
In continuation of investigation for environmentally benign protocol for new solvents termed deep eutectic solvents (DESs), it is herein reported results concerning the toxicity and cytotoxicity of choline chloride (ChCl) based DESs with four hydrogen bond donors including glycerine, ethylene glycol, triethylene glycol and urea. The toxicity was investigated using two Gram positive bacteria Bacillus subtilis and Staphylococcus aureus, and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The cytotoxicity effect was tested using the Artemia salina leach. It was found that there was no toxic effect for the tested DESs on all of the studied bacteria confirming their benign effects on these bacteria. Nevertheless, it was found that the cytotoxicity of DESs was much higher than their individual components (e.g. glycerine, ChCl) indicating that their toxicological behavior is different. For our best knowledge this is the first time that toxicity and cytotoxicity of DESs were studied. The toxicity and cytotoxicity of DESs varied depending on the structure of components. Careful usage of the terms non-toxicity and biodegradability must be considered. More investigation on this matter is required.
Recently, deep eutectic solvents (DESs) have shown their new and interesting ability for chemistry through their involvement in variety of applications. This study introduces carbon nanotubes (CNTs) functionalized with DES as a novel adsorbent for Hg(2+) from water. Allyl triphenyl phosphonium bromide (ATPB) was combined with glycerol as the hydrogen bond donor (HBD) to form DES, which can act as a novel CNTs functionalization agent. The novel adsorbent was characterized using Raman, FTIR, XRD, FESEM, EDX, BET surface area, TGA, TEM and Zeta potential. Response surface methodology was used to optimize the removal conditions for Hg(2+). The optimum removal conditions were found to be pH 5.5, contact time 28 min, and an adsorbent dosage of 5 mg. Freundlich isotherm model described the adsorption isotherm of the novel adsorbent, and the maximum adsorption capacity obtained from the experimental data was 186.97 mg g(-1). Pseudo-second order kinetics describes the adsorption rate order.
Deep eutectic solvents (DESs) have been touted recently as potential alternatives to ionic liquids (ILs). Although they possess core characteristics that are similar to those of ILs (e.g., low volatility, non-flammability, low melting points, low vapor pressure, dipolar nature, chemical and thermal stability, high solubility, and tuneability), DESs are superior in terms of the availability of raw materials, the ease of storage and synthesis, and the low cost of their starting materials. As such, they have become the subject of intensive research in various sectors, notably the chemical, electrochemical, and biological sectors. To date, the applications of DESs have shown great promise, especially in the medical and biotechnological fields. In spite of these various achievements, the safety concern for these mixtures must be sufficiently addressed. Indeed, in order to exploit the vast array of opportunities that DESs offer to the biological industry, first, they must be established as safe mixtures. Hence, the biotechnological applications of DESs only can be implemented if they are proven to have negligible or low toxicity profiles. This review is the first of its kind, and it discusses two current aspects of DES-based research. First, it describes the properties of these mixtures with ample focus on their toxicity profiles. Second, it provides an overview of the breakthroughs that have occurred and the foreseeable prospects of the use of DESs in various biotechnological and biological applications.
Deep eutectic solvents (DESs) are a class of green solvents analogous to ionic liquids, but less costly and easier to prepare. The objective of this study is to remove lead (Pb) from a contaminated soil by using polyol based DESs mixed with a natural surfactant saponin for the first time. The DESs used in this study were prepared by mixing a quaternary ammonium salt choline chloride with polyols e.g. glycerol and ethylene glycol. A natural surfactant saponin obtained from soapnut fruit pericarp, was mixed with DESs to boost their efficiency. The DESs on their own did not perform satisfactory due to higher pH; however, they improved the performance of soapnut by up to 100%. Pb removal from contaminated soil using mixture of 40% DES-Gly and 1% saponin and mixture of 10% DES-Gly and 2% saponin were above 72% XRD and SEM studies did not detect any major corrosion in the soil texture. The environmental friendliness of both DESs and saponin and their affordable costs merit thorough investigation of their potential as soil washing agents.
The purpose of this study was to investigate the cytotoxic profiles of different ternary natural deep eutectic solvents (NADESs) containing water. For this purpose, five different NADESs were prepared using choline chloride as a salt, alongside five hydrogen bond donors (HBD) namely glucose, fructose, sucrose, glycerol, and malonic acid. Water was added as a tertiary component during the eutectics preparation, except for the malonic acid-based mixture. Coincidentally, the latter was found to be more toxic than any of the water-based NADESs. A trend was observed between the cellular requirements of cancer cells, the viscosity of the NADESs, and their cytotoxicity. This study also highlights the first time application of the conductor-like screening model for real solvent (COSMO-RS) software for the analysis of the cytotoxic mechanism of NADESs. COSMO-RS simulation of the interactions between NADESs and cellular membranes' phospholipids suggested that NADESs strongly interacted with cell surfaces and that their accumulation and aggregation possibly defined their cytotoxicity. This reinforced the idea that careful selection of NADESs components is necessary, as it becomes evident that organic acids as HBD highly contribute to the increasing toxicity of these neoteric mixtures. Nevertheless, NADESs in general seem to possess relatively less acute toxicity profiles than their DESs parents. This opens the door for future large scale utilization of these mixtures.
In this study, the anticancer potential and cytotoxicity of natural deep eutectic solvents (NADESs) were assessed using HelaS3, PC3, A375, AGS, MCF-7, and WRL-68 hepatic cell lines. NADESs were prepared from choline chloride, fructose, or glucose and compared with an N,N-diethyl ethanolammonium chloride:triethylene glycol DES. The NADESs (98 ≤ EC50 ≥ 516 mM) were less toxic than the DES (34 ≤ EC50 ≥ 120 mM). The EC50 values of the NADESs were significantly higher than those of the aqueous solutions of their individual components but were similar to those of the aqueous solutions of combinations of their chief elements. Due to the uniqueness of these results, the possibility that NADESs could be synthesized intracellularly to counterbalance the cytotoxicity of their excess principal constituents must be entertained. However, further research is needed to explore this avenue. NADESs exerted cytotoxicity by increasing membrane porosity and redox stress. In vivo, they were more destructive than the DES and induced liver failure. The potential of these mixtures was evidenced by their anticancer activity and intracellular processing. This infers that they can serve as tools for increasing our understanding of cell physiology and metabolism. It is likely that we only have begun to comprehend the nature of NADESs.
The applications of eutectic systems, including deep eutectic solvents (DESs), in diverse sectors have drawn significant interest from researchers, academicians, engineers, medical scientists, and pharmacists. Eutecticity increases drug dissolution, improves drug penetration, and acts as a synthesis route for drug carriers. To date, DESs have been extensively explored as potential drug delivery systems on account of their unique properties such as tunability and chemical and thermal stability. This review discusses two major topics: first, the application of eutectic mixtures (before and after the introduction of DES) in the field of drug delivery systems, and second, the most promising examples of DES pharmaceutical activity. It also considers future prospects in the medical and biotechnological fields. In addition to the application of DESs in drug delivery systems, they show greatly promising pharmaceutical activities, including anti-fungal, anti-bacterial, anti-viral, and anti-cancer activities. Eutecticity is a valid strategy for overcoming many obstacles inherently associated with either introducing new drugs or enhancing drug delivery systems.
Deep eutectic solvent (DES) affinities with cellular membranes structures dictate the degree of cytotoxicity that results from these interactions. The physicochemical properties of choline chloride (ChCl)-DESs suggest non-negligible cytotoxicities that were attested by published researches. In this study, the profiles of novel N,N-diethylammonium chloride (DAC)-based-deep eutectic solvents (DESs) prepared with various hydrogen bond donors (urea, glycerol, ethylene glycol, malonic acid, and zinc chloride) were compared to those of ChCl-DESs by using HelaS3, AGS, MCF-7, and WRL-68 cancer cell lines. The molecular interactions between salts and cellular membranes were investigated to explain the observed cytotoxicity. The results show that ChCl-based DESs (279 ≤ IC50 ≥ 1260 mM) were less toxic than DAC-based DESs (37 ≤ IC50 ≥ 109 mM). COSMO-RS analysis emphasized the importance of salt hydrophobicity with regards to DESs cytotoxicity. Malonic acid increased hydrophobicity and cytotoxicity in general, thus highlighting the potential of ammonium salt-based DESs as anticancer agents.