52
penetration of a fluorescent marker into the MCF-7 cells. The deep eutectic solvents
containing ethylene glycol and triethylene glycol had more effect that the other two.
The redox properties of the deep eutectic solvents were also studied. Firstly, the
generation of reactive oxygen species (ROS) by MCF-7 cells was measured by a
fluorogenic technique. The deep eutectic solvents caused a dose-dependent increase
in reactive oxygen species production, which was particularly marked with choline
chloride:triethylene glycol. Somewhat paradoxically, the authors also measured the
antioxidant activity of the deep eutectic solvents, using quercetin as a positive control. Their radical scavenging capacity was found to be less than 1% of that of quercetin (Hayyan et al. 2015).
In a follow-up study, Hayyan et al. investigated the effect of introducing water
into the deep eutectic solvents on the toxicity toward human cancer cell lines as
described above (Hayyan et al. 2016). Deep eutectic solvents that contained choline
chloride with fructose, glucose, sucrose, or glycerol with water as a third component showed half maximal inhibitory concentration values above 100 mM, while a
deep eutectic solvent composed of choline chloride and malonic acid alone, without
water, was much more toxic. Since the viscosity of this solvent was not higher than
some of the water-containing ones, and taking into account results from the literature, it was concluded that the presence of organic acids is a main source of deep
eutectic solvent toxicity. They also used molecular modelling to investigate the possible interactions between deep eutectic solvents and membrane phospholipids.
This predicted that deep eutectic solvents could interact with the cell surface.
Somewhat different in vitro results were obtained by Radošević et al. who examined the cytotoxicity of deep eutectic solvents composed of choline chloride and
five different hydrogen bond donors (glucose, fructose, xylose, glycerol, and malic
acid) toward two human cell lines (HeLa and MCF-7) using the 2-(4-iodophenyl)3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) reduction assay
(Radošević et al. 2016). They found that the concentration that reduced
2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1)
metabolism by 50% was more than 2 mg/mL for all compositions. However, a deep
eutectic solvent containing oxalic acid, although efficient for the application under
consideration (extract of antioxidants from grape skin), was discarded because of
slight toxicity (Radošević et al. 2015). In this study, in contrast to the results of Wen
et al. (Wen et al. 2015), a high level of biodegradability was found for the tested
solvents, with the lowest level being recorded for the solvent with oxalic acid. In a
further study, a third human cell line, HEK293T, was added to the panel tested
(Radošević et al. 2018). Only deep eutectic solvents containing organic acids (for
example, citric acid) showed appreciable toxicity. These results were confirmed by
Mitar et al. (Mitar et al. 2019), who also demonstrated the antioxidative properties
of the natural deep eutectic solvents. In this work, a further criterion was added –
corrosiveness toward metal (steel). This was found to be extremely low for all the
deep eutectic solvents tested, meaning that they could be used in pipelines and reactors without any problem.
C.-H. Nguyen et al.
penetration of a fluorescent marker into the MCF-7 cells. The deep eutectic solvents
containing ethylene glycol and triethylene glycol had more effect that the other two.
The redox properties of the deep eutectic solvents were also studied. Firstly, the
generation of reactive oxygen species (ROS) by MCF-7 cells was measured by a
fluorogenic technique. The deep eutectic solvents caused a dose-dependent increase
in reactive oxygen species production, which was particularly marked with choline
chloride:triethylene glycol. Somewhat paradoxically, the authors also measured the
antioxidant activity of the deep eutectic solvents, using quercetin as a positive control. Their radical scavenging capacity was found to be less than 1% of that of quercetin (Hayyan et al. 2015).
In a follow-up study, Hayyan et al. investigated the effect of introducing water
into the deep eutectic solvents on the toxicity toward human cancer cell lines as
described above (Hayyan et al. 2016). Deep eutectic solvents that contained choline
chloride with fructose, glucose, sucrose, or glycerol with water as a third component showed half maximal inhibitory concentration values above 100 mM, while a
deep eutectic solvent composed of choline chloride and malonic acid alone, without
water, was much more toxic. Since the viscosity of this solvent was not higher than
some of the water-containing ones, and taking into account results from the literature, it was concluded that the presence of organic acids is a main source of deep
eutectic solvent toxicity. They also used molecular modelling to investigate the possible interactions between deep eutectic solvents and membrane phospholipids.
This predicted that deep eutectic solvents could interact with the cell surface.
Somewhat different in vitro results were obtained by Radošević et al. who examined the cytotoxicity of deep eutectic solvents composed of choline chloride and
five different hydrogen bond donors (glucose, fructose, xylose, glycerol, and malic
acid) toward two human cell lines (HeLa and MCF-7) using the 2-(4-iodophenyl)3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) reduction assay
(Radošević et al. 2016). They found that the concentration that reduced
2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1)
metabolism by 50% was more than 2 mg/mL for all compositions. However, a deep
eutectic solvent containing oxalic acid, although efficient for the application under
consideration (extract of antioxidants from grape skin), was discarded because of
slight toxicity (Radošević et al. 2015). In this study, in contrast to the results of Wen
et al. (Wen et al. 2015), a high level of biodegradability was found for the tested
solvents, with the lowest level being recorded for the solvent with oxalic acid. In a
further study, a third human cell line, HEK293T, was added to the panel tested
(Radošević et al. 2018). Only deep eutectic solvents containing organic acids (for
example, citric acid) showed appreciable toxicity. These results were confirmed by
Mitar et al. (Mitar et al. 2019), who also demonstrated the antioxidative properties
of the natural deep eutectic solvents. In this work, a further criterion was added –
corrosiveness toward metal (steel). This was found to be extremely low for all the
deep eutectic solvents tested, meaning that they could be used in pipelines and reactors without any problem.
C.-H. Nguyen et al.