54
those containing tetrabutylammonium chloride were toxic. As far as the hydrogen
bond acceptors tested were concerned (butanoic acid, hexanoic acid, 1-propanol,
ethylene glycol, and urea), only butanoic acid was toxic as an individual agent,
while the deep eutectic solvents formed between this and tetramethylammonium
chloride were only slightly toxic and choline chloride-butanoic acid was nontoxic.
Shekaari et al. measured the cytotoxicity of three deep eutectic solvents (choline
chloride with ethylene glycol, glycerol, and urea) against A549 lung cells using
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction as
the criterion of toxicity and obtained half maximal inhibitory concentration values
in the low millimolar range (Shekaari et al. 2019). Choline chloride-based deep
eutectic solvents were evaluated for toxicity against HEK-293 human embryonic
kidney cells by Ahmadi et al. (Ahmadi et al. 2018). The hydrogen bond donors were
different sugars or alcohols. They observed that the solvents were more toxic than
their starting components but that this toxicity was moderate, with half maximal
inhibitory concentration values derived from 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) reduction between 4 and 75 millimolar. The
toxicity observed was lower than that of a classical imidazolium-based ionic liquid
used in comparison. Of course, to obtain the half maximal inhibitory concentration
values, the formulations must have been diluted to different extents in cell culture
medium, so the interactions between the components of the deep eutectic solvents
will have been altered.
Haraźna et al. recently proposed a new type of hydrogen bond donor: a mixture
of (R)-3-hydroxyheptanoic and (R)-3-hydroxynonanoic acids derived from a bacterial cell wall polymer (Haraźna et al. 2019). These were used to form ionic liquids
or deep eutectic solvents with a number of hydrogen bond acceptor, including choline chloride. Toxicity was assessed against the mouse embryonic fibroblast (MEF)
3 T3 cell line using a fluorescence microscopy technique to distinguish between live
and dead cells. No reduction in cell viability was observed for concentrations up to
500 μg/mL of the choline chloride-based deep eutectic solvents. This deep eutectic
solvent was also found to be completely biodegradable in 5 days in a standard test
with activated sludge.
2.2.3 Toxicity Toward Plants, Invertebrates, and Fish
The study of Wen et al. included a plant (garlic, Allium sativum) and an invertebrate
(hydra, Hydra sinensis) (Wen et al. 2015). Deep eutectic solvents containing choline
chloride or choline acetate with urea, glycerol, acetamide, or ethylene glycol in
various proportions were tested. Some deep eutectic solvents or their components
reduced root growth in garlic bulbs, in particular choline chloride and glycerol both
had strong effects, but lower toxicity was observed when they were combined as a
deep eutectic solvent. Similarly, the choline salts, particularly the chloride, were
found to be detrimental to hydra growth, but the deep eutectic solvents were less
toxic than the sum of their parts (Fig. 2.2).
C.-H. Nguyen et al.
those containing tetrabutylammonium chloride were toxic. As far as the hydrogen
bond acceptors tested were concerned (butanoic acid, hexanoic acid, 1-propanol,
ethylene glycol, and urea), only butanoic acid was toxic as an individual agent,
while the deep eutectic solvents formed between this and tetramethylammonium
chloride were only slightly toxic and choline chloride-butanoic acid was nontoxic.
Shekaari et al. measured the cytotoxicity of three deep eutectic solvents (choline
chloride with ethylene glycol, glycerol, and urea) against A549 lung cells using
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction as
the criterion of toxicity and obtained half maximal inhibitory concentration values
in the low millimolar range (Shekaari et al. 2019). Choline chloride-based deep
eutectic solvents were evaluated for toxicity against HEK-293 human embryonic
kidney cells by Ahmadi et al. (Ahmadi et al. 2018). The hydrogen bond donors were
different sugars or alcohols. They observed that the solvents were more toxic than
their starting components but that this toxicity was moderate, with half maximal
inhibitory concentration values derived from 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) reduction between 4 and 75 millimolar. The
toxicity observed was lower than that of a classical imidazolium-based ionic liquid
used in comparison. Of course, to obtain the half maximal inhibitory concentration
values, the formulations must have been diluted to different extents in cell culture
medium, so the interactions between the components of the deep eutectic solvents
will have been altered.
Haraźna et al. recently proposed a new type of hydrogen bond donor: a mixture
of (R)-3-hydroxyheptanoic and (R)-3-hydroxynonanoic acids derived from a bacterial cell wall polymer (Haraźna et al. 2019). These were used to form ionic liquids
or deep eutectic solvents with a number of hydrogen bond acceptor, including choline chloride. Toxicity was assessed against the mouse embryonic fibroblast (MEF)
3 T3 cell line using a fluorescence microscopy technique to distinguish between live
and dead cells. No reduction in cell viability was observed for concentrations up to
500 μg/mL of the choline chloride-based deep eutectic solvents. This deep eutectic
solvent was also found to be completely biodegradable in 5 days in a standard test
with activated sludge.
2.2.3 Toxicity Toward Plants, Invertebrates, and Fish
The study of Wen et al. included a plant (garlic, Allium sativum) and an invertebrate
(hydra, Hydra sinensis) (Wen et al. 2015). Deep eutectic solvents containing choline
chloride or choline acetate with urea, glycerol, acetamide, or ethylene glycol in
various proportions were tested. Some deep eutectic solvents or their components
reduced root growth in garlic bulbs, in particular choline chloride and glycerol both
had strong effects, but lower toxicity was observed when they were combined as a
deep eutectic solvent. Similarly, the choline salts, particularly the chloride, were
found to be detrimental to hydra growth, but the deep eutectic solvents were less
toxic than the sum of their parts (Fig. 2.2).
C.-H. Nguyen et al.