50
with ethylene glycol and 1-propanol as hydrogen bond donors. Mixture toxicity
theory was used to analyze the results obtained with the deep eutectic solvents and
with their components separately. Neither the individual components nor the solvents showed excessive toxicity. A model in which the hydrogen bond donor and
hydrogen bond acceptor acted on different sites was found to give reasonable agreement with the data and allow the toxicity of deep eutectic solvents to be predicted.
Among the hydrogen bond acceptor, toxicity increased with the length of the carbon
chain: tetramethylammonium chloride being the least toxic and tetrapropylammonium chloride the most toxic (Macário et al. 2018a). In another study, the same
approach was applied to deep eutectic solvents based on choline chloride as hydrogen bond donor with a number of hydrogen bond acceptors including ethylene glycol and urea (Macário et al. 2018b). In this case, they observed an antagonistic
effect between the components of the deep eutectic solvents so that the mixture was
less toxic than the sum of the parts. In particular, choline chloride with urea or
1-propanol gave products with very low toxicity, making them suitable for use as
alternative “green” solvents.
Juneidi et al. used four fungal species (Phanerochaete chrysosporium, Aspergillus
niger, Lentinus tigrinus, and Candida cylindracea) as their reporter organisms
(Juneidi et al. 2016). The deep eutectic solvents tested were based on choline chloride with alcohols, sugars, organic acids, urea, and zinc chloride as the hydrogen
bond donor component. Only zinc chloride and organic acids showed growthinhibiting effects on fungi, which were reduced slightly when these components
were in the form of a deep eutectic solvent rather than presented as individual
compounds.
A recent review suggested that antimicrobial testing of deep eutectic solvents
was better performed in liquid suspension culture than by antibiograms so that toxicity could be monitored as a function of time (Torregrosa-Crespo et al. 2020).
Using a novel deep eutectic solvent composition, acetylcholine chloride:acetamide
1:2, they observed toxicity to Escherichia coli at concentrations above 300 nM and
that this was partially due to acidification of the medium by degradation products of
deep eutectic solvent components. This highlights the necessity of studying the stability of deep eutectic solvents over time as well as working with freshly prepared
material.
2.2.2 Toxicity Toward Human Cells Lines and Ex Vivo
Studies on Skin
The team of Hayyan has studied the toxicity of deep eutectic solvents based on
choline chloride with four different hydrogen bond donors toward a panel of human
cell lines using a variety of criteria to assess toxicity (Hayyan et al. 2015). Again,
the deep eutectic solvents studied were choline chloride with glycerol, ethylene
glycol, triethylene glycol, and urea, always in a 1:3 ratio. The cells lines were PC3
C.-H. Nguyen et al.
with ethylene glycol and 1-propanol as hydrogen bond donors. Mixture toxicity
theory was used to analyze the results obtained with the deep eutectic solvents and
with their components separately. Neither the individual components nor the solvents showed excessive toxicity. A model in which the hydrogen bond donor and
hydrogen bond acceptor acted on different sites was found to give reasonable agreement with the data and allow the toxicity of deep eutectic solvents to be predicted.
Among the hydrogen bond acceptor, toxicity increased with the length of the carbon
chain: tetramethylammonium chloride being the least toxic and tetrapropylammonium chloride the most toxic (Macário et al. 2018a). In another study, the same
approach was applied to deep eutectic solvents based on choline chloride as hydrogen bond donor with a number of hydrogen bond acceptors including ethylene glycol and urea (Macário et al. 2018b). In this case, they observed an antagonistic
effect between the components of the deep eutectic solvents so that the mixture was
less toxic than the sum of the parts. In particular, choline chloride with urea or
1-propanol gave products with very low toxicity, making them suitable for use as
alternative “green” solvents.
Juneidi et al. used four fungal species (Phanerochaete chrysosporium, Aspergillus
niger, Lentinus tigrinus, and Candida cylindracea) as their reporter organisms
(Juneidi et al. 2016). The deep eutectic solvents tested were based on choline chloride with alcohols, sugars, organic acids, urea, and zinc chloride as the hydrogen
bond donor component. Only zinc chloride and organic acids showed growthinhibiting effects on fungi, which were reduced slightly when these components
were in the form of a deep eutectic solvent rather than presented as individual
compounds.
A recent review suggested that antimicrobial testing of deep eutectic solvents
was better performed in liquid suspension culture than by antibiograms so that toxicity could be monitored as a function of time (Torregrosa-Crespo et al. 2020).
Using a novel deep eutectic solvent composition, acetylcholine chloride:acetamide
1:2, they observed toxicity to Escherichia coli at concentrations above 300 nM and
that this was partially due to acidification of the medium by degradation products of
deep eutectic solvent components. This highlights the necessity of studying the stability of deep eutectic solvents over time as well as working with freshly prepared
material.
2.2.2 Toxicity Toward Human Cells Lines and Ex Vivo
Studies on Skin
The team of Hayyan has studied the toxicity of deep eutectic solvents based on
choline chloride with four different hydrogen bond donors toward a panel of human
cell lines using a variety of criteria to assess toxicity (Hayyan et al. 2015). Again,
the deep eutectic solvents studied were choline chloride with glycerol, ethylene
glycol, triethylene glycol, and urea, always in a 1:3 ratio. The cells lines were PC3
C.-H. Nguyen et al.