60
glutamic acid, both theoretically and experimentally, using density functional theory and molecular dynamics (Gutiérrez et al. 2019).
Thioflavin T is a fluorescent molecule that undergoes a change when bound to
amyloid fibrils and can therefore be used as a sensor for neurogenerative diseases.
Gautam et al. studied the fluorescence behavior of this molecule in two deep eutectic solvents: choline chloride:urea 1:2 and N,N-diethylethanolammonium
chloride:urea 1:2 (Gautam et al. 2018). High quantum yield and fluorescence lifetime were obtained in both solvents.
Palmelund et al. (2019). performed a similar study comparing experimentally
determined solubility with theoretical predictions from conductor-like screening
model for real solvents for a range of eleven active molecules in six deep eutectic
solvents compositions and three conventional solvents (water, ethanol, and polyethylene glycol 300). A good correlation was observed between the results, suggesting
that predictive techniques could be used to reduce the number of experimental
determinations. For most of the molecules tested, conventional solvents gave the
best solubility, but often the best solvent was ethanol, which could bring toxicity
and safety problems. However, for paracetamol and especially for celecoxib, their
highest solubility was obtained in a deep eutectic solvent.
Anti-inflammatory and Analgesic Drugs
Nonsteroidal anti-inflammatory drugs suffer from low water solubility. Lu et al.
determined the solubility of five such drugs (aspirin, acetaminophen, ketoprofen,
naproxen, and ibuprofen) in a panel of deep eutectic solvents based on choline chloride, ethylammonium chloride, tetrapropylammonium bromide, betaine, or choline
bitartrate as the hydrogen bond acceptor and a variety of sugars, alcohols, organic
acids, and urea as the hydrogen bond donor (Lu et al. 2016). Good solubility was
obtained in 17 selected deep eutectic solvents, but the authors were not able to predict solubility by looking at various physical properties of the deep eutectic solvents
or at the hydrogen bond acceptor to hydrogen bond donor ratio. They also monitored the stability of aspirin in a choline chloride:1,2-propanediol (propylene glycol) 1:2 solvents compared with pure water and a 1:1 solvent:water mixture and
observed a reduced rate of cleavage to salicylic acid at 80 °C in the deep eutectic
solvent.
A later study by Mokhtarpour et al. focused on naproxen solubility in three deep
eutectic solvent compositions: choline chloride:ethylene glycol 1:2, choline
chloride:urea 1:2, and choline chloride:malonic acid 1:1 (Mokhtarpour et al. 2019a).
All compositions increased the drug solubility more than 3300-fold with malonic
acid as the hydrogen bond donor. They used several modelling procedures to attempt
to predict solubility and performed density measurements to probe the interactions
between the solvent and the solute. They also report a similar study with indomethacin
in deep eutectic solvents composed of tetrabutylammonium bromide with ethylene
glycol or glycerol (Mokhtarpour et al. 2019b). An increase of solubility of over
C.-H. Nguyen et al.
glutamic acid, both theoretically and experimentally, using density functional theory and molecular dynamics (Gutiérrez et al. 2019).
Thioflavin T is a fluorescent molecule that undergoes a change when bound to
amyloid fibrils and can therefore be used as a sensor for neurogenerative diseases.
Gautam et al. studied the fluorescence behavior of this molecule in two deep eutectic solvents: choline chloride:urea 1:2 and N,N-diethylethanolammonium
chloride:urea 1:2 (Gautam et al. 2018). High quantum yield and fluorescence lifetime were obtained in both solvents.
Palmelund et al. (2019). performed a similar study comparing experimentally
determined solubility with theoretical predictions from conductor-like screening
model for real solvents for a range of eleven active molecules in six deep eutectic
solvents compositions and three conventional solvents (water, ethanol, and polyethylene glycol 300). A good correlation was observed between the results, suggesting
that predictive techniques could be used to reduce the number of experimental
determinations. For most of the molecules tested, conventional solvents gave the
best solubility, but often the best solvent was ethanol, which could bring toxicity
and safety problems. However, for paracetamol and especially for celecoxib, their
highest solubility was obtained in a deep eutectic solvent.
Anti-inflammatory and Analgesic Drugs
Nonsteroidal anti-inflammatory drugs suffer from low water solubility. Lu et al.
determined the solubility of five such drugs (aspirin, acetaminophen, ketoprofen,
naproxen, and ibuprofen) in a panel of deep eutectic solvents based on choline chloride, ethylammonium chloride, tetrapropylammonium bromide, betaine, or choline
bitartrate as the hydrogen bond acceptor and a variety of sugars, alcohols, organic
acids, and urea as the hydrogen bond donor (Lu et al. 2016). Good solubility was
obtained in 17 selected deep eutectic solvents, but the authors were not able to predict solubility by looking at various physical properties of the deep eutectic solvents
or at the hydrogen bond acceptor to hydrogen bond donor ratio. They also monitored the stability of aspirin in a choline chloride:1,2-propanediol (propylene glycol) 1:2 solvents compared with pure water and a 1:1 solvent:water mixture and
observed a reduced rate of cleavage to salicylic acid at 80 °C in the deep eutectic
solvent.
A later study by Mokhtarpour et al. focused on naproxen solubility in three deep
eutectic solvent compositions: choline chloride:ethylene glycol 1:2, choline
chloride:urea 1:2, and choline chloride:malonic acid 1:1 (Mokhtarpour et al. 2019a).
All compositions increased the drug solubility more than 3300-fold with malonic
acid as the hydrogen bond donor. They used several modelling procedures to attempt
to predict solubility and performed density measurements to probe the interactions
between the solvent and the solute. They also report a similar study with indomethacin
in deep eutectic solvents composed of tetrabutylammonium bromide with ethylene
glycol or glycerol (Mokhtarpour et al. 2019b). An increase of solubility of over
C.-H. Nguyen et al.