3
TEG
Triethylene glycol
THEDES Therapeutic deep eutectic solvents
U
Urea
VA
Valeric acid
1.1 Introduction
The discovery of the deep eutectic solvents (DES) was a major breakthrough in the
world of green chemistry. Deep eutectic solvents are frequently defined as binary or
ternary mixtures of compounds that are able to associate mainly via hydrogen
bonds. Combining these compounds at a certain molar ratio results in a eutectic
mixture (Zhang et al. 2012). The word “eutectic” comes from the Ancient Greek
εὔτηκτος or eútēktos, which means easily melted, and a eutectic point represents
the chemical composition and temperature at which a mixture of two solids becomes
fully molten at the lowest melting temperature, relative to that of either compounds.
However, defining a deep eutectic solvent is still a controversial subject, and there
are various reported definitions that do not really distinguish deep eutectic solvents
from other mixtures, since all the mixtures of immiscible solid compounds present
a eutectic point and considering that numerous compounds are able to form hydrogen bonds when put together (Coutinho and Pinho 2017). Given that the presence of
a eutectic point or hydrogen bonding between components is not a sufficient condition to define a “deep eutectic solvent” and in order to clarify what a deep eutectic
solvent is and what makes it special compared to other mixtures, Martins et al.
recently defined deep eutectic solvent as “a mixture of two or more pure compounds
for which the eutectic point temperature is below that of an ideal liquid mixture,
presenting significant negative deviations from ideality (ΔT 2 > 0),” where ΔT 2
stands for the temperature depression which is the difference between the ideal and
the real eutectic point (Martins et al. 2019). The same authors stated that it is important that the temperature depression results in a liquid mixture at operating temperature, regardless of the mixture composition. The fact that there is no fixed
composition offers an even greater tunability for these systems.
Although deep eutectic solvents were extensively studied, especially in the past
decade, there is still a lack of understanding the principle behind deep eutectic solvent’s formation and properties. It all started almost 20 years ago, when Abbott
et al. were looking for liquids that can overcome the moisture sensitivity and high
cost of some common ionic liquids (Abbott et al. 2001). In this study, numerous
mixtures based on different quaternary ammonium salts and metal salts were tested,
and it turned out that choline chloride (ChCl) mixed with zinc chloride in a 1:2
molar ratio presents the lowest freezing point (23–25 °C). Thereafter, the same
authors investigated eutectic mixtures of quaternary ammonium salts and hydrogen
bond donors (HBD) and named them “deep eutectic solvents” (Abbott et al. 2003).
The lowest freezing point (12 °C) was obtained with 1:2 ChCl:urea. This significant
depression of the freezing point, compared to that of ChCl (302 °C) or urea (U)
(133 °C), is due to hydrogen bonding between urea molecules and chloride ion as
1 Understanding the Basics and Properties of Deep Eutectic Solvents
TEG
Triethylene glycol
THEDES Therapeutic deep eutectic solvents
U
Urea
VA
Valeric acid
1.1 Introduction
The discovery of the deep eutectic solvents (DES) was a major breakthrough in the
world of green chemistry. Deep eutectic solvents are frequently defined as binary or
ternary mixtures of compounds that are able to associate mainly via hydrogen
bonds. Combining these compounds at a certain molar ratio results in a eutectic
mixture (Zhang et al. 2012). The word “eutectic” comes from the Ancient Greek
εὔτηκτος or eútēktos, which means easily melted, and a eutectic point represents
the chemical composition and temperature at which a mixture of two solids becomes
fully molten at the lowest melting temperature, relative to that of either compounds.
However, defining a deep eutectic solvent is still a controversial subject, and there
are various reported definitions that do not really distinguish deep eutectic solvents
from other mixtures, since all the mixtures of immiscible solid compounds present
a eutectic point and considering that numerous compounds are able to form hydrogen bonds when put together (Coutinho and Pinho 2017). Given that the presence of
a eutectic point or hydrogen bonding between components is not a sufficient condition to define a “deep eutectic solvent” and in order to clarify what a deep eutectic
solvent is and what makes it special compared to other mixtures, Martins et al.
recently defined deep eutectic solvent as “a mixture of two or more pure compounds
for which the eutectic point temperature is below that of an ideal liquid mixture,
presenting significant negative deviations from ideality (ΔT 2 > 0),” where ΔT 2
stands for the temperature depression which is the difference between the ideal and
the real eutectic point (Martins et al. 2019). The same authors stated that it is important that the temperature depression results in a liquid mixture at operating temperature, regardless of the mixture composition. The fact that there is no fixed
composition offers an even greater tunability for these systems.
Although deep eutectic solvents were extensively studied, especially in the past
decade, there is still a lack of understanding the principle behind deep eutectic solvent’s formation and properties. It all started almost 20 years ago, when Abbott
et al. were looking for liquids that can overcome the moisture sensitivity and high
cost of some common ionic liquids (Abbott et al. 2001). In this study, numerous
mixtures based on different quaternary ammonium salts and metal salts were tested,
and it turned out that choline chloride (ChCl) mixed with zinc chloride in a 1:2
molar ratio presents the lowest freezing point (23–25 °C). Thereafter, the same
authors investigated eutectic mixtures of quaternary ammonium salts and hydrogen
bond donors (HBD) and named them “deep eutectic solvents” (Abbott et al. 2003).
The lowest freezing point (12 °C) was obtained with 1:2 ChCl:urea. This significant
depression of the freezing point, compared to that of ChCl (302 °C) or urea (U)
(133 °C), is due to hydrogen bonding between urea molecules and chloride ion as
1 Understanding the Basics and Properties of Deep Eutectic Solvents