Journal of Molecular Liquids 379 (2023) 121676

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Journal of Molecular Liquids

journal homepage: www.elsevier.com/locate/molliq

Green and sustainable solvents of the future: Deep eutectic solvents

Aditi Prabhune, Ranjan Dey ⇑
Department of Chemistry, BITS Pilani K K Birla Goa Campus, Zuarinagar, Goa 403726, India

a r t i c l e i n f o a b s t r a c t

Article history: Deep Eutectic solvents (DESs) can be termed as the New Age Solvents that have emerged as potential
Received 11 December 2022 alternatives to conventional solvents in many industrial applications. These encompass various types
Revised 3 March 2023 of DES, their synthesis, multifarious industrial applications, and superiority over industrial solvents
Accepted 17 March 2023
and Ionic Liquids (ILs). This burgeoning interest in the DES has stemmed from their very specific charac-
Available online 21 March 2023
teristics of being safe, less hazardous, ‘‘green” as compared to ILs, biodegradable, ease of being prepared
in commercial proportions, low cost of preparation and several other interesting features. Within a very
Keywords:
short span of time, DESs have been employed for a large and diverse range of applications including sep-
Deep eutectic solvents
Natural deep eutectic solvents
aration processes, extraction of solvents, pharmaceutical processing, environmental protection, material
Sustainable synthesis etc. This review brings out the recent happenings in the field of DES research, types and syn-
Applications thesis. It also sheds light on commercial applications of DESs as green and sustainable solvents of the
future as a feasible alternative to the present day hazardous and carcinogenic industrial solvents. The
reusability, regeneration, scalability for industrial applications, promising applications at commercial
scale have also been discussed together with theoretical and computational models.
Ó 2023 Elsevier B.V. All rights reserved.

1. Introduction extraction, drug delivery and several other applications [2,3]. Mil-
lions of gallons of these solvents are consumed globally in these
For the past several decades, a major part of the industrial com- industries for various product formulations and synthesis [1,4].
munity particularly those dealing with chemical, pharmaceutical, The solvent usage by such industries is about 80–90% of total mass
petrochemical, construction, reservoir engineering, beverages, and they also account for 80–85% waste it produces [3,5]. Very
dyes, adhesives and allied industries have been completely depen- large human population is exposed to these solvents directly or
dent on the usage of industrial solvents [1,2]. The applications of indirectly through various means. The downside of these is that a
these solvents are not limited to these industries but also include vast majority of them are Volatile Organic Compounds (VOCs) with
a high degree of toxicity and volatility, and whose usage leads to
very serious and irreparable environmental hazards [6-8]. A vast
Abbreviations: VOCs, Volatile Organic Compounds; ILs, Ionic Liquids; DESs, Deep majority of VOCs are carcinogenic and mutagenic [9] and pro-
Eutectic Solvents; ES, Eutectic solvents; HBD, Hydrogen Bond Donor; HBA,
longed exposure to solvents and VOCs can cause reproductive haz-
Hydrogen Bond Acceptor; EMLs, Eutectic Molecular Liquids; NADES, Natural Deep
Eutectic Solvents; TBACl, tetrabutylammonium chloride; ChCl, choline chloride; ards, respiratory problems, skin and eye irritation [10-13]. The
FTIR, Fourier Transform Infrared Spectroscopy; DFT, Density Function Theory; MD, untreated disposal of these solvents can severely harm the envi-
Molecular dynamics; QSPR, Quantitative Structure-Property Relationship; COSMO- ronment through water bodies, air pollution, soil pollution, etc.
RS, Conductor Like Screening Model for Real Solvents; VFT, Vogel-Fulchur- [14-16].
Tammann; ML, Machine Learning; EPW, Electrochemical Potential Window; HDES,
Hydrophobic Deep Eutectic Solvents; DESs-UAE, DESs-based ultrasound extraction;
The environmental concerns emanating due to the vast con-
ESW, Electrochemical Stability Window; LiTFSI, lithium bis(trifluoromethane)sulf sumption of these highly toxic and environmentally hazardous
onimide; DSSCs, Dye-sensitized solar cells; RFBs, Redox Flow Batteries; SPE, Solid chemicals have generated a deep concern for moving towards
Polymer Electrolyte; PETEA, pentaerythritol tetra-acrylate; EG-CA DES, Ethylene greener and more sustainable solvents which would be aligned
glycol-citric acid; PEG-OA DES, polyethylene glycol-oxalic acid; PEG-CA DES,
with the 12 Green principles of environmental chemistry. Chemical
polyethylene glycol-citric acid; ZnO, Zinc oxide; UAE, Ultrasound assisted extrac-
tion; NADES-A-MHD, NADES assisted microwave hydro distillation; THEDES, and pharmaceutical industries have been restricted from the usage
Therapeutic Deep Eutectic Solvents; API, Active Pharmaceutical Ingredient; EAF, of toxic and environmentally susceptible solvents but still needs
electric arc furnace. essential properties like polarity and solubility of particular sol-
⇑ Corresponding author.
vents in production. These solvents are carefully replaced or cho-
E-mail address: ranjandey@goa.bits-pilani.ac.in (R. Dey).

https://doi.org/10.1016/j.molliq.2023.121676
0167-7322/Ó 2023 Elsevier B.V. All rights reserved.
A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

sen according to Solvent Selection Guide that has been set up by component [31,46]. Similar to ILs, the thermophysical properties
pharmaceutical companies [17]. Some of the 12 green principles of DESs can be tuned and enhanced with varied combinations of
include atom economy, usage of less hazardous chemicals for syn- HBAs and HBDs, changing molar concentration ratios of HBDs
thesis, design and use of safer solvents and chemicals, real-time and HBAs, and using them with cosolvent [49]. The tunability of
analysis for pollution prevention, etc. [18]. The scientific and thermophysical properties like density and viscosity is beneficial
research community at large is on a continuous quest for develop- when a process requires a task-specific media [50].
ing and employing greener and benign alternatives which include Inspired by the concept of eutectic mixtures, D. Yu and T. Mu
water [19,20], gas-expanded liquids [21], liquid polymers [22,23], [51] successfully synthesized Eutectic Molecular Liquids (EMLs).
supercritical fluids [24,25], liquids derived from biomass [23], ionic They differ from ILs and DESs as EMLs are formed between molec-
liquids (ILs) [26-29] and deep eutectic solvents (DESs) [30-33]. ular compounds via noncovalent interactions. These noncovalent
Earlier, ILs were considered to be environmentally harmless interactions cause decrease in charge density in polar compound
compounds till some studies came up with their toxicity. ILs were and hence depression in the melting point of EMLs. On the other
accounted as ‘‘Green Solvent” because of their negligible vapour hand, the concept of inverted Deep Eutectic solvents proposed by
pressure which reduces harm similar to VOCs. Evaporation of ionic Yu et al. [52] is based on host–guest interactions wherein the inter-
liquids into the environment may be insignificant however, their action of the molecular compound occurs with the cation of the
solubility in water may seriously harm aquatic biota and also their ionic compound. These new proposed types of DESs are different
high stability makes them less biodegradable [34].Toxicity is from the conventional DESs. The inverted DESs cannot be eutectic
mostly observed due to cationic moiety, its side chain length and molecular liquids which have two molecular compounds as their
anions [34,35]. The toxicity of ILs in bacteria is more hazardous constituents wherein the inverted DESs contain an ionic compound
compared to traditional solvents [36]. Furthermore, ILs have a and a molecular compound as its constituent.
few more shortcomings like such as high viscosity, limited solute
solubility, corrosivity, poor degradability and high production cost.
3. Types of DESs
Deep Eutectic Solvents (DESs) have been introduced as a suit-
able alternative to ILs to overcome their drawbacks. In the past
The DES composition in general is represented as Catþ X zY
two decades, DESs have been extensively researched witnessing
an exponential and phenomenal growth with more than 2000 plus where Cat þ is any ammonium, phosphonium or sulphonium cation
papers published in the year 2022 [37]. Eutectic solvents (ES) are and X is Lewis base while Y is Lewis acid. The complex formation
liquid mixtures formed by mixing solid components and liquid takes place between X and Y species (z is a number of Y molecules
phase is observed when solid–liquid equilibrium is established to interacting with an anion) [31]. A wide variety of DESs have been
form eutectic system showing significant decrease in melting developed based on complex agents used. They are subdivided into
points [38]. The term ‘‘deep” is emphasized when depression in five types and represented in Fig. 1. Type I DESs are prepared from
melting point is significantly lower than that of the predicted quaternary ammonium salts and metal chlorides which are similar
eutectic temperature when ideal thermodynamic behaviour of liq- to metal halides and imidazolium salts composites. Type II of DESs
uid phase is assumed between DES precursors [39]. DESs are anal- consists of quaternary ammonium salts and metal chloride
ogous to ILs as they share similar characteristics and properties as hydrates. Type III DESs are composed of choline chloride and HBDs
ILs. But they have advantages like low volatility, non-toxicity, like alcohols, amides, carbohydrates, etc. and they are widely stud-
biodegradability, non-flammability and chemical stability over ied due to their adaptable nature and important property of solvat-
conventional industrial solvents and ILs [40]. In the recent years, ing transition metal species. This type of DESs can be tailored as its
DESs have shown tremendous potential for various commercial physical properties depend on the HBD used in the mixture
applications with a lot of research carried on cosmetics, electrode- [31,44]. Type IV DESs are made from metal chloride with HBD. A
position, biomass, CO2 capture, separation and extraction pro- new class of DES (Type V) is emerging which consists of non-
cesses, synthesis, bio-catalysis etc.[41-43]. ionic molecular HBD and HBA. Hydrogen bonding is observed to
be dominant in this type of DESs [38,39].

2. Deep Eutectic solvents (DESs) 4. Synthesis of DESs

DESs are made from two or more solids that form a eutectic The components utilized for the synthesis of DESs are safe and
mixture through hydrogen bonding, having lower melting points economical [43]. Synthesis of DES can be carried out using several
than the melting points of constituent components [44]. DES con- methods. The most common synthesis of DES involves the addition
sists of two main parts, a Hydrogen Bond Donor (HBD) and a of an appropriate amount of HBD and HBA into a flask which is
Hydrogen Bond Acceptor (HBA). The electrostatic interactions, later on stirred and heated to form a colourless liquid [44,53].
Hydrogen bonding, van der Waals interactions and lattice energy Another method includes mixing aqueous solutions of HBD and
plays a vital role in the formation of DESs [31,45]. HBDs and HBAs HBA in a certain ratio and then freeze-drying these aqueous solu-
can be large and non-symmetric ions with low lattice energy and tions at a lower temperature to obtain a viscous, clear liquid
low melting point [31]. The decrease in melting point of eutectic [44,54]. Grinding methods have been utilized for synthesis consid-
mixtures occurs due to the presence of strong interactions taking ering pharmaceutical purposes where two components are mixed
place between the anion of HBA and complexing agent HBD and ground together till a homogenous, clear liquid is formed
[46,47]. The breaking of the bond requires less energy as a large [41,55]. Vacuum evaporating method has been incorporated in
ion and a small charge is present [48]. In DESs, the strong interac- the synthesis of Natural Deep Eutectic Solvents (NADES) where
tions present result in an increase in the effective size of HBD and components dissolved into water are evaporated under vacuum
conversely decreasing interactions between constituent cations at low temperature to obtain a liquid. This liquid is further kept
and anions which causes depression in the melting point [45]. for drying in a desiccator with silica gel till constant weight is
Another reason for a decrease in the melting point of DESs is obtained [41,56]. Since there are no by-products or use of exten-
charge delocalization caused by hydrogen donor moiety and HBA sive methods or solvents for DES synthesis, it generates zero waste

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A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

Fig. 1. Types of deep eutectic solvents.

and is inexpensive for large-scale production. Atom economy is (QSPR) to predict viscosity of DESs with accuracy using Conductor
maximizing incorporation of starting material into final product Like Screening Model for Real Solvents (COSMO-RS).
in the chemical process and reducing by-products or waste mate-
rial [57]. The atom economy of the final product of DES is 100% 5. Applications of DESs
since all initial components are used completely in the final pro-
duct and hence it also bypasses the purity assessment of the final The DES and ILs have similar physical properties such as tun-
product [42]. ability, low vapour pressure and nonflammability with advantages
The formation of DES is dependent on two main factors viz. HBD like inexpensive method, low production cost and environmentally
and HBA combinations and the mole ratio in which they are mixed. benign nature. The chemical properties of DESs such as acidity, vis-
A study involving various combinations of HBA including tetra- cosity, ionicity and electrochemical stability also play a vital role in
butylammonium chloride (TBACl), choline chloride (ChCl) and thy- an applicative prospect.
mol along with few more HBAs combined with large number of
chiral HBDs was carried out by Hopkins et al.[58]. The HBA/HBD 5.1. Acidity
were taken in various ratios ranging from 1 : 1  1 : 6 and
1 : 1  12 : 1 but the evaluation of mixtures was mostly carried Acidic DESs are used in biomass conversion, drug solubilization,
out on 1 : 1; 1 : 2; 3 : 1; 2 : 1 molar ratio. The obtained database
delignification, fractionation, catalysis, extraction, and dissolution
showed that TBACl as a HBA formed liquid mixtures at room tem- [61]. Acidity of DESs can be measured by processes which include
perature most effectively. 93 various and unique HBDs and HBAs
pH probe, Hammett acidity function measurement using indicator
combinations in various ratios were also studied. Almost 32 com- [61,62]. Recently, Zhou et al. [63] have utilized spectroscopic tech-
binations were observed to be liquid at room temperature. 24
nique using acetonitrile as IR and trimethyl phosphine oxide as
unique HBD: HBA combinations were liquid at all ratios. The study NMR probe to characterize acidity of commonly used DES without
[58] concludes that all the liquid mixtures obtained at room tem-
addition of solvents.
peratures consists of simple eutectic mixtures along with some
DESs and structural diversity of HBA and HBD can affect the liquid
5.2. Viscosity
formation of mixtures [58].
DESs are formed via hydrogen bonding network between donor
The stronger interactions present within the DES components
and acceptor. These interactions are often studied experimentally
can affect physicochemical properties like density and transport
using Fourier Transform Infrared Spectroscopy (FTIR) to verify
properties like viscosity, ionicity and conductivity. There are vari-
bonding sites and hydrogen bonding. The Density Function Theory
ous established experimental methods for measuring viscosity
(DFT) has also been employed to identify and analyse vibrations
and theoretical methods to evaluate viscosity. Classical empirical
and geometry optimization. Gautam et al.[59] have studied two
equations such as Arrhenius equation and Vogel-Fulcher-
carboxylic acid-choline chloride DES using both FTIR and DFT
Tammann (VFT), Jones-dole expression are frequently used
method where they identified strong hydrogen bond between
[61,62]. Recently, predictive model for viscosity developed by
chlorine ion and respective carboxylic acid and several other weak
Dey and Biswas [64] have been proving to work very well on var-
hydrogen bonds indicating stability of DES. Molecular dynamics
ious mixtures including DES mixtures [65,66]. Furthermore,
(MD) simulation can also be utilised to understand hydrogen bond-
Machine Learning (ML), a more advanced method, have been uti-
ing in DESs. Viscosity and gas solubility determine absorption
lized by Shi et al.[67] to predict viscosity accurately and to gener-
capacity and selectivity of a solvent for CO2 capture processes.
ate knowledge about optimization and design of material.
Through extensive range of HBD and HBA combinations, it is con-
venient to find the suitable DES using computational modelling
5.3. Electrochemical stability and ionicity
than experimental hassle. Kurnia et al. [60] have developed a sim-
ple model based on Quantitative Structure-Property Relationship
DESs as an electrolyte has high potential application in energy
storage devices. Ionicity as an effective fraction of ions taking part
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A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

in conduction was proposed which can be studied using Walden ubility of hydrophobic solvents without any reactive reactions.
plot. It is based on Walden rule which relates molar conductivity Hydrophobic DES (HDES) composed of Thymol and tetra-decanol
to viscosity [68]. In depth studies of ionicity and conductivity can (2:1 M ratio) has been synthesized by Naga Sai et al., [76] for selec-
give a better insight into microscopic behaviour and diffusion tive extraction of biomass derived from furfural. Gonzalez et al.
mechanism which can be used to develop tailor-made DES with [77], have used menthol based HDESs in the extraction process
high ionicity. Another essential requirement is electrochemical sta- of phenolic compounds from diluted aqueous solutions which are
bility of electrolyte for their use in electrochemical synthesis, bat- generated from biomass, to enhance the sugar fermentation pro-
teries and supercapacitors. This stability is usually characterised cess. HDES is composed of menthol and organic acids like dode-
using Electrochemical Potential Window (EPW) which is the volt- canoic acid, decanoic acid and octanoic acid which shows
age difference between the cathodic and anodic limit [69]. The promising results where HDESs could extract phenolic compound
electrode potential stability window is the range where substance easily than glucose.
under study remains inert or does not undergo oxidation or reduc- The increased use of pesticides to eliminate pests over the years
tion. Li et al. [69] studied electrochemical stability of 23 DESs and has led to a higher concentration of micropollutants [72]. It is also
33 ILs of different composition using cyclic voltammetry and found dangerous to living organisms, water bodies and soil due to the
DESs composed of methyl urea and ChCl have largest electrochem- bio-accumulative effect [78]. HDESs composed of DL-Menthol
ical potential window. and tetrabutylammonium chloride salt as HBAs and various acids
DESs have wide applications (Fig. 2) in Electrodeposition, sepa- like acetic acid, pyruvic acid, levulinic acid, etc. as HBDs have been
ration and gas capture, extraction processes, synthesis, battery and used in the extraction process of pesticides from water by Florindo
power systems, nanomaterials and pharmaceutical industries, etc., et al. [74] and later their efficiency has been compared with the ILs
[41]. which are commonly used for the same. The results showed up to
80% extraction efficiency for water-stable DES based on DL-
5.4. Extraction processes menthol and acids for studied pesticides. DES based on Betaine
and urea, methyl urea, D-sorbitol, ethylene glycol, D(+)glucose
Dias et al. [70] have developed DES from Sugars like D-sorbitol, and glycerol as HBD have been synthesized and successfully used
xylitol and D(+)xylose which act as HBD and cholinium chloride as for protein extraction [79]. Extraction of components with medic-
HBA. The thermophysical properties of DES are dependent on the inal properties with efficiency along with less environmental risk
molar ratio of HBD:HBA and temperature. These sugar-based DES and cost-effective method is in high demand. Flavonoid compo-
may have applications in the food industry and separation pro- nents like amentoflavone, robustaflavone which have anticancer,
cesses. Newly developed DES were mostly Hydrophilic until van antimicrobial and antioxidant properties have been isolated from
Osch et. al.[71], synthesized Hydrophobic DES (HDES) consisting Selaginella uncinata.
of a fatty acid and a quaternary ammonium salt. It opened up a Qin et al.[80] have synthesized 30 different DESs composed of
new application of DES where water-immiscible substances or sol- choline chloride, Betaine, Proline and lactic acid as HBDs with var-
vents are involved. Since then, plenty of Hydrophobic DES and ious HBAs like urea, malic acid, glucose, sorbitol, etc. for extraction
their applications have been researched [72-74]. HDES have been of amentoflavone and robustaflavone from S. uncinata. The DESs-
recently in use for environmentally benign extraction techniques. based ultrasound extraction method (DESs-UAE) was also pro-
They have been used in the isolation of biomolecules, extraction posed over the traditional extraction methods like reflux, macera-
of heavy metals, and removal of pesticides from agricultural run- tion and percolation to improve efficiency, energy loss and time
offs [75]. The studies showed that the usage of HDES enhanced consumption of the process. The outcome showed that proline-
the extraction process of some micro analytes due to increased sol- lactic acid gives highly efficient extraction of amentoflavone and
robustaflavone from S. uncinate. The DESs-UAE method showed
high extraction rates under optimized conditions with less time
consumption indicating improvement over traditional methods
[80].

5.5. Electrodeposition

Electroplating or electrodeposition had been conventionally

done using aqueous acidic or basic solutions [31]. These electro-
plating solutions require high solubility of metal salts, electro-
chemical stability, high conductivity and low ohmic losses. DESs
show high solubility of metal salts, metal oxides and hydroxides
[31]. Electrodeposition, metal coatings and related industries
recently have been using Ionic liquids and DESs for the processes.
One of the well-known DES called ‘‘Ethaline” based on ethylene
glycol and choline chloride in a ratio of 2:1 have been used for
the electrodeposition of Nickel (Ni) and the outcome was com-
pared with electrodeposition of the same metal from two aqueous
solutions [81]. The morphology of the deposits on ionic nickel plat-
ing obtained was nanocrystalline for DES while micro-crystalline
for two aqueous solutions. The Ni deposit from DES was less rough
and mirror-bright finish while other had rough surfaces and matte
finish [81].
Metals and their alloys yield unique properties like corrosion
resistance and mechanical properties which have wide applica-
tions in engineering, chemical and automobile industries. Elec-
Fig. 2. Applications of DESs. tropolishing is an important electrochemical method used to
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obtain desired metal finish and the surface of metals and alloys. It A review by Chakrabarti et al. [92] states various advantages of
improves surface texture making it clean, bright, smooth and cor- DESs over conventional solvents and ILs like the environmentally
rosion resistant. Recently, ILs as well as DESs are being used for benign nature of DESs, no specific requirement of inert atmosphere
electropolishing of metal surfaces as an alternative to conventional for experiments, the high solubility of metal oxides, low manufac-
methods. Relatively high viscosity and slow diffusion of DESs are turing cost and wide variety of combinations of HBDs-HBAs. Li
characteristic properties that make their use ideal under the diffu- et al. [93] presented a novel DES-based gel electrolyte with rapid
sion control process of electropolishing [82]. Electropolishing has self-healing properties. Cyclic stability and life span of batteries
been tried on various metals such as Ni, Co [83], Al [84] and various can be enhanced with self-healing solid polymer electrolyte
steels. Kityk et al.[82] have tried electropolishing for the first time (SPE). This self-healing gel electrolyte was prepared by in situ
on two different types of commercial bronze metals (AMPCO 22 copolymerization of self-healing monomers with pentaerythritol
and AMPCO 712) using ethaline and results show increased corro- tetra-acrylate (PETEA) and DES electrolyte [93]. The electrolyte dis-
sion resistivity and decreased roughness of a surface. Kityk et al. played self-smoothening of surface crack in 30 min. along with
[85] have also electropolished Ti-based biomedical alloy using high ionic conductivity, non-combustibility and wide electrochem-
ethaline. The process improved the surface properties of Ti-based ical voltages. As a result of these characteristics, when this gel elec-
alloy by reducing roughness and forming a specific surface pattern trolyte coupled with solid-state lithium batteries having lithium
that had nanoscale irregularities in prolonged hemispheres. anode and LiFePO4 cathode, it produced a high specific capacity
The morphology of metal deposits can be tuned using various (135.4 mA h g -1) with durable cyclic stability [93].
additives and it is dependent on DES compositions. The additives
such as nicotinic acid, methyl nicotinate, boric acid and hydantoin 5.7. Synthesis
have been used with ethaline for the electrodeposition of cobalt.
The surface morphology was observed to be changed, flat, shiny Another important application of DESs is found in synthesis like
and uniform compared to a deposition without additives. The pres- organic compounds, nanomaterial, polymer, etc. [94]. It is also
ence of additives also caused changes in the nucleation and growth used as a solvent in plenty of organic reactions [95]. Metal oxalates
mechanism of cobalt deposition [86]. Recently, Bohlen et al.,[87] are in high demand due to their properties like large surface area
have worked on Indium deposition using DESs based on choline and unique physicochemical properties which are applied in elec-
chloride and ethylene glycol on copper, glassy carbon and plat- trochemistry. Yang et al.[96] recently synthesized multi-metal
inum electrode. It presents the first-time application of Indium oxalate by a solvothermal method in different DESs such as Ethy-
deposited electrode used as a catalyst to electrochemical CO2 lene glycol-citric acid (EG-CA DES), polyethylene glycol-oxalic acid
reduction to formate. (PEG-OA DES), polyethylene glycol-citric acid (PEG-CA DES). The
quinary oxalate (FeCoNiCuZn)(C2O4). 2H2O was synthesised for
5.6. Energy storage the first time and proved to be an efficient Oxygen Evolution Reac-
tion in electrocatalysts and supercapacitor cathodes [96]. Zinc
New development in technologies like cell phones, computers oxide (ZnO) is one of the semiconducting materials that has been
and many more power-dependent devices demands advanced used extensively over the decades for various applications like
and better energy storage materials. Currently, Lithium-ion batter- photodetectors, LEDs, degrading organic pollutants and dyes in
ies are the best invention for energy storage that has been used in wastewater, biomedicals, solar cells, sensors, etc. [97,98]. These
numerous applications. But it holds some drawbacks like toxicity properties can be affected by tuning of size and shape and mor-
and availability of material, high production cost, short life cycle phology of ZnO nanoparticles. Mustafa et al. [98] have used
and electrolyte safety at a high current rate [88]. It is necessary betaine-based DES for the synthesis of ZnO nanoparticles. The syn-
to replace such materials with safe, flame-resistant, non- thesized nanoparticles possess a relatively large surface area and
hazardous substances. DESs have been considered as potential stability in aqueous media.
electrolytes due to their properties like high conductivity, non- DESs composed of choline chloride and Glycerol, 1,4 Butanediol,
flammability, large electrochemical stability window (ESW), non- ethylene glycol and Xylitol has been utilized for the synthesis of
corrosive and low vapour pressure [41,89]. Millia et al. [88] exper- vanadium phosphorus oxide [99]. Mu et al. [100] have highlighted
imented with two different DESs; ethylene glycol/choline chloride the usage of DES as a precursor to synthesis of various substances.
(3:1 mol/mol) and L-(+)-lactic acid/choline chloride (2:1 mol/mol); Cicco et al.[101] have reported the usage of DES as environmen-
to dissolve lithium bis(trifluoromethane)sulfonimide (LiTFSI) and tally friendly reaction media for allylic alcohol addition reaction.
LiPF6 salts. The output shows good ionic conductivity, thermal The reaction yield is very high (up to 99%) and occurs at room tem-
and electrochemical stability. A review by Puttaswamy et al. [89] perature. DES have also been used in addition reactions of ketones
states various formulation of DESs and their physicochemical prop- and imines (Vidal et al) in air at ambient temperatures thereby
erties, interactions with different metal salts and electrochemical providing an alternative and cheaper and safer synthesis route
performance which further have been successfully implemented [102,103]. DES have also been employed for carrying out C–H acti-
in DESs as an electrolyte in different batteries such as Li-ion, Na- vation reaction involving direct arylation of 5-octylthieno[3,4-c]
ion and Al-ion/air and supercapacitors. pyrrole-4,6-dione with functionalized aryl iodide in reline [104].
Dye-sensitized solar cells (DSSCs) have high potential as energy Several well-known reactions like Suzuki-Miyaura cross-coupling,
storage, efficient and low cost, easy fabricating device but face a Michael addition and condensation using DES as both solvent
similar problem of the use of hazardous VOCs in preparation. Bol- and catalyst have been reported [105,106]. The heterogenetic char-
drini et al. [90] first time proposed the use of aqueous-based cho- acter of DES makes them a suitable candidate for solvothermal
line chloride DES as an electrolyte for DSSCs which showed a synthesis of several materials especially eutectic systems as the
successful outcome. Redox Flow Batteries (RFBs) are another precursor [100].
large-scale storage options in which electrolytes dissolve redox
active material and is circulated to the reaction site by the pump. 5.8. Natural deep eutectic solvents (NADES)
It is necessary for RFBs that electrolytes should possess maximum
solubility of redox-active material in a solvent. Various metal- In the past few years, the newly emerging concept of Natural
based and organic eutectic electrolytes have been implemented Deep Eutectic Solvents (NADES) have been widely accepted and
in various RFBs [91]. vigorously researched. It was introduced by Choi et al.[107] in
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2011 which puts NADES into a category made of primary metabo- 5.9. Therapeutic deep eutectic solvents (THEDES)
lites like sugars, organic acids and amino acids. These NADES are
mixtures of various metabolites which largely occur in the cell DESs are proven to be a potential medium for various chemical
and also play a vital role in biological processes like germination, processes and are considered economical alternatives for commer-
dehydration and cryoprotection. Dai et al. [56] hypothesized the cial use in the pharmaceutical and drug industries. The bioavail-
presence of alternative medium to water and lipid in organisms ability and solubility of a drug are crucial for effective drug
which is necessary for many biological processes, and it was fur- delivery. The majority of market drugs have poor solubility in
ther evidently seen from the results that led to the invention of water and over 40% of new drugs require formulation for dissolu-
more than 100 NADES [33,56]. NADES are naturally and abun- tion and solubility [121,122]. Numerous studies revealed that the
dantly present in food components and so their use in food formu- use of Active Pharmaceutical Ingredient (API) as eutectic in biolog-
lation obviates additional steps of purification processes which are ical systems can notably enhance solubility, bioactivity, permeabil-
necessary in conventional solvents [108]. ity, intestinal absorption and controlled release of drugs [122-124].
NADESs have been used in biorefinery to convert biomass and The involvement of bioactive eutectic materials having active prin-
agricultural waste into various useful products through extrac- ciple can benefit biomedical applications [125]. Thus, another class
tion, separation [108]. NADESs have been employed in the extrac- of DESs has been developed consisting of APIs with DESs called
tion of phenolic acids, volatile oils, flavonoids, saponins, alkaloids, Therapeutic DESs (THEDES) [125]. It was studied for the first time
polysaccharides and many more bioactive components from nat- by Stott and co-workers [126] in 1998 where they used ibuprofen
ural resources. They have also been helpful to improve the solu- with various terpenes such as menthol, thymol, etc. to find a
bility of bioactive compounds and chemical stability which can potential eutectic formulation for improved transdermal drug
be employed in biomedical applications [109,110]. Razboršek delivery. Since then, plenty and rigorous research has been carried
et al.[111] have worked on four different DESs developed using out to find potential THEDESs for various drugs improving their
Choline chloride as HBA and urea, lactic acid, sugars like fructose efficacy. Silva et al. [127] have studied THEDES composed of men-
and glucose as HBD. They were utilised for extraction of phenolic thol and saturated fatty acids such as stearic acid, myristic acid and
compounds from black chokeberry which is a rich source of lauric acid for their potential role in wound dressing. The charac-
bioactive phenolic compound. The obtained results were also terization and assessment were performed to evaluate the physic-
compared with frequently used Ultrasound assisted (UAE) ochemical properties and bioactivity of THEDES. It is found that
methanolic extraction method. It shows high extraction efficiency menthol and Stearic acid shows the most promising formulation
when DES is utilized for extraction than the conventional for wound healing ability [127].
methanolic extraction method. The stability of Carthamin, a red Tuberculosis is an infectious disease caused by bacteria named
pigment in the Safflower, was observed to be improved when Mycobacterium tuberculosis complex and is treated with multiple
sugar-based NADES having less water content were utilized for anti-bacterial drugs in combination for several months [128,129].
extraction over the traditional method [112]. NADES composed Santos and group [129] have researched THEDES composed of
of lactic acids, choline chloride and 1,2 propanediol has been suc- ethambutol, a bacteriostatic and anti-tuberculosis drug, and L-
cessfully used in the extraction process of phenolic compounds, arginine, an amino acid consumed through daily diet. The stable
chalcones [113]. eutectic mixture was obtained with the incorporation of citric acid
The physicochemical properties of NADES can be fine-tuned and and water along with ethambutol and L-arginine in specific molar
enhanced for required extraction with a suitable combination of ratios. The study shows better solubility and permeability of the
HBA and HBD. Grapes, a simple and widely available fruit, recently drug when incorporated as THEDES [129]. Over the past few years,
garnered attention due to its health-beneficiary properties of phe- several more anti-tuberculosis drugs incorporating THEDES were
nolic groups like flavanols, stilbenes, etc., present in it [114,115]. introduced by various research groups [130].
Studies also suggest that grapes may have anticancer, anti- Pereira et al. [131] have developed a potential anticancer agent
inflammatory and antioxidant properties [115]. Usually, these using THEDESs based on terpenes like menthol, linalool and safra-
compounds are extracted using a conventional extraction process. nal, which has anticancer properties, with nonsteroidal anti-
NADES based on choline chloride and glucose, fructose, xylose, inflammatory drugs such as flurbiprofen, ketoprofen and ibupro-
malic acid and glycerol were used to get phenolic grape skin fen. The tailor-made DESs with selectiveness towards the disease
extracts by Radošević et al [115]. Their bioactivity and toxicity can be very helpful to improve the therapeutical properties of
were tested in vitro using two human tumour cell lines. The find- drugs with less side effects [131]. Kang and co-workers [132]
ings show NADES based on choline chloride and malic acid shows developed a high-load nano-emulsion with novel DES which is fur-
higher efficiency of extraction as well as a good antioxidant and ther utilized in inhalation drugs with improved bioavailability. A
antiproliferative activity [115]. novel DES from Pirfenidone, a drug for the treatment of idiopathic
Recently, NADES assisted microwave hydro distillation method pulmonary fibrosis and N-acetylcysteine was discovered and their
(NADES-A-MHD) has been utilized for successfully extracting up to physicochemical properties were studied [132]. An oral adminis-
1.39% essential oil from Angelica sinensis Radix under optimized tration of Pirfenidone dosage is complex and extremely high. Pul-
conditions [116]. NADES and some DESs containing organic acids monary drug delivery is carried through inhalation of the drug. It
were observed to be possessing and enhancing the antimicrobial is seen that over the traditional emulsion and suspension dosage,
activity of certain compounds [117-119]. Grønlien et al. [120] the use of DES nano-emulsions has advantages like permeability
described the first time ever study of solubility, thermal properties and protein-avoidant. The study shows that the administration of
and structural behaviour of protein collagen with selective NADES this DES as a nano-emulsion and via the pulmonary route is supe-
to investigate the potential healing and antibacterial properties of rior to earlier methods for the treatment of idiopathic pulmonary
both. The selected NADES consists of citric acid and xylitol in a 1:1 fibrosis [132].
ratio, which is further diluted into various aqueous solutions along
with two collagens, atelocollagen and telocollagen. The study
showed that both collagens with undiluted NADES are more sus- 6. Green aspects of DESs
ceptible to molecular changes than acetic acid and this intramolec-
ular network between constituent components is maintained till In recent times, DESs has been a new buzzword in the scientific
dilution  1 : 200 [120]. community and also stands up to the expectations in applicative
6
A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

perspective. It is necessary to analyse the strengths, weaknesses, of conventional solvents. Biodegradability, environmental-
opportunities and threats (SWOT) of DESs to develop and practice friendly, nonflammability, non-volatility, tunability, solubility
more sustainable and economical methods for commercial use and and many more properties have given a prospective as future of
it is illustrated in Fig. 3. solvents to DESs. However, it is necessary to consider that the
The commercial usage of DES is still in its nascent stage and production and designing process of DESs should satisfy environ-
major industrial implementation is yet to take place. Some pilot mental and economical requisites.
plants have been undertaken for different applications. One major Reusability and regeneration are essential aspects for green
advantage that DES has over other green solvent alternatives is chemistry. Abro et al. [137] studied capability of DESs used in
that it can be easily produced in large scale batches and thus suit- desulfurization of fuel oils for their reusability and regeneration.
able for scaling up for industrial applications [31]. Some advances They have reported that with the increase in the number of the
have been made in the field of bio catalysis which shows promise extraction cycles, the capacity of the DES to desulfurize decreases
of potential scaling up in the future [133]. A hybrid DES compris- without regeneration of DESs. But with the regenerated DESs, it
ing of choline chloride, ethylene glycol, and urea was used for shows good efficiency with very slight loss. The challenge for the
large scale extraction of lead and zinc from electric arc furnace recyclability of the DES is in the extraction process in trying to
(EAF) dust [134]. Ali et al. [135] have used a pilot plant for the scale up the processes. Another interesting aspect affecting the
extraction of thiophene and scaled up from 10 g to more than extraction is the temperature with respect to energy consumption.
1000 g. Rente et al. [136] have carried out extraction of grape Literature shows that some DES viz., metal DES [138] and ammo-
anthocyanins with DES from a laboratory to an industrial scale nium DES [139] exhibit inverse extraction efficiency with temper-
which can be used in the cosmetic industry. The biggest hurdle ature rise while some like oxalate DES show increased efficiency.
in the extraction process for the DES during the scaling up oper- Table 1 mentions comparison of the characteristics of DESs, ionic
ations arises due to the viscosity which is often higher than that liquids and conventional solvents in green perspective.

Fig. 3. SWOT analysis of DES.

Table 1
Characteristics of conventional solvents, ionic liquids and DESs.

Conventional solvents Ionic liquids Deep eutectic solvents

Composition Organic liquids Cations and Anions HBD and HBA
Volatility High Low Low
Solubility Weak High High
Flammability Usually, flammable Non-flammable Non-flammable
Tunability No [140,141] Yes, unlimited range of combinations [140] Yes, unlimited range of combinations [140]
Biodegradability Few solvents are biodegradable No [35] Yes
Recyclability and Reproducibility Low, for selective solvents Yes[142] Yes[142]
Cost Less expensive Expensive [143] Less expensive [143]
Toxicity High, majority are carcinogenic Low to atmosphere, high to Aquatic biota [34] Low [144]
Atom Economy Very low Moderate High

7
A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

7. Conclusions [15] H. Ali, E. Khan, I. Ilahi, Environmental chemistry and ecotoxicology of

hazardous heavy metals: Environmental persistence, toxicity, and
bioaccumulation, J Chem. 2019 (2019), https://doi.org/10.1155/2019/
It is interesting to note that the interest in DESs and their mul- 6730305.
tifarious applications has undergone tremendous growth in the [16] R. Naidu, B. Biswas, I.R. Willett, J. Cribb, B. Kumar Singh, C. Paul Nathanail, F.
Coulon, K.T. Semple, K.C. Jones, A. Barclay, R. John Aitken, Chemical pollution:
past decade or so. Although ILs and DESs show a certain number
a growing peril and potential catastrophic risk to humanity, Environ Int. 156
of similarities in their physicochemical properties; the difference (2021), https://doi.org/10.1016/J.ENVINT.2021.106616.
in their chemical properties sets them widely apart keeping in [17] F.P. Byrne, S. Jin, G. Paggiola, T.H.M. Petchey, J.H. Clark, T.J. Farmer, A.J. Hunt,
C. Robert McElroy, J. Sherwood, Tools and techniques for solvent selection:
mind the recent reports on IL toxicity leading to very different
green solvent selection guides, Sustainable Chemical Processes 2016 4:1. 4
and diverse applications of the DESs in comparison to the ILs. But (2016) 1–24 doi: 10.1186/S40508-016-0051-Z.
there is still a requirement to validate the non-toxicity of DESs. [18] P. Anastas, N. Eghbali, Green chemistry: principles and practice, Chem Soc
In past years, several studies have come up questioning the term Rev. 39 (2009) 301–312, https://doi.org/10.1039/B918763B.
[19] M.O. Simon, C.J. Li, Green chemistry oriented organic synthesis in water,
‘‘Green” solvent for DESs [145]. There is still a lack of predictive Chem Soc Rev. 41 (2012) 1415–1427, https://doi.org/10.1039/C1CS15222J.
methodology for mapping the toxicity behaviour of DESs [146]. [20] C.-J. Li, P.T. Anastas, Handbook of Green Chemistry, Volume 5:, Green
The dynamic study of DESs and emerging alternative technologies Solvents, Reactions in Water., Wiley-VCH, 2013.
[21] P.G. Jessop, B. Subramaniam, Gas-expanded liquids, Chem Rev. 107 (2007)
will pave the way for the usage of DESs as a cleaner, greener and 2666–2694, https://doi.org/10.1021/CR040199O/ASSET/IMAGES/LARGE/
more environmentally sustainable solvent in the days to come. CR040199OF00022.JPEG.
[22] N.F. Leininger, R. Clontz, J.L. Gainer, D.J. Kirwan, Polyethylene glycol-water
and polypropylene glycol-water solutionsas benign reaction solvents, Chem
Data availability Eng Commun. 190 (2003) 431–444.
[23] D.J. Heldebrant, H.N. Witt, S.M. Walsh, T. Ellis, J. Rauscher, P.G. Jessop, Liquid
polymers as solvents for catalytic reductions, Green Chem. 8 (2006) 807–815,
No data was used for the research described in the article. https://doi.org/10.1039/B605405F.
[24] P.G. Jessop, W. Leitner, Chemical synthesis using supercritical fluids, John
Wiley & Sons, 2008.
Declaration of Competing Interest [25] A. Clifford, T. Clifford, Fundamentals of supercritical fluids, Oxford University
Press, 1999.
[26] D. Dhiman, M. Bisht, A.P.M. Tavares, M.G. Freire, P. Venkatesu, Cholinium-
The authors declare that they have no known competing finan- based ionic liquids as efficient media for improving the structural and
cial interests or personal relationships that could have appeared thermal stability of immunoglobulin G antibodies, ACS Sustain Chem Eng. 10
to influence the work reported in this paper. (2022) 5404–5420, https://doi.org/10.1021/ACSSUSCHEMENG.1C07979/.
[27] S.P. Padinhattath, B. Chenthamara, R.L. Gardas, Ionic liquids as alternative
solvents for energy conservation and environmental engineering, Acta,
References Innovations. 38 (2021) 62–79, https://doi.org/10.32933/
ActaInnovations.38.6.
[28] A. Basaiahgari, R.L. Gardas, Ionic liquid–based aqueous biphasic systems as
[1] N. Winterton, The green solvent: a critical perspective, Clean Technologies
sustainable extraction and separation techniques, Curr Opin Green Sustain
and Environmental Policy 2021 23:9. 23 (2021) 2499–2522 doi: 10.1007/
Chem. 27 (2021), https://doi.org/10.1016/J.COGSC.2020.100423.
S10098-021-02188-8.
[29] V. Singh, K.D. Amirchand, R.L. Gardas, Ionic liquid-nanoparticle based hybrid
[2] G. Wypych, M. Matsumoto, S. Isken, J.A.M. de Bont, K. Botzenhart, T. Hahn, F.
systems for energy conversion and energy storage applications, J Taiwan Inst
Schweinsberg, T. Yamane, K.D. Hasenclever, P.J. Wakelyn, P.J. Wan, G. Volland,
Chem Eng. 133 (2022), https://doi.org/10.1016/J.JTICE.2022.104237.
M. Bauer, C. Barthélémy, M. Serageldin, D. Reeves, SOLVENTS USE IN VARIOUS
[30] T. Welton, Solvents and sustainable chemistry, Proceedings. Mathematical,
INDUSTRIES, Handbook of Solvents, Volume 2: Use, Health, and Environment.
Physical, and Engineering Sciences / The Royal Society. 471 (2015) doi:
(2019) 901–1124 doi: 10.1016/B978-1-927885-41-3.50003-6.
10.1098/RSPA.2015.0502.
[3] Solvents and sustainability | Feature | Chemistry World, (n.d.). https://
[31] E.L. Smith, A.P. Abbott, K.S. Ryder, Deep eutectic solvents (DESs) and their
www.chemistryworld.com/features/solvents-and-sustainability/3008751.
applications, Chem Rev. 114 (2014) 11060–11082, https://doi.org/10.1021/
article (accessed December 10, 2022).
cr300162p.
[4] What are Industrial Solvents and Where are They Typically Used? - Maratek
[32] C. Florindo, F. Lima, B.D. Ribeiro, I.M. Marrucho, Deep eutectic solvents:
Environmental, (n.d.). https://www.maratekenvironmental.com/what-are-
overcoming 21st century challenges, Curr Opin Green Sustain Chem. 18
industrial-solvents-and-where-are-they-typically-used/.
(2019) 31–36, https://doi.org/10.1016/j.cogsc.2018.12.003.
[5] K. Häckl, W. Kunz, Some aspects of green solvents, Comptes Rendus Chimie.
[33] L.I.N. Tomé, V. Baião, W. da Silva, C.M.A. Brett, Deep eutectic solvents for the
21 (2018) 572–580, https://doi.org/10.1016/J.CRCI.2018.03.010.
production and application of new materials, Appl Mater Today. 10 (2018)
[6] C.H. Halios, C. Landeg-Cox, S.D. Lowther, A. Middleton, T. Marczylo, S.
30–50, https://doi.org/10.1016/J.APMT.2017.11.005.
Dimitroulopoulou, Chemicals in European residences – Part I: A review of
[34] J. Flieger, M. Flieger, Ionic liquids toxicity—benefits and threats, Int J Mol Sci.
emissions, concentrations and health effects of volatile organic compounds
21 (2020) 1–41, https://doi.org/10.3390/ijms21176267.
(VOCs), Sci. Total Environ. 839 (2022), https://doi.org/10.1016/J.
[35] M.T. Garcia, N. Gathergood, P.J. Scammells, Biodegradable ionic liquids, Green
SCITOTENV.2022.156201.
Chemistry. 7 (2005) 9–14, https://doi.org/10.1039/B411922C.
[7] K. Zhang, S. Chang, E. Wang, Q. Zhang, Y. Fan, Y. Bai, M. Zhang, Q. Fu, W. Jia,
[36] C.W. Cho, T.P.T. Pham, Y. Zhao, S. Stolte, Y.S. Yun, Review of the toxic effects of
Occurrence, health risk, and removal efficiency assessment of volatile organic
ionic liquids, Sci. Total Environ. 786 (2021), https://doi.org/10.1016/j.
compounds in drinking water treatment plants (DWTPs): An investigation of
scitotenv.2021.147309.
seven major river basins across China, J Clean Prod. 372 (2022), https://doi.
[37] Scopus - Analyzer search results. https://www.scopus.com/term/analyzer.
org/10.1016/J.JCLEPRO.2022.133762.
uri?sid=70a06ddbb8084ae591b4f4c731829d1f&origin=
[8] O.C. Ulker, O. Ulker, S. Hiziroglu, Volatile Organic Compounds (VOCs) Emitted
resultslist&src=s&s=TITLE-ABS-KEY%28%22deep+eutectic+solvents%22%29
from Coated Furniture Units, Coatings 2021, Vol. 11, Page 806. 11 (2021) 806
+AND+PUBYEAR+%3e+2018&sort=plf-
doi: 10.3390/COATINGS11070806.
f&sdt=b&sot=b&sl=58&count=6414&analyzeResults=Analyze
[9] A.J. Li, V.K. Pal, K. Kannan, A review of environmental occurrence, toxicity,
+results&txGid=353bee44cbb472055383fbcdc5dd55ff.
biotransformation and biomonitoring of volatile organic compounds, Environ.
[38] D.O. Abranches, J.A.P. Coutinho, Type V deep eutectic solvents: Design and
Chem. Ecotoxicol. 3 (2021) 91–116, https://doi.org/10.1016/J.
applications, Curr Opin Green Sustain Chem. 35 (2022), https://doi.org/
ENCECO.2021.01.001.
10.1016/J.COGSC.2022.100612.
[10] F.D. Dick, Solvent neurotoxicity, Occup Environ Med. 63 (2006) 221, https://
[39] D.O. Abranches, M.A.R. Martins, L.P. Silva, N. Schaeffer, S.P. Pinho, J.A.P.
doi.org/10.1136/OEM.2005.022400.
Coutinho, Phenolic hydrogen bond donors in the formation of non-ionic deep
[11] J.A. Bonventre, Solvents, Encyclopedia of Toxicology: Third Edition. (2014)
eutectic solvents: the quest for type V DES, Chem. Commun. 55 (2019)
356–357 doi: 10.1016/B978-0-12-386454-3.01063-0.
10253–10256, https://doi.org/10.1039/C9CC04846D.
[12] Q. Zhao, Y. Li, X. Chai, L. Xu, L. Zhang, P. Ning, J. Huang, S. Tian, Interaction of
[40] S. Juneja, S. Pandey, Water miscibility, surface tension, density, and dynamic
inhalable volatile organic compounds and pulmonary surfactant: Potential
viscosity of hydrophobic deep eutectic solvents composed of capric acid,
hazards of VOCs exposure to lung, J. Hazard Mater. 369 (2019) 512–520,
menthol, and thymol, J. Chem. Eng. Data. 67 (2022) 3400–3413, https://doi.
https://doi.org/10.1016/J.JHAZMAT.2019.01.104.
org/10.1021/acs.jced.2c00495.
[13] Y. Ma, X. He, K. Qi, T. Wang, Y. Qi, L. Cui, F. Wang, M. Song, Effects of
[41] B.B. Hansen, S. Spittle, B. Chen, D. Poe, Y. Zhang, J.M. Klein, A. Horton, L.
environmental contaminants on fertility and reproductive health, J. Environ.
Adhikari, T. Zelovich, B.W. Doherty, B. Gurkan, E.J. Maginn, A. Ragauskas, M.
Sci. 77 (2019) 210–217, https://doi.org/10.1016/J.JES.2018.07.015.
Dadmun, T.A. Zawodzinski, G.A. Baker, M.E. Tuckerman, R.F. Savinell, J.R.
[14] S. Mehra, M. Singh, P. Chadha, Adverse impact of textile dyes on the aquatic
Sangoro, Deep eutectic solvents: a review of fundamentals and applications,
environment as well as on human beings, Toxicol Int. 28 (2021) 165–176,
https://doi.org/10.18311/ti/2021/v28i2/26798.

8
A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

Chem Rev. 121 (2021) 1232–1285, https://doi.org/10.1021/ACS. [66] J. Hekayati, S. Raeissi, A global transform for the general formulation of liquid
CHEMREV.0C00385/. viscosities with significant linearizing benefits: a case study on ionic liquid
[42] D.J. Ramon, G. Guillena, eds., Deep Eutectic Solvents: Synthesis, Properties mixtures, Phys. Chem. Chem. Phys. 23 (2021) 22551–22566, https://doi.org/
and Applications, Wiley-VCH, 2020. 10.1039/D1CP02033A.
[43] S. Benabid, Y. Benguerba, I.M. AlNashef, N. Haddaoui, Theoretical study of [67] D. Shi, F. Zhou, W. Mu, C. Ling, T. Mu, G. Yu, R. Li, Deep insights into the
physicochemical properties of selected ammonium salt-based deep eutectic viscosity of deep eutectic solvents by an XGBoost-based model plus SHapley
solvents, Journal of Molecular Liquids 285 (2019) 38–46. Additive exPlanation, Phys. Chem. Chem. Phys. 24 (2022) 26029–26036,
[44] S.P. Ijardar, V. Singh, R.L. Gardas, Revisiting the physicochemical properties https://doi.org/10.1039/d2cp03423a.
and applications of deep eutectic solvents, Molecules. 27 (2022), https://doi. [68] Y. Wang, W. Chen, Q. Zhao, G. Jin, Z. Xue, Y. Wang, T. Mu, Ionicity of deep
org/10.3390/molecules27041368. eutectic solvents by Walden plot and pulsed field gradient nuclear magnetic
[45] B.Y. Zhao, P. Xu, F.X. Yang, H. Wu, M.H. Zong, W.Y. Lou, Biocompatible deep resonance (PFG-NMR), Phys. Chem. Chem. Phys. 22 (2020) 25760–25768,
eutectic solvents based on choline chloride: characterization and application https://doi.org/10.1039/d0cp01431a.
to the extraction of rutin from Sophora japonica, ACS Sustain Chem Eng. 3 [69] Q. Li, J. Jiang, G. Li, W. Zhao, X. Zhao, T. Mu, The electrochemical stability of
(2015) 2746–2755, https://doi.org/10.1021/ACSSUSCHEMENG.5B00619/. ionic liquids and deep eutectic solvents, Sci China Chem. 59 (2016) 571–577,
[46] R. Sharma, K.J. Jisha, R.L. Gardas, N. Malek, S.P. Ijardar, Insights into https://doi.org/10.1007/s11426-016-5566-3.
experimental and theoretical approach to physicochemical properties of [70] M. Carolina Gipiela Corrêa Dias, F. Oliveira Farias, R. Cazelato Gaioto, E.
aqueous PEGylated deep eutectic solvents at T=(293.15–323.15) K, J Mol Liq. Kaspchak, M. Conceição da Costa, L. Igarashi-Mafra, M.R. Mafra,
366 (2022), https://doi.org/10.1016/J.MOLLIQ.2022.120278. Thermophysical characterization of deep eutectic solvents composed by D-
[47] R. Sharma, K.K. Athira, R.L. Gardas, N. Malek, S.P. Ijardar, Physicochemical and sorbitol, xylitol or D(+)xylose as hydrogen bond donors, J. Mol. Liq. 354
acoustic characterization of binary mixtures of tetraalkylammonium (2022), https://doi.org/10.1016/j.molliq.2022.118801.
bromide: PEG based DES and water, J Mol Liq. 367 (2022), https://doi.org/ [71] D.J.G.P. van Osch, L.F. Zubeir, A. van den Bruinhorst, M.A.A. Rocha, M.C. Kroon,
10.1016/J.MOLLIQ.2022.120386. Hydrophobic deep eutectic solvents as water-immiscible extractants, Green
[48] M. Avalos, R. Babiano, P. Cintas, J.L. Jiménez, J.C. Palacios, Greener media in Chem. 17 (2015) 4518–4521, https://doi.org/10.1039/c5gc01451d.
chemical synthesis and processing, Angewandte Chemie Int. Ed. 45 (2006) [72] P. Gutiérrez-Sánchez, P. Navarro, S. Álvarez-Torrellas, J. García, M. Larriba,
3904–3908, https://doi.org/10.1002/ANIE.200504285. Extraction of neonicotinoid pesticides from aquatic environmental matrices
[49] A. Al-Ghamdi, D. Saini, M. Singh, N.I. Malek, Nonideal behavior of aqueous with sustainable terpenoids and eutectic solvents, Sep. Purif. Technol. 302
deep eutectic solvents based on tetrabutylphosphonium bromide and (2022), https://doi.org/10.1016/J.SEPPUR.2022.122148.
ethylene glycol/glycerol, J Chem Eng Data. 67 (2022) 2963–2973, https:// [73] J. Lee, D. Jung, K. Park, Hydrophobic deep eutectic solvents for the extraction
doi.org/10.1021/ACS.JCED.2C00372/. of organic and inorganic analytes from aqueous environments, TrAC Trends
[50] V. Khokhar, D. Dhingra, S. Pandey, Effect of temperature and composition on Anal. Chem. 118 (2019) 853–868, https://doi.org/10.1016/J.
density and dynamic viscosity of (lanthanide metal salts + urea) deep eutectic TRAC.2019.07.008.
solvents, J Mol Liq. 360 (2022), https://doi.org/10.1016/J. [74] C. Florindo, L.C. Branco, I.M. Marrucho, Development of hydrophobic deep
MOLLIQ.2022.119396. eutectic solvents for extraction of pesticides from aqueous environments,
[51] D. Yu, T. Mu, Strategy to form eutectic molecular liquids based on Fluid Phase Equilib 448 (2017) 135–142, https://doi.org/10.1016/J.
noncovalent interactions, J. Phys. Chem. B. 123 (2019) 4958–4966, https:// FLUID.2017.04.002.
doi.org/10.1021/acs.jpcb.9b02891. [75] D.J.G.P. van Osch, C.H.J.T. Dietz, S.E.E. Warrag, M.C. Kroon, The curious case of
[52] D. Yu, H. Mou, H. Fu, X. Lan, Y. Wang, T. Mu, ‘‘Inverted” deep eutectic solvents hydrophobic deep eutectic solvents: a story on the discovery design, and
based on host-guest interactions, Chem. Asian J. 14 (2019) 4183–4188, applications, ACS Sustain Chem. Eng. 8 (2020) 10591–10612, https://doi.org/
https://doi.org/10.1002/asia.201901365. 10.1021/ACSSUSCHEMENG.0C00559/.
[53] A.P. Abbott, D. Boothby, G. Capper, D.L. Davies, R.K. Rasheed, Deep eutectic [76] M.S.N. Sai, D. De, D. Gariya, B. Satyavathi, Thermophysical characterization of
solvents formed between choline chloride and carboxylic acids: versatile terpenoid based hydrophobic deep eutectic solvent and its Vapour-Liquid
alternatives to ionic liquids, J. Am. Chem. Soc. 126 (2004) 9142–9147, https:// equilibrium studies with furfural, J Mol Liq. 364 (2022), https://doi.org/
doi.org/10.1021/JA048266J/SUPPL_FILE/JA048266JSI20040521_085323.PDF. 10.1016/j.molliq.2022.120056.
[54] M.C. Gutiérrez, M.L. Ferrer, C.R. Mateo, F. del Monte, Freeze-drying of aqueous [77] E.J. González, M. González-Miquel, I. Díaz, M. Rodríguez, C. Fontela, R.
solutions of deep eutectic solvents: a suitable approach to deep eutectic Cañadas, J. Sánchez, Enhancing aqueous systems fermentability using
suspensions of self-assembled structures, Langmuir. 25 (2009) 5509–5515, hydrophobic eutectic solvents as extractans of inhibitory compounds, Sep.
https://doi.org/10.1021/LA900552B/SUPPL_FILE/LA900552B_SI_001.PDF. Purif. Technol. 250 (2020), https://doi.org/10.1016/j.seppur.2020.117184.
[55] C. Florindo, F.S. Oliveira, L.P.N. Rebelo, A.M. Fernandes, I.M. Marrucho, [78] A.F. Hernández, T. Parrón, A.M. Tsatsakis, M. Requena, R. Alarcón, O. López-
Insights into the synthesis and properties of deep eutectic solvents based Guarnido, Toxic effects of pesticide mixtures at a molecular level: their
on cholinium chloride and carboxylic acids, ACS Sustain. Chem. Eng. 2 (2014) relevance to human health, Toxicology 307 (2013) 136–145, https://doi.org/
2416–2425, https://doi.org/10.1021/SC500439W/SUPPL_FILE/ 10.1016/J.TOX.2012.06.009.
SC500439W_SI_001.PDF. [79] N. Li, Y. Wang, K. Xu, Y. Huang, Q. Wen, X. Ding, Development of green
[56] Y. Dai, J. van Spronsen, G.J. Witkamp, R. Verpoorte, Y.H. Choi, Natural deep betaine-based deep eutectic solvent aqueous two-phase system for the
eutectic solvents as new potential media for green technology, Anal. Chim. extraction of protein, Talanta 152 (2016) 23–32, https://doi.org/10.1016/J.
Acta. 766 (2013) 61–68, https://doi.org/10.1016/J.ACA.2012.12.019. TALANTA.2016.01.042.
[57] L.-N. Song Qing-Wen and He, Atom Economy, in: R.A. Meyers (Ed.), [80] G. Qin, J. Lei, S. Li, Y. Jiang, L. Qiao, M. Ren, Q. Gao, C. Song, S. Fu, J. Zhou, S.
Encyclopedia of Sustainability Science and Technology, Springer New York, Xiao, M. Zhang, G. Wang, Efficient, green extraction of two biflavonoids from
New York, NY, 2018: pp. 1–21 doi: 10.1007/978-1-4939-2493-6_1001-1. Selaginella uncinata with deep eutectic solvents, Microchem. J. 183 (2022),
[58] T.A. Hopkins, L. VandenElzen, B.P. Nelson, V. Vaid, J. Brickley, P. Ariza, G. https://doi.org/10.1016/J.MICROC.2022.108085.
Whitacre, I. Patel, O. Gooch, M. Bechman, C. Jordan, Chiral solvent discovery: [81] A.P. Abbott, A. Ballantyne, R.C. Harris, J.A. Juma, K.S. Ryder, A comparative
exploring chiral eutectic mixtures and deep eutectic solvents, Ind. Eng. Chem. study of nickel electrodeposition using deep eutectic solvents and aqueous
Res. 62 (2022) 32, https://doi.org/10.1021/ACS.IECR.2C03702/. solutions, Electrochim Acta. 176 (2015) 718–726, https://doi.org/10.1016/J.
[59] R. Gautam, N. Kumar, J.G. Lynam, Theoretical and experimental study of ELECTACTA.2015.07.051.
choline chloride-carboxylic acid deep eutectic solvents and their hydrogen [82] A.A. Kityk, F.I. Danilov, V.S. Protsenko, V. Pavlik, M. Boča, Y. Halahovets,
bonds, J. Mol. Struct. 1222 (2020), https://doi.org/10.1016/J. Electropolishing of two kinds of bronze in a deep eutectic solvent (Ethaline),
MOLSTRUC.2020.128849. Surf Coat Technol 397 (2020), https://doi.org/10.1016/J.
[60] K. Adi Kurnia, M. Zunita, J.A.P. Coutinho, I. Gede Wenten, D. Santoso, SURFCOAT.2020.126060.
Development of quantitative structure-property relationship to predict the [83] W.O. Karim, A.P. Abbott, S. Cihangir, K.S. Ryder, Electropolishing of nickel and
viscosity of deep eutectic solvent for CO2 capture using molecular descriptor, cobalt in deep eutectic solvents, Doi: 10.1080/00202967.2018.1470400. 96
J. Mol. Liq. 347 (2022), https://doi.org/10.1016/j.molliq.2021.118239. (2018) 200–205 doi: 10.1080/00202967.2018.1470400.
[61] M. Zhang, X. Zhang, Y. Liu, K. Wu, Y. Zhu, H. Lu, B. Liang, Insights into the [84] A.A. Kityk, V.S. Protsenko, F.I. Danilov, O.v. Kun, S.A. Korniy, Electropolishing
relationships between physicochemical properties, solvent performance, and of aluminium in a deep eutectic solvent, Surf Coat Technol. 375 (2019) 143–
applications of deep eutectic solvents, Environ. Sci. Pollut. Res. 2021 28:27. 28 149, https://doi.org/10.1016/J.SURFCOAT.2019.07.018.
(2021) 35537–35563 doi: 10.1007/S11356-021-14485-2. [85] A. Kityk, V. Protsenko, F. Danilov, V. Pavlik, M. Hnatko, J. Šoltýs, Enhancement
[62] Y. Marcus, Deep eutectic solvents, Springer International Publishing (2019), of the surface characteristics of Ti-based biomedical alloy by electropolishing
https://doi.org/10.1007/978-3-030-00608-2. in environmentally friendly deep eutectic solvent (Ethaline), Colloids Surf A
[63] F. Zhou, R. Shi, Y. Wang, Z. Xue, B. Zhang, T. Mu, Acidity scales of deep eutectic Physicochem Eng Asp. 613 (2021), https://doi.org/10.1016/J.
solvents based on IR and NMR, Phys. Chem. Chem. Phys. 24 (2022) 16973– COLSURFA.2020.126125.
16978, https://doi.org/10.1039/d2cp01816k. [86] J.A. Juma, The effect of organic additives in electrodeposition of Co from deep
[64] R. Dey, P. Biswas, A novel and effective approach for viscosity prediction of eutectic solvents, Arab. J. Chem. 14 (2021), https://doi.org/10.1016/J.
binary and multicomponent liquid mixtures, J Mol Liq. 265 (2018) 356–360, ARABJC.2021.103036.
https://doi.org/10.1016/j.molliq.2018.06.012. [87] B. Bohlen, D. Wastl, J. Radomski, V. Sieber, L. Vieira, Electrochemical CO2
[65] D. Peng, A. Alhadid, M. Minceva, Modeling the viscosity of binary eutectic reduction to formate on indium catalysts prepared by electrodeposition in
systems at different compositions and temperatures, J Mol Liq. 373 (2023), deep eutectic solvents, Electrochem. Commun. 110 (2020), https://doi.org/
https://doi.org/10.1016/J.MOLLIQ.2023.121258. 10.1016/J.ELECOM.2019.106597.

9
A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

[88] L. Millia, V. Dall’Asta, C. Ferrara, V. Berbenni, E. Quartarone, F.M. Perna, V. [109] D. Li, Natural deep eutectic solvents in phytonutrient extraction and other
Capriati, P. Mustarelli, Bio-inspired choline chloride-based deep eutectic applications, Front Plant Sci. 13 (2022) 3344, https://doi.org/10.3389/
solvents as electrolytes for lithium-ion batteries, Solid State Ion. 323 (2018) FPLS.2022.1004332/BIBTEX.
44–48, https://doi.org/10.1016/J.SSI.2018.05.016. [110] A. Paiva, R. Craveiro, I. Aroso, M. Martins, R.L. Reis, A.R.C. Duarte, Natural deep
[89] R. Puttaswamy, C. Mondal, D. Mondal, D. Ghosh, An account on the deep eutectic solvents - Solvents for the 21st century, ACS Sustain Chem Eng. 2
eutectic solvents-based electrolytes for rechargeable batteries and (2014) 1063–1071, https://doi.org/10.1021/sc500096j.
supercapacitors, Sustain. Mater. Technol. 33 (2022) e00477. [111] M.I. Razboršek, M. Ivanović, P. Krajnc, M. Kolar, Choline chloride based
[90] C.L. Boldrini, N. Manfredi, F.M. Perna, V. Trifiletti, V. Capriati, A. Abbotto, Dye- natural deep eutectic solvents as extraction media for extracting phenolic
sensitized solar cells that use an aqueous choline chloride-based deep compounds from chokeberry (Aronia melanocarpa), Molecules. 25 (2020),
eutectic solvent as effective electrolyte solution, Energy Technol. 5 (2017) https://doi.org/10.3390/molecules25071619.
345–353, https://doi.org/10.1002/ENTE.201600420. [112] Y. Dai, R. Verpoorte, Y.H. Choi, Natural deep eutectic solvents providing
[91] C. Zhang, L. Zhang, G. Yu, Eutectic electrolytes as a promising platform for enhanced stability of natural colorants from safflower (Carthamus
next-generation electrochemical energy storage, Acc Chem Res. 53 (2020) tinctorius), Food Chem. 159 (2014) 116–121, https://doi.org/10.1016/J.
1648–1659, https://doi.org/10.1021/ACS.ACCOUNTS.0C00360/. FOODCHEM.2014.02.155.
[92] M.H. Chakrabarti, F.S. Mjalli, I.M. Alnashef, M.A. Hashim, M.A. Hussain, L. [113] Y. Liu, J.B. Friesen, J.B. McAlpine, D.C. Lankin, S.N. Chen, G.F. Pauli, Natural
Bahadori, C.T.J. Low, Prospects of applying ionic liquids and deep eutectic deep eutectic solvents: properties, applications, and perspectives, J Nat Prod.
solvents for renewable energy storage by means of redox flow batteries, 81 (2018) 679–690, https://doi.org/10.1021/acs.jnatprod.7b00945.
Renew. Sustain. Energy Rev. 30 (2014) 254–270, https://doi.org/10.1016/J. [114] A. Teixeira, N. Baenas, R. Dominguez-Perles, A. Barros, E. Rosa, D.A. Moreno, C.
RSER.2013.10.004. Garcia-Viguera, Natural bioactive compounds from winery by-products as
[93] Q. Li, Z. Zhang, Y. Li, H. Li, Z. Liu, X. Liu, Q. Xu, Rapid self-healing gel electrolyte health promoters: a review, Int. J. Mol. Sci. 15 (2014) 15638-15678. 15 (2014)
based on deep eutectic solvents for solid-state lithium batteries, ACS Appl 15638–15678 doi: 10.3390/IJMS150915638.
Mater Interfaces. 14 (2022) 49708, https://doi.org/10.1021/ [115] K. Radošević, N. Ćurko, V. Gaurina Srček, M. Cvjetko Bubalo, M. Tomašević, K.
ACSAMI.2C12445/. Kovačević Ganić, I. Radojčić Redovniković, Natural deep eutectic solvents as
[94] B. Tang, K.H. Row, Recent developments in deep eutectic solvents in chemical beneficial extractants for enhancement of plant extracts bioactivity, LWT. 73
sciences, Monatsh Chem. 144 (2013) 1427–1454, https://doi.org/10.1007/ (2016) 45–51, https://doi.org/10.1016/j.lwt.2016.05.037.
s00706-013-1050-3. [116] Y. Fan, Q. Li, An efficient extraction method for essential oil from angelica
[95] M. Shaibuna, L.v. Theresa, K. Sreekumar, Neoteric deep eutectic solvents: sinensis radix by natural deep eutectic solvents-assisted microwave
history, recent developments, and catalytic applications, Soft Matter. 18 hydrodistillation, Sustain. Chem. Pharm. 29 (2022), https://doi.org/10.1016/
(2022) 2695–2721, https://doi.org/10.1039/D1SM01797G. J.SCP.2022.100792.
[96] H. Yang, Z. Cheng, P. Wu, Y. Wei, J. Jiang, Q. Xu, Deep eutectic solvents [117] P. Zhou, D. Tang, J. Zou, X. Wang, An alternative strategy for enhancing
regulation synthesis of multi-metal oxalate for electrocatalytic oxygen stability and antimicrobial activity of catechins by natural deep eutectic
evolution reaction and supercapacitor applications, Electrochim Acta. 427 solvents, LWT. 153 (2022), https://doi.org/10.1016/J.LWT.2021.112558.
(2022), https://doi.org/10.1016/J.ELECTACTA.2022.140879. [118] K.O. Wikene, H.V. Rukke, E. Bruzell, H.H. Tønnesen, Investigation of the
[97] S. Thakur, S.K. Mandal, Precursor- and time-dependent morphological antimicrobial effect of natural deep eutectic solvents (NADES) as solvents in
evolution of ZnO nanostructures for comparative photocatalytic activity antimicrobial photodynamic therapy, J. Photochem. Photobiol. B. 171 (2017)
and adsorption dynamics with methylene blue dye, ACS Omega. 5 (2020) 27–33, https://doi.org/10.1016/J.JPHOTOBIOL.2017.04.030.
16670–16680, https://doi.org/10.1021/acsomega.0c01555. [119] J. Yu, S. Xu, G. Goksen, C. Yi, P. Shao, Chitosan films plasticized with choline-
[98] S.M. Mustafa, A.A. Barzinjy, A.H. Hamad, S.M. Hamad, Betaine-based deep based deep eutectic solvents: UV shielding, antioxidant, and antibacterial
eutectic solvents mediated synthesis of zinc oxide nanoparticles at low properties, Food Hydrocoll. 135 (2023), https://doi.org/10.1016/J.
temperature, Ceram Int. 48 (2022) 28951–28960, https://doi.org/10.1016/J. FOODHYD.2022.108196.
CERAMINT.2022.04.131. [120] K.G. Grønlien, M.E. Pedersen, H.H. Tønnesen, A natural deep eutectic solvent
[99] Y. Shi, F. Dai, T. Zhang, B. He, R. Zhang, R. Liu, B. Ren, Hydroxyl-rich deep (NADES) as potential excipient in collagen-based products, Int. J. Biol.
eutectic solvents assistant synthesis of VPO and its application in selective Macromol. 156 (2020) 394–402, https://doi.org/10.1016/j.
oxidation of n-butane, ChemistrySelect. 5 (2020) 6907–6917, https://doi.org/ ijbiomac.2020.04.026.
10.1002/SLCT.202001090. [121] S. Kalepu, V. Nekkanti, Insoluble drug delivery strategies: review of recent
[100] D. Yu, Z. Xue, T. Mu, Deep eutectic solvents as a green toolbox for synthesis, advances and business prospects, Acta Pharm. Sin B. 5 (2015) 442–453,
Cell Rep Phys Sci. 3 (2022), https://doi.org/10.1016/j.xcrp.2022.100809. https://doi.org/10.1016/J.APSB.2015.07.003.
[101] L. Cicco, M.J. Rodríguez-Álvarez, F.M. Perna, J. García-Álvarez, V. Capriati, [122] M.S. Rahman, R. Roy, B. Jadhav, M.N. Hossain, M.A. Halim, D.E. Raynie,
One-pot sustainable synthesis of tertiary alcohols by combining ruthenium- Formulation, structure, and applications of therapeutic and amino acid-based
catalysed isomerisation of allylic alcohols and chemoselective addition of deep eutectic solvents: an overview, J. Mol. Liq. 321 (2021), https://doi.org/
polar organometallic reagents in deep eutectic solvents, Green Chemistry. 19 10.1016/J.MOLLIQ.2020.114745.
(2017) 3069–3077, https://doi.org/10.1039/C7GC00458C. [123] M.H. Zainal-Abidin, M. Hayyan, G.C. Ngoh, W.F. Wong, C.Y. Looi, Emerging
[102] C. Vidal, J. García-Álvarez, A. Hernán-Gõmez, A.R. Kennedy, E. Hevia, frontiers of deep eutectic solvents in drug discovery and drug delivery
Introducing Deep eutectic solvents to polar organometallic chemistry: systems, J. Controlled Release. 316 (2019) 168–195, https://doi.org/10.1016/J.
chemoselective addition of organolithium and grignard reagents to ketones JCONREL.2019.09.019.
in air, Angewandte Chemie International Edition. 53 (2014) 5969–5973, [124] A.R.C. Duarte, A.S.D. Ferreira, S. Barreiros, E. Cabrita, R.L. Reis, A. Paiva, A
https://doi.org/10.1002/ANIE.201400889. comparison between pure active pharmaceutical ingredients and therapeutic
[103] C. Vidal, J. García-Álvarez, A. Hernán-Gómez, A.R. Kennedy, E. Hevia, deep eutectic solvents: Solubility and permeability studies, Eur. J. Pharm.
Exploiting deep eutectic solvents and organolithium reagent partnerships: Biopharm. 114 (2017) 296–304, https://doi.org/10.1016/J.EJPB.2017.02.003.
chemoselective ultrafast addition to imines and quinolines under aerobic [125] L. Lomba, C.B. García, M.P. Ribate, B. Giner, E. Zuriaga, Applications of deep
ambient temperature conditions, Angewandte Chemie International Edition. eutectic solvents related to health, synthesis, and extraction of natural based
55 (2016) 16145–16148, https://doi.org/10.1002/ANIE.201609929. chemicals, Appl. Sci. (Switzerland). 11 (2021), https://doi.org/10.3390/
[104] A. Punzi, D.I. Coppi, S. Matera, M.A.M. Capozzi, A. Operamolla, R. Ragni, F. app112110156.
Babudri, G.M. Farinola, Pd-catalyzed thiophene-aryl coupling reaction via C- [126] P.W. Stott, A.C. Williams, B.W. Barry, Transdermal delivery from eutectic
H bond activation in deep eutectic solvents, Org Lett. 19 (2017) 4754–4757, systems: enhanced permeation of a model drug, ibuprofen, J. Controlled
https://doi.org/10.1021/ACS.ORGLETT.7B02114. Release. 50 (1998) 297–308, https://doi.org/10.1016/S0168-3659(97)00153-
[105] Q. Li, K. Sun, Y. Shao, S. Zhang, Z. Yan, L. Zhang, Q. Liu, Y. Wang, X. Hu, 3.
Coordination of acidic deep eutectic solvent-chromium trichloride catalytic [127] J.M. Silva, C.v. Pereira, F. Mano, E. Silva, V.I.B. Castro, I. Sá-Nogueira, R.L. Reis,
system for efficient synthesis of fructose to 5-hydroxymethylfurfual, Ind Eng A. Paiva, A.A. Matias, A. Rita, C. Duarte, Therapeutic role of deep eutectic
Chem Res. 59 (2020) 17554–17563, https://doi.org/10.1021/ACS. solvents based on menthol and saturated fatty acids on wound healing, ACS
IECR.0C01218/. Appl Bio Mater. 2 (2019) 4346–4355, https://doi.org/10.1021/
[106] V. Pelliccioli, G. Dilauro, S. Grecchi, S. Arnaboldi, C. Graiff, F.M. Perna, P. Vitale, acsabm.9b00598.
E. Licandro, A. Aliprandi, S. Cauteruccio, V. Capriati, Ligand-free suzuki- [128] G. Sandhu, Tuberculosis: current situation, challenges and overview of its
miyaura cross-coupling reactions in deep eutectic solvents: synthesis of control programs in India, J. Glob Infect Dis. 3 (2011) 143, https://doi.org/
benzodithiophene derivatives and study of their optical and electrochemical 10.4103/0974-777X.81691.
performance, European J Org Chem. 2020 (2020) 6981–6988, https://doi.org/ [129] F. Santos, M.I.P.S. Leitão, A.R.C. Duarte, Properties of Therapeutic Deep
10.1002/EJOC.202000889. Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment,
[107] Y.H. Choi, J. van Spronsen, Y. Dai, M. Verberne, F. Hollmann, I.W.C.E. Arends, Molecules 2019, Vol. 24, Page 55. 24 (2018) 55 doi: 10.3390/
G.J. Witkamp, R. Verpoorte, Are natural deep eutectic solvents the missing MOLECULES24010055.
link in understanding cellular metabolism and physiology?, Plant Physiol 156 [130] F. Oliveira, F. Santos, A.R.C. Duarte, Therapeutic Deep Eutectic Systems
(2011) 1701–1705, https://doi.org/10.1104/PP.111.178426. towards the Treatment of Tuberculosis and Colorectal Cancer: Opportunities
[108] A. Mišan, J. Nadpal, A. Stupar, M. Pojić, A. Mandić, R. Verpoorte, Y.H. Choi, The and Challenges, Molecules 2021, Vol. 26, Page 7022. 26 (2021) 7022 doi:
perspectives of natural deep eutectic solvents in agri-food sector, Crit Rev 10.3390/MOLECULES26227022.
Food Sci Nutr. 60 (2020) 2564–2592, https://doi.org/10.1080/ [131] J. Pereira, M. Miguel Castro, F. Santos, A. Rita Jesus, A. Paiva, F. Oliveira, A.R.C.
10408398.2019.1650717. Duarte, Selective terpene based therapeutic deep eutectic systems against

10
A. Prabhune and R. Dey Journal of Molecular Liquids 379 (2023) 121676

colorectal cancer, Eur. J. Pharm. Biopharmaceut. 175 (2022) 13–26, https:// [139] C. Li, D. Li, S. Zou, Z. Li, J. Yin, A. Wang, Y. Cui, Z. Yao, Q. Zhao, Extraction
doi.org/10.1016/J.EJPB.2022.04.008. desulfurization process of fuels with ammonium-based deep eutectic
[132] J.H. Kang, M.S. Yang, T.K. Kwon, D.W. Kim, C.W. Park, Inhaled deep eutectic solvents, Green Chem. 15 (2013) 2793–2799, https://doi.org/10.1039/
solvent based-nanoemulsion of pirfenidone in idiopathic pulmonary fibrosis, C3GC41067F.
J. Controlled Release. 352 (2022) 570–585, https://doi.org/10.1016/J. [140] S. Sowmiah, V. Srinivasadesikan, M.C. Tseng, Y.H. Chu, On the Chemical
JCONREL.2022.10.045. Stabilities of Ionic Liquids, Molecules 2009, Vol. 14, Pages 3780-3813. 14
[133] N. Guajardo, C.R. Müller, R. Schrebler, C. Carlesi, P. Domínguez De María, Deep (2009) 3780–3813 doi: 10.3390/MOLECULES14093780.
eutectic solvents for organocatalysis, biotransformations, and multistep [141] S.N. Turosung, B. Ghosh, B. Ghosh, Application of ionic liquids in the
organocatalyst/enzyme combinations, ChemCatChem. 8 (2016) 1020–1027, upstream oil industry – a review, Int. J. Petrochem. Res. 1 (2017) 50–60,
https://doi.org/10.1002/CCTC.201501133. https://doi.org/10.18689/IJPR-1000110.
[134] A.P. Abbott, J. Collins, I. Dalrymple, R.C. Harris, R. Mistry, F. Qiu, J. Scheirer, W. [142] L. Benvenutti, A.A.F. Zielinski, S.R.S. Ferreira, Which is the best food emerging
R. Wise, Processing of electric arc furnace dust using deep eutectic solvents, solvent: IL, DES or NADES?, Trends Food Sci Technol. 90 (2019) 133–146,
Aust. J. Chem. 62 (2009) 341–347, https://doi.org/10.1071/CH08476. https://doi.org/10.1016/J.TIFS.2019.06.003.
[135] E. Ali, S. Mulyono, M. Hadj-Kali, Scaling-up liquid-liquid extraction [143] J. Płotka-Wasylka, M. de la Guardia, V. Andruch, M. Vilková, Deep eutectic
experiments with deep eutectic solvents, new developments in biology, solvents vs ionic liquids: similarities and differences, Microchem. J. 159
Biomedical and Chemical Engineering and Material Science, ISBN: 978-1- (2020), https://doi.org/10.1016/J.MICROC.2020.105539.
61804-284-2. [144] Q. Wen, J.X. Chen, Y.L. Tang, J. Wang, Z. Yang, Assessing the toxicity and
[136] D. Rente, M. Cvjetko Bubalo, M. Panić, A. Paiva, B. Caprin, I. Radojčić biodegradability of deep eutectic solvents, Chemosphere. 132 (2015) 63–69,
Redovniković, A.R.C. Duarte, Review of deep eutectic systems from laboratory https://doi.org/10.1016/J.CHEMOSPHERE.2015.02.061.
to industry, taking the application in the cosmetics industry as an example, J [145] M. Hayyan, M.A. Hashim, A. Hayyan, M.A. Al-Saadi, I.M. AlNashef, M.E.S.
Clean Prod. 380 (2022), https://doi.org/10.1016/J.JCLEPRO.2022.135147. Mirghani, O.K. Saheed, Are deep eutectic solvents benign or toxic?,
[137] R. Abro, N. Kiran, S. Ahmed, A. Muhammad, A.S. Jatoi, S.A. Mazari, U. Salma, N. Chemosphere 90 (2013) 2193–2195, https://doi.org/10.1016/J.
v. Plechkova, Extractive desulfurization of fuel oils using deep eutectic CHEMOSPHERE.2012.11.004.
solvents – a comprehensive review, J. Environ. Chem. Eng. 10 (2022), https:// [146] L. Lomba, M.P. Ribate, E. Zaragoza, J. Concha, M.P. Garralaga, D. Errazquin, C.B.
doi.org/10.1016/J.JECE.2022.107369. García, B. Giner, Deep Eutectic Solvents: Are They Safe?, Applied Sciences
[138] C. Li, J. Zhang, Z. Li, J. Yin, Y. Cui, Y. Liu, G. Yang, Extraction desulfurization of 2021, Vol. 11, Page 10061. 11 (2021) 10061 doi: 10.3390/APP112110061.
fuels with ‘metal ions’ based deep eutectic solvents (MDESs), Green Chem. 18
(2016) 3789–3795, https://doi.org/10.1039/C6GC00366D.

11