159
ionic liquid development, it has been known that the once-popular [PF 6 ]
−
anion
hydrolyzed in the presence of water generating HF, and other perfluorinated anions,
represented by [NTf 2 ]
−
, had prohibitively high cost for most applications – definitely for those where deep eutectic solvents would be replacing conventional solvents (George et al. 2015). In consequence, the strategies used to generate
hydrophobic deep eutectic solvents have relied on increasing lipophilicity (hydrophobicity) by introduction of long hydrocarbon chains. The prominent ionic liquid
example of this is the tetraalkylphosphonium ionic liquid trihexyl(tetradecyl)phosphonium chloride, [P 6 6 6 14 ]Cl. It features a very hydrophilic in nature chlorideanion,
but the addition of long alkyl chains to the quaternary cation center enhances hydrophobicity. Unfortunately, this came at the price of increasing viscosity of the produced liquids, which could be detrimental to mass transport in extraction systems
(Souza et al. 2019).
Another approach to use non-fluorinated ionic liquids for extractions from aqueous media was based on ionic liquids being effectively salts, therefore prone to
salting-out effect. Generating biphasic liquid mixtures between hydrophilic ionic
liquids and water was first described in 2003 (Gutowski et al. 2003) where the formation of ionic liquid-aqueous biphasic systems induced by the addition of kosmotropic agents such as K 3 PO 4 was demonstrated. The more hydrophobic ion pair,
typically the organic cation from the ionic liquid and the anion that sits lower in the
Hofmeister series (Hyde et al. 2017), is salted-out, forming a biphasic mixture in
which both phases contain water and a salt. Aqueous biphasic system formation has
been demonstrated across a range of ionic liquids and kosmotropic agents (Freire
et al. 2012), allowing “soft” partitioning and extraction of biomolecules including
proteins (Pei et al. 2009) and pharmaceuticals (McQueen and Lai 2019; Oppermann
et al. 2011). It has been reported that this approach offers the advantage of mild
operating conditions, necessary to maintain protein structure and functionality without inducing denaturization (Shukla et al. 2018). Further benefit came from tunability of these ionic liquid systems, where the effectiveness would be manipulated by
changing the phase-forming components (ions) and concentrations. However, in
ionic liquid aqueous biphasic system media, both phases are water-rich and hydrophilic, which poses an intrinsic limitation, restricting their applicability to hydrophilic substrates.
Shortcomings associated with each type of hydrophobic ionic liquid system
drove the development of hydrophobic deep eutectic solvents, targeted at benign,
inexpensive, and preferably low viscosity media.
5.2.2 Hydrophobicity Through Organic Salts
with Hydrophobic Hydrogen Bond Donors
In 2015, Kroon and co-workers (van Osch et al. 2015) described the first family of
hydrophobic deep eutectic solvents containing quaternary ammonium salts,
[N 4444 ]Cl and [N 8888 ]Cl, where [N nnnn ]
+
is a tetraalkylammonium cation with n long
5 Hydrophobic Deep Eutectic Solvents
ionic liquid development, it has been known that the once-popular [PF 6 ]
−
anion
hydrolyzed in the presence of water generating HF, and other perfluorinated anions,
represented by [NTf 2 ]
−
, had prohibitively high cost for most applications – definitely for those where deep eutectic solvents would be replacing conventional solvents (George et al. 2015). In consequence, the strategies used to generate
hydrophobic deep eutectic solvents have relied on increasing lipophilicity (hydrophobicity) by introduction of long hydrocarbon chains. The prominent ionic liquid
example of this is the tetraalkylphosphonium ionic liquid trihexyl(tetradecyl)phosphonium chloride, [P 6 6 6 14 ]Cl. It features a very hydrophilic in nature chlorideanion,
but the addition of long alkyl chains to the quaternary cation center enhances hydrophobicity. Unfortunately, this came at the price of increasing viscosity of the produced liquids, which could be detrimental to mass transport in extraction systems
(Souza et al. 2019).
Another approach to use non-fluorinated ionic liquids for extractions from aqueous media was based on ionic liquids being effectively salts, therefore prone to
salting-out effect. Generating biphasic liquid mixtures between hydrophilic ionic
liquids and water was first described in 2003 (Gutowski et al. 2003) where the formation of ionic liquid-aqueous biphasic systems induced by the addition of kosmotropic agents such as K 3 PO 4 was demonstrated. The more hydrophobic ion pair,
typically the organic cation from the ionic liquid and the anion that sits lower in the
Hofmeister series (Hyde et al. 2017), is salted-out, forming a biphasic mixture in
which both phases contain water and a salt. Aqueous biphasic system formation has
been demonstrated across a range of ionic liquids and kosmotropic agents (Freire
et al. 2012), allowing “soft” partitioning and extraction of biomolecules including
proteins (Pei et al. 2009) and pharmaceuticals (McQueen and Lai 2019; Oppermann
et al. 2011). It has been reported that this approach offers the advantage of mild
operating conditions, necessary to maintain protein structure and functionality without inducing denaturization (Shukla et al. 2018). Further benefit came from tunability of these ionic liquid systems, where the effectiveness would be manipulated by
changing the phase-forming components (ions) and concentrations. However, in
ionic liquid aqueous biphasic system media, both phases are water-rich and hydrophilic, which poses an intrinsic limitation, restricting their applicability to hydrophilic substrates.
Shortcomings associated with each type of hydrophobic ionic liquid system
drove the development of hydrophobic deep eutectic solvents, targeted at benign,
inexpensive, and preferably low viscosity media.
5.2.2 Hydrophobicity Through Organic Salts
with Hydrophobic Hydrogen Bond Donors
In 2015, Kroon and co-workers (van Osch et al. 2015) described the first family of
hydrophobic deep eutectic solvents containing quaternary ammonium salts,
[N 4444 ]Cl and [N 8888 ]Cl, where [N nnnn ]
+
is a tetraalkylammonium cation with n long
5 Hydrophobic Deep Eutectic Solvents