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Nucleic Acids
As a result of their specific base-pairing properties, nucleic acids have many applications in biomedical science, both in therapeutic and diagnostic scenarios.
However, nucleic acid structures are not extremely stable in aqueous solution.
Tateishi-Karimata and Sugimoto have reviewed work in which nucleic acids have
been dissolved in a hydrated ionic liquid composed of choline dihydrogen phosphate and a deep eutectic solvent made of choline chloride and urea (TateishiKarimata and Sugimoto 2014). They reported differences in base-pairing compared
with sodium chloride solution and a stabilization of triplexes in ionic liquid and
quadruplexes in deep eutectic solvent. Since these structures are used in a number
of devices in nanomedicine, this is an important result. Gállego et al. studied the
formation of deoxyribonucleic acid nanostructures in deep eutectic solvents using
atomic force microscopy, mobility on agarose gels, and circular dichroism (Gállego
et al. 2015). They observed that a deep eutectic solvent composed of choline chloride and glycerol in a 1:4 ratio allowed folding into complex structures that could be
transferred into aqueous solution.
Proteins
Ionic liquids and deep eutectic solvents are also attracting much interest as alternative solvents for proteins, for both fundamental studies and applications in medicine
and biotechnology. The three-dimensional structure of protein molecules is essential for their function but is only marginally stable, being held together by a large
number of weak interactions: hydrogen bonds, electrostatic interactions, van de
Waals forces, and hydrophobic interactions. It follows that the solvent has a profound influence on protein conformation and activity. Given that, as discussed by
Choi et al. many components of deep eutectic solvents are found in living cells and
may be involved in survival of stress conditions, they could be considered as a
potential alternative to aqueous solvents for proteins (Choi et al. 2011). This hypothesis was investigated by Sanchez-Fernandez et al. with respect to two model proteins: lysozyme and bovine serum albumin (BSA) (Sanchez-Fernandez et al. 2017).
Two main physiochemical techniques were used to probe the protein structure: circular dichroism and small-angle neutron scattering (SANS). In particular, circular
dichroism in the far-ultraviolet (far-UV) region gives an indication of the secondary
structure of the protein and allows the proportion of α-helix, β-sheet, and random
coil to be estimated. On the other hand, the near-UV region gives information on the
tertiary structure.
The solubility of bovine serum albumin, bovine pancreatic α-chymotrypsinogen,
bacteria subtilisin, and hen egg white lysozyme in a panel of low transition
temperature mixtures was tested by Su and Klibanov (Su and Klibanov 2015). The
solubilities depended on the DES composition and the structures of the proteins
themselves and in some cases the solubility approached that observed in water. The
enzymatic activity of lysozyme was tested in a number of mixtures and found to be
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations
Nucleic Acids
As a result of their specific base-pairing properties, nucleic acids have many applications in biomedical science, both in therapeutic and diagnostic scenarios.
However, nucleic acid structures are not extremely stable in aqueous solution.
Tateishi-Karimata and Sugimoto have reviewed work in which nucleic acids have
been dissolved in a hydrated ionic liquid composed of choline dihydrogen phosphate and a deep eutectic solvent made of choline chloride and urea (TateishiKarimata and Sugimoto 2014). They reported differences in base-pairing compared
with sodium chloride solution and a stabilization of triplexes in ionic liquid and
quadruplexes in deep eutectic solvent. Since these structures are used in a number
of devices in nanomedicine, this is an important result. Gállego et al. studied the
formation of deoxyribonucleic acid nanostructures in deep eutectic solvents using
atomic force microscopy, mobility on agarose gels, and circular dichroism (Gállego
et al. 2015). They observed that a deep eutectic solvent composed of choline chloride and glycerol in a 1:4 ratio allowed folding into complex structures that could be
transferred into aqueous solution.
Proteins
Ionic liquids and deep eutectic solvents are also attracting much interest as alternative solvents for proteins, for both fundamental studies and applications in medicine
and biotechnology. The three-dimensional structure of protein molecules is essential for their function but is only marginally stable, being held together by a large
number of weak interactions: hydrogen bonds, electrostatic interactions, van de
Waals forces, and hydrophobic interactions. It follows that the solvent has a profound influence on protein conformation and activity. Given that, as discussed by
Choi et al. many components of deep eutectic solvents are found in living cells and
may be involved in survival of stress conditions, they could be considered as a
potential alternative to aqueous solvents for proteins (Choi et al. 2011). This hypothesis was investigated by Sanchez-Fernandez et al. with respect to two model proteins: lysozyme and bovine serum albumin (BSA) (Sanchez-Fernandez et al. 2017).
Two main physiochemical techniques were used to probe the protein structure: circular dichroism and small-angle neutron scattering (SANS). In particular, circular
dichroism in the far-ultraviolet (far-UV) region gives an indication of the secondary
structure of the protein and allows the proportion of α-helix, β-sheet, and random
coil to be estimated. On the other hand, the near-UV region gives information on the
tertiary structure.
The solubility of bovine serum albumin, bovine pancreatic α-chymotrypsinogen,
bacteria subtilisin, and hen egg white lysozyme in a panel of low transition
temperature mixtures was tested by Su and Klibanov (Su and Klibanov 2015). The
solubilities depended on the DES composition and the structures of the proteins
themselves and in some cases the solubility approached that observed in water. The
enzymatic activity of lysozyme was tested in a number of mixtures and found to be
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations