Ionic-Liquid-Mediated Extraction and Separation Processes for Bioactive Compounds: Past, Present, and Future Trends

Abstract

Ionic liquids (ILs) have been proposed as promising media for the extraction and separation of bioactive compounds from the most diverse origins. This critical review offers a compilation on the main results achieved by the use of ionic-liquid-based processes in the extraction and separation/purification of a large range of bioactive compounds (including small organic extractable compounds from biomass, lipids, and other hydrophobic compounds, proteins, amino acids, nucleic acids, and pharmaceuticals). ILs have been studied as solvents, cosolvents, cosurfactants, electrolytes, and adjuvants, as well as used in the creation of IL-supported materials for separation purposes. The IL-based processes hitherto reported, such as IL-based solid-liquid extractions, IL-based liquid-liquid extractions, IL-modified materials, and IL-based crystallization approaches, are here reviewed and compared in terms of extraction and separation performance. The key accomplishments and future challenges to the field are discussed, with particular emphasis on the major lacunas found within the IL community dedicated to separation processes and by suggesting some steps to overcome the current limitations.

Figure 1

Distribution of the works dealing with each IL-based technique for the extraction and separation of small organic extractable compounds from biomass. The radial graphs display the number of scientific works addressing distinct families of natural compounds.

Figure 2

Chemical structures of small organic compounds extracted and separated from biomass using IL-based techniques.

Figure 3

ILs used for the extraction and separation of small organic extractable compounds from biomass as a function of cation–anion combinations. The usage incidence (number of articles) is represented by the circles’ size, which proportionally increases as follows: [0–5] < [5–10] < [10–15] < [15–30] < [30–40].

Figure 4

Schematic diagrams of integrated processes based on ILs comprising the extraction and separation of small organic extractable compounds from biomass and further IL recovery and reuse.^,,

Figure 5

Distribution of the works dealing with each IL-based technique for the extraction and separation of lipids and related compounds. The radial graphs display the number of scientific works addressing distinct classes of lipids and related compounds.

Figure 6

Chemical structures of lipids and related compounds extracted and separated with IL-based separation techniques.

Figure 7

ILs used for the extraction and separation of lipids and related compounds as a function of cation–anion combinations. The usage incidence (number of articles) is represented by the size of the circles, which proportionally increases as follows: [0–3] < [3–6] < [6–9] < [9–12] < [12–20].

Figure 8

Schematic diagrams of integrated processes based on ILs comprising the extraction and purification of lipids and related compounds.^,

Figure 9

Distribution of the works dealing with each IL-based technique for the extraction and separation of amino acids. The radial graphs display the number of scientific works addressing distinct types of amino acids.

Figure 10

Chemical structures, names, and abbreviations of all amino acids extracted and separated with IL-based techniques.

Figure 11

ILs used for the extraction and separation of amino acids as a function of cation–anion combinations. The usage incidence (number of articles) is represented by the size of the circles, which proportionally increases as follows: [0–2] < [2–4] < [4–6] < [6–8] < [8–9].

Figure 12

Schematic diagram of integrated processes based on IL-based ABS comprising the extraction and purification of amino acids from complex mixtures.^,

Figure 13

Schematic diagram of an integrated process on the extraction and recovery of amino acids using IL-based LLE, with a pH-aided back-extraction step.

Figure 14

Schematic representation of IL-based TPP processes for the chiral resolution of racemic mixtures of amino acids.

Figure 15

Schematic representation of IL-based SPE processes for the selective separation of enantiomeric mixtures of amino acids.

Figure 16

Distribution of the works dealing with each IL-based technique for the extraction and separation of proteins. The radial graphs display the number of scientific works which have addressed distinct types of proteins.

Figure 17

ILs used for the extraction and separation of proteins as a function of cation–anion combinations. The usage incidence (number of articles) is represented by the size of the circles, which increases proportionally as follows: [0–3] < [3–6] < [6–9] < [9–19].

Figure 18

Schematic representation of an integrated process for the recovery of proteins, comprising the production and separation/purification steps, as well as the recycling of the phase-forming components of IL-based ABS. (A) Process highlighting the recovery of the target protein by dialysis. (B) Process including a thermoseparating polymer that facilitates the recycling and reuse of the ABS phase forming agents.

Figure 19

Schematic representation of the integrated process for the recovery of proteins, comprising their production, separation/purification, recovery, and recycling of the phase-forming components based on the use of hydrophobic ILs for LLE. (A) Process with the recovery of the target protein by back-extraction and recycling of the IL. (B) Process including a thermoseparating polymer that facilitates the recycling and reuse of the phase-forming agents.

Figure 20

Schematic representation of the integrated process for the recovery of LF from whey based on an IL-based TPP strategy and direct recycling and reuse of the phases.

Figure 21

Schematic representation of the recovery of proteins from complex mixtures using surfactant-based systems: (A) microemulsion system comprising the pretreatment of the human samples, separation/purification of the target protein, and a back-extraction step and (B) IL-based AMBS.^,

Figure 22

Schematic representation of an integrated process for the recovery of proteins using IL-MNPs, including the recycling and reuse of the material.

Figure 23

Distribution of the works dealing with each IL-based technique for the extraction and separation of nucleic acids. The radial graphs display the number of scientific works addressing DNA and RNA.

Figure 24

ILs used for the separation and purification of nucleic acids as a function of cation–anion combinations. The usage incidence (number of articles) is represented by the size of the circles, which proportionally increases as follows: 1 < 2 < 3.

Figure 25

Distribution of the works dealing with each IL-based technique for the extraction and separation of pharmaceuticals. The radial graphs display the number of scientific works addressing distinct types of pharmaceuticals.

Figure 26

Chemical structures of the pharmaceuticals extracted and separated with IL-based separation processes.

Figure 27

ILs used for the separation and purification of pharmaceuticals as a function of cation–anion combinations. The usage incidence (number of articles) is represented by the size of the circles, which proportionally increases as follows: [0–2] < [2–4] < [4–6] < [6–9].

Figure 28

Schematic representation of the integrated process comprising the production, separation/purification, recovery of the target molecule, and recycling of solvents in two-phase LLE comprising ILs. A and B correspond to processes where an induced precipitation with CO₂ and back-extraction^, approaches were used to recover the pharmaceuticals, while C represents the process of purification of an intermediate of aliskiren synthesis.

Figure 29

Schematic representation of integrated processes for the recovery of drugs, comprising the production, separation/purification of the drug and contaminants/excipients, isolation of the drug, and recycling of the phase-forming components in IL-based ABS. (A) Process with ABS with both separation/purification and back-extraction steps, (B) process where both hydrophilic and hydrophobic ILs are used for the separation/purification and isolation of target pharmaceuticals, and (C) process for the valorization of pharmaceutical wastes using aqueous solutions of ILs.

Figure 30

Schematic representation of the integrated processes proposed, comprising production, extraction, and purification through crystallization using (A) antisolvents^,− or (B) cooling crystallization^,, and the recycling of the IL.