Supported Ionic Liquids Used as Chromatographic Matrices in Bioseparation—An Overview

Abstract

Liquid chromatography plays a central role in biomanufacturing, and, apart from its use as a preparative purification strategy, either in biopharmaceuticals or in fine chemicals industries, it is also very useful as an analytical tool for monitoring, assessing, and characterizing diverse samples. The present review gives an overview of the progress of the chromatographic supports that have been used in the purification of high-value products (e.g., small molecules, organic compounds, proteins, and nucleic acids). Despite the diversity of currently available chromatographic matrices, the interest in innovative biomolecules emphasizes the need for novel, robust, and more efficient supports and ligands with improved selectivity. Accordingly, ionic liquids (ILs) have been investigated as novel ligands in chromatographic matrices. Given herein is an extensive review regarding the different immobilization strategies of ILs in several types of supports, namely in silica, Sepharose, and polymers. In addition to depicting their synthesis, the main application examples of these supports are also presented. The multiple interactions promoted by ILs are critically discussed concerning the improved selectivity towards target molecules. Overall, the versatility of supported ILs is here considered a critical point to their exploitation as alternatives to the more conventional liquid chromatographic matrices used in bioseparation processes.

Ionic-liquid-based approaches to improve biopharmaceuticals downstream processing and formulation

“…The outstanding properties of ILs in the biomedicine field have spurred a high interest within the scientific community ( Kianfar and Mafi, 2020 ; Curreri et al, 2021 ; Bernardo et al, 2022 ). ILs are organic salts displaying a set of relevant properties, e.g., tailored polarity, non-flammability and non-volatility at ambient conditions, low-vapor or negligible pressure, high thermal and chemical stabilities and high solvation ability, making them attractive for a variety of applications ( Castro et al, 2019 ; Kianfar and Mafi, 2020 ; Jadhav et al, 2021 ).…”

“…ILs are organic salts displaying a set of relevant properties, e.g., tailored polarity, non-flammability and non-volatility at ambient conditions, low-vapor or negligible pressure, high thermal and chemical stabilities and high solvation ability, making them attractive for a variety of applications ( Castro et al, 2019 ; Kianfar and Mafi, 2020 ; Jadhav et al, 2021 ). ILs are considered “designer solvents” since their cations and anions can be carefully selected to provide a variety of compounds with unique physicochemical properties and biological activity ( Castro et al, 2019 ; Curreri et al, 2021 ; Jadhav et al, 2021 ; Bernardo et al, 2022 ). In the biomedical and pharmaceuticals fields, ILs were mostly investigated to develop anti-cancer drugs ( Yen and Chu, 2004 ), antimicrobial compounds ( Pernak et al, 2003 ), and controlled drug release systems ( Jaitely et al, 2008 ), to improve the catalytic efficiency of enzymes and to increase the thermal stability of proteins ( Erbeldinger et al, 2000 ; Baker et al, 2004 ; Kumar et al, 2017 ; Schindl et al, 2019 ), and to act as excipients in synthetic drugs formulation to improve the solubility, permeability, activity, bioavailability, and stability ( Moniruzzaman et al, 2010 ; Pedro et al, 2020 ; Lin et al, 2021 ).…”

“…SILs comprising [C 3 C 1 im]Cl and [N 3114 ]Cl were the best adsorbent materials for the effective and selective isolation of the target compound, with binding capacities of 16.3 and 15.6 μmol g −1 , respectively ( Pereira et al, 2021 ). It is important to highlight that this remarkable applicability of ILs as chromatographic ligands results from ILs diversity in terms of the chemical structures and functional groups, allowing the establishment of a variety of interactions with the target biomolecule, such as hydrophobic and electrostatic interactions, as reviewed by Bento et al (2021) and Bernardo et al (2022) . The potential of using macroporous polymeric supports functionalized with ILs to purify nucleic acids was reported by Neves et al (2020) .…”

“…Regarding IL-based strategies in the downstream processing of biopharmaceuticals, including not only IL-ABS but also SILs, there are three major strengths: i) their versatility and improved/tailored separation performance for different types of biopharmaceuticals from a myriad of sources; ii) the possibility of process integration; iii) and scalability. Due to the outstanding properties presented by ILs, that are transferred to SILs, it is possible to design numerous combinations of ionic components to improve the performance of the envisioned application ( Castro et al, 2019 ; Kianfar and Mafi, 2020 ; Curreri et al, 2021 ; Jadhav et al, 2021 ; Bernardo et al, 2022 ). However, a proper selection of the cation and anion should consider the envisaged physicochemical properties of the final formulation, the formulation biocompatibility, and the biological activity of the biomolecules.…”

Progress in the applications of biocompatible ionic liquids: renewable commodity production, catalytic and pharmaceutical approaches – a review

“…Recent reviews have detailed applications of ILs in drug delivery, 17 biomedical fields, 18 compound recovery, 19 gas absorption, 20 nanoparticle synthesis and modification, 21 photonic materials, 22 lubricants, 23 metal deposition, 24 fuel cells, 25 and protein purification. 26 Fig. 2 schematically displays these applications.…”