Functionalized Ionic Liquids for Biologics Purification, Drug Formulation, and Greenhouse F-gases Reclamation
João M. M. ARAÚJO1, Ana B. PEREIRO1, Julio E. SOSA1, Joana C. BASTOS1, Sara F. CARVALHO1
1LAQV, REQUIMTE, Departamento de Química, NOVA School of Science and Technology, NOVA University Lisbon, Caparica, Portugal
Sustainability challenges have advanced the research in unconventional solvents, separation techniques and drug development. A thriving research field is the use of ionic liquids (ILs) in biologics purification, pharmaceutical applications, and greenhouse gases (GHG) absorption.
ILs have emerged as one of the most attractive solutes for aqueous biphasic systems (ABS), with outstanding performance in the extraction of targeted biologics. Recently, we proposed a benign cholimium-based ILs route for ABS, disclosed novel ABS composed of fluorinated ILs (FILs) and demonstrated that FILs reduce the impact of the addition of water upon the IL’s H-bond acceptance ability. Herein, bioprivileged ILs were implemented to develop more versatile and amenable to be tuned ABS. To understand their potential as extractive platforms of biologics, the ternary phase diagrams, the polarity parameters of the coexisting phases, and the partition coefficients, stability and activity of the targeted biologics were determined. Finally, to highlight the interactions between model biologics and the ABS-phase components and better understand the interactions ruling the partition, UV-VIS spectrophotometry, intrinsic fluorescence, nano-differential scanning calorimetry, circular dichroism and microscale thermophoresis measurements were attained. Additionally, the standard batch (macroscale ABS) was compared with flow-through processes (microfluidic setups).
Likewise, the development of ILs that are themselves active pharmaceutical ingredients (APIs) are advantageous building-up platforms, granting the potential to modulate the water solubility and the membrane permeation properties of an API. Also, the formulation of FILs-based drug delivering systems for therapeutic proteins open new avenues for the application of functionalized ILs in the pharmaceutical field. The presented results clearly demonstrate that, within the green chemistry framework, a bioprivileged IL platform constitutes a viable alternative for enhancing (i) the bioavailability and diverse pharmacological properties of commonly available over-the-counter APIs, and (ii) the delivery and stabilization of valuable therapeutic proteins.
Also, the environmental impact of fluorinated gases (F-gases) emissions, as well as the market value of some F-gases, are fostering the development of technologies to reclaim and reuse F-gases. F-gases are commonly used in refrigerant systems and other industrial applications, implemented as substitutes for ozone-depleting substances (e.g., CFCs), they are powerful greenhouse gases (GHG) with global warming potential (GWP) up to 20 000 times greater than CO2. In the EU their emissions have increased up to 60% since 1990. EU regulation targets to cut the emissions of F-gases by 2/3 up 2030, compared to the levels of 2014. An example for reclamation and reuse is R-32, from the EU phase-down of R-410A (one of the most used refrigerants; R-32/R-125, 50/50 wt.%), driving the switch from R-410A (GWP 2088) to R-32 (GWP 675; neat or blends with lower GWP), that allows 68% CO2 equivalent reductions to the use of lower GWP refrigerant. Herein, FILs (also FIL-based eutectic systems) were investigated as promising candidates for the absorption and selective separation of three of the most used F-gases in domestic refrigeration (R-32, R-125, and R-134a). Further, ILs with high F-gas uptake capacity and selectivity were supported on silica and their potential as media for selective F-gas sorption was studied.
ILs have emerged as one of the most attractive solutes for aqueous biphasic systems (ABS), with outstanding performance in the extraction of targeted biologics. Recently, we proposed a benign cholimium-based ILs route for ABS, disclosed novel ABS composed of fluorinated ILs (FILs) and demonstrated that FILs reduce the impact of the addition of water upon the IL’s H-bond acceptance ability. Herein, bioprivileged ILs were implemented to develop more versatile and amenable to be tuned ABS. To understand their potential as extractive platforms of biologics, the ternary phase diagrams, the polarity parameters of the coexisting phases, and the partition coefficients, stability and activity of the targeted biologics were determined. Finally, to highlight the interactions between model biologics and the ABS-phase components and better understand the interactions ruling the partition, UV-VIS spectrophotometry, intrinsic fluorescence, nano-differential scanning calorimetry, circular dichroism and microscale thermophoresis measurements were attained. Additionally, the standard batch (macroscale ABS) was compared with flow-through processes (microfluidic setups).
Likewise, the development of ILs that are themselves active pharmaceutical ingredients (APIs) are advantageous building-up platforms, granting the potential to modulate the water solubility and the membrane permeation properties of an API. Also, the formulation of FILs-based drug delivering systems for therapeutic proteins open new avenues for the application of functionalized ILs in the pharmaceutical field. The presented results clearly demonstrate that, within the green chemistry framework, a bioprivileged IL platform constitutes a viable alternative for enhancing (i) the bioavailability and diverse pharmacological properties of commonly available over-the-counter APIs, and (ii) the delivery and stabilization of valuable therapeutic proteins.
Also, the environmental impact of fluorinated gases (F-gases) emissions, as well as the market value of some F-gases, are fostering the development of technologies to reclaim and reuse F-gases. F-gases are commonly used in refrigerant systems and other industrial applications, implemented as substitutes for ozone-depleting substances (e.g., CFCs), they are powerful greenhouse gases (GHG) with global warming potential (GWP) up to 20 000 times greater than CO2. In the EU their emissions have increased up to 60% since 1990. EU regulation targets to cut the emissions of F-gases by 2/3 up 2030, compared to the levels of 2014. An example for reclamation and reuse is R-32, from the EU phase-down of R-410A (one of the most used refrigerants; R-32/R-125, 50/50 wt.%), driving the switch from R-410A (GWP 2088) to R-32 (GWP 675; neat or blends with lower GWP), that allows 68% CO2 equivalent reductions to the use of lower GWP refrigerant. Herein, FILs (also FIL-based eutectic systems) were investigated as promising candidates for the absorption and selective separation of three of the most used F-gases in domestic refrigeration (R-32, R-125, and R-134a). Further, ILs with high F-gas uptake capacity and selectivity were supported on silica and their potential as media for selective F-gas sorption was studied.