Acute Aquatic Toxicity and Biodegradability of Fluorinated Ionic Liquids

Abstract

Several novel fluorinated ionic liquids (FILs), fully miscible with water and with excellent surfactant behavior, have been studied for pharmacological applications. The use of these novel FILs as drug delivery systems can improve the bioavailability, stability and efficacy of therapeutic proteins. An initial screening of toxicity in four different human cell lines indicated that some of the FILs possess low cytotoxicity. An environmental hazard assessment of these compounds, in the context of Green Pharmacy, is necessary before a pharmaceutical application takes place. In this work, ecotoxicity tests have been performed in aquatic species with different levels of biological organization (Vibrio fischeri, Daphnia magna and Lemna minor) to evaluate intrinsic hazard that these FILs might pose after being released to the aquatic environment from the human body or from industrial processes. Additionally, the biodegradability of these compounds has been evaluated using microorganisms from wastewater treatment plants.

Tailor-Made Fluorinated Ionic Liquids for Protein Delivery

“…These toxic effects were much less pronounced or null in perfluorobutanesulfonate substituents, which have also been proved to not induce an oxidative damage in HepG2 cells and have a very low toxicity to mammalian cells, birds, algae, invertebrates, fish, and sewage organisms [ 26 , 27 , 31 ]. This profile is in line with the results of cytotoxicity and ecotoxicity studies performed with FILs based on the perfluorobutanesulfonate anion [ 17 , 23 , 24 ]. The resistance of these compounds to degradation, either by hydrolysis or photolysis, is a concern limited by their reduced bioaccumulation (bioconcentration factor <1) and low toxicity [ 26 , 27 ].…”

“…This family combines several and unique properties inherent to traditional fluorinated surfactants and to ionic liquids, such as chemical and biological inertness, low vapor pressure, high thermal and chemical stability, low surface tension, and ability to form stable self-assembled structures [ 17 , 18 , 19 , 20 , 21 , 22 ]. By playing with the cation and anion core, as well as changing the length of the alkyl and fluorinated chains, it is possible to obtain FILs with a complete water miscibility, with hydrophilic behavior, low toxicity in different human cells (intestinal (Caco-2), hepatic (HepG2), endothelial (EA.hy926), and skin (HaCaT)), and almost negligible ecotoxicity towards different aquatic microorganisms [ 17 , 20 , 22 , 23 , 24 ]. These characteristics are in clear contrast to the persistent, bioaccumulative, and toxic nature of several traditional fluorinated compounds [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

“…Recently, FILs based on imidazolium, pyridinium, and cholinium cations, conjugated with the perfluorobutanesulfonate anion, were tested for the encapsulation of lysozyme [ 32 ]. These FILs were selected based on a previous screening on their thermophysical, surfactant, cytotoxic, and ecotoxic properties [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. In this previous work, it was proved that the activity, stability, and secondary structure of lysozyme was not affected up to concentrations three times higher than the first critical aggregation concentration of the selected FILs [ 32 ].…”

Unveiling the Influence of Non-Toxic Fluorinated Ionic Liquids Aqueous Solutions in the Encapsulation and Stability of Lysozyme

“…FILs are characterized by low surface tension, high surfactant power, elevated surface activity with a highly amphiphilic character, and consequently a high aggregation behavior [20][21][22][23]. The possibility to design FILs that are completely miscible in water [21][22][23], with negligible cytotoxicity and ecotoxicity [24,25], and maintaining all the characteristics mentioned above, makes them even more biocompatible. FILs in a water-rich phase show smaller CACs than the conventional hydrogenated and fluorinated surfactants, which proves their rich aggregation behavior [21][22][23].…”

Functionalization of fluorinated ionic liquids: A combined experimental-theoretical study

“…The growing interest in task-specific ILs has empowered their functionalization through the introduction of functional groups in their structures, such as polar oxygenated features as hydroxyl, ester or ether groups [3]. The addition of polar groups can drastically reduce their cytotoxicity and ecotoxicity, as well as enhance their biodegradability, increasing their sustainability [4][5][6][7]. Several works showed that the introduction of a hydroxyl group in the cationic alkyl chain of imidazoliumbased ILs decreases the thermal stability and self-aggregation behavior while increasing the viscosity, density, polarity and hydrophilicity [3,[8][9][10].…”