## 2 Topical Research Areas Related to Ionic Liquids and the Contribution of Spiroammonium Compounds
### Green Chemistry and the IL Concepts
#### 2.2.4 Creation of the Low-Toxic Ionic Liquids and the Variants of Their Use
Low toxicity and low environmental persistence, combined with their previously demonstrated excellent solvent properties for the selective extraction of lignin, indicate that ILs of this type are highly suitable candidates for large-scale applications. The [PERSON] group studied the dissolving ability of N-acetyl amino acids and N-alkylolinium-based ILs when used as co-solvents (0.2-1 mol%) with water in relation to poorly water-soluble drugs, namely sodium diclofenac and paracetamol. In the first case, 20 new biocompatible ionic liquids based on N-alkylolinium cations and N-acetyl amino acids anions were prepared [85]. In the second case, the number of ILs was 12; N-alkylolinium cations were taken as cations and sulfonate and succinyl alanine anions as anions [86]. It turned out that these new ILs were able to increase the water solubility of drugs up to four times in pure water and can be considered potential candidates for drug delivery applications. The transdermal delivery of sparingly soluble drugs is challenging due to the need for a drug carrier. Among the fluid systems for transdermal delivery, attention has been focused on microemulsions (MEs) [87]. The prepared MEs were composed of a hydrophilic IL (choline formate [Ch][For], choline lactate [Ch][Lac], and choline propionate [Ch][Pro]), used as the non-aqueous polar phase, and a surface-active IL (choline oleate [Ch][Ole]) was used as the surfactant in combination with sorbitan laurate in a continuous oil phase [88]. The selected ILs were all biologically active ions. An in vitro drug permeation study using pig skin showed the significantly enhanced permeation of acyclovir when using a ME. The maximum solubility of ACV in the ILs was 203, 208, and 278 mg/mL for [Ch][For], [Ch][Lac], and [Ch][Pro], respectively, significantly higher when compared with Milli-Q (0.41 mg/mL). Therefore, three [Ch][CA] ILs consisting of choline as the cation and a long-chain (C18) fatty acid as the anion [Ch][Ole] are considered to be safe and biocompatible for further studies relating to transdermal delivery systems. Cholinium amino acid-based ILs have found applications in an extremely important industry. Chemically recycling poly(ethylene terephthalate) (PET) to monomers is a key strategy in tackling issues arising from persistent plastic pollution in the environment. PET, which is among the most used polymers in modern society, was converted to bishydroxyethyl 1 erephthalate (BHET) using ILs based on cholinium salts, including amino acid anions: glycinate ([Ch][Gly]), lysine ([Ch][Lys]), and alanine ([Ch][Ala]). The optimal reaction conditions under which a conversion of 85% and a yield of 51% were achieved were obtained via the use of [Ch][Gly] as a catalyst at 150 \({}^{\circ}\)C for 6 h [89]. The diversity in structure, the variety in chirality, and the large occurrence of carbohydrates in nature have led to the development of carbohydrate-based ILs, also known as CHILs. They are expected to overcome limitations in aquatic ecotoxicity and poor biodegradability [90]. A systematic study on the influence of different ether groups on the secondary OH groups as well as different configurations on physical properties such as melting point, thermostability, and especially the influence on cell toxicity has been carried out on a series of carbohydrate pyridinium salts based on \(\alpha\)- and \(\beta\)-methyl-, \(\beta\)-allyl-, and \(\beta\)-phenyl D-glucopyranose, as well as four 1-deoxypentoses with anions (trifluoromethylenesulfonate, toyslate, and mesylate) [91]. The method of introducing a thiophenyl group in the anomeric center followed by reduction with tributulin hydride was established based on peracetylated D-ribose as the starting compound. As a result of a series of successive stages, a reproducible strategy for the synthesis of new carbohydrate-based pyridinium salts was developed.