**2. Ionic Liquids**

Regarding the history of ILs, and events that are responsible for their presence in many fields of science, it is first of all necessary to define the criteria used in the presentation of this subject. Considering the period of their greatest popularity, that is, the last two decades, we can accept the work of scientists who in their publications focused primarily on modifications of compounds in order to obtain the desired properties and identify their applications. However, to acquire information about the discovery of compounds that were ILs, although no one was aware of this and such a definition was not used, we should return to the mid 19th century. At that time, a by-product known as "red oil" was obtained in the Friedel-Crafts reaction. As shown later, this was the first recorded IL [33]. In the following years, Gabriel and Warner also made an important contribution to the development of ILs. In 1888, for the first time, they synthesized ethanol-ammonium nitrate [34]. Although all previous events were very important, the synthesis of ethylammonium nitrate by Walden in 1914 has most often appeared in publications in the context of the discovery of ILs [35]. Of course, it should be mentioned that in the case of ILs, as in all grea<sup>t</sup> discoveries, there are opinions that although Walden synthesized the compounds, he could not use them in practice and his success is over-emphasized [36]. Nevertheless, it was undoubtedly an important stage in the development of ILs. During the following years, there were further syntheses of the compounds and attempts to use them, among others by Yoke and his colleagues [37] and Koch and co-workers [38]. However, in more modern times, with the current compounds that are used in research, it is necessary to focus on analytical methods and

extraction techniques. Considering the application of ILs, Pool's research should be mentioned, in which, using current knowledge, ILs were used in GC as stationary phases [39]. The results of this study prompted the beginning of their further development in this field and became the inspiration for subsequent publications. The 1980s were also important due to the synthesis of ILs based on the imidazolium cation, which are currently widely used in laboratories [40]. This event was important because the existing compounds of ILs had significant limitations in their application, while the imidazolium group provided new opportunities for researchers. Following the trend, subsequent years of research into the use of ILs increased knowledge about them, and consequently led to the introduction of some standards in this area. At the turn of the 20th century, ILs began to function under the name Task-specific Ionic Liquids (TSILs) [41] and companies marketing the first commercially available ILs appeared [42]. Increased access and the positive opinion of the scientific community prompted attempts to apply them to novel projects. In 1998, for the first time, ILs were used as extractants for LLE [43], and in 2005, they were used to coat SPME fibers [44]. Recent years have seen a period of their participation in advanced research, but this will be discussed in detail in subsequent sections. However, it should be highlighted that the most important factor responsible for the rich and long history of ILs is their specific structures, illustrated in Figure 2, which provide the enormous possibilities of these compounds. The cation-anion combinations, described in most definitions, create many possibilities for structure modification, and can thus change the properties of the designed compounds. The cations may have one or more nitrogen, sulfur, phosphorus or oxygen atom in the structure, described as ammonium, sulfonium, phosphonium or oxonium cations, respectively, but in most cases, they are large organic aromatic moieties: pyridinium, piperidinium and the most widely used imidazolium cations. In turn, anions are much smaller and can be both organic and inorganic. In research, tetrafluoroborate ([BF4]), hexafluorophosphate ([PF6]) and halogen anions, and many other compositions appear.

**Figure 2.** Examples of popular anions and cations of ILs used in analytical methods.

Besides the selection of the cation and anion, an important aspect that a ffects further results is the substituents on the cation, and especially the alkyl chain, the length, branching and position of which have a huge influence on applications of ILs [45]. To fully understand the unique properties of an IL, it is also necessary to pay attention to Coulombic interactions occurring in the molecules, dipole-dipole interactions, Van der Waals forces and hydrogen bonds [46]. It is estimated that the number of available combinations may allow up to 1018 di fferent ILs to be obtained [47]. The di fferences in the size of the cation and anion, the asymmetry in the structure as well as the mentioned interactions mean that they have no regular, crystalline structure and the delocalization of the cation and anion composition is very possible. Thanks to this, their melting temperature does not exceed 100 ◦C, and in many cases it is close to room temperature (RTIL) [48]. This feature distinguishes ILs from typical inorganic salts, which, due to the much stronger Coulombic and hydrogen interactions, have a melting point of even above 400 ◦C. Equally as interesting as their melting point is the viscosity of ILs, which is at a higher level than that of organic solvent. Knowledge of these parameters is necessary when an IL is used in separation and detection techniques. The electrostatic interactions in alkyl chain cations have an enormous impact on viscosity. Coulomb forces, H-bonding and π-π dipole lead to increases in the flow resistance, and additionally, the presence of van der Waals interactions between the cation and anion, depending on the size of the molecule, also causes interactions in the same direction. This property can be modified by changing the temperature or adding an organic solvent [49–52]. Viscosity also influences another property, namely electrochemical conductivity. Thanks to their ionic structure, ILs can carry a charge, but this possibility is not the same for all compounds. When the flow resistance increases, conductivity becomes more di fficult. However, increasing the temperature and mixing with organic solvents improves the results. Furthermore, the size of molecules can hinder access to the charge, so it is necessary to select the appropriate cations, which are large ions [53]. ILs are widely used in sample preparation techniques because they can be created as both hydrophilic and hydrophobic compounds that mix with water, and/or organic solvents [54]. It has been proven that the change in the position of the methyl group in the cation determines the change in the acid-base character, and therefore the C2 position is strongly acidic, which a ffects the interaction with other compounds [55]. The thermal stability of ILs is also important. As studies have shown, the majority of popular ILs are stable even above 300 ◦C, which is of grea<sup>t</sup> importance during GC analysis, where a high temperature is required. As with previous properties, the size and type of ions, pKa, chain length and electrostatic interactions determine the stability of individual ILs. Halogen anions, probably due to their nucleophilic character, have less stability than other inorganic anions, while the most stable is bis(trifluoromethanesulfonyl)imide ([Nf2T]). In turn, among the cations, the stability of pyrrolidinium and piperidinium is lower than that of imidazolium, regardless of the anion used [56–58]. An interesting property is also the insignificant vapor pressure which occurs at elevated temperatures. Zaitaus et al. confirmed the influence of the structure of ILs on vapor pressure. In their study, the absolute vapor pressures for a series of [CnMIM][BF4] ionic liquids with (n = 2, 4, 6, 8, and 10) were measured. The results of experiments confirmed that an increase in the number of carbon atoms in the alkyl chain in the imidazolium cation caused a decrease in absolute vapor pressures. However, this e ffect was di fferent for the homologies of [CnMIM][BF4] and [CnMIM][Nf2T]. Moreover, it was observed that the volatility for [CnMIM][BF4] was significantly lower in comparison to [CnMIM][Nf2T]. In addition, ILsaddedtoorganicsolventsalsoreducedtheirevaporation[59–61].

It should be noted that there are a huge variety of IL combinations, so it is di fficult to establish a clear classification. The most popular approach concerns the structure of these compounds (Table 1). A more detailed description concerns three generations of ILs in view of the anion or cation used. The first includes molecules with specific physical properties, which are described in the previous paragraph. The second generation includes ILs for which it is possible to tune their chemical and physical properties and then to use them for a specific purpose, while the last group are compounds with biological activity [62]. From the point of view of analytical applications, it seems reasonable to focus attention on a large and diverse IL group referred to as Task-specific Ionic Liquids. The results of

subsequent tests confirmed that apart from typical ILs, it is necessary to design more specific molecules to achieve a specific goal. This led to the use of ILs in polymerization processes. ILs as monomers can form combinations with other molecules, thus improving the results.




**Table 1.** *Cont.*

The currently applied analytical methods use the structure and properties of ILs to create polymeric connections with cyclodextrins (CDs) [63] or magnetic imprinted nanoparticles (MILs) [64]. In addition, polymeric ionic liquids (PILs) can also be synthesized by a co-polymerization process [65]. Their participation in the molecular imprinting technique used to develop sorbents of monolithic columns has also been noted. Another, large subclass of ILs are chiral ionic liquids (CILs). Recent scientific reports show that amino acids can be used for the synthesis of CILs. Their carboxyl or amine functional groups determine the chiral nature and function in the structure (cation or anion). The use of amino acids results from the trend of reducing toxicity and the use of natural compounds [66]. In addition, these "designer molecules" are also used as chiral selectors in aqueous two-phase systems (ATPS) [67].
