Evidence of a reverse side-chain effect of tris(pentafluoroethyl)trifluorophosphate [FAP]-based ionic liquids against pathogenic bacteria.

Increased interest in ionic liquids (ILs) is due to their designable and tunable unique physicochemical properties, which are utilized for a wide variety of chemical and biotechnological applications. ILs containing the tris(pentafluoroethyl)trifluorophosphate ([FAP]) anion have been shown to have excellent hydrolytic, electrochemical and thermal stability and have been successfully used in various applications. In the present study the influence of the cation on the toxicity of the [FAP] anion was investigated. Due to the properties of [FAP] ILs, the IL-toxicity of seven cations with [FAP] compared to [Cl] was examined by determination of minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) on six Gram-positive and six Gram-negative clinically-relevant bacteria. For the first time, to our knowledge, the results provide evidence for a decrease in toxicity with increasing alkyl side-chain length, indicating that the combination of both ions is responsible for this 'reverse side-chain effect'. These findings could portend development of new non-toxic ILs as green alternatives to conventional organic solvents.

Predictability of ionic liquid toxicity from a SAR study on different systematic levels of pathogenic bacteria.

Ionic liquids (ILs), a new class of solvents with unique and tunable physicochemical properties, were initially envisioned as working alternatives to traditional organic solvents. However, they have now proven to have a wide range of alternative chemical and biochemical applications. Due to their increasing use, environmental and toxicity concerns are growing, but resolutions are hindered by the sheer number of possible variants. In order to assess and possibly predict IL-toxicity, a structure-activity relationship (SAR) approach was adopted using defined structural motifs. These included varied cationic alkyl side-chain lengths, cation lipophilicity and diverse anion effects. The predictive powers of such SARs in respect of antibacterial effects were compared using a total of 28 ILs on six Gram-negative and six Gram-positive pathogenic bacteria. Endpoints were minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC). Results indicate that while certain limited IL-toxicity responses in bacteria can be predicted from SARs, they caution that predictions cannot be generalized across species. This study demonstrates the complex species-specific nature of IL-toxicity and the current limitations of SAR predictability.