Synthesis, biocompatibility, and antimicrobial properties of glucose-based ionic liquids

Abstract

The diversity in structure, the variety in chirality, as well as the large occurrence of carbohydrates in nature, led to the development of the next generation of ionic liquids (ILs). These carbohydrate-based ionic liquids, also known as CHILs, are expected to overcome limitations such as aquatic ecotoxicity and poor biodegradability. In this work, we present the glucosyl imidazolium ILs, obtained via a simple two to three-step synthesis with total yields up to 90%. These compounds were obtained with several variations in alkyl- and aromatic side chains, glycosidic groups, anions, and protecting groups to study the influence of these variations on the biocompatibility and antimicrobial properties of the CHILs. The in vitro studies confirmed the biocompatibility of most of the CHILs for L929 mouse fibroblasts at 10⁻² mol L⁻¹, a feat not achieved by commercial imidazolium ILs. We could confirm observed trends, like increased cytotoxicity with increasing alkyl chain length, as well as higher fluorinated anions. Additionally, some of the here reported novel CHILs had significantly higher IC₅₀ values than comparable imidazolium, pyridinium, and pyrrolidinium-based ILs. Additionally, antibiotic resistance is an increasingly serious threat to global health. Consequently, the development of new substances with antibiotic properties is of high priority. The before-synthesized CHILs were investigated in their overall antimicrobial behavior towards a Gram-negative strain (Escherichia coli K-12), a Gram-positive strain (Bacillus subtilis), as well as a common yeast (Candida auris WT) via the disk diffusion test. The minimum inhibition concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) were determined from the active substances. Similar to the biocompatibility experiments, correlations can be found between the length of the alkyl chain, the non-polarity of the structure, as well as the amount of fluorine in the counterion. For Candida auris, GMIM-NTf₂ as well as GOIM-I show the strongest effect, with a MIC and MFC of 1 mmol L⁻¹ and 5 mmol L⁻¹, respectively.