Antimicrobial and Toxicity Evaluation of Imidazolium-Based Dicationic Ionic Liquids with Dicarboxylate Anions

Imidazolium-based dicationic ILs (DILs) presenting antimicrobial activity and relatively low toxicity are highly desirable and are envisioned for use in live tissue to prevent bacterial or fungal infections. In this context, we present here DILs with dicarboxylate anions [C-n(MIM)(2)[C-n(MIM)(2)][CO2-(CH2)(m)CO2], in which n = 4, 6, 8, and 10, and m = 0, 1, 2, 3, 4, and 5. The results showed that DILs with an alkyl chain spacer of ten carbons were active against yeasts and the bacterial strains tested. However, most of the DILs were cytotoxic and toxic at 1 mM. By contrast, DILs with alkyl chains possessing less than ten carbons were active against some specific Candidas and bacteria (mainly S. aureus), and they showed moderate cytotoxicity. The best activity against Gram-positive bacteria was observed for [C-4(MIM)(2)][Pim] toward MRSA. For the DILs described herein, their level of toxicity against C. elegans was lower than that of most of the mono- and dicationic IL analogs with other anions. Our results showed that the presence of carboxylate anions reduces the toxicity of DILs compared to DILs containing halide anions, which is particularly significant to the means of designing biologically active compounds in antimicrobial formulations.

Automated summary

This study introduces imidazolium-based dicationic ILs with dicarboxylate anions, showing that DILs with a ten-carbon alkyl chain spacer are active against yeasts and tested bacterial strains, but most are toxic. DILs with less than ten carbons in the alkyl chain show activity against specific fungi and bacteria with moderate cytotoxicity.