Identification of new pyridinium ionic liquids tagged with Schiff bases: Design, synthesis, in silico ADMET predictions and biological evaluations

Abstract

The discovery of a novel series of task-specific fluorinated pyridinium ionic liquids (TsILs) tagged with Schiff bases is reported using ultrasound-assisted and conventional syntheses. The synthesis required the quaternization of the appropriate pyridine Schiff base, followed by the metathesis of the resulting task-specific halogenated pyridinium ILs. The structures of the ILs were established by analytical and spectral data (IR, 1H NMR, 13C NMR, 19F NMR and mass spectrometry). In vitro antimicrobial activities of the synthesized ILs on both gram-positive (Bacillus cereus, Enterococcus faecalis, and Staphylococcus aureus) and gram-negative (Proteus mirabilis, Escherichia coli, and Pseudomonas aeruginosa) bacterial strains and two fungal strains (Candida albicans and Aspergillus brasiliensis) were evaluated. Ionic liquids 8, 18, 19 and 20 appear to be the most active antimicrobials among the synthesized series. Preliminary studies were carried out to understand the relationship between the molecular structures and the inhibition activities of the synthesized ILs. In addition, the results of in silico studies revealed that all compounds exhibited good pharmacokinetic, bioavailability and toxicity profiles. Furthermore, drug likeness analysis suggests that the synthesized ILs might have appropriate oral absorption and brain penetration for application. In vivo computed LD50 values (2.59–2.78 mol/kg) were calculated for rat acute toxicity, and the compounds were found to be non-toxic and in a safe range for further study.