A convergence of synthesis and antimicrobial research: imidazolium based dicationic ionic liquids

Abstract

The rising challenge of developing effective antimicrobial agents to combat a broad spectrum of bacterial infections, while mitigating the risk of drug resistance, has prompted extensive exploration into alternative treatment strategies. This paper focuses on the synthesis and characterization of imidazolium-based dicationic ionic liquids with the aim of addressing this crucial healthcare need. A total of 16 distinct compounds were successfully synthesized and systematically characterized using Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) techniques. The investigation into the antibacterial activity of these ionic liquids showcased their potential as promising antimicrobial agents. Drawing on the advantageous properties of ionic liquids, such as reduced toxicity and outstanding antimicrobial efficacy. Our study specifically explores dicationic imidazolium-based ionic liquids with two different spacers: 1,3-dibromopropane and (E)-1,4-dibromobut-2-ene. Thorough analysis using ¹H NMR, ¹³C NMR, FTIR, and TGA techniques provided valuable insights into the molecular structures and thermal properties of the synthesized compounds. Antibacterial assays were conducted to evaluate the efficacy of various combinations of these ionic liquids against bacterial strains, including Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Methicillin-resistant Staphylococcus aureus. Remarkably, the ionic liquids containing the bisulphate anion exhibited exceptional antibacterial results compared to other combinations. The structure-activity relationship of the most prominent ionic liquids identified in the antibacterial assays was analyzed by DFT studies. Additionally, molecular docking was employed to investigate the molecular interactions involved in the antibacterial activities. ILs can be utilized as effective candidates against infections to avoid disabilities.

Keywords: Antibacterial; Dicationic; Disability; Docking; Imidazolium; Ionic liquids; Rehabilitation.

Scheme 1

Synthesis scheme of anion exchange of bisulphate, dichloroacetate, and acetate anions with but-2-ene imidazolium based DIL

Scheme 2

Synthesis scheme of anionic exchange of hexafluorophospate, methane sulfonate, bis (trifluoromethanesulfonyl) imide, and tetrafluoroborate with but-2-ene imidazolium based dicationic ionic liquids

Scheme 3

Synthesis scheme of anionic exchange of acetate, bisulphate, dichloroacteate, and tetrafluororborate with propane imidazolium based DIL

Scheme 4

Synthesis scheme of anion exchange of hexaflourophosphate, methane sulfonate and bis (trifluoromethanesulfonyl)imide anions with propane imidazolium based DIL

Fig. 1

TGA curves of propane based ILs

Fig. 2

TGA curves of but-2-ene based ILs

Fig. 3

Antibacterial Activity of propane based ILs

Fig. 4

Antibacterial activity of propane based ILs

Fig. 5

Antibacterial activity of but-2-ene based ILs

Fig. 6

Antibacterial activity of but-2-ene based ILs

Fig. 7

Optimized geometries of the selected ILs

Fig. 8

Electrostatic potential (ESP) maps for the optimized geometries of the ILs

Fig. 9

Representation of the frontier molecular orbitals (FMO) energy levels and their energy gaps

Fig. 10

3D docked conformations and 2D interaction diagrams of the cationic core moieties of ILs against the bacterial β-lactamase proteins