Synthesis and antibacterial studies of p-anisidinium-based ionic liquids: Experimental, DFT calculations and molecular docking

Most research studies focus on deep eutectic solvents due to the lack of biodegradation of ionic liquids (ILs). Given their antimicrobial, biological and chemical properties that result from various cation and anion combinations, these liquid salts emerged as promising and alternative solvents for volatile organic solvents. As more of ILs are continuously being synthesized or metathesized, and with their properties not fully evaluated, the importance and degradation of ILs is continuously being evaluated, especially for industrial applications. Herein, a series of p-anisidinium-based ILs including p-anisidinium acetate [p-anis][OAc], p-anisidinium trifluoromethanesulfonate [p-anis][OTf] and p-anisidinium nitrate [p-anis][NO₃] were synthesized, characterized and evaluated for antibacterial potencies. The obtained thermograms from both thermogravimetric analysis (TGA) and differential scanning colorimetry (DSC) illustrated [p-anis][OTf] as the most thermally stable amongst the examined solvents. The acidity levels of the ILs estimated using Hammett's acidity function revealed Ho values in the range of 4.12 to 5.17. Antibacterial potency of the compounds was evaluated using the microbial susceptibility testing against selected Gram-positive and Gram-negative bacteria using agar well diffusion method and revealed diverse degrees of susceptibility of the test organisms. Bacillus and E. coli bacterial strains showed moderate to strong susceptibility against [p-anis][NO₃]. Density Functional Theory (DFT) analysis using B3LYP/6–311 + G revealed insight into the electronic properties, including optimization energies, dipole moments, and HOMO-LUMO energy levels, which were used to derive chemical reactivity descriptors. The HOMO-LUMO gap and related parameters highlighted the stability and reactivity of the ionic liquids, with [p-Anis][NO₃] exhibiting the highest predicted reactivity. Molecular docking studies against Escherichia coli (PDB ID: 1KZN) and Pseudomonas aeruginosa (PDB ID: 6P8U) revealed notable binding affinities. [p-Anis][OAc] showed the highest binding affinity with 1KZN (−6.7 kcal/mol), while [p-Anis][OTf] had the strongest interaction with 6P8U (−7.6 kcal/mol).