Structurally Tailored Antibacterial Quaternary Ammonium Salts with Ionic Liquid Properties for Antimicrobial Purposes: Design and Thermophysical Insights

Biofilm-forming bacteria pose therapeutic and industrial challenges due to their heightened resistance to antimicrobials and their role in surface contamination and material degradation. Quaternary ammonium salts (QASs), especially those with ionic liquid (IL)-like properties, have emerged as promising agents for controlling biofilms. This study reports the synthesis and characterization of a series of structurally tailored antibacterial QAS, some displaying IL-like behavior, and evaluates their antimicrobial activity. The tested organism was <i>Pseudomonas delhiensis</i> PS27, a multidrug-resistant Gram-negative environmental strain isolated from a site contaminated with perfluoroalkyl and polyfluoroalkyl substances (PFASs). Owing to its high resilience, <i>P. delhiensis</i> PS27 serves as a robust model for assessing the efficacy of biocidal agents. Thermophysical properties, including phase transitions and thermal stability, were evaluated using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) to ensure the compounds' practical applicability. Among the most effective compounds, the ionic liquid [C₁₄C₂OHMor]Br and the piperidinium salt [C₁C₁₄Pip]Br exhibited notable antibacterial activity, though the morpholinium derivative showed reduced efficacy likely due to oxygen-related lower toxicity. The [C₁C₁₄Pip]₃[Trim] demonstrated ionic liquid properties combined with strong antibacterial effects and high thermal stability. Additionally, novel di-imidazolium ILs, [<i>o</i>-xyl-(C₈Im)₂]-[Docu]₂ and [<i>o</i>-xyl-(C₈Im)₂]-[Tos]₂, showed enhanced antimicrobial performance. Overall, the study highlights key structure-activity relationships and identifies promising candidates for the development of advanced antifouling technologies, particularly polymer-based coatings and slippery-liquid-infused porous surfaces (SLIPs).