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

TL;DR

This study develops new antibacterial compounds with ionic liquid properties to combat biofilm-forming bacteria, especially a resistant strain of Pseudomonas delhiensis.

Contribution

The paper introduces structurally tailored quaternary ammonium salts with IL-like properties and evaluates their antimicrobial and thermophysical performance.

Findings

The ionic liquid [C14C2OHMor]Br and piperidinium salt [C1C14Pip]Br showed strong antibacterial activity.

Novel di-imidazolium ILs demonstrated enhanced antimicrobial performance and thermal stability.

Structure–activity relationships were identified for potential use in antifouling technologies like SLIPs.

Abstract

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 Pseudomonas delhiensis PS27, a multidrug-resistant Gram-negative environmental strain isolated
from a site contaminated with perfluoroalkyl and polyfluoroalkyl substances
(PFASs). Owing to its high resilience, P. delhiensis 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, [o-xyl­(C8Im)2]­[Docu]2 and [o-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).

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