Hydroxylated Alkyl and Phenyl Phosphonium Ionic Liquids Exhibit Enhanced Antibacterial and Anti-Biofilm Activity

The rapid emergence of antimicrobial resistance has intensified the search for alternative antimicrobial scaffolds that target both planktonic bacteria and biofilm-associated infections. In this study, a series of hydroxylated phosphonium ionic liquids derived from triphenylphosphonium (TPP+) and trihexylphosphonium (THP+) cations bearing C3, C6, C7, and C10 ω-hydroxyalkyl chains were synthesized and evaluated for their antibacterial and anti-biofilm activities. Antibacterial activity was determined using broth microdilution assays against Staphylococcus aureus and Escherichia coli, while anti-biofilm activity was assessed by disrupting preformed biofilms using a 96-pin microtiter plate system and crystal violet staining. The results showed that antibacterial activity was strongly influenced by the amphiphilic balance of the compounds, particularly the alkyl chain length and the nature of the phosphonium core. Derivatives bearing C6OH–C10OH chains exhibited the highest antibacterial activity, whereas short-chain analogs displayed markedly reduced potency. THP derivatives were notably more active against E. coli bacteria, consistent with their higher hydrophobicity and activity consistent with membrane interaction. In addition, THP derivatives demonstrated greater biofilm disruption, achieving up to ~90% biomass removal in E. coli biofilms, with C6OH–C7OH derivatives showing the most favorable activity profile. Hemolysis assays indicated low erythrocyte toxicity at concentrations close to antibacterial MIC values, indicating a favorable selectivity window. Overall, these findings highlight phosphonium ionic liquids as promising antimicrobial agents with activity consistent with membrane interaction and provide structure–activity insights for the rational design of new antibacterial and anti-biofilm compounds.