Sterically Hindered Quaternary Phosphonium Salts (QPSs): Antimicrobial Activity and Hemolytic and Cytotoxic Properties

Abstract

Structure-activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have been studied to a lesser extent. In the present study, a broad range of sterically hindered quaternary phosphonium salts (QPSs) based on tri-tert-butylphosphine was tested for their activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans, Trichophyton mentagrophytes var. gypseum). The cation structure was confirmed to determine their biological activity. A number of QPSs not only exhibit high activity against both Gram-positive and -negative bacteria but also possess antifungal properties. Additionally, the hemolytic and cytotoxic properties of QPSs were determined using blood and a normal liver cell line, respectively. The results show that tri-tert-butyl(n-dodecyl)phosphonium and tri-tert-butyl(n-tridecyl)phosphonium bromides exhibit both low cytotoxicity against normal human cells and high antimicrobial activity against bacteria, including methicillin-resistant strains S. aureus (MRSA). The mechanism of QPS action on microbes is discussed. Due to their high selectivity for pathogens, sterically hindered QPSs could serve as effective tunable biocides.

Keywords: QPS; antimicrobial activity; cytotoxicity; fungicidal activity; hemolytic properties; phosphonium ionic liquids.

Figure 1

Hemotoxic and cytotoxic activity of QPSs, expressed in terms of HC₅₀ and IC₅₀.

Figure 2

Selectivity of QPSs for bacteria (S. aureus 209 P and MRSA-1) compared to red blood cells.

Figure 3

Selectivity of QPSs for bacteria (S. aureus 209 P and MRSA-1) compared to Chang liver cells.

Figure 4

The percentage of crystal violet in S. aureus 209 P supernatant after 30 min incubation with various concentrations (µg/mL) of the test compounds and CTAB. The optical density of the sample at a wavelength of 540 nm with the dye in the absence of cells was taken as 100%.

Figure 5

Picture of a zone-of-inhibition-test result of 1% 12a coating plastic sample (PC+); (A) zone of inhibition of P. aeruginosa and (B) zone of inhibition of S. aureus.