Synthesis, antimicrobial effect and surface properties of hydroxymethyl-substituted pyridinium salts
Abstrakt
Quaternary Ammonium Salts (QAS) make up the majority of the group of cationoic surfactants. Their countless applications in chemistry, the food industry and textile industry are indubitable.
The antibacterial and antifungal effect of the various novel QAS is usually referred to in comparison with commercially used benzalkonium and pyridinium salts, since such compounds have found widespread use as common disinfectants e.g. in hospitals as prevention against nosocomial infections. We have prepared 15 new compounds based on hydroxymethylpyridine in different positions (2, 3, 4) and the different length of lipophilic alkyl chain on the quaternary nitrogen (C10-18).
The compounds were characterized with analytical data (NMR, HRMS) and tested for in vitro antimicrobial activity. The highest, and submicromolar antimicrobial activity was achieved for the 3- hydroxymethylpyridinium salts substituted with longer alkyl chains (C-14, C-16 and C-18).
N-hexadecyl- 3-hydroxymethylpyridinium bromide (10b) showed even better performance than standard benzalkonium salts. Conductometric analysis confirmed the trend of decreasing CMC with elongation of the alkyl side chain.
Generally, the location of the hydroxymethyl function on the pyridinium scaffold induced only negligible changes in antimicrobial efficacy. Finally, potential use of the N-alkylhydroxymethylpyridinium salts in practice was supported by MMT tests which proved relatively low cytotoxicity of the compounds.
Conclusion: We have designed, synthesized and characterized three series of cationic surfactants based on 2-, 3- and 4-hydroxymethylpyridine. The cationic surfactants differ in the length of alkyl side-chain (C-10, C-12, C-14, C-16, C-18).
The antimicrobial effect was evaluated against four groups of microorganisms (gram-positive and gram-negative bacteria, yeasts, and filamentous fungi). The Critical Micelle Concentrations (CMC) were measured by conductivity method, and finally cytotoxicity tests were performed.