Self-assembly of hydroxyethylated pyrrolidinium amphiphiles as a tool for the fabrication of nanosized systems with tunable multifunctional activity

A novel homologous series of pyrrolidinium derivatives bearing a hydroxyethyl group and alkyl chain of varying length (2-(hydroxyethyl)-1-methyl-1-alkylpyrrolidinium bromides, MPS-n(OH), where n = 12, 14, 16, 18) has been synthesized and systematically studied. The influence of the hydroxyethyl substituent position on the self-assembly, solubilizing effect, and biological activity of the amphiphiles has been analyzed. An increase in the alkyl tail length by a methylene unit generally led to a 3 to 3.3-fold decrease in the critical micelle concentration. It was found that the amphiphiles exhibit a high solubilizing capacity toward nonsteroidal anti-inflammatory drugs naproxen and indomethacin. The introduction of the hydroxyethyl fragment significantly enhanced the solubilizing activity of MPS-n(OH) toward the hydrophobic dye Orange OT. In the case of the octadecyl homologue, the solubilization efficiency increased by 2.6 times compared to its analogues. It was found that MPS-12(OH) exhibits significant blood biocompatibility with a low hemolysis (HC₅₀ ≥ 200 µM). Besides the hexadecyl homologue demonstrates strong bactericidal effect against most Gram-positive bacteria, including methicillin-resistant strains (0.5–3.9 µg/mL). The potential of pyrrolidinium amphiphiles as micellar catalysts for the hydrolytic degradation of the organophosphorus ecotoxicant paraoxon has been demonstrated.