Novel self-assembling systems based on imidazolium amphiphiles with cleavable urethane fragment for construction of soft nanocontainers for biomedicine application

In the framework of this report the bottom-up strategy has been used for the development of novel soft nanocontainers through self-assembly of homologous series of newly synthesized amphiphilic compounds of N-(2-ethylaminocarbonyloxyethyl)-N-alkylimidazolium bromides. Their aggregation properties, solubilization capacity, antimicrobial activity, membranotropic properties and capability to form lipoplexes have been investigated. Using various physico-chemical techniques it has been demonstrated that introduction of urethane moiety into amphiphile structure results in the 2-3-fold decrease of critical micelle concentration in comparison with their unsubstituted counterparts. It has been suggested, that interaction of amphiphiles with DNA decamer is predominantly driven by cooperative electrostatic interactions. Membranotropic properties of novel amphiphiles could be regulated by the change of the length of hydrophobic tail; with these properties being the more markedly expressed in the case of the lower homologue. Estimation of antimicrobial activity against several strains of microorganisms has revealed, that these amphiphiles were by several-fold more active toward Staphylococcus aureus, Bacillus cereus bacteria and Candida albicans fungi in comparison with reference compounds – norfloxacin and ketoconazole. Hemolytic activity of these amphiphiles has not exceeded 0.9% under bactericide and bacteriostatic concentrations. The combination of advanced characteristics allows us to recommend these amphiphiles for fabrication of soft materials with the wide spectrum of practically useful properties like effective nanocontainers for drug and gene delivery, capable of crossing the cell membrane, and harmless for human agents against pathogenic microorganisms. •Novel amphiphiles bearing imidazolium and urethane moieties have been synthesized.•All compounds have a high capability to interact with decanucleotide.•Novel amphiphiles exhibited high antimicrobial properties and low hemolytic activity.•Membranotropic properties strongly depend on the length of alkyl tail of surfactants studied.