Self-Aggregation, Antimicrobial Activity and Cytotoxicity of Ester-Bonded Gemini Quaternary Ammonium Salts: The Role of the Spacer.

Five ester-bonded gemini quaternary ammonium surfactants C-E-C (n = 2, 4, 6), with a flexible spacer group, and C-B-C (m = 1, 2), with rigid benzene spacers, were synthesized via a two-step reaction and analyzed. Furthermore, the effects of the spacer structure, spacer length and polymerization degree on the self-aggregation, antimicrobial activity and cytotoxicity of C-E-C and C-B-C and their corresponding monomer -dodecyl-,,-trimethyl ammonium chloride DTAC were investigated. The results showed that C-E-C and C-B-C had markedly lower critical micellar concentration (CMC) values and lower surface tension than DTAC. Moreover, the CMC values of C-E-C and C-B-C decreased with increasing spacer length. In the case of equivalent chain length, the rigidity and steric hindrance of phenylene and 1,4-benzenediyl resulted in larger CMC values for C-B-C than for C-E-C. The antibacterial ability of C-E-C and C-B-C was assessed using () and () based on minimum inhibitory concentrations (MICs). Furthermore, C-E-C and C-B-C exhibited higher antimicrobial activity than DTAC and had stronger function toward than . The antimicrobial activity was enhanced by increasing the spacer chain length and decreased with the increased rigidity of the spacers. The cytotoxic effects of C-E-C and C-B-C in cultured Hela cells were evaluated by the standard CCK8 method based on half-maximal inhibitory concentration (IC). The cytotoxicity of C-E-C and C-B-C was significantly lower than alkanediyl-α,ω-bis(dimethyldodecylammonium) bromide surfactants and DTAC. The spacer structure and the spacer length could induce significant cytotoxic effects on Hela cells. These findings indicate that the five ester-bonded GQASs have stronger antibacterial activity and lower toxicity profile, and thus can be used in the pharmaceutical industry.