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 C12-En-C12(n = 2, 4, 6), with a flexible spacer group, and C12-Bm-C12(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 C12-En-C12and C12-Bm-C12and their corresponding monomerN-dodecyl-N,N,N-trimethyl ammonium chloride DTAC were investigated. The results showed that C12-En-C12and C12-Bm-C12had markedly lower critical micellar concentration (CMC) values and lower surface tension than DTAC. Moreover, the CMC values of C12-En-C12and C12-Bm-C12decreased 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 C12-Bm-C12than for C12-En-C12. The antibacterial ability of C12-En-C12and C12-Bm-C12was assessed usingEscherichia coli(E. coli) andStaphylococcus albus(S. aureus) based on minimum inhibitory concentrations (MICs). Furthermore, C12-En-C12and C12-Bm-C12exhibited higher antimicrobial activity than DTAC and had stronger function towardS. aureusthanE. coli. The antimicrobial activity was enhanced by increasing the spacer chain length and decreased with the increased rigidity of the spacers. The cytotoxic effects of C12-En-C12and C12-Bm-C12in cultured Hela cells were evaluated by the standard CCK8 method based on half-maximal inhibitory concentration (IC50). The cytotoxicity of C12-En-C12and C12-Bm-C12was 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.Keywords:gemini surfactant;ester;antimicrobial activity;spacer;cytotoxicity