| Quaternary ammonium surfactants with cationic and amphiphilic features have been widely used as antibacterials in daily chemical,biological,and pharmaceutical fields.Recent studies have demonstrated that compared with monomers,cationic amphiphilic aggregates show greater advantages in antibacterial activities.However,the interaction mode of aggregates with bacterial membranes remains unclear.Therefore,the development of cationic surfactants with strong self-assembly ability and bearing fluorophores favors for the development of highly efficient antibacterials and the understanding of their antibacterial mechanism.In this thesis,the tetraphenyl ethylene(TPE)with aggregation-induced emission(AIE)property was introduced to construct cationic and amphiphilic molecules as antibacterials.The photophysical and self-assembly properties and antibacterial activities of obtained cationic and amphiphilic molecules were studied and the interaction of their aggregates with bacteria was monitored based on the fluorescence properties of TPE moiety to reveal their antibacterial mechanism.The main conclusions are listed as follows:1.Double-tailed quaternary ammonium surfactants containing TPE moiety was developed,their self-assembly properties were regulated by changing the position of the quaternary ammonium head group,and thus to control their antibacterial activity.The interaction of the aggregates with bacteria was monitored based on the fluorescence properties of the TPE group.The results showed that the critical aggregation concentration(CAC)valuesof three molecules in PBS were evaluated to be 3.3 μM,1.6 μM and 3.0 μM,respectively.Above the CAC,they formed positively charged cubic aggregates with the dimensions of 250 nm,450 nm,and 300 nm,respectively.The killing efficiency of these aggregates against S.aureus followed the order of T6N4C>T2N8C>T10NC,and 100%killing efficiency was obtained at the concentrations of 10 μM,20 μM and 50 μM for T6N4C,T2N8C and T10NC,respectively.The fluorescence imaging,SEM and zeta potential results showed that the aggregates formed by three molecules killed S.aureus by destroying the bacterial membrane,but presented the different membrane-distupting dynanics.With the lowest CAC value,i.e.,the strongest self-assembly ability,T6N4C took the shortest time to reach 100%antibacterial activity.Also,T6N4C had good biocompatibility.When the concentration of T6N4C increased to 100 μM,the cell viability remained still about 100%.Therefore,cationic amphiphilic molecules with strong self-assembly ability exhibit strong bactericidal activity.2.Gemini-type quaternary ammonium surfactants containing TPE moiety were designed and synthesized,and their aggregation behavior was regulated by varying the hydrophobic chain length,and thus to control their antibacterial activity.The interaction between the aggregates and bacteria was monitored based on the fluorescence properties of TPE groups.The CAC values of the four molecules in PBS were 0.60,0.58,0.56 and 0.36μM.Above CAC,they formed positively-charged spherical aggregates with the size of 105 nm,250 nm,100 nm,and 280 nm,respectively.The antibacterial efficiency of these aggregates against S.aureus followed the order of C8-TPE-C8>C10-TPE-C10>C12-TPE-C12>C14-TPE-C14.As for C8-TPE-C8,C10-TPE-C10 and C12-TPE-C12,their killing efficiency against S.aureus reached 100%at 5 μM,20 μM and 100 μM,respectively.However,in the case of C14-TPE-C14,its killing efficiency was only 74%at the concentration of 100 μM.The fluorescence imaging,SEM and zeta potential results showed that the aggregates formed by the four molecules exhibited antibacterial activity by disrupting the bacterial membrane of S.aureus.The molecules with shorter hydrophobic chains formed the aggregates with loose structures,which are easier to dissociate into monomers and insert into or penetrate the bacterial membrane when interacting with bacteria,thus showing highly efficient bactericidal activity.Therefore,C8-TPE-C8 with short hydrophobic chain showed the highest antibacterial activity against S.aureus.Also,C8-TPE-C8 with short hydrophobic chain showed low cytotoxic side effects and good biocompatibility.3.Bola-type quaternary ammonium surfactant containing TPE moiety as the hydrophobic skeleton were developed,their aggregation behavior was regulated by changing the hydrophobicity of the linker groups,and thus to control their antibacterial property.Further,the interaction between their aggregates and bacteria was monitored based on the change in emission wavelength of three amphiphiles before and after aggregation.The CAC values of the three molecules in PBS solution were 33.9 μM,3.70 μM and 1.81 μM,respectively.Above the CAC,the three molecules formed positively-charged cubic aggregates with the dimension of 200 nm,150 nm and 400 nm,respectively.The antibacterial efficiency of these aggregates against S.aureus followed the order of TO6C>T2OE>TO2C,and 100%killing efficiency was achieved at the concentration of 10μM,100 μM and 100μ M,respectively.Fluorescence imaging and fluorescence spectroscopy were used to study the interaction between the aggregates formed by the three molecules and S.aureus.In the case of TO2C molecules with significantly different emission wavelengths at the aggregate state(456 nm)and monomer state(480 nm),it was observed that the emission wavelength of TO2C molecules added to the bacteria significantly shifted from 456 nm to 470 nm state when adding into S.aureus.This clearly confirmed that the aggregate was bound to the bacterial surface by electrostatic interaction,then dissociated into monomers and inserted into bacterial membranes to exhibit killing activity.Therefore,the aggregates are more prone to disassemble into monomers upon contact with bacteria,which facilitates their insertion into bacterial membrane.But on the other hand,the dynamics of membrane destruction is positively associated with the ability of monomers to disrupt bacterial membranes.These two factors contribute to their antibacterial activity. |
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