Synthesis And Antibacterial Application Of Novel Phosphonium N-Halamine Biocides

With rapid development of the society and deterioration of environment, large-scale infection issues caused by pathogenic microorganisms outbreaks frequently, which is attracting more and more attention around the world. Therefore, people’s demand of highly effective, safe and broad-spectrum antibacterial agents is badly urgent. Quaternary phosphonium salt, a kind of antibacterial agent containing similar structure with quaternary ammonium salt, has even better antibacterial activity than quaternary ammonium salt in that phosphorus atom has larger radius than nitrogen atom, so the polarization of phosphonium salt is larger and it’s easier for phosphonium salt to attract negatively charged microorganisms. N-halamine is a type of broad-spectrum antibacterial agent which can be regenrated effectively. The antibacterial mechanism of N-halamine relies on the strong oxidation susceptibility of N-halogen group, so little has been reported about the corresponding microbe resistance. However, the hydrophilicity of N-halamine structural unit is relatively poor, which has restricted its application to a certain extent.In this thesis, we combined the N-halamine unit and quaternary phosphonium unit via covalent bond for the first time. Starting from commercial 5,5-dimethyl hydantoin as a raw material, the target compounds were prepared via N-alkylation reaction on DMH ring, the quaternary phosphonium salt reaction to give quaternary phosphonium type salt, and the final chlorination reaction of N-halamine precursors, with total yield of around 55%. The NMR data were obtained to characterize all the synthetic intermediate compounds as well as the target antibacterial phosphonium N-halamines.It has confirmed that all these newly developed phosphonium N-halamine compounds have good water solubility. Antibacterial tests against E. coli ATCC 25922 were performed and the following conclusions could be obtained:(1) The phosphonium N-halamine compounds designed in this thesis have even better antibacterial activity than the reported ammonium N-halamine compound.(2) By increasing the length of hydrophobic alkyl chain between the N-halamine group and the quaternary phosphonium group, the antibacterial activity at first increases, but decrease in the end. When the length of the hydrophobic alkyl chain reaches to 12-CH2-, the best antibacterial activity of all thel tested samples was achieved, which was probably caused by synergistic effect between N-halamine unit and quaternary phosphonium group.In addition, this thesis also provides two alternative total synthesis routs regarding immobilizing phosphonium N-halamine that contains a siloxane group, and some beneficial organic synthesis attempt has been made.