Synthesis Of Organic Conjugated Small Molecules And Their Antibacterial Applications

The emergence of drug-resistant bacteria and their infectious diseases are increasingly threatening human life and health.The development of an antibacterial method that can effectively kill bacteria,has little toxic and side effects on the human body,and is not easy to develop drug resistance is essential for the treatment of diseases caused by bacteria.Among the reported antibacterial therapies,photothermal therapy has the characteristics of less trauma,short treatment cycle,low toxic and side effects,good selectivity,and resistance to drug resistance,so it has more advantages in antibacterial therapy.In photothermal therapy,the performance of photothermal conversion materials plays an important role in the therapeutic effect.In this dissertation,based on the structural and performance advantages of organic conjugated small molecules,with the help of molecular engineering and hybrid assembly strategies,the application research of organic small molecular photothermal materials in antibacterial.The dissertation mainly includes the following chapters.Chapter 1:The harm of drug-resistant bacterial infection,the developed antimicrobial materials,antimicrobial methods and their research progress were briefly described.Then,the design idea of this paper was put forward.Chapter 2:In order to obtain an antibacterial material with high photothermal conversion efficiency,two organic conjugated small molecules(M1 and M2)with the same main structure but different bridging methods were designed and synthesized by molecular engineering strategy.M1 and M2 conjugated molecules are composed of pyrrolopyrrole,thiophene and thiadiazole groups.The difference is that a bridging group(ethynyl)is introduced into the M2 molecule.Tests of photophysical and photothermal properties show that the introduction of ethynyl groups can enhance the light absorption capacity of conjugated molecules,and improve their photothermal performance.The nano-particles that can be used for biological antibacterial by nano-precipitation method,and the photothermal killing research on drug-resistant E.coli,S.aureus and C.albicans was carried out.The prepared nanoparticles were further used wound infection treatment infected S.aureus in mice.The results show that conjugated small molecule nanoparticles can effectively kill bacteria in wounds and promote the healing of infected wounds in mice.This work not only provides new photothermal materials for the treatment of bacterial infection wounds,but also proposes new ideas for the design of organic photothermal materials with excellent synthetic properties.Chapter 3:Based on the above work,a new system of photothermal/chemodynamic therapy antibacterial was developed under the mediation of metal Fe²⁺ions.The organic conjugated molecule M1 was coordinated with Fe²⁺,and the amphiphilic material PLGA₁₅₀₀-PEG₃₅₀₀ was wrapped to form water-soluble nanozyme M1-Fe NPs.The introduction of Fe²⁺can enhance the?-?stacking between M1 molecules and improve its photothermal conversion performance.At the same time,Fe²⁺can also mediate the catalytic decomposition of H₂O₂ to produce hydroxyl radicals(·OH),which can be used for sterilization.Under irradiation of 660 nm laser,the constructed inorganic/organic hybrid assembly can generate more heat,which can not only cause damage the bacteria,but also increase the rate of·OH production by H₂O₂,further kill bacteria,and achieve the synergistic bactericidal effect of photothermal and chemodynamic therapy.Studies on the treatment of bacteria and their infected wounds in vivo and in vitro show that the organic/inorganic hybrid nano-assembly can effectively kill bacteria and effectively heal wounds infected by S.aureus in mice.This work provides a new method for improving the photothermal properties of organic conjugated small molecules,and promotes the development of photothermal and chemodynamic combined therapy.Chapter 4:Summarize the work content of the thesis and look forward to it...