【作者】 王军；

【导师】 陈秋云；

【作者基本信息】 江苏大学 ， 化学工程与技术， 2023， 硕士

【摘要】 致病菌感染是人类生命健康安全的主要威胁之一,而抗生素长期用于细菌治疗会导致耐药菌的出现,从而降低治疗效果。因此,开发新型高效并有效降低耐药性风险的治疗策略成为致病菌研究的目标之一。卟啉作为自然界广泛存在的具有可见光-近红外光吸收特性的有机光敏剂,因其良好的光动力学性能,可作为一种潜在的光响应抑菌剂。本论文总结了光感应抗菌剂的研究进展,设计制备了三种新型卟啉衍生的抑菌剂;将卟啉和黑磷等生物可代谢材料通过金属配位组装为纳米抑菌剂,提高细菌靶向能力,联合光热和光动力学疗法能显著提升细菌抑制效率。研究了抗菌剂的结构、组成及性能,并进一步探究了对大肠杆菌和金黄色葡萄球菌的抑制效率及机制。本文主要内容及创新性研究结果如下:（1）黑磷铕卟啉的制备及其抑菌性能研究:首先研究了黑磷（BP）与铕离子(Eu³⁺)的配位作用并制备了铕负载的纳米材料（BP@Eu）,随后通过铕与5,10,15,20-四（4-羧基苯基）卟啉（TCPP）配位获得新型黑磷铕卟啉（BP@Eu-TCPP）。拉曼、红外及XPS谱图证明了Eu-P和Eu-O配位键的存在。研究结果显示BP@Eu-TCPP的光热性能、光热稳定性和抑菌效率显著高于BP;BP@Eu-TCPP对牛血清蛋白和脂肪酶有较强的亲和力,其结合常数分别为9.26×10³和6.52×10²。进一步研究发现BP@Eu-TCPP由于铕与TCPP的作用使TCPP光动力学性能被抑制,而精氨酸与BP@Eu-TCPP相互作用,通过形成TCPP-L-Arg复合物,恢复了荧光与光动力学性能。BP@Eu-TCPP可作为一种精氨酸检测的荧光开启型探针,其检出限为4.02μM。进一步研究了BP@Eu-TCPP抗菌机制,发现其能够改变细菌原始形态,破坏细胞壁的完整性并干扰细菌对铁离子的吸收、丙酮酸及NADH/NAD⁺的正常氧化还原平衡。研究结果表明BP@Eu-TCPP是一种精氨酸激活的光动力学光热抑菌剂和精氨酸荧光感应探针。（2）金属卟啉共价有机框架包裹黑磷镓的制备及其抑菌性能研究:制备了黑磷镓（BP@Ga）,利用其为模板诱导5,10,15,20-四（4-氨基苯基）卟啉（TAPP）和对苯二甲酰氯通过酰胺键连接形成纳米多孔材料,并铜离子配位组装,得到多孔球状黑磷基卟啉铜共价有机框架材料（BPGa@COF-Cu）。BPGa@COF-Cu具备良好的红光驱动产生单线态氧与光热性能。实验表明BPGa@COF-Cu具有类纳米酶作用,能催化过氧化氢产生羟基自由基。该化合物在光照下对大肠杆菌和金黄色葡萄球菌的最小杀菌浓度分别仅为1和3μg/m L。BPGa@COF-Cu还能通过光激活方式破坏细菌细胞壁。结果表明,BPGa@COF-Cu是一种的光热光动力学化学动力学多模式协同抑菌剂。（3）金属卟啉纤维素的制备及抑菌性能研究:利用5,10,15,20-四（4-酰肼基苯基）卟啉（THPP）和二醛纤维素（DAC）通过共价亚胺键偶联,制备了一种卟啉纤维素（CEL-THPP）,并研究其与锌离子的组装,最终得到光响应多孔金属卟啉纤维素（CEL-THPP@Zn）。CEL-THPP@Zn禁带宽度为1.69 e V,在400-900 nm有着宽吸收谱带,并且在662 nm具有较强的荧光发射;因此,在红光照射下CEL-THPP@Zn的单线态氧产生能力优于CEL-THPP;进一步研究发现,CEL-THPP@Zn对大肠杆菌和金黄色葡萄球菌均展示了较好的抑制作用,并且对细菌有着富集作用。综上所述,CEL-THPP@Zn是一种表面多孔球棒状结构发光纤维,具有良好的细菌吸附性能,在黑暗和光照作用下均显示了优异的广谱抑菌作用。更多还原

【Abstract】 Pathogenic bacterial infections are one of the main threats to the healthy security of human life,but the long-term use of antibiotics can lead to the emergence of drug-resistance,which can reduce the effectiveness of treatment.Therefore,developing new and efficient treatment strategies that effectively reduce the risk of drug resistance has become one of the major challenges of pathogenic bacteria research.Porphyrins,as an organic photosensitizer with visible near-infrared light absorption properties that are widely present in nature,can be used as a potential photoresponsive antibacterial agent due to their excellent photodynamic properties.However,the poor water solubility of porphyrins leads to weaker antibacterial activity.Bio-metabolizable materials such as porphyrins and black phosphorus are assembled into nano-inhibitors through metal coordination to improve bacterial targeting via electrostatic action,and the combination of photothermal and photodynamic therapies can significantly enhance bacterial inhibition efficiency.Therefore,the thesis summarized the research progress of light-sensing antibacterial agents,I have designed and prepared three new porphyrin-derived antibacterial agents,investigated their structure,composition and performance,and further explored the inhibition efficiency and mechanism against E.coli and S.aureus.The main findings are as follows:（1）Preparation of black phosphorus europium porphyrins and research on its antibacterial properties:In this section,the coordination of black phosphorus（BP）with europium ions(Eu³⁺)was first investigated and Eu-loaded nanomaterials（BP@Eu）were prepared,followed by black phosphorus europium porphyrins（BP@Eu-TCPP）obtained by coordination of europium with 5,10,15,20-tetrakis（4-carboxyphenyl）porphyrin（TCPP）.Raman,FT-IR and XPS spectras demonstrate the presence of Eu-P and Eu-O coordination bonds.The results showed that the photothermal properties,photothermal stability and inhibition efficiency of BP@Eu-TCPP were significantly higher than those of BP;BP@Eu-TCPP had a stronger affinity for bovine serum protein and lipase with binding constants of 9.26*10³and6.52*10²respectively.Further studies revealed that BP@Eu-TCPP inhibited the photodynamic properties of TCPP due to the interaction of europium with TCPP;L-arginine could interact with BP@Eu-TCPP to restore the fluorescence and photodynamic properties by forming a TCPP-L-Arg complex.BP@Eu-TCPP can act as a fluorescent turn-on probe for the detection of arginine with a detection limit of4.02μM.The antibacterial mechanism of BP@Eu-TCPP was further investigated and found to be able to alter the original morphology of bacteria,disrupt the integrity of the cell wall and interfere with the uptake of iron ions,pyruvate and the normal redox balance of NADH/NAD⁺by bacteria.The results show that BP@Eu-TCPP is an L-arginine-activated photodynamic photothermal inhibitor and an L-arginine fluorescence-sensing probe.（2）Preparation of porphyrin covalent organic frameworks encapsulated with gallium black phosphorus and research on their antibacterial properties:In this section,black phosphorus gallium（BP@Ga）was prepared and used as a template to induce 5,10,15,20-tetra（4-aminophenyl）porphyrin（TAPP）and terephthaloyl chloride to form nanoporous materials by amide bonding,followed by copper ion coordination assembly to obtain porous spherical black phosphorus-based porphyrin-copper covalent organic framework materials（BPGa@COF-Cu）.BPGa@COF-Cu has been proven to have high performance in the red light driven generation of single line oxygen and photothermal properties.It was shown that BPGa@COF-Cu acted as a nanoenzyme and catalyzed the production of hydroxyl radicals from hydrogen peroxide.The minimum bactericidal concentration of this compound against E.coli and S.aureus under light was only 1 and 3μg/m L,respectively.BPGa@COF-Cu also disrupt bacterial biofilms by photoactivation.The results show that BPGa@COF-Cu was a synergistic agent for bacterial inhibition that combines photothermal,photodynamic,and chemical dynamic modals.（3）Preparation of metalloporphyrin cellulose and research on its antibacterial properties:In this section,a porphyrin cellulose（CEL-THPP）was prepared using 5,10,15,20-tetra（4-hydrazinyl phenyl）porphyrin（THPP）and dialdehyde cellulose（DAC）by covalent acylhydrazone coupling,with the assembly of Zn ions investigated,resulting in a light-responsive porous metalloporphyrin cellulose（CEL-THPP@Zn）.CEL-THPP@Zn showed a forbidden band width of 1.69e V,a broad absorption band at 400-900 nm and strong fluorescence emission at 662nm.Therefore,the single-linear oxygen production capacity of CEL-THPP@Zn under red light irradiation was superior to that of CEL-THPP.Further studies revealed that CEL-THPP@Zn demonstrated good inhibition of both E.coli and S.aureus and had an adsorption effect on the bacteria.In summary,CEL-THPP@Zn is a surface porous spherical rod-shaped luminescent fibre with a good bacterial adsorption performance,showing a superior broad-spectrum bacterial inhibition in both dark and light conditions.更多还原