Abstract：
Photodynamic therapy has always been an antibacterial tool for solving multi-drug resistant bacteria problem, but the side effects and the low efficiency due to the high aggregation and low solubility of photosensitizers limit its application. Due to the anti-inflammatory effect of caffeic acid, two novel photosensitizers (CA-1-TBO, CA-TBO) were synthesized by conjugating caffeic acid with toluidine blue O (TBO). The structures have been characterized by 1HNMR and high-resolution mass spectrometry. The UV-vis absorption, fluorescence spectra and the octanol-water partition coefficient of two photosensitizers were measured to evaluate their photophysical properties and hydrophilic/hydrophobic properties. Compared with parent TBO, the two modified photosensitizers have shown a higher quantum yield and kinetics constants of singlet oxygen, which has been supported by the simulation results of density functional theory. As drug-resistant representatives of gram-positive and gram-negative bacteria, respectively, S. aureus and P. aeruginosa have been used for in vitro antibacterial experiments. The sterilization efficiencies of the two modified photosensitizers far exceed that of parent TBO. The results of the octanol-water partition coefficient and fluorescence quantification showed that modified photosensitizers CA-1-TBO and CA-TBO could be more accumulated than parent TBO. Based on scanning electron microscopy images, protein gel electrophoresis, and the conductivity of the bacterial solution, the possible mechanism of improved antibacterial photodynamic efficiencies could be induced by membrane permeability due to the caffeic acid effect. The findings demonstrate the significant potential of natural phenolic compounds in the development of photosensitizer molecules with characteristics such as more efficient, biocompatible and less side effects.
摘要：
光动力疗法一直是解决多药耐药菌问题的抗菌工具,但是由于光敏剂的高聚集性和低溶解度而导致的副作用和低效率限制了其应用。由于咖啡酸的抗炎作用，两种新型光敏剂（CA-1-TBO，通过将咖啡酸与甲苯胺蓝O（TBO）缀合合成CA-TBO）。结构已通过1HNMR和高分辨率质谱表征。UV-vis吸收，测量了两种光敏剂的荧光光谱和辛醇-水分配系数，以评估它们的光物理性质和亲水/疏水性能。与父TBO相比，两种改性光敏剂显示出更高的量子产率和单线态氧的动力学常数，这得到了密度泛函理论模拟结果的支持。作为革兰阳性菌和革兰阴性菌的耐药代表,分别,金黄色葡萄球菌和铜绿假单胞菌已用于体外抗菌实验。两种改性光敏剂的灭菌效率远远超过母体TBO。辛醇-水分配系数和荧光定量的结果表明，改性光敏剂CA-1-TBO和CA-TBO可以比母体TBO更多地积累。基于扫描电子显微镜图像，蛋白质凝胶电泳,和细菌溶液的电导率，由于咖啡酸的作用，膜的通透性可以诱导抗菌光动力效率提高的可能机制。研究结果表明，天然酚类化合物在光敏剂分子的开发中具有重要的潜力，具有更高效，生物相容性和较少的副作用。
