Zdubek Anna, Maliszewska Irena, Grabowiecka Agnieszka, Kowalczyk Rafał, Turek Bartosz
Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
ACS Omega. 2024 Nov 22;9(49):48629-48641. doi: 10.1021/acsomega.4c07696. eCollection 2024 Dec 10.
The purpose of this work was to examine the effect of phosphoric and bisaminophosphinic acids on the effectiveness of photoinactivation of with 5-aminolevulinic acid (5-ALA) as a precursor of protoporphyrin IX. Two diode lasers λ = 404 nm (radiation intensity 26 mW cm) and λ = 630 nm (radiation intensity 55 mW cm) were used as sources of light. The most effective agent was ()-(-)-1,1'-binaphthyl-2,2'-diylhydrogen phosphate, and a significant improvement in bactericidal effect of 5-ALA-aPDI was achieved by pretreating with this compound at nontoxic concentrations of 0.368 mM. It was found that 15 min of blue light illumination was enough to achieve bacterial cell mortality of 99.999%. Photoelimination of this pathogen using red light was less effective, and the required killing effect (at least 99.99%) was not achieved until 45 min of exposure. The mechanism of increased pathogen destruction by the examined acids is multifaceted and includes not only the destabilization of the outer bacterial cell membrane by organophosphates but also an increase in the level of protoporphyrin IX in cells due to chelation of iron ions. Furthermore, a synergistic effect of intracellular photosensitizers and ()-(-)-1,1'-binaphthyl-2,2'-diylhydrogen phosphate acting as an additional blue/red light-induced photosensitizer cannot be excluded.
本研究的目的是考察磷酸和双氨基次膦酸对以5-氨基乙酰丙酸(5-ALA)作为原卟啉IX前体的光灭活效果的影响。使用两台二极管激光器,波长分别为λ = 404 nm(辐射强度26 mW/cm²)和λ = 630 nm(辐射强度55 mW/cm²)作为光源。最有效的试剂是()-(-)-1,1'-联萘-2,2'-二基磷酸氢酯,通过用浓度为0.368 mM的无毒该化合物预处理,5-ALA介导的光动力灭活的杀菌效果得到显著改善。结果发现,蓝光照射15分钟足以实现99.999%的细菌细胞死亡率。使用红光对该病原体进行光消除效果较差,直到照射45分钟才达到所需的杀灭效果(至少99.99%)。所研究的酸增加病原体破坏的机制是多方面的,不仅包括有机磷酸盐使细菌外细胞膜不稳定,还包括由于铁离子螯合导致细胞中原卟啉IX水平升高。此外,不能排除细胞内光敏剂与作为额外的蓝/红光诱导光敏剂的()-(-)-1,1'-联萘-2,2'-二基磷酸氢酯之间的协同作用。