高效率阳离子型光敏剂的设计及其在低辐照剂量光动力抗菌中应用

doi:10.6023/cjoc202503024

有机化学 ›› 2025, Vol. 45 ›› Issue (11): 4143-4151.DOI: 10.6023/cjoc202503024 上一篇下一篇

研究论文

高效率阳离子型光敏剂的设计及其在低辐照剂量光动力抗菌中应用

白雪^a, 谢祎黎^b, 李君缘^a, 莫梓华^a, 万清^a^,^c^,^*()

^a 南昌航空大学材料科学与工程学院南昌 330036
^b 豫章师范学院生态与环境学院南昌 330103
^c 华南理工大学聚集诱导发光高等研究院广州 510530

收稿日期:2025-03-24 修回日期:2025-06-07 发布日期:2025-08-18
基金资助:
国家自然科学基金(52303233); 中国科协青年人才托举(2023QNRC001); 江西省自然科学基金(20224BAB214001); 江西省自然科学基金(20232BAB203026); 广东省基础与应用基础研究基金(2023A1515110186)

Design of High Efficiency Cationic Photosensitizer and Its Application in Low Irradiation Dose Photodynamic Antibacterial

Xue Bai^a, Yili Xie^b, Junyuan Li^a, Zihua Mo^a, Qing Wan^a^,^c^,^*()

^a School of Materials Science and Engineering, Nanchang Hangkong University, Nanchang 330063
^b School of Ecology and Environment, Yuzhang Normal University, Nanchang 330103
^c Aggregation-Induced Emission (AIE) Institute, South China University of Technology, Guangzhou 510530

Received:2025-03-24 Revised:2025-06-07 Published:2025-08-18
Contact: *E-mail: wanqingwork@nchu.edu.cn
Supported by:
National Natural Science Foundation of China(52303233); Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(2023QNRC001); Natural Science Foundation of Jiangxi Province(20224BAB214001); Natural Science Foundation of Jiangxi Province(20232BAB203026); Guangdong Basic and Applied Basic Research Foundation(2023A1515110186)

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摘要/Abstract

荧光成像介导光动力疗法具有原位可视化、精准治疗、操作方便和无耐药性等诸多优势, 已经在癌细胞和耐药菌的成像及治疗领域展现重要的应用潜力. 光敏剂是光动力疗法的重要组成部分, 其产生的荧光强度和活性氧(ROS)效率直接影响光诊疗效果. 传统方法主要通过强化分子内电荷转移或引入重原子效应以促进系间窜越(ISC)过程, 从而产生较多的三线态能量, 但严重猝灭了光敏剂的发光效率. 因此, 发展可以同时提高光敏剂荧光和ROS效率的分子设计方法具有重要的研究意义. 此文报道了一种通过在电子给体和受体间引入不同刚性程度的稠环基元以提高分子摩尔吸光系数的策略, 不仅提高光敏剂的荧光量子效率, 同时大大提高光敏剂产生I和II型ROS效率. 以三苯胺作为电子给体, 吡啶盐作为电子受体, 在电子给体和受体之间分别引入苯、萘和芘稠环基元, 设计和制备了三种阳离子型光敏剂(TPA-B-PI, TPA-N-PI和TPA-Py-PI), 并详细研究了所制备光敏剂的光物理和光敏性能. 研究结果表明, 由于芘分子的吸光截面更大, 致使TPA-Py-PI具有更佳的摩尔吸光系数, 受激激发后产生更多的单线态和三线态激子, 从而表现出最佳的荧光量子效率和I/II型ROS效率. 光动力抗菌实验结果显示, 光敏剂TPA-Py-PI对金黄色葡萄球菌(S. aureus)、抗药性金黄色葡萄球菌(MRSA)和大肠杆菌(E. coli)均表现良好的光动力抗菌效果. 并且, TPA-Py-PI在低浓度(25 nmol/L)和低辐照剂量(20 mW/cm²)条件下对MRSA实现了99.99%的抗菌效果.

关键词: 光动力疗法, 阳离子光敏剂, 摩尔吸光系数, 抗菌

Fluorescent image-guided photodynamic therapy (PDT) has many advantages such as in situ visualization, precision treatment, easy operation, and no drug resistance, which has shown important application potential in the imaging and treatment of cancer cells and drug-resistant bacteria. Photosensitizer (PS) is an important part of PDT, and its fluorescence and reactive oxygen species (ROS) efficiency directly affect phototherapeutic effect. Traditional methods mainly enhance the intramolecular charge transfer or introduction of the heavy atom effect to promote the intersystem crossing (ISC) process to produce more triplet energy, but seriously quenching the fluorescent efficiency of the PS. Therefore, it is important to develop molecular engineering that can improve simultaneously the fluorescence and ROS efficiency of PS. This work reports a strategy to improve the molecular molar absorption coefficient by introducing fusing ring units with different rigidity between the electronic donor and acceptor, which not only improves the photoluminescence quantum efficiency, but also greatly improving the efficiency of producing type I/II ROS. Using triphenylamine as electronic donor and cationic pyridine as acceptor, three cationic PSs (TPA-B-PI, TPA-N-PI and TPA-Py-PI) with different molar absorption coefficients were designed and prepared by introducing benzene, naphthalene and pyrene rings between electronic donor and acceptor. The photophysical and photo-sensitive properties of the PSs were researched in detail. Experimental results showed that, owing to the larger absorption cross section of pyrene molecule, TPA-Py-PI exhibited a superior molar absorption coefficient. Furthermore, more singlet and triplet excitons were generated after excitation, resulting in the best fluorescence quantum efficiency and type I/II ROS efficiency. The results of photodynamic antibacterial experiment showed that the TPA-Py-PI had good antibacterial effect on Staphylococcus aureus (S. aureus), drug-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). Moreover, TPA-Py-PI achieved good antibacterial efficiency of 99.99% against MRSA at low concentration (25 nmol/L) and irradiation dose (20 mW/cm²).

Key words: photodynamic therapy, cationic photosensitizer, molar absorbance coefficient, antibacterial

引用此文

白雪, 谢祎黎, 李君缘, 莫梓华, 万清. 高效率阳离子型光敏剂的设计及其在低辐照剂量光动力抗菌中应用[J]. 有机化学, 2025, 45(11): 4143-4151.

Xue Bai, Yili Xie, Junyuan Li, Zihua Mo, Qing Wan. Design of High Efficiency Cationic Photosensitizer and Its Application in Low Irradiation Dose Photodynamic Antibacterial[J]. Chinese Journal of Organic Chemistry, 2025, 45(11): 4143-4151.

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图/表 5

图式1. 化合物TPA-B-PI, TPA-N-PI和TPA-Py-PI的合成路线

Scheme 1. Synthestic route of compound TPA-B-PI, TPA-N-PI, and TPA-Py-PI

图1. 基于MX-062/6-31G (d,p)计算的TPA-B-PI, TPA-N-PI和TPA-Py-PI的HOMO和LUMO电子分布图

Figure 1. Electronic distribution of HOMOs and LUMOs of TPA-B-PI, TPA-N-PI and TPA-Py-PI calculated by using the MX-062/6-31G (d,p) basis set

图2. (A) TPA-B-PI, TPA-N-PI和TPA-Py-PI在THF中的紫外-可见吸收光谱、(B)荧光发射光谱和(C)归一化荧光发射光谱

Figure 2. (A) UV-Vis absorption, (B) PL spectra and (C) normalized PL spectra of TPA-B-PI, TPA-N-PI and TPA-Py-PI in THF Concentration of PS: 10 μmol/L

图3. (A) ABDA探针在含有PS的DMSO/H2O混合液中吸收强度的变化、(B) DHR123探针和(C) HPF探针在含有PS的DMSO/ H2O混合液中荧光强度的变化

Figure 3. (A) Change of absorption intensity of ABDA probe in PSs-contained DMSO/H2O mixture; (B) Change of fluorescence intensity of DHR123 probe and (C) HPF probe in PSs-contained DMSO/H2O mixture Concentration of PS: 10 μmol/L, concentration of ABDA: 20 μmol/L, concentration of DHR123: 5 μmol/L, concentration of HPF: 5 μmol/L, DMSO/H2O (V/V=1/99), white light power: 30 mW/cm2

图4. 通过平板稀释法在有或无白光照射条件下作用后光敏剂对S. aureus和MRSA的(A)抑菌平板图和(B)菌落计数统计(白光20 mW/cm2, 20 min)

Figure 4. After the action with or without white light irradiation by the plate dilution method, the photosensitizer (A) bacteriostatic plate image and (B) colony count statistics for S. aureus and MRSA (20 mW/cm2, 20 min under white light)

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高效率阳离子型光敏剂的设计及其在低辐照剂量光动力抗菌中应用

Design of High Efficiency Cationic Photosensitizer and Its Application in Low Irradiation Dose Photodynamic Antibacterial

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