Lu Yao, Zhang Yutao, Wu Xia, Pu Ruihua, Yan Chenxu, Liu Weimin, Liu Xiaogang, Guo Zhiqian, Zhu Wei-Hong
Key Laboratory for Advanced Materials, Institute of Fine Chemicals, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology Shanghai 200237 China
Fluorescence Research Group, Singapore University of Technology and Design 8 Somapah Road Singapore 487372 Singapore.
Chem Sci. 2024 Jun 24;15(31):12431-12441. doi: 10.1039/d4sc01915f. eCollection 2024 Aug 7.
Singlet oxygen (O), as a fundamental hallmark in photodynamic therapy (PDT), enables ground-breaking clinical treatment in ablating tumors and killing germs. However, accurate monitoring of O remains a significant challenge in probe design, with primary difficulties arising from inherent photo-induced side reactions with poor selectivity. Herein, we report a generalizable zwitterionic strategy for ultra-stable near-infrared (NIR) chemiluminescent probes that ensure a highly specific [2 + 2] cycloaddition between fragile electron-rich enolether units and O in both cellular and dynamic domains. Innovatively, zwitterionic chemiluminescence (CL) probes undergo a conversion into an inert ketone excited state with an extremely short lifetime through conical intersection (CI), thereby affording sufficient photostability and suppressing undesired photoreactions. Remarkably, compared with the well-known commercial O probe SOSG, the zwitterionic probe QMI exhibited an ultra-high signal-to-noise ratio (SNR, over 40-fold). Of particular significance is that the zwitterionic CL probes demonstrate excellent selectivity, high sensitivity, and outstanding photostability, thereby making a breakthrough in real-time tracking of the FDA-approved 5-ALA-mediated PDT process in living mice. This innovative zwitterionic strategy paves a new pathway for high-performance NIR chemiluminescent probes and high-fidelity feedback on O for future biological and medical applications.
单线态氧（O）作为光动力疗法（PDT）的一个基本标志，在消融肿瘤和杀灭病菌方面实现了开创性的临床治疗。然而，在探针设计中，对单线态氧的精确监测仍然是一项重大挑战，主要困难源于固有的光诱导副反应，选择性较差。在此，我们报告了一种适用于超稳定近红外（NIR）化学发光探针的两性离子策略，该策略确保了脆弱的富电子烯醚单元与单线态氧在细胞和动态领域均能发生高度特异性的[2 + 2]环加成反应。创新的是，两性离子化学发光（CL）探针通过锥形交叉（CI）转化为寿命极短的惰性酮激发态，从而提供足够的光稳定性并抑制不期望的光反应。值得注意的是，与著名的商业单线态氧探针SOSG相比，两性离子探针QMI表现出超高的信噪比（SNR，超过40倍）。特别重要的是，两性离子CL探针表现出优异的选择性、高灵敏度和出色的光稳定性，从而在实时跟踪活小鼠中FDA批准的5-氨基乙酰丙酸介导的光动力疗法过程方面取得了突破。这种创新的两性离子策略为高性能近红外化学发光探针以及对单线态氧的高保真反馈开辟了一条新途径，以用于未来的生物和医学应用。
