单线态氧双光子荧光探针检测机理的研究

Singlet oxygen fluorescence probe technology can timely and efficiently identify singlet oxygen in tissues and provide important technical means for monitoring and evaluating photodynamic therapy (PDT) process at the molecular level. Compared with traditional single-photon fluorescent probes, two-photon fluorescent probes have advantages in larger penetration depth and less damage to the sample, providing a promising strategy to detect singlet oxygen. Therefore, elucidating the fluorescent detection mechanism and designing novel high-performance two-photon fluorescent probes have great scientific value. In this project, we propose to establish molecular models to simulate the interaction between the probes and singlet oxygen, and investigate the reaction path to reveal the specific recognition mechanism at molecular level. The probe fluorescence intensity change is performed with frontier molecular orbital analysis and potential energy surface scanning, and then analyzed by the photo-induced electron transfer (PET) mechanism to explore the detection mechanism of two-photon probes. With the aid of theoretical computation, we propose to screen and construct fluorescent probes with better performance.In addition, we propose to design a novel fluorescent probe based on intramolecular charge transfer (ICT) instead of PET.

单线态氧荧光探针技术可及时高效地对组织中单线态氧进行特异性识别，为分子层面监测评估光动力治疗（PDT）过程及治疗效果提供重要的技术手段。相对于传统的单光子荧光探针，双光子荧光探针具有穿透深度大、对样品损伤小等优点，在单线态氧检测领域具有更广阔的应用前景。因此，对单线态氧双光子荧光探针检测技术进行详细研究，阐明荧光探针的检测机理，并设计新型高性能双光子荧光探针，具有非常重要的科学意义。本项目通过建立分子模型，模拟探针与单线态氧的相互作用过程，搜寻反应路径，在分子层面揭示蒽环结构对单线态氧的特异性识别机制；结合前线分子轨道分析和势能面扫描，分析光诱导电子转移机理（PET）带来的探针荧光强度变化，解析探针的检测原理；通过理论筛查荧光基团的双光子性能，构建性能更优的荧光探针，同时，突破PET机理，设计基于分子内电荷转移机理（ICT）的新型荧光探针。

单线态氧荧光探针技术可及时高效地对组织中单线态氧进行特异性识别，为分子层面监测评估光动力治疗（PDT）过程及治疗效果提供重要的技术手段。相对于传统的单光子荧光探针，双光子荧光探针具有穿透深度大、对样品损伤小等优点，在单线态氧检测领域具有更广阔的应用前景。因此，对单线态氧双光子荧光探针检测技术进行详细研究，阐明荧光探针的检测机理，并设计新型高性能双光子荧光探针，具有非常重要的科学意义。本项目在理论计算层面对单线态氧双光子荧光探针进行了研究。项目使用BS-DFT方法模拟了含有单线态氧分子的体系，通过反应路径搜寻，从原子分子层面解释蒽环结构对单线态氧的特异性识别机制；通过前线分子轨道模拟和基态及激发态势能面扫描，揭示了光诱导电子转移（PET）和分子内电荷转移（ICT）机制在检测过程中的作用；并通过理论结合实验，设计了2款新型双光子荧光探针。同时，通过对PET和ICT检测机制的理解，开发了多款基于碳量子点的荧光探针。配合本单位（合作课题组）开发的双光子荧光显微镜，实现了细胞层面的双光子荧光成像。项目共发表了SCI论文6篇，申请了发明专利5项，其中2项专利获得了授权。