基于双发色团的稀土卟啉-碳量子点荧光探针构建及在不同构型G-四链体的分析应用

G-quadruplex structure in DNA is one of the important targets of anti-tumor drug design, and establishing sensitivity analysis method for it is particularly important. To solve the problem of accurately and rapidly distinguishing among G-quadruplexes with different configurations, in this project, we will use the quantum simulation method and experiment method to explore the target molecular design and functional modification of rare earth porphyrin. And a new method of in situ co-valence bond construction will be used to synthesise a novel double-chromosome rare earth porphyrin-carbon quantum dots fluorescent probe. And then take advantages of unique dual fluorescence of the probe, a multispectral data array will be constructed which will be used to the qualitative and quantitive analysis of G-quadruplexes with different configurations. This project will study the effect of rare earth porphyrin-carbon quantum dots on the G-quadruplex sensing properties, reveal the interaction mechanism, and establish the structure-effect relationship between rare earth porphyrin-carbon quantum dots and fluorescence response, in order to accurately identify and detect of G-quadruplexes with different configurations in the complex matrix. The idea have not been reported, the project will provide a new analytical method for the rapid analysis of G-quadruplex with different configurations, analysis and study of anti-cancer drugs targeted at G-quadruplexes, and this project is of great scientific significance and have application value for the utilisation of fine chemicals based on rare earth and nanoporphyrins.

DNA中G-四链体结构是抗肿瘤药物设计的重要靶点之一，建立G-四链体的灵敏分析方法尤为重要。针对目前不同构型G-四链体难以快速准确区分的难题，本项目将量子化学计算和实验研究相结合的方法，并拟用共价键原位构筑法设计制备可识别不同构型G-四链体的稀土卟啉-碳量子点荧光探针，利用其独特的双发色团荧光性，构建多元光谱数据阵列，从而实现对不同构型G-四链体进行定性定量解析。本项目将研究稀土卟啉-碳量子点微观结构对G-四链体传感性能的影响，建立稀土卟啉-碳量子点与不同构型G-四链体荧光响应的构效关系，揭示其相互作用机制，从而实现对复杂基质中不同构型G-四链体的准确识别。该思路尚未见文献报道，本项目为不同构型G-四链体的快速检测和以G-四链体为靶点的抗癌药物分析研究提供新的分析手段，其研究结果对基于稀土和纳米卟啉的精细化工品资源化利用具有重要的科学意义和应用价值。

针对目前不同构型G-四链体识别的探针靶向分子设计及功能性修饰规律不清楚、荧光探针与不同构型 G-四链体的构效关系及作用机制不明确，难以快速准确的对复杂生物体系中不同 G-四链体构型进行快速、准确定量表征等问题。本项目首先制备了一种N,P共掺杂碳纳米管负载CoPx多孔材料，通过简单的制备方法获得廉价的非贵金属类复合催化剂，得到碳纳米管氮、磷共掺杂的高效氧还原反应催化剂（NC@CoPx/PyCNT-900），对纳米卟啉的修饰规律进行了初步探索。随后，本项目对量子点-卟啉系统的响应性能进行了探索优化，设计制备了一种基于双量子点-纳米卟啉荧光可视化纸基传感器的有机磷农药检测新方法。通过利用ZnTPyP纳米化后可以更好结合目标物的特点，结合量子点“Turn-off-on”模型减小环境干扰的优势，实现了微量有机磷农残的高选择性和高灵敏性可视化检测。最后，本研究对量子点-纳米卟啉系统对不同构型DNA及G-四链体的识别性能进行了深入研究，构建了一种新型纳米卟啉-CdTe量子点体系对不同构型DNA的识别方法。该传感器可以用于区分由K+、Na+和无离子形成的不同构型的G-四链体，还可用于观察G-四链体构型的动态转换，为体内不同结构DNA的快速定性定量分析方面提供了方向。该研究结果丰富了生物医药、精细化工等领域中的DNA快速分析方法。