Faculty of Chemical and Food Technology, Ho Chi Minh City University of Technology and Education, 1 Vo Van Ngan, Thu Duc City, Ho Chi Minh City, Vietnam.
Department of Chemistry, University of Houston, 4800 Calhoun Rd., TX 77004, Houston, USA.
Angew Chem Int Ed Engl. 2023 Aug 1;62(31):e202300467. doi: 10.1002/anie.202300467. Epub 2023 Jun 27.
Studies of organometallic reactions in living cells commonly rely on ensemble-averaged measurements, which can obscure the detection of reaction dynamics or location-specific behavior. This information is necessary to guide the design of bioorthogonal catalysts with improved biocompatibility, activity, and selectivity. By leveraging the high spatial and temporal resolution of single-molecule fluorescence microscopy, we have successfully captured single-molecule events promoted by Ru complexes inside live A549 human lung cells. By observing individual allylcarbamate cleavage reactions in real-time, our results revealed that they occur with greater frequency inside the mitochondria than in the non-mitochondria regions. The estimated turnover frequency of the Ru complexes was at least 3-fold higher in the former than the latter. These results suggest that organelle specificity is a critical factor to consider in intracellular catalyst design, such as in developing metallodrugs for therapeutic applications.
在活细胞中进行的有机金属反应研究通常依赖于整体平均测量，这可能会掩盖对反应动力学或特定位置行为的检测。这些信息对于指导设计具有更好生物相容性、活性和选择性的生物正交催化剂是必要的。通过利用单分子荧光显微镜的高空间和时间分辨率，我们成功地捕捉到了 Ru 配合物在活 A549 人肺细胞内促进的单分子事件。通过实时观察单个烯丙基氨基甲酸酯裂解反应，我们的结果表明，这些反应在线粒体中的发生频率高于非线粒体区域。Ru 配合物的估计周转率在前一种情况下至少高出 3 倍。这些结果表明，细胞器特异性是细胞内催化剂设计中需要考虑的一个关键因素，例如为治疗应用开发金属药物。
