Li Wei, Zou Juan, Zhu Shiyu, Mao Xianxian, Tian Hongyan, Wang Xiaojian
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China.
Chemistry. 2019 Aug 6;25(44):10328-10332. doi: 10.1002/chem.201902834. Epub 2019 Jul 11.
Bioorthogonal reactions have widespread applications in biological systems, and development of new bioorthogonal reactions has been of great interest over the past two decades. In this work, the design and synthesis of a family of fluorinated dibenzocyclooctynes (FDIBOs) are reported. The electron-deficient nature of fluorine atoms significantly accelerated the reaction of cyclooctynes in 1,3-dipolar cycloadditions, with either benzyl azide or ethyl diazoacetate, compared to conventional dibenzocyclooctyne (DIBO). In addition, FDIBOs showed unique trackable properties owing to the high NMR sensitivity of the naturally abundant F isotope. Biological molecules, including a monosaccharide, a peptide, and a protein, were tested with FDIBOs, and these reactions could be easily monitored by F NMR spectroscopy to evaluate the progress of the conjugation reactions. In addition, labeling of live cells was also demonstrated with metabolically modified bacteria to expand the possible applications of FDIBOs.
生物正交反应在生物系统中有着广泛的应用，在过去二十年里，新型生物正交反应的开发一直备受关注。在这项工作中，报道了一类氟化二苯并环辛炔（FDIBOs）的设计与合成。与传统的二苯并环辛炔（DIBO）相比，氟原子的缺电子性质显著加速了环辛炔与苄基叠氮或重氮乙酸乙酯的1,3-偶极环加成反应。此外，由于天然丰度的F同位素具有高核磁共振灵敏度，FDIBOs表现出独特的可追踪特性。使用FDIBOs对包括单糖、肽和蛋白质在内的生物分子进行了测试，这些反应可以通过F NMR光谱轻松监测，以评估共轭反应的进程。此外，还通过代谢修饰的细菌证明了对活细胞的标记，以扩展FDIBOs的可能应用。
