Development Of Cycloaddition And Non-hydrolyzed Staudinger Reactions Based On Polyfluorinated Aromatic Azides And Applications

Bioorthogonal chemistry,due to its ability to be carried out in aqueous solution,high selectivity and consistent with naturally occurring functional groups,has become a powerful new tackle for investigating biological systems.It helps to explore the structure and function of biomolecules in biological systems.The development of highly efficient bioorthogonal reactions is critical for biological materials and chemical biology.Due to the SPAAC and the Staudinger reaction rate,we want to introduce a fluorine group on the aromatic azide to produce a faster Staudinger ligation,a cycloaddition click reaction,etc.The primary coverage of this thesis is based on development of cycloaddition and non-hydrolyzed Staudinger reactions based on polyfluorinated aromatic azides and applications.1.Designed and synthesized to introduce a difluoro atom in the ortho position of the aromatic azide.With a single fluorine atom and a fluorine-free atom as a control,the probe can undergo a faster cycloaddition click reaction.We further developed a rapid SPAAC reaction with tetrafluoroaromatic azide with a kinetic constant of 3.60 M-1s-1.This is one of the fastest SPAAC reactions reported so far.We made this reaction for efficient covalent labeling of proteins and for bioimaging of mitochondria in living cells.2.The design of the synthesized ortho-difluoroaromatic azide can further increase the Staudinger ligation reaction rate.We found a non-hydrolyzed Staudinger reaction(NSR),and further developed a non-hydrolyzed Staudinger reaction based on tetrafluorinated aromatic azide.The reaction was applied for efficient labeling of proteins,DNA,and RNA.3.Designed and developed a bisazido linker for chemoselective dual functioning,based on non-hydrolyzed Staudinger reaction,cycloaddition click reaction,using a one-pot reaction to obtain bifunctional molecules.The bioorthogonal reaction was distinguished in one pot.A bifunctional FRET molecule with good yield was prepared for two-color bioimaging in living cells.This work demonstrated that the non-hydrolyzed Staudinger reaction can be used in combination with else bioorthogonal reactions without using any catalyst.