Synthesis And Application Of Hyamine-modified BODIPY

Mitochondria,the energy powerhouse of the cell,are play vital roles in the cytoplasm of almost all eukaryotic cells.The foremost function of mitochondria is to produce ATP;however,some evidences have shown that mitochondrial dysfunction associated with neurodegenerative disease,such as Alzheimer's,Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis.In mitochondria,biothiols play a key role in maintaining the redox environment to avoid or repair oxidative damage leading to dysfunction and cell death.Changes in mitochondrial biothiols can reflect physiological and pathological processes in vivo.There are many ways to detect this phenomenon,and the most convenient method is fluorescence imaging.In recent years,4,4-difluoro-4-bora-3a,4a-diaza-s-indacene(BODIPY)dyes have been favored by scientific researchers in fluorescence imaging technology,which is mainly attributed to the excellent properties of the dyes: high molar extinction coefficient,high fluorescence quantum yield,good photo-stability,more structural modification sites,narrow fluorescence spectra FWHM,and good tolerance of solvent polarity and pH value.Researchers often replace the carbon atoms at the meso positions of BDOIPY dyes with nitrogen atoms to construct Aza-BODIPY,and replace the 1,3,5,and 7 positions with aromatic rings so that the maximum absorption wavelength and emission wavelength can be in the near infrared region.However,this kind of modification will result in large conjugate system and poor water solubility.In addition,the dyes have no subcellular targeting ability,which limits the application of dyes in biology.Based on organic chemistry,analytical chemistry and biology,we designed the amino quaternary ammonium salt modified Aza-BODIPY to enhance the water solubility;and designed quaternary hydroxypyridine and quaternary pyridinium at the meso position of BODIPY.For this purpose,we have carried out the following works:In the second chapter,based on previous studies of Aza-BODIPY dyes and literature research,we designed and synthesized twelve amino-modified Aza-BODIPY boron-substituted derivatives.We expected that introduction of amino groups and quaternary ammonium salts can improve the solubility of Aza-BODIPY,which have long wavelength.Using Aza-BODIPY as the basic structure,diethylamino group structure was introduced into the para-position of the 3,5-position benzene ring.We synthesized twelve kinds of Aza-BODIPY,and three of them were selected for quaternary ammonium saltation.By analyzing the ultraviolet absorption and fluorescence spectral data of the above fifteen Aza-BODIPY dyes,we study the changes of wavelength,fluorescence quantum yield,half-width and Stocks shift.In the third chapter,the 1,7-benzocyclol Cl-BODIPY structure were designed and synthesized.Based on the PET effect,the fluorescence probes,which carry mercaptopyridinium component at the meso position,were constructed.Moreover,the pyridinium component may act as both the mitochondrial targeting moiety and electronic sink to turn-off the fluorescence of fluorophore.Furthermore,we tested the reaction rapid and the mitochondrial targeting ability of the probe.