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BODIPY and BOPHY derivatives: synthesis, spectroscopy and microscopy

Book - Dissertation

BODIPY is a well-known fluorophore, used in many applications because of its brightness, chemostability, photostability and sharp absorption and emission peaks. There are many methods for functionalization, and the spectroscopic properties are tunable by changing the substitution pattern. The use of BODIPYs in modern fluorescence microscopy techniques, however, remains limited.Given this background, three different reactive BODIPY dyes were synthesized, to covalently couple with SNAP fusion proteins. A blue-shifted meso-aminoBODIPY with moderate quantum yield of fluorescence did not show enough contrast, because of the hindrance of the autofluorescence signal of cells in the blue spectral region. The red-shifted azaBODIPY derivative formed insoluble bright fluorescent aggregates, which prevented proper imaging. A third, highly fluorescent BODIPY, emitting at 576 nm, did not have these problems, and under the right conditions yielded a promising imaging fluorophore. In the second part, a new double boron-chelated fluorophore called BOPHY is introduced. An α-dichlorinated derivative, 3,8-dichloroBOPHY, was obtained in 51 % yield starting from unsubstituted pyrrole. Subsequent functionalization via nucleophilic aromatic substitutions with O-, N- and S-nucleophiles was achieved in high yields. Palladium catalyzed cross coupling reactions, particularly Stille and Sonogashira coupling reactions, led to red-shifted chromophores. The absorption maxima of the synthesized dyes vary from 442 to 545 nm, with emission maxima ranging from 474 to 612 nm and quantum yields of fluorescence in solution from <1 % to 100 %.The substitution pattern of BOPHY was further explored by introducing a methyl and phenyl substituent on the meso-position. 5,10-DimethylBOPHY was isolated as a solid, but is unstable in solution. A phenyl substituent at the meso position of BOPHY proved to be impossible, as chelation stopped at a single BF2-unit. Starting from 3,8-dichloroBOPHY and a halogenated phenol derivative, ring fusion was successfully used as a strategy to red shift the BOPHY fluorophore, while keeping a high quantum yield of fluorescence. This strategy makes the use of complicated, substituted pyrroles redundant, and resulted in a π-extended benzofuran-fused BOPHY.
Publication year:2019