Development of fluorescent probes based on the benzothiadiazole scaffold

Sammanfattning: Fluorescent probes are valuable imaging tools for studying biological processes on a cellular level. While antibody-based fluorescence imaging typically requires fixation of cells, small-molecule fluorophores have the advantage that they can often be used for live-cell imaging. In the last decade, the electron-poor 2,1,3-benzothiadiazole scaffold has impressively emerged as a useful acceptor fragment in fluorescent probes for bioimaging (and for applications in organic electronics). Some of the reported benzothiadiazole-based fluorophores allow for specific imaging of intracellular lipid droplets, which are lipid-rich organelles that can be found in various types of cells. Dysregulated lipid metabolism and the accumulation of lipid droplets are strongly associated with diseases such as obesity, diabetes, and cancer. For instance, lipid droplets play an important role in the energy metabolism of cancer cells. Fluorescence imaging of lipid droplets can therefore be used for studying various types of cancer and is considered as a biomarker for cancer diagnosis and prognosis.In this work, various donor-acceptor fluorophores based on the benzothiadiazole scaffold were synthesized. Extensive photophysical characterization in different solvents shed light on the structure-property relationships of these compounds. For instance, dual emission from the locally excited state and the intramolecular charge transfer state was observed for many compounds – the equilibrium of which was strongly dependent on the electronic nature of the substituent and the polarity of the solvent. Cell studies revealed five promising new compounds for fluorescence imaging of lipid droplets in cancer cells. One of these molecules featured an off-on fluorescence behavior in hypoxic (i.e., oxygen deficient) cancer cells. Calculation of octanol/water partition coefficients (logP) revealed that only the most lipophilic compounds in this study (logP ≥ 4) reliably accumulated in, and stained, lipid droplets.