Sulfur speciation defined subcellular localization of coumarin derivatives: Correlation of structural relationship to biological behaviors

Abstract Targeted-delivery is of great importance to molecular probes and drugs for cell biology study. Herein we reported 11 sulfur-containing coumarins as cell imaging probes. Different sulfur speciation of the 4 representative coumarins SC1-SC4 renders them significantly different subcellular localizations and cellular uptake pathways: SC1 containing thioether group located in lysosomes, while sulfoxide and sulfone compounds SC2 and SC3 distributed in the whole cell. Furthermore, the cationic sulfonium containing compound SC4 was internalized by clathrin-mediated endocytosis and localized at mitochondria. By analyzing the molecular parameters of all 11 coumarins, we found that different sulfur speciation affected their lipophilicity and electrostatic surface potential. These two key factors play roles in altering biological behaviors of the coumarins. The results revealed the importance of sulfur speciation on the physicochemical properties and thus subcellular localization of bioprobes. This is useful for designing new functional bioprobes.