Chalcogen Bonding Boosts the Uptake of Small Molecules in Mammalian Cells.

Chalcogen bonding, a noncovalent interaction between the chalcogen atom (S, Se, and Te) and Lewis base, plays crucial roles in catalysis, anion recognition, protein confirmation, enzyme activity, and drug design. Herein, we show that chalcogen bonding can be used as a driving force to enhance the uptake of small molecules in mammalian cells. A systematic investigation using several chalcogen-containing fluorescent molecules reveal that the cellular uptake strongly depends on the nature of chalcogen atom and the compounds with heavier chalcogen atoms (Se and Te), which can form stronger chalcogen bonds, are preferentially taken up by the cells. This study suggests that the biological activities of chalcogen-based compounds may depend not only on their chemical reactivity but also on their chalcogen bond forming ability with the cell membrane.