A Single Heteroatom Controls Halogen-versus Chalcogen-Bond-Driven Cellular Uptake

Abstract

Halogen and chalcogen bonds can both promote membrane recognition, but how they compete within the same scaffold remains unclear. Here we develop a modular set of fluorescent probes in which a single heteroatom (O/S/Se) and a 2-halogen substituent (F–I) systematically alters the cell permeability. The oxygen analogues exhibit strongly halogen-dependent uptake consistent with halogen-bond-driven recognition, whereas sulfur and selenium analogues are internalized predominantly via chalcogen-bonding with minimal dependence on the halogen.