Hydrophilic–Hydrophobic Balance Regulates Aggregation and Red/NIR Fluorescence of Carbohydrate‐Conjugated Ar , O ‐BODIPYs

ABSTRACT Aggregation‐responsive fluorescent probes are attractive for biological applications because molecular recognition can be transduced into optical signals through changes in molecular assembly. In this study, we report a series of carbohydrate‐conjugated Ar , O ‐BODIPYs that exhibit red/near‐infrared (NIR) fluorescence responsive to their aggregation state in aqueous media. The carbohydrate‐conjugated Ar , O ‐BODIPYs were readily synthesized by copper‐catalyzed azide–alkyne cycloaddition. Although the compounds exhibited intense fluorescence in DMSO, their fluorescence was strongly quenched in aqueous media. Dynamic light scattering, atomic force microscopy, and fluorescence lifetime measurements revealed that this quenching was associated with the formation of nanoscale aggregates. Importantly, the extent of aggregation and fluorescence quenching depended on the hydrophilic–hydrophobic balance between the Ar , O ‐BODIPY core and the appended carbohydrate moieties. Binding of a carbohydrate‐conjugated Ar , O ‐BODIPY to concanavalin A induced a pronounced fluorescence enhancement, indicating that protein binding promotes disruption of the quenched aggregates. Among the compounds examined, the glucose‐conjugated derivative showed the highest fluorescence intensity in living cells and efficiently stained several cell lines in the red/NIR region. These results demonstrate that controlling the hydrophilic–hydrophobic balance provides a useful molecular design strategy for tuning aggregation, fluorescence response, and cellular uptake, enabling carbohydrate‐conjugated Ar , O ‐BODIPYs to function as aggregation‐responsive fluorescent probes for protein recognition and bioimaging.