On the Photophysics and Contrasting Cavitand Binding of a Fluorescent Amphiphilic Benzothiazole

Benzothiazoles, including the cationic thioflavin T and its variants, are of immense interest because of their therapeutic potential and applications as biomolecular fluorescence probes. This study investigates the photophysics of an interesting benzothiazole derivative, TEG‐BTA‐2, that combines a neutral thioflavin T type of moiety (BTA‐2) with a tetraethylene glycol chain (TEG). Unlike thioflavin T, TEG‐BTA‐2 is highly fluorescent and shows multiple prototropic transformations. Monoprotonated TEG‐BTA‐2 is found to exist in two isomeric forms, each having characteristic absorption, emission, and fluorescence lifetimes. Furthermore, TEG‐BTA‐2 shows strong affinity toward the cavitands α ‐, β ‐, and γ ‐cyclodextrins (CDs). The binding constants of TEG‐BTA‐2 with the cavitands are considerably higher than that of thioflavin T, which is attributed to its neutral charge and favorable hydrophobic/H‐bonding interactions provided by the TEG chain. Interestingly, it is found that the size of the macrocyclic cavity plays a pivotal role in controlling the fluorescence response of TEG‐BTA‐2 due to formation of complexes with different stoichiometries. In contrast to the fluorescence enhancement observed with α CD and β CD, the interaction of TEG‐BTA‐2 with γ CD leads to fluorescence quenching. These results provide valuable insights for development of thioflavin T‐inspired benzothiazole molecules as fluorescent markers and diagnostic agents.