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 αCD and βCD, the interaction of TEG-BTA-2 with γCD leads to fluorescence quenching. These results provide valuable insights for development of thioflavin T-inspired benzothiazole molecules as fluorescent markers and diagnostic agents.