Turn-on benzothiadiazole-based molecular rotor, photophysical characterization and sensing of amyloid aggregates

In this study we have reported the design, synthesis, and evaluation of a novel series of benzothiadiazole (BTD)-based fluorescent molecular rotors (5a-5l) for the selective detection of amyloids on model hen egg white lysozyme (HEWL) protein. These probes were designed on the basis of Donor-π-acceptor (D-π-A) framework, were synthesized and characterized by NMR and HRMS. The photophysical study of probes in phosphate-buffered saline (PBS) pH 7.4 revealed that the probes were less emissive in aqueous solvent. The probes displayed turn-on fluorescence with increasing viscosity displaying a 56-fold enhancement for probe 5i. All the probes displayed an enhancement of emission intensity on interaction with HEWL aggregates and probe 5i being the best amongst all displaying a 77-fold enhancement. The limit of detection of probe 5i was calculated to be 0.015 μM for sensing of HEWL aggregates. These findings suggest that BTD-based molecular rotors are promising fluorescent probes for amyloid sensing.