Rhenium Complexes of Bis(benzothiazole)-Based Tetraarylethylenes as Selective Luminescent Probes for Amyloid Fibrils.

Abstract

Probes for monitoring aggregation of amyloid beta (Aβ) peptides are crucial to advance understanding of the molecular pathogenesis of Alzheimer's Disease (AD). Here, we report luminescent tricarbonyl rhenium complexes of tetraarylethylene (TAE) ligands featuring bis(benzothiazole) chelating groups in combination with (oligo)thiophene units that have been designed for monitoring amyloid fibrillation. Variation in the number of thiophenes influenced the photophysical properties of these complexes, as well as their binding affinities toward Aβ42 fibrils. All complexes displayed submicromolar Kd's for binding Aβ42 aggregates accompanied by up to 34-fold enhanced luminescence and red-shifted emission wavelengths. The high binding affinities and desirable photophysical properties of these complexes render them potential alternatives to established fluorescent Aβ probes such as thioflavin T. Additionally, the general and modular design approach implemented in this study should facilitate development of second-generation TAE-based diagnostic tools for studying protein aggregation in AD and other neurological diseases.