2-Phenylbenzothiazolyl iridium complexes as inhibitors and probes of amyloid β aggregation.

The aggregation of amyloid β (Aβ) peptides is a significant hallmark of Alzheimer's disease (AD), and the detection of Aβ aggregates and the inhibition of their formation are important for the diagnosis and treatment of AD, respectively. Herein, we report a series of benzothiazole-based Ir(III) complexes HN-1 to HN-8 that exhibit appreciable inhibition of Aβ aggregation in vitro and in living cells. These Ir(III) complexes can induce a significant fluorescence increase when binding to Aβ fibrils and Aβ oligomers, while their measured log  D values suggest these compounds could have enhanced blood-brain barrier (BBB) permeability. In vivo studies show that HN-1, HN-2, HN-3, and HN-8 successfully penetrate the BBB and stain the amyloid plaques in AD mouse brains after a 10-day treatment, suggesting that these Ir(III) complexes could act as lead compounds for AD therapeutic and diagnostic agent development.