Salen-based bifunctional chemosensor for copper (II) ions: Inhibition of copper-induced amyloid-β aggregation

Disruption of copper homeostasis is associated with a number of severe diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Wilson's disease, and Menkes syndrome. Given this association, the detection and capture of Cu²⁺ in biological fluids and tissues may provide a new direction for the diagnosis and treatment of related disorders. The current analytical approaches, however, are challenging due to the high cost, complexity, and long time required to prepare and analyze samples. Here, we report a novel salen ligand, namely N,N'-(1,2-phenylene)bis(1-(1H-imidazol-4-yl)methanimine) (pimi), which can readily detect and concurrently capture Cu²⁺ from aqueous as well as biological mediums. Pimi can selectively and specifically detect Cu²⁺ from biofluid and cellular samples with rapid ccresponse time (<3 s) and an ultra-sensitive detecting limit (2.7 nM). More importantly, pimi showed excellent environmental tolerance and had a very wide pH range for detecting Cu²⁺ in a variety of biological samples. Attributed to the strong binding affinity and selectivity towards Cu²⁺, pimi was found to capture Cu²⁺ ions from Cu-Aβ complexes, thus inhibiting copper-induced aggregation of Aβ and protecting neuronal cells from the toxicity of aggregated Aβ. These results provide a compelling starting point for further fine-tuning of salen-based chemosensor for the diagnosis and treatment of diseases associated with the hyperaccumulation of copper.