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Anal Chim Acta. 2020 Feb 8;1097:144-152. doi: 10.1016/j.aca.2019.10.072. Epub 2019 Nov 12.

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

Author information

1
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China. Electronic address: xiaoheiyu79@gdut.edu.cn.
2
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China.
3
Warshel Institute for Computational Biology, School of Science and Engineering, School of Life and Heath Sciences, The Chinese University of Hong Kong, Shenzhen, 518172, PR China.
4
Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University & Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, PR China. Electronic address: l_wang1009@jnu.edu.cn.
5
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.
6
Molecular Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 01890, USA.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; Amyloid-β; Chemosensor; Copper ion; Fluorescent probe

PMID:
31910954
DOI:
10.1016/j.aca.2019.10.072

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