Amyloid β Aggregate-Sensitive Red Fluorescent Dipolar Probes

Abstract

Changes in the viscosity of the microenvironment, such as protein aggregation, are closely related to various diseases, and it is very important to detect them when diagnosing diseases. In this study, four types of dipolar probes were developed based on an electronic push？pull system consisting of 6-(dimethylamino)naphthalene derivatives and benzothiazole derivatives as electron donors and acceptors, respectively. The probes had a red fluorescence property of approx. 617？646 nm in high-viscosity solvents, which was supported by time-dependent density functional theory (TDDFT) calculations. In particular, the fluorescence change of one of the probes, 3-(6-(dimethylamino)naphthalen-2-yl)-2-(6-methoxybenzo[d]thiazol-2-yl)acrylonitrile (MBTCN), increased by a factor of 506 times with an increase in the ratio of glycerol in the glycerol/water mixed solution. MBTCN was used to detect amyloid β (Aβ) aggregates that cause Alzheimer’s disease against tau and albumin. Molecular docking studies have shown that the probes interact with the HIS14, ILE32, GLY33, and LEU34 residues of Aβ. The probe is applied to ex vivo fluorescence imaging for Aβ aggregates in the brain of a mouse model with Alzheimer’s disease.