A High Affinity Red Fluorescence and Colorimetric Probe for Amyloid β Aggregates

Abstract

A major challenge in the Alzheimer’s disease (AD) is its timely diagnosis. Amyloid β (Aβ) aggregates have been proposed as the most viable biomarker for the diagnosis of AD. Here, we demonstrate hemicyanine-based benzothiazole-coumarin ( TC) as a potential probe for the detection of highly toxic Aβ ₄₂ aggregates through switch-on, enhanced (~30 fold) red fluorescence (E _max = 654 nm) and characteristic colorimetric (light red to purple) optical outputs. Interestingly, TC exhibits selectivity towards Aβ ₄₂ fibrils compared to other abnormal protein aggregates. TC probe show nanomolar binding affinity ( K _a  = 1.72 × 10 ⁷ M ⁻¹) towards Aβ ₄₂ aggregates and also displace ThT bound to Aβ ₄₂ fibrils due to its high binding affinity. The Aβ ₄₂ fibril-specific red-shift in the absorption spectra of TC responsible for the observed colorimetric optical output has been attributed to micro-environment change around the probe from hydrophilic-like to hydrophobic-like nature. The binding site, binding energy and changes in optical properties observed for TC upon interaction with Aβ ₄₂ fibrils have been further validated by molecular docking and time dependent density functional theory studies.