Molecular Rotors: What Lies Behind the High Sensitivity of the Thioflavin-T Fluorescent Marker

作者：Nadav Amdursky, Yuval Erez, Dan Huppert · 发表于：Accounts of Chemical Research · 年份：2012 · DOI：10.1021/ar300053p · 被引用次数：417 · 研究领域：Lanthanide and Transition Metal Complexes、Photochemistry and Electron Transfer Studies、Molecular Sensors and Ion Detection

Thioflavin-T (ThT) can bind to amyloid fibrils and is frequently used as a fluorescent marker for in vitro biomedical assays of the potency of inhibitors for amyloid-related diseases, such as Alzheimer's disease, Parkinson's disease, and amyloidosis. Upon binding to amyloid fibrils, the steady-state (time-integrated) emission intensity of ThT increases by orders of magnitude. The simplicity of this type of measurement has made ThT a common fluorescent marker in biomedical research over the last 50 years. As a result of the remarkable development in ultrafast spectroscopy measurements, researchers have made substantial progress in understanding the photophysical nature of ThT. Both ab initio quantum-mechanical calculations and experimental evidence have shown that the electronically excited-state surface potential of ThT is composed of two regimes: a locally excited (LE) state and a charge-transfer (CT) state. The electronic wave function of the excited state changes from the initial LE state to the CT state as a result of the rotation around a single C-C bond in the middle of the molecule, which connects the benzothiazole moiety to the dimethylanilino ring. This twisted-internal-CT (TICT) is responsible for the molecular rotor behavior of ThT. This Account discusses several factors that can influence the LE-TICT dynamics of the excited state. Solvent, temperature, and hydrostatic pressure play roles in this process. In the context of biomedical assays, the binding to amyloid ...