Journal article
Molecular Rotors: What Lies Behind the High Sensitivity of the Thioflavin-T Fluorescent Marker
Accounts of Chemical Research, Vol.45(9), pp.1548-1557
Sep/2012
Abstract
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 Tiff 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 fibrils inhibits the internal rotation of the molecular segments and as a result, the electron cannot cross into the nonradiative "dark" CT state. The LE state has high oscillator strength that enables radiative excited-state relaxation to the ground state. This process makes the ThT molecule light up in the presence of amyloid fibrils. In the literature, researchers have suggested several models to explain nonradiative processes. We discuss the advantages and disadvantages of the various no
Details
- Title
- Molecular Rotors; What Lies Behind the High Sensitivity of the Thioflavin-T Fluorescent Marker
- Creators
- Nadav Amdursky (null) - The Weizmann Institute of ScienceYuval Erez (null) - 972WIS_INST___89Dan Huppert (null)
- Resource Type
- Journal article; Review
- Publication Details
- Accounts of Chemical Research, Vol.45(9), pp.1548-1557; Sep/2012
- Number of pages
- 10
- Language
- English
- DOI
- https://doi.org/10.1021/ar300053p
- Grant note
- NA
- Record Identifier
- 993262028603596
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