Time Resolved Photoelectron Spectroscopy of Thioflavin T Photoisomerization: A Simulation Study

Abstract

The excited state isomerization of thioflavin T (ThT) is responsible for the quenching of its fluorescence in a non-restricted environment. The fluorescence quantum yield increases substantially upon binding to amyloid fibers. Simulations reveal that the variation of the twisting angle between benzothiazole and benzene groups (ϕ1) is responsible for the sub-picosecond fluorescence quenching. The evolution of the twisting process can be directly probed by photoelectron emission with energies ε ≥ 1.0 eV before the molecule reaches the ϕ1-twisted configuration (~300 fs).

Fluorescent dyes in the context of DNA‐binding: The case of Thioflavin T

“…From both theoretical and spectroscopic studies, the proposed behavior for the solvated dye is that the molecule is photoexcited to its lowest Franck–Condon locally excited (LE) state and then exhibits an ultrafast twisting to its excited state minimum, during which a CT to the benzothiazole group occurs. As shown in these previous studies, the excitation induces a large torsional relaxation combined with a significant bending: to quantify this distortion two angles are introduced, namely the twisting angle, and the bending angle, α (see Figure ).…”

“…For the isolated dye, 37 and 1 in the ground state, while 90 and 24 in the excited state, in good agreement with the results reported in Refs. [ ]. When moving to water solution, the ground state remains almost unchanged ( 38 ), but on excitation, two minima are found, a “planar” ( 28 ) and a twisted one ( 90 ), respectively, with the twisted one being 11 kcal/mol more stable than the LE.…”

“…Thioflavin T (ThT, see Figure ) is known to behave as a (positively charged) molecular rotor, whose photophysical properties significantly depend on the viscosity of the medium . Its “light‐switch” mechanism is in fact related to intramolecular torsions around the CC bond between benzothiazole (BTZ) and dimethylaniline (DMA) fragments . Such a twisting allows a change in the nature of the vertically populated excited state from a locally excited (LE) to a charge‐transfer (CT) state.…”

Effect of acidic and basic pH on Thioflavin T absorbance and fluorescence

“…Despite the wide usage of the ThT assay, the exact photophysics associated with its fluorescence quenching and the molecular mechanism of the ThT binding to amyloid fibrils are not fully understood. Recent studies give an overview of the up-to-date findings on different ThT-binding models (Groenning 2010;Ren et al 2013;Amdursky et al 2012;Robbins et al 2012;Wolfe et al 2010;Krebs et al 2005). It seems most likely that the ThT monomer binds to β-sheets such that its long axis is perpendicular to the β-strands.…”

Ultrafast Twisting Dynamics of Thioflavin‐T: Spectroscopy of the Twisted Intramolecular Charge‐Transfer State

“…[30] Recently, the simulation of photoelectron spectra of ThT by Ren et al revealed that torsional relaxation around the central bond took place in about 300 fs. [31] The sensitivity of the bond-twisting process on the microviscosity and rigidity of the surrounding medium was the main reason behind the excellent fluorescence sensing ability of ThT. [32] Despite the reason behind the amyloid fibril sensitivity of ThT being largely understood, several intricate points regarding the dynamics of the excited state of ThT have been disputed recently.…”