Ultrafast Charge Transfer Dynamics of Thioflavin T Probed by Time-Resolved Raman Spectroscopy

Area of Science:

• Biophysical Chemistry
• Spectroscopy
• Molecular Dynamics

Background:

• Thioflavin T (ThT) is a vital fluorescent dye for detecting amyloid fibrils in neurodegenerative diseases like Alzheimer's and Parkinson's.
• ThT fluorescence is modulated by intramolecular charge transfer (ICT), but its structural basis remains experimentally unconfirmed.
• Understanding ThT's structural dynamics during ICT is crucial for interpreting its fluorescence signals in biological contexts.

Purpose of the Study:

• To experimentally elucidate the structural transformations of Thioflavin T (ThT) during the intramolecular charge transfer (ICT) process.
• To investigate the coupling between the ICT coordinate and molecular vibrational modes in ThT.

Main Methods:

• Time-resolved Raman spectroscopy, including femtosecond stimulated Raman spectroscopy (FSRS) and impulsive stimulated Raman spectroscopy (ISRS).
• Time-dependent density functional theory (TD-DFT) calculations to model electronic states and vibrational properties.
• Evaluation of vibrational reorganization energies between ground and excited states.

Main Results:

• Direct experimental evidence of structural changes in ThT during ICT, specifically a bend in the benzothiazole ring and a twist in the dimethylaniline group.
• Demonstration of strong coupling between the ICT coordinate and low-frequency deformation modes of ThT.
• Computational results strongly support the experimental observations of structural dynamics.

Conclusions:

• The study provides the first direct experimental evidence of ThT structural changes accompanying ICT.
• These findings clarify the photophysical mechanisms underlying ThT fluorescence modulation.
• The results enhance the understanding of ThT as a probe for amyloid structures and disease mechanisms.