Computational study of thioflavin T torsional relaxation in the excited state

Quantum-chemical calculations of the Thioflavin T (ThT) molecule in the ground S-0 and first excited singlet S-1 states were carried out. It has been established that ThT in the ground state has a noticeable nonplanar conformation: the torsion angle phi between the benzthiazole and the dimethylaminobenzene rings has been found to be similar to 37 degrees. The energy barriers of the intramolecular rotation appearing at phi = 0 and 90 degrees are quite low: semiempirical AM1 and PM3 methods predict values similar to 700 cm(-1) and ab initio methods similar to 1000-2000 cm(-1). The INDO/S calculations of vertical transitions to the S-1((abs)) excited state have revealed that energy E-S1((abs)) is minimal for the twisted conformation with phi = 90 degrees and that the intramolecular charge-transfer takes place upon the ThT fragments' rotation from phi = 0 to 90 degrees. Ab initio CIS/RHF calculations were performed to find optimal geometries in the excited S-1 state for a series of conformers having fixed phi values. The CIS calculations have predicted a minimum of the S-1 state energy at phi similar to 21 degrees; however, the energy values are 1.5 times overestimated in comparison to experimental data. Excited state energy dependence on the torsion angle phi, obtained by the INDO/S method, reveals that E-S1((fluor)) is minimal at phi = similar to 80-100 degrees, and a plateau is clearly observed for torsion angles ranging from 20 to 50 degrees. On the basis of the calculation results, the following scheme of photophysical processes in the excited S-1 state of the ThT is suggested. According to the model, a twisted internal charge-transfer (TICT) process takes place for the ThT molecule in the excited singlet state, resulting in a transition from the fluorescent locally excited (LE) state to the nonfluorescent TICT state, accompanied by torsion angle phi growth from 37 to 90 degrees. The TICT process effectively competes with radiative transition from the LE state and is responsible for significant quenching of the ThT fluorescence in low-viscosity solvents. For viscous solvents or when the ThT molecule is located in a rather rigid microenvironment, for example, when it is bound to amyloid fibrils, internal rotation in the dye molecule is blocked due to steric hindrance, which results in suppression of the LE -> TICT quenching process and in a high quantum yield of fluorescence.