New fluorescent molecular rotors (FMRs) were developed by modification of the Thioflavin T (ThT) structure via introduction of methyl and methoxy groups. Effects of the substituents on fluorescence properties and twisted intramolecular charge transfer (TICT) rate in the excited state of the molecules were studied using steady-state fluorescence and time-resolved absorption spectroscopy. Quantum chemical calculations of the molecules in the ground and excited states were carried out to aid interpretation of the experimental results. Only cationic forms of ThT derivatives have FMR properties and exhibit viscosity-dependent fluorescence. The TICT rate was found to be affected by the size of the molecular fragments, which experience mutual rotation, dihedral angle φ between the fragments in the ground state as well as their donor/acceptor properties. © 2019 World Scientific Publishing Company.

Stsiapura V.I.

Gogoleva S.D.

Maskevich A.A.

Buganov O.V.

Tikhomirov S.A.

Lugovski A.A.

Baruah K.

Sarma B.K.

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Shiv Nadar University

Effect of Substituents on TICT Rate in Thioflavin T-Based Fluorescent Molecular Rotors

International Journal of Nanoscience

Fluorescent molecular rotors (FMR) have wide range of applications due to high sensitivity of their emission intensity to microenvironment viscosity. Thioflavin T (ThT), which exhibits FMR properties, is widely used as fluorescent probe for in vitro detection of amyloid fibrils (AF) due to its high affinity and “light-up” feature (fluorescence quantum yield of ThT changes by ∼3 orders of magnitude upon binding to AF). At physiological pH, ThT is positively charged and, therefore, it does not cross blood-brain barrier (BBB). It has been proposed that neutral derivatives of ThT are more likely to cross BBB, which should make them suitable for in vivo applications. However, for in vivo applications as fluorescent imaging agents, the neutral ThT derivatives must retain the FMR properties of ThT. In this paper, we examined whether neutral ThT derivatives exhibit FMR properties by studying the effect of solvent viscosity on their fluorescence intensity and decay lifetime. We observed that while the cationic ThT derivatives possess FMR properties, the neutral forms behave as regular highly-emitting fluorophores. Further, quantum chemical calculations in gas phase showed significant differences in the shape of excited state potential energy surfaces for the neutral and cationic derivatives of ThT. While, for charged ThT derivatives, the E(S1*) energy is minimal for the twisted conformation with dihedral angle φ = 90° between molecular fragments, the coplanar conformation with φ = 0° (or 180°) is more favorable for the neutral derivatives. From our experimental and theoretical studies we conclude that the neutral ThT derivatives lack FMR properties as their photoexcitation does not induce twisting motion coupled with internal charge transfer and, therefore, their specificity as fluorescent imaging agents for AF detection is lower than that of parent ThT. © 2018 Elsevier B.V.

Journal of Photochemistry and Photobiology A: Chemistry

Neutral derivatives of Thioflavin T do not exhibit viscosity-dependent fluorescence

Accounts of Chemical Research

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

Journal of Biological Engineering

Environment-sensitive behavior of fluorescent molecular rotors

The Journal of Physical Chemistry B

Thioflavin T as a Molecular Rotor: Fluorescent Properties of Thioflavin T in Solvents with Different Viscosity

Org. Biomol. Chem.

Molecular rotors—fluorescent biosensors for viscosity and flow