Chalcogen-Substituted Molecular Rotors as Polarity and Viscosity Sensors for Amyloid-β Fibril Formation and...

Fluorescent molecular rotors (FMRs) sense their local environment by coupling emission to intramolecular rotation and twisted intramolecular charge transfer (TICT). Here we introduce a compact chromone-based donor-π-acceptor platform in which the acceptor is systematically chalcogen-substituted from O → S → Se → Te. This simple, isostructural series allows us to isolate the effect of chalcogen variation on ICT/TICT processes without changing the molecular framework. Steady-state spectroscopy and DFT reveal progressively narrowed HOMO-LUMO gaps and strengthened charge-transfer character across the series, consistent with heavier-chalcogen polarizability. The dyes exhibit strong solvatochromism and function as viscosity-sensitive probes: their emission intensity increases steadily with higher glycerol content, following the Förster-Hoffmann relationship. They also show a large increase in brightness from water to glycerol and have high quantum yields in viscous media. The probes are chemically robust against common interferents and pH within biologically relevant ranges. By exploiting rotor immobilization, the dye series exhibits strong, time-dependent fluorescence upon binding to amyloid-β (Aβ1-42) fibrils, comparable to Thioflavin T but with a red-shifted emission. In live HeLa cells the rotors are cell-permeable and biocompatible, yielding bright organelle labeling and reporting microviscosity changes induced by ionophore or lipid-loading treatments. Collectively, this study establishes chalcogen-substituted chromone rotors as a tunable, dual-function platform for polarity/viscosity mapping and amyloid detection and provides clear structure-property rules across the O/S/Se/Te series that can guide next-generation FMR design.