Modulation of intramolecular freedom for tuning fluorescence imaging and photooxidation of amyloid-β aggregates.

Alzheimer's disease (AD) is distinguished by amyloid-β (Aβ) deposition and plaque formation, prompting significant interest in fluorescence imaging and photooxidation of Aβ aggregates for diagnostic and intervention purposes. However, the molecular engineering required to modulate fluorescence imaging and photooxidation of Aβ presents notable challenges. Here, we present the design of four small molecules (BTD-SZ, BTD-YD, BTD-TA-SZ, and BTD-TA-YD) aimed at investigating the influence of intramolecular freedom of movement on imaging and photooxidation. Notably, BTD-SZ exhibits exceptional fluorescence properties, offering promising potential for non-invasive detection of Aβ plaques in vivo . Furthermore, by converting dimethylamine into triphenylamine to restrict intramolecular freedom of movement in the aggregate state, we synthesized a photosensitizer denoted as BTD-TA-SZ. This compound demonstrates aggregation-induced photooxidation (AIP), effectively impeding Aβ aggregation under light irradiation in vivo . Thus, the modulation of intramolecular freedom of movement emerges as a pivotal molecular engineering strategy for developing photosensitizers for the diagnosis and intervention of AD, offering insights into innovative approaches for combating this debilitating condition.