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Misfolded proteins produce aberrant fibrillar aggregates, called amyloids, which contain cross-β-sheet higher order structures. The species generated in the aggregation process ( i.e. , oligomers, protofibrils, and fibrils) are cytotoxic and can cause various diseases. Interfering with the amyloid formation of proteins could be a drug development target for treating diseases caused by aberrant protein aggregation. In this review, we introduce a variety of chemical catalysts that oxygenate amyloid proteins under light irradiation using molecular oxygen as the oxygen atom donor ( i.e. , photooxygenation catalysts). Catalytic photooxygenation strongly inhibits the aggregation of amyloid proteins due to covalent installation of hydrophilic oxygen atoms and attenuates the neurotoxicity of the amyloid proteins. Recent in vivo studies in disease model animals using photooxygenation catalysts showed promising therapeutic effects, such as memory improvement and lifespan extension. Moreover, photooxygenation catalysts with new modes of action, including interference with the propagation of amyloid core seeds and enhancement in the metabolic clearance of amyloids in the brain, have begun to be identified. Manipulation of catalytic photooxygenation with secured amyloid selectivity is indispensable for minimizing the side effects in clinical application. Here we describe several strategies for designing catalysts that selectively photooxygenate amyloids without reacting with other non-amyloid biomolecules.

Tau amyloid formation and deposition are responsible for the onset of Alzheimer's disease. In particular, the seeding activity of the tau protein plays an important role in the spreading of tau pathology via its propagation in the human brain. Here we demonstrate that catalytic photo-oxygenation markedly suppresses tau seeding activity, resulting in the inhibition of amyloid formation, both in vitro and in cultured cells.

The photophysical properties of newly identified B,B-fluoro-perfluoroalkyl BODIPYs ( 2 and 3 ), which possess a fluoro group and a trifluoromethyl or pentafluoroethyl group at the boron center, were investigated. B,B-Fluoro-perfluoroalkyl BODIPYs 2 and 3 exhibited better photophysical/chemical properties than B,B-difluoro-BODIPY 1 , as follows: (1) higher photostability both in methanol solvent and in a live cell environment, (2) higher stability against acid degradation, and (3) improved fluorescence signal-to-noise ratios in a cell system. These favorable properties of B,B-fluoro-perfluoroalkyl BODIPYs are likely due to the highly electron-withdrawing nature of the perfluoroalkyl groups on the boron atom, which reduces the reactivity to 1 O 2 and strengthens the complexation of the dipyrromethene ligands to the boron atom. Thus, B,B-fluoro perfluoroalkyl BODIPYs may be useful functional molecules for various applications.