RESUMO
The activation of N2 , CO2 or H2 O to energy-rich products relies on multi-electron transfer reactions, and consequently it seems desirable to understand the basics of light-driven accumulation of multiple redox equivalents. Most of the previously reported molecular acceptors merely allow the storage of up to two electrons. We report on a terphenyl compound including two disulfide bridges, which undergoes four-electron reduction in two separate electrochemical steps, aided by a combination of potential compression and inversion. Under visible-light irradiation using the organic super-electron donor tetrakis(dimethylamino)ethylene, a cascade of light-induced reaction steps is observed, leading to the cleavage of both disulfide bonds. Whereas one of them undergoes extrusion of sulfur to result in a thiophene, the other disulfide is converted to a dithiolate. These insights seem relevant to enhance the current fundamental understanding of photochemical energy storage.
RESUMO
Alzheimer's Disease (AD) is the most widespread form of dementia, with one of the pathological hallmarks being the formation of neurofibrillary tangles (NFTs). These tangles consist of phosphorylated Tau fragments. Asparagine endopeptidase (AEP) is a key Tau cleaving enzyme that generates aggregation-prone Tau fragments. Inhibition of AEP to reduce the level of toxic Tau fragment formation could represent a promising therapeutic strategy. Here, we report the first orthosteric, selective, orally bioavailable, and brain penetrant inhibitors with an irreversible binding mode. We outline the development of the series starting from reversible molecules and demonstrate the link between inhibition of AEP and reduction of Tau N368 fragment both in vitro and in vivo.