No abstract

The discovery of effective therapeutics targeting amyloid-β (Aβ) aggregates for Alzheimer’s disease (AD) has been very challenging, which suggests its complicated etiology associated with multiple pathogenic elements. In AD-affected brains,...

Aggregates of both metal-free amyloid-β (Aβ) and metal-bound Aβ (metal-Aβ) are accumulated in the brain affected by Alzheimer's disease. To control metal-free and metal-bound Aβ species, chemical reagents capable of modulating their aggregation profiles have been developed. As an effort, the reactivity of natural products such as flavonoids with metal-free Aβ and metal-Aβ has been investigated to identify their use as chemical reagents and structural features essential for such reactivity. This review illustrates the effects of flavonoids containing a catechol or pyrogallol group on metal-free and metal-mediated Aβ aggregation pathways. In addition, the studies regarding the structure-activity relationship of flavonoids against metal-free Aβ or metal-Aβ are discussed.

We report orobol as a multifunctional isoflavone with the ability to (i) modulate the aggregation pathways of both metal-free and metal-bound amyloid-β, (ii) interact with metal ions, (iii) scavenge free radicals, and (iv) inhibit the activity of acetylcholinesterase. Such a framework with multifunctionality could be useful for developing chemical reagents to advance our understanding of multifaceted pathologies of neurodegenerative disorders, including Alzheimer’s disease.

limited fundamentally, and more tunable charge carriers must be found. Organic molecules are compelling candidates, [5][6][7] because there is an inexhaustible supply of carbon, hydrogen, nitrogen, and oxygen on earth. In principle, their properties can be varied over a great range by changing the molecular architecture and employing functional groups. The ideal charge carrier should display fully reversible redox reactions without degradation, be highly soluble in water, and operate at neutral pH.Robust redox-activity can be achieved using aromatic systems that delocalize the charge across the whole molecule for extra stability. But the non-polar nature of aromatics can lower the solubility in water. Another serious challenge is that the radical intermediates may be highly reactive leading to undesirable side reactions and fading of the battery performance. The pH of the electrolyte solutions during battery operation deserves special attention. Because many organic systems employ proton-coupled electron transfer to achieve charge neutrality, [7][8][9][10][11][12] highly acidic or basic conditions are often encountered. However, an excess of H + ions can corrode cell components and trigger undesirable reactions. [13] In addition, highly concentrated OHin the alkaline solution diminishes volumetric energy density. [13,14] Naphthalene diimide (NDI) is an ideal platform for systematically implementing advantageous design principles, because it Organic redox-active molecules are a promising platform for designing sustainable, cheap, and safe charge carriers for redox flow batteries. However, radical formation during the electron-transfer process causes severe side reactions and reduces cyclability. This problem is mitigated by using naphthalene diimide (NDI) molecules and regulating their π-π interactions. The longrange π-stacking of NDI molecules, which leads to precipitation, is disrupted by tethering four ammonium functionalities, and the solubility approaches 1.5 m in water. The gentle π-π interactions induce clustering and disassembling of the NDI molecules during the two-electron transfer processes. When the radical anion forms, the antiferromagnetic coupling develops tetramer and dimer and nullifies the radical character. In addition, short-range-order NDI clusters at 1 m concentration are not precipitated but inhibit crossover. They are disassembled in the subsequent electron-transfer process, and the negatively charged NDI core strongly interacts with ammonium groups. These behaviors afford excellent RFB performance, demonstrating 98% capacity retention for 500 cycles at 25 mA cm -2 and 99.5% Coulombic efficiency with 2 m electron storage capacity.