Extensive research has linked the amyloid-beta (Aβ) peptide to neurological dysfunction in Alzheimer's disease (AD). Insoluble Aβ plaques in the AD patient brain contain high concentrations of advanced glycation end-products (AGEs) as well as transition metal ions. This research elucidated the roles of Aβ, sugars, and Cu in the oxidative stress mechanism of AD at the molecular level. Mass spectral (MS) analysis of the reactions of Aβ with two representative sugars, ribose-5-phosphate (R5P) and methylglyoxal (MG), revealed Lys-16 and Arg-5 as the primary glycation sites. Quantitative analysis of superoxide [Formula: see text] production by a cyt c assay showed that Lys-16 generated four times as much [Formula: see text] as Arg-5. Lys-16 and Arg-5 in Aβ are both adjacent to histidine residues, which are suggested to catalyze glycation. Additionally, Lys-16 is close to the central hydrophobic core (Leu-17-Ala-21) and to His-13, both of which are known to lower the pKa of the residue, leading to increased deprotonation of the amine and an enhanced glycation reactivity compared to Arg-5. Gel electrophoresis results indicated that all three components of AD plaques-Aβ, sugars, and Cu-are necessary for DNA damage. It is concluded that the glycation of Aβ with sugars generates significant amounts of [Formula: see text], owing to the rapid glycation of Lys-16 and Arg-5. In the presence of Cu, [Formula: see text] converts to hydroxyl radical (HO·), the source of oxidative stress in AD.

Palladium-catalyzed allylic aminations have been widely studied due to their synthetic utility 1 and the increasing availability of highly enantioselective versions. 2 We recently reported that reversible nucleophilic addition can lower the observed enantioselectivity of allylic amination reactions with a wide range of prototypical chiral ligands. 3 Amatore, Jutand, et al. 4a have found that nucleophilic addition of amines was reversible with the bidentate ligand dppb but irreversible with the monodentate ligand PPh 3. Based on our interest in chiral ligand design and specific studies with PHOX ligands, 5,6 we wanted to investigate the key ligand, solvent, and base additive factors governing the reversibility of nucleophilic addition of amines.

Polydimethylsiloxane (PDMS) elastomer has emerged as one of the most frequently applied materials in microfluidics. However, precise and large-scale surface micromachining of PDMS remains challenging, limiting applications of PDMS for microfluidic structures with high-resolution features. Herein, surface patterning of PDMS was achieved using a simple yet effective method combining direct photolithography followed by reactive-ion etching (RIE). This method incorporated a unique step of using oxygen plasma to activate PDMS surfaces to a hydrophilic state, thereby enabling improved adhesion of photoresist on top of PDMS surfaces for subsequent photolithography. RIE was applied to transfer patterns from photoresist to underlying PDMS thin films. Systematic experiments were conducted in the present work to characterize PDMS etch rate and etch selectivity of PDMS to photoresist as a function of various RIE parameters, including pressure, RF power, and gas flow rate and composition. We further compared two common RIE systems with and without bias power and employed inductively coupled plasma and capacitively coupled plasma sources, respectively, in terms of their PDMS etching performances. The RIE-based PDMS surface micromachining technique is compatible with conventional Si-based surface and bulk micromachining techniques, thus opening promising opportunities for generating hybrid microfluidic devices with novel functionalities.