Summary: Recent studies suggest that advanced glycation endproducts play an important role in cardiovascular complications of ageing, diabetes and end-stage renal failure. Since highly elevated levels of advanced glycation endproducts are present in serum of patients on maintenance haemodialysis, an accurate and rapid assay for their determination would be useful. This would be particularly valuable for monitoring the removal of advanced glycation endproducts by novel dialysis membranes, as well as the effect of new drugs for the inhibition of their formation.Measurement of advanced glycation endproducts in serum was performed by two competitive ELISAs, using a monoclonal antibody directed against imidazolone, an advanced glycation endproduct formed by the reaction of arginine with 3-deoxyglucosone, and a polyclonal antibody directed against keyhole limpet haemocyanin-advanced glycation endproduct, as well as by quantitative fluorescence spectroscopy.Each of the assays showed significant differences between the controls and the maintenance haemodialysis patients. Advanced glycation endproduct levels determined by each of the ELISAs correlated with total and protein-bound fluorescence, but not with each other, suggesting a variable distribution of advanced glycation endproducts on serum proteins among the maintenance haemodialysis patients.
We report a remote functionalization strategy, which allows the Z-selective synthesis of silyl enol ethers of (hetero)aromatic and aliphatic ketones via Ni-catalyzed chain walking from a distant olefin site. The positional selectivity is controlled by the directionality of the chain walk and is independent of thermodynamic preferences of the resulting silyl enol ether. Our mechanistic data indicate that a Ni(I) dimer is formed under these conditions, which serves as a catalyst resting state and, upon reaction with an alkyl bromide, is converted to [Ni(II)-H] as an active chain-walking/functionalization catalyst, ultimately generating a stabilized η3-bound Ni(II) enolate as the key selectivity-controlling intermediate.
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