Chelation-induced diradical formation as an approach to modulation of the amyloid-β aggregation pathway.

ABSTRACT: Current approaches toward modulation of metal-induced Aβ aggregation pathways involve the development of small molecules that bind metal ions, such as Cu(ii) and Zn(ii), and interact with Aβ. For this effort, we present the enediyne-containing ligand (Z)-N,N'-bis[1-pyridin-2-yl-meth(E)-ylidene]oct-4-ene-2,6-diyne-1,8-diamine (PyED), which upon chelation of Cu(ii) and Zn(ii) undergoes Bergman-cyclization to yield diradical formation. The ability of this chelation-triggered diradical to modulate Aβ aggregation is evaluated relative to the non-radical generating control pyridine-2-ylmethyl-(2-{[(pyridine-2-ylmethylene)-amino]-methyl}-benzyl)-amine (PyBD). Variable-pH, ligand UV-vis titrations reveal pKa = 3.81(2) for PyBD, indicating it exists mainly in the neutral form at experimental pH. Li

SUBMITTER: Porter MR 

PROVIDER: S-EPMC5811126 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature