Salpyran: A Cu(II) Selective Chelator with Therapeutic Potential.

We report the rational design of a tuneable Cu(II) chelating scaffold, 2-(((2-((pyridin-2-ylmethyl)amino)ethyl)amino)methyl)phenol, Salpyran. This tetradentate (3N,1O) ligand is predicated to have suitable permeation, has an extremely high affinity for Cu compared to clioquniol (pCu7.4 = 10.65 vs 5.91) and exhibits excellent selectivity for Cu(II) over Zn(II) in aqueous media. Solid and solution studies corroborate the formation of a stable [Cu(II)(3N,1O)]+ monocationic species at physiological pH values (7.4). Its action as an antioxidant was tested in ascorbate, tau and human prion protein assays which reveal that Salpyran prevents the formation of reactive oxygen species (ROS) from the binary Cu(II)/H2O2 system demonstrating its potential use as a therapeutic small molecule metal chelator (SMMC).