Chemical speciation and biodistribution studies of copper(II) complexes of poly(amine)amide ligands

Formation constants of Cu2+, Zn2+ and Ca2+ with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (L1), N,N′-bis(2-hydroxyiminopropionyl)propane-1,3-diamine (L2) and (1,15)-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane (L3) were determined by glass electrode potentiometry at 25 °C and an ionic strength of 0.15 mol dm−3. Zinc and calcium were found to form weak complexes with all three ligands. Copper formed stable complexes with the [CuLH−1] species predominating. Electronic spectra suggest that [CuLH−1] is square-planar. Speciation calculations using a blood-plasma model predict that L1 and L2 are able to mobilise Cu2+ in vivo. Biodistribution studies using 64Cu-labeled [CuLH−1] show a high uptake of copper by the liver.