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

Abstract

Formation constants of Cu 2+, Zn 2+ and Ca 2+ with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (L 1), N, N ′-bis(2-hydroxyiminopropionyl)propane-1,3-diamine (L 2) and (1,15)-bis( N, N-dimethyl)-5,11-dioxo-8-( N-benzyl)-1,4,8,12,15-pentaazapentadecane (L 3) 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 L 1 and L 2 are able to mobilise Cu 2+ in vivo. Biodistribution studies using 64Cu-labeled [CuLH −1] show a high uptake of copper by the liver.