Dalton transactions (Cambridge, England : 2003)

Solution chemistry of 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane with metal ions of biological interest-Insights toward active metal ion containing therapeutics and diagnostic agents.

PMID 17028712


The equilibrium constants of Cu(II), Zn(II), Ca(II) and Gd(III) with 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane (La) have been studied at 25 degrees C and an ionic strength of 0.15 mol dm-3. Copper forms more stable complexes with La than the other metal ions investigated. This is probably due to the ease with which Cu(II) deprotonates the nitrogen donor atoms of the amide groups. UV/Vis spectrophotometric data indicate tetradentate binding of the ligand towards copper in [CuLaH-1] and pentadentate binding in [CuLaH-2]. Octanol-water partition coefficients of Cu(II)-La complexes indicate that although these species are largely hydrophilic, approximately 5.62% of the [CuLaH-1] complex goes into the organic phase. This percentage may promote dermal absorption of copper with a calculated penetration rate of 3.75x10(-4) mm h-1. The [CuLaH-1] species which predominates at pH 7.4 is a poor mimic of native copper-zinc superoxide dismutase. Blood-plasma simulation studies predict that La is unable to increase the low molecular mass copper fraction in vivo. This has been confirmed by biodistribution patterns, which are similar to those of 64CuCl2.