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

Article abstract of DOI:10.1039/b602977a

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 (L^a) have been studied at 25 °C and an ionic strength of 0.15 mol dm^-3. Copper forms more stable complexes with L^a 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 [CuL^aH_-1] and pentadentate binding in [CuL ^aH_-2]. Octanol-water partition coefficients of Cu(ii)-L^a complexes indicate that although these species are largely hydrophilic, approximately 5.62% of the [CuL^aH_-1] complex goes into the organic phase. This percentage may promote dermal absorption of copper with a calculated penetration rate of 3.75 × 10^-4 mm h^-1. The [CuL^aH_-1] species which predominates at pH 7.4 is a poor mimic of native copper-zinc superoxide dismutase. Blood-plasma simulation studies predict that L^a 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 ⁶⁴CuCl ₂. The Royal Society of Chemistry 2006.