Computer simulation of nickel in blood-plasma following the in vitro investigations of complex formation chemistry with polyamine(amide) ligands.

In- and out-of-cell potentiometric techniques have been used to determine the formation constants for nickel(II) with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (L(1)), N,N[prime or minute]-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)) at 25 degrees C and an ionic strength of 0.15 mol dm(-3). Nickel(II) forms stable complexes with L(1) and L(2) where square-planar [NiLH(-1)] and [NiLH(-2)] species predominate under alkaline conditions. The square-planar coordination of nickel by L(1) has been confirmed by a single-crystal X-ray structure, UV/Vis spectrometry and molecular mechanics calculations of the [NiL(1)H(-1)] complex. The introduction of a third amine group into L(3) dramatically decreases the ligand's ability to complex Ni(II). This results from a change in structure of the complex which decreases the ability of the metal ion to promote the dissociation of the amide protons. Using a model of blood plasma, the high binding ability of L(1) towards Ni(II) is calculated to decrease the mobilisation of Cu(II) in plasma by approximately 65%. [CuL(1)H(-1)] is currently under investigation as an anti-inflammatory agent.