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 (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) at 25 °C and an ionic strength of 0.15 mol dm−3. Nickel(II) forms stable complexes with L1 and L2 where square-planar [NiLH−1] and [NiLH−2] species predominate under alkaline conditions. The square-planar coordination of nickel by L1 has been confirmed by a single-crystal X-ray structure, UV/Vis spectrometry and molecular mechanics calculations of the [NiL1H−1] complex. The introduction of a third amine group into L3 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 L1 towards Ni(II) is calculated to decrease the mobilisation of Cu(II) in plasma by approximately 65%. [CuL1H−1] is currently under investigation as an anti-inflammatory agent