title: Computer simulation of nickel in blood-plasma following the in vitro investigations of complex formation chemistry with polyamine(amide) ligands.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch, 7700, South Africa.
authors.forename: Edmund T
authors.initials: ET
authors.lastname: Nomkoko
authors.forename: Graham E
authors.initials: GE
authors.lastname: Jackson
authors.forename: Bandile S
authors.initials: BS
authors.lastname: Nakani
authors.forename: Susan A
authors.initials: SA
authors.lastname: Bourne
mesh_terms: D003198:Computer Simulation; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009532:Nickel / Q000097:blood*; D009757:Nylons / Q000737:chemistry*; D009942:Organometallic Compounds / Q000097:blood*; D011073:Polyamines / Q000737:chemistry*; D011199:Potentiometry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008024:Ligands; D009757:Nylons; D009942:Organometallic Compounds; D011073:Polyamines; D009532:Nickel