Nickel(II), copper(II) and zinc(II) binding properties and cytotoxicity of tripodal, hexadentate tris(ethylenediamine)--analogue chelators.

Academic Article


  • Three tripodal hexamine chelators based on cis,cis-1,3,5-triaminocyclohexane (tach) have been synthesized and their aqueous coordination chemistry with Ni(II), Cu(II) and Zn(II) is reported. The chelators have a 2-aminoethyl pendant arm attached to each nitrogen of tach, specifically 'tachen'(N,N',N''-tris(2-aminoethyl)cyclohexane-cis,cis-1,3,5-triamine), and two with S,S,S-chiral pendant arms, 'tachpn'(N,N',N''-tris(2-aminopropyl)cyclohexane-cis,cis-1,3,5-triamine) and 'tachbn'(N,N',N''-tris(2-amino-3-phenylpropyl)cyclohexane-cis,cis-1,3,5-triamine. These chelators complex Ni(II), Cu(II) and Zn(II) in aqueous or aqueous/methanolic medium. The crystalline products [M(II)L](X)2 are isolated, where M = Ni(II), Cu(II) or Zn(II), L = tachen, tachpn or tachbn, and X = ClO4-. Crystallographic study of selected tachpn and tachbn complexes shows the chelate arms are constrained in a Lambda(deltadeltadelta) configuration about M(II), which is attributed to their chirality. Solution UV-vis spectroscopy of the Ni(II) and Cu(II) complexes indicates six-coordination and little effect of the pendant arm substitution on ligand-field strength. The single exception is [Cu(tachbn)]2+, whose spectrum is consistent with five-coordination in solution. The cytotoxicities of tachen, tachpn and tachbn toward cultured cancer cells is in the order tachen < tachpn < tachbn < tachpyr, where tachpyr is the aminopyridyl chelator N,N',N''-tris(2-pyridylmethyl)cyclohexane-cis,cis-1,3,5-triamine. The cytotoxicity difference is attributed to an order of increasing lipophilicity, tachen < tachpn < tachbn.
  • Authors

  • Ye, Neng
  • Park, Gyungse
  • Przyborowska, Ann M
  • Sloan, Paula E
  • Clifford, Thomas
  • Bauer, Cary B
  • Broker, Grant A
  • Rogers, Robin D
  • Ma, Rong
  • Torti, Suzy V
  • Brechbiel, Martin W
  • Planalp, Roy
  • Status

    Publication Date

  • May 7, 2004
  • Keywords

  • Animals
  • Cations, Divalent
  • Cell Line, Tumor
  • Cell Survival
  • Chelating Agents
  • Copper
  • Crystallography, X-Ray
  • Ethylenediamines
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Models, Molecular
  • Molecular Structure
  • Nickel
  • Organometallic Compounds
  • Zinc
  • Digital Object Identifier (doi)

    Pubmed Id

  • 15252622
  • Start Page

  • 1304
  • End Page

  • 1311
  • Volume

  • 0
  • Issue

  • 9