title: Nickel(II), copper(II) and zinc(II) binding properties and cytotoxicity of tripodal, hexadentate tris(ethylenediamine)--analogue chelators.
abstract: 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.affiliation: Department of Chemistry, University of New Hampshire, Durham, NH 03824-3598, USA.
authors.forename: Neng
authors.initials: N
authors.lastname: Ye
authors.forename: Gyungse
authors.initials: G
authors.lastname: Park
authors.forename: Ann M
authors.initials: AM
authors.lastname: Przyborowska
authors.forename: Paula E
authors.initials: PE
authors.lastname: Sloan
authors.forename: Thomas
authors.initials: T
authors.lastname: Clifford
authors.forename: Cary B
authors.initials: CB
authors.lastname: Bauer
authors.forename: Grant A
authors.initials: GA
authors.lastname: Broker
authors.forename: Robin D
authors.initials: RD
authors.lastname: Rogers
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.forename: Suzy V
authors.initials: SV
authors.lastname: Torti
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Roy P
authors.initials: RP
authors.lastname: Planalp
mesh_terms: D000818:Animals; D002413:Cations, Divalent / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry*
chemical_list: D002413:Cations, Divalent; D002614:Chelating Agents; D005029:Ethylenediamines; D009942:Organometallic Compounds; D003300:Copper; D009532:Nickel; D015032:Zinc