Nickel(II), copper(II) and zinc(II) binding properties and cytotoxicity of tripodal, hexadentate tris(ethylenediamine)--analogue chelators.
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.
Ye
Neng
N
Department of Chemistry, University of New Hampshire, Durham, NH 03824-3598, USA.
Park
Gyungse
G
Przyborowska
Ann M
AM
Sloan
Paula E
PE
Clifford
Thomas
T
Bauer
Cary B
CB
Broker
Grant A
GA
Rogers
Robin D
RD
Ma
Rong
R
Torti
Suzy V
SV
Brechbiel
Martin W
MW
Planalp
Roy P
RP
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*
D002413:Cations, Divalent; D002614:Chelating Agents; D005029:Ethylenediamines; D009942:Organometallic Compounds; D003300:Copper; D009532:Nickel; D015032:Zinc