The DNA binding site specificity and antiproliferative property of ternary Pt(ii) and Zn(ii) complexes of phenanthroline and N,N′-ethylenediaminediacetic acid

Abstract

The binding site specificity of the ternary complexes, [M(II)(phen)(edda)] (M(II) = Pt²⁺ and Zn²⁺; phen = 1,10-phenanthroline; edda = N,N′-ethylenediaminediacetic acid), for the self-complementary oligonucleotides (ODNs), ds(C₁G₂C₃G₄A₅A₆T₇T₈C₉G₁₀C₁₁G₁₂)₂ (ODN1) and ds(C₁G₂C₃G₄T₅A₆T₇A₈C₉G₁₀C₁₁G₁₂)₂ (ODN2), was studied by NMR measurements. The results indicated that [Pt(II)(phen)(edda)] was partially intercalated between C₃/G₁₀ and G₄/C₉ base pairs of ODN1 and ODN2 in the major grooves, whereas [Zn(II)(phen)(edda)] was bound specifically to the TATA region of ODN2 in the minor groove and to the terminal G₂/C₁₁ base pair of ODN1 in the major groove. The preference for the TATA sequence over the AATT sequence in the binding of [Zn(phen)(edda)] was attributed to the wider minor groove width of the TATA sequence. The bindings of the complexes to ct-DNA were also studied by UV, CD, and fluorescence spectroscopy. Additionally, the antiproliferative property of [Pt(II)(phen)(edda)] towards MCF7 breast cancer cells and normal MCF10-A cells was compared with that of [Zn(II)(phen)(edda)].