Chemical reactivity and DNA sequence specificity of formally monofunctional and bifunctional bis(platinum) complexes

The synthesis of the formally monofunctional bis(platinum) complex [(Pt(NH3)3)mu-H2N(CH2)4NH2-(trans-PtCl(NH3)2)]3+ (1,0/t) is reported. The interactions of this species and the formally bifunctional bis(platinum) complex [(trans-PtCl(NH3)2)2H2N(CH2)4NH2]Cl2(1,1/t,t) with DNA were investigated. Comparison was made with the monomeric [PtCl(dien)]Cl, (Pt(DIEN)), and cis-[PtCl2(NH3)2], (cis-DDP). The initial rates of reaction with small self-complementary oligonucleotides 5'-ATATATN4ATATAT-3' (N4 = GCGC and N4 = GGCC) were calculated. For all compounds, the GGCC oligonucleotide reacted faster than the GCGC counterpart. The order of reactivity of the platinum compounds for the GCGC oligonucleotide was 1,1/t,t > 1,0/t > Pt(DIEN) > cis-DDP. The reaction of 1,0/t and 1,1/t,t with poly(dG-dC).poly(dG-dC) was also investigated using circular dichroism (CD) spectroscopy where both compounds were shown to induce a B-->Z conformational change.