Bifunctional bioorganometallic Iridium(III)-Platinum(II) complexes incorporating both intercalative and covalent DNA binding capabilities

The DNA binding of bifunctional Ir-III-Pt-II complexes containing [(eta 5-Cp*)Ir(dppz)](2+) and [Pt(terpy)](2+) or trans-[PtL2L'](2+) fragments (L = NH3, L' = DMF; L = H2O, L' = NH3) bridged by flexible kappa S:kappa N(amino) -coordinated methionine-containing peptides has been studied by UV/Vis and CD spectroscopy. Stable intercalative binding of the Ir-III fragment of the complexes [{(eta 5-Cp*)Ir(dppz)}(mu-peptide-kappa S:kappa N)[Pt(terpy)}]-(CF3SO3)(4) (5) (peptide = H-Gly-Gly-Phe-Met-OH; H-Gly-OH = glycine, H-Phe-OH = L-phenylalanine, H-Met-OH = L-methionine) and 6 [peptide = H-(Ala)(4)-Met-OH; H-Ala-OH = L-alanine] is indicated by their steady decrease in absorbance at maxima between 350 and 390 nm on titration with CT DNA and by the bathochromic shifts of these maxima. Binding constants K-b of 1.4(4) x 10(6) M-1 for both 5 and 6 and site sizes s of 2.8(l) and 2.2(l), respectively, are in accordance with this monofunctional mode. Both peptide chain length and the site(s) of the labile Pt-II substituents DMF or H2O play an important role in determining the degree of intercalation of the Ir-III fragment and the extent of helix distortion caused by simultaneous covalent binding of Pt-II centres for the DNA interaction of the complexes [{(eta 5 - Cp*)Ir(dppz)}(mu-peptide-kappa S: kappa N) {trans- (PtL2L')}](4+) 7-10. Whereas both 9 and 10 (L = H2O, L'= NH3; peptide = H-Gly-Met-OH or H-Gly-Gly-MetOH) exhibit a high degree of bifunctional binding [9, K-b 1.1(5) x 10(6) M-1, S = 1.3(l); 10, K-b = 1.4(7) x 10(6) M-1, s = 2. 1 (1)] CD spectroscopy indicates that a more pronounced reorganisation of the DNA helix is required for the former complex with its shorter peptide. Effective intercalation is also observed for 8 (L = NH3, L' = DMF; peptide = H-Gly-Gly-Met-OH) but not for 7 with the analogous Pt-II fragment but a shorter bridging peptide (H-Gly-Met-OH).