Introduction 1 2 3 4 5 6 9 2 + 10 11 12 14 2 2+ 15 2 4 2 15 2 16 17 18 3 19 20 3 cis 21 24 N 1 4 2 cis 1 19 Fig. 1 1 3  2 2 Fig. 2 ODN I ODN II arrowheads  Materials and methods N 1 2 2 3 15 1 2-(2-(3-(1,10-Phenanthrolin-3-yloxy)-1-(1,10-phenanthrolin-8-yloxy)propan-2-ylamino)ethyl)isoindoline-1,3-dione 4 N 5 N 4 2 4 2 4 6 1 3 δ J J J J J J J J J J 13 3 δ m z + 37 29 6 4 + + 37 28 6 4 + 37 28 6 4 2 N 1 6 2 4 N 1 7 1 d 3 δ J J J J J J J J 13 d 3 δ m z + 29 27 6 2 + 29 26 6 2 2 2 N 1 2 7 2 4 2 N 1 2 1 1 d 6 δ J J J J 195 6 δ ν −1 29 26 2 6 2 1 4 2 1 2 g 2 λ max m z 58 52 6 12 4 2 2 2+ Cytotoxicity 1 2 Solutions of complexes for experiments with DNA One millimolar DMSO solutions of the complexes investigated were prepared, and were subsequently diluted with Milli-Q water. Nuclease activity on supercoiled DNA −1 −1 Time-course experiments of DNA cleavage −1 32 2 25 32 4 32 26 Comparison of the platinum–ODN adducts formed with the different complexes 5′-end-labeled ODN I (2 μM) was annealed to 1 equiv of its complementary strand ODN II in 1,100 μL of Tris–HCl (20 mM, pH 7.2) by heating to 90 °C for 5 min, followed by slow cooling to room temperature. Then, 60 μL of this solution was incubated with 60 μL of the complex solution (6 or 20 μM) for 20 h at 37 °C, followed by precipitation with 100 μL of sodium acetate buffer (3 M, pH 5.2) and 1,300 μL of cold ethanol. Pellets were rinsed with ethanol and lyophilized. Samples were dissolved in formamide containing bromophenol blue and xylene cyanol and heated for 3 min at 90 °C before being loaded on the gel. Platinum–DNA adducts were analyzed by denaturing 20% polyacrylamide gel electrophoresis, then by phosphorimagery. Taq 2 Taq 27 Comparison of the cleavage patterns of ODN I–ODN II induced by the copper complexes 1 2 3 2 2 27 Results and discussion Design and synthesis of a heterodinuclear platinum–copper complex 7 cis 1 2 1 7 3 2 1 2 1 2 4 195 1 1 2 2 Scheme 1 1 2 i ii 2 2 iii 2 4 iv 2  Cleavage of supercoiled DNA 2 3 3 2 3 3 2 3 2 3 3 2 3 19 28 29 15 2 19 Fig. 3 2 3 Lane 1 Lane 2 2 Lane 3 2 Lane 4 2 Lane 5 2 Lane 6 3 Lane 7 3 Lane 8 3 Lane 9 3  2 3 4 3 19 3 2 4 2 Fig. 4 2  Analysis of the platinum adducts on ODN I of the ODN I–ODN II duplex target 5 cis 5 Fig. 5 a 32 Lane 1 Lane 2 Lane 3 Lane 4 1 Lane 5 1 Lane 6 2 Lane 7 2 b 1 2 Taq Lane 1 Lane 2 Lane 3 1 Lane 4 2 c 1 2 Large arrows small arrows  5 5 1 5 1 2 5 2 1 2 19 1 2 5 1 2 Taq 23 30 39 5 5 1 2 1 2 Taq 1 2 1 2 5 1 2 1 1 Taq 1 Cleavage of the ODN I strand of the ODN I–ODN II duplex 1 3 6 40 41 Fig. 6 a 1 3 lane 1 lane 2 Materials and methods 3 b a 1 2  1 2 1 3 3 6 3 6 1 2 3 18 6 2 6 3 3 2 2 6 8 2 1 1 2 2 6 1 2 1 3 6 6 1 5 1 3 6 6 1 2 6 1 2 Cleavage of the ODN II strand of the ODN I–ODN II duplex 7 1 7 2 7 1 2 Fig. 7 1 3 lane 1 lane 2 Materials and methods 1 2  1 2 7 2 1 2 Comparison between the cleavage of duplex and single-stranded DNA 2 8 Fig. 8 2 2 asterisk  2 2 2 2 9 2 Fig. 9 2 asterisk  8 3 15 Concluding remarks 2 3 1 2 1 2 Taq 1 2 1 2 1 2 1 1 2 2 Electronic supplementary material Below is the link to the electronic supplementary material.
 ESM1 (PDF 89.7 kb)