14 min− 1 in its absence. These observations from the LD measurement are in agreement with the results obtained from electrophoresis.

The redox potential for the Cu(bpy)2 complex was observed at − 0.222 V with a peak to peak separation of 0.201 V. On the other hand, no significant redox activity was found for the Zn(bpy)2 and Cd(bpy)2 complexes. Therefore, the ability of electron Selleckchem BMS 354825 donation of the metal complex is essential for the efficient DNA oxidative cleavage induced by the Cu(bpy)2 complex, even though the redox potential of the DNA bound Cu(bpy)2 complex might be different from that in the absence of dsDNA. The oxidation of the central metal ion to produce the oxygen radical, which is an essential reactive oxygen species in DNA cleavage induced by the Cu(bpy)2 complex is required for the proposed intermediate, [Cu(I)-O2 ⇌ Cu(II)-·O2−], mentioned previously. The amount of DNA-bound metal complex can be another factor that affects the DNA cleavage efficiency. However, in

the M(bpy)2 case, the amount of metal complex that is associated with DNA is not Olaparib an important factor because the Zn(bpy)2 and Cd(bpy)2 complexes are completely inactive. Indeed, the amounts of DNA bound metal complex estimated from the measured association constants for Cu(bpy)2, Zn(bpy)2 and Cd(bpy)2 were 89.9 μM, 60.9 μM and 47.6 μM, respectively. These values do not appears to be proper for elucidating the active–inactive catalytic effect observed for the metal complexes. The binding mode of any drug to dsDNA can be categorized as intercalation, minor or major groove binding, or external 6-phosphogluconolactonase binding. In intercalation binding mode, in which the planar moiety of the intercalating drug is parallel to the DNA base-pairs, a negative LD signal in the drug’s absorption region is expected because it orients perpendicular to the flow direction. Therefore, the positive LD signal observed in the ligand absorption region clearly rejects the possibility of the intercalation of any ligand of the Cu complex. Similar positive LD signals were observed for the Zn(bpy)2 and Cd(bpy)2 complexes at the time of mixing (Fig.

S3). In minor groove binding mode, which is often observed for positively charged and partially fused aromatic hydrocarbons, a positive LD signal appears in this case due to an angle of near 45° between the electric transitions of the drug and the local DNA helix axis. A well-known example of minor groove binding molecules is 4′,6-diamidino-2-phenylindole [40]. Based on the similar positive LD signal in the ligand absorption for all dsDNA-M(bpy)2 adducts (data not shown), at least some part of the ligand of all the complexes tested in this study conceivably fit into the narrow minor groove. Therefore, the binding mode of the M(bpy)2 complexes is similar and cannot be the main factor determining the observed difference in the catalytic effect. Detailed analysis of the binding geometry was outside the scope of this study.