A dinuclear copper(II) complex [Cu-2(II)(PD'O-)(H2O)(2)](ClO4)(3) (5) with terminal Cu(II) - H2O moieties and a Cu center dot center dot center dot Cu distance of 4.13 A (X-ray structure) has been synthesized and characterized by EPR spectroscopy (ferromagnetic coupling observed) and cyclic voltammetry. Dizinc(II) and mononuclear copper(II) analogues [Zn-2(II)(PD'O-)(H2O)(2)](3+) (7) and [Cu-II(mPD'OH)(H2O)](2+) (6), respectively, have also been synthesized and structurally characterized. Reacting 5/MPA/O-2 (MPA)(3-) mercaptopropionic acid) with DNA leads to a highly specific oxidation of guanine (G) at a junction between single- and double-stranded DNA. Mass spectrometric analysis of the major products indicates a gain of +18 and +34 amu relative to initial DNA strands. The most efficient reaction requires G at the first and second unpaired positions of each strand extending from the junction. Less reaction is observed for analogous targets in which the G cluster is farther from the junction or contains less than four Gs. Consistent with our previous systems, the multinuclear copper center is required for selective reaction; mononuclear complex 6 is not effective. Hydrogen peroxide as a substitute for MPA/O-2 also does not lead to activity. Structural analysis of a [Cu-2(II)(PD'O-)(G)](3+) complex (8) and dizinc analogue [Zn-2(II)(PD'O-)(G)](ClO4)(3) (9) (G) guanosine) reveals coordination of the G O6 and N7 atoms with the two copper ( or zinc) centers and suggests that copper - G coordination likely plays a role in recognition of the DNA target. The Cu-2-O-2 intermediate responsible for guanine oxidation appears to be different from that responsible for direct-strand scission induced by other multinuclear copper complexes; the likely course of reaction is discussed.