The development of new DNA cleavage agents is of interest for the designing of synthetic restriction enzymes,"] for an understanding of the structure of DNA, ['] and for pharmaceutical application^.^^] We have recently directed our ef-forts at investigating functional metal complexes that initiate DNA cleavage by unusual mechanisms,141 and have reported efficient cleavage of DNA by the dicationic complex lL5I (bpy = 2,2'-bipyridine, tpy = terpyridine). 1 was generated via oxidation of 2 [Eqs. (a) and (b)J.["J [Ru"OHz(bpy)(tpy)12+ [Ru"'OH(bpy)(tpy)12+ + e-+ H + (a) 2 [Ru"'OH(bpy)(tpy)12+ [ R~'~O ( b p y ) ( t p y ) ]~+ + e -+ H + (b) 1The DNA cleavage with 1 can be effected either stoichiometrically by addition of 1 to the DNA or electrocatalytically by application of a potential of 0.8 V to a solution of DNA and 2.['I In attempts to increase the binding affinity of these agents, we have now prepared the dicationic complex 3 (dppz = dipyridophenazine, see Scheme 1).The planar dppz ligand imparts high DNA affinity to the complex 4."] Studies with topoisomerase showed that 4 unwinds DNA by 30°, strongly implicating an intercalative binding mode. Complex 4 has very attractive photophysical properties, but does not exhibit DNA cleavage reactivity. Complex 3 also exhibits a high DNA affinity while retaining the DNA cleavage reactivity of the Ru"OH,/RU'"O functionality. Furthermore, the X-ray crystal structure of this complex shows extensive x-stacking of the planar dppz ligand (see Fig. 3), which may provide insight into the high DNA affinity of dppz complexes.Reaction of Ru (tpy)Cl, with dppz in the presence of triethylamine affords the complex [RuCl(dppz)(tpy)]CI. Treatment of an aqueous solution of this complex with AgCIO, leads to the precipitation of 3-(C104), . H,O, in the form of black crystals suitable for X-ray structure analysis. The complex exhibits a typical Ru" --t py(x*) metal-ligand charge transfer (MLCT) absorption band with A,,,,, = 482 nm (E = 12000 M-lcm-'). In aqueous solution, the complex is oxidized sequentially to the dicationic Ru" complex [Eqs. (c) and (d)]. 3 [Ru'"OH(dppz)(tpy)]*+ + e -+ H' (C) [Ru"'(dppz)(tpy)12+ [ R~'~O ( d p p z ) ( t p y ) ]~+ + e -+ H + ( 4 5 At pH 7, E,,,(Ru~"/Ru") = 0.56 V and E,,,(Ru'"/Ru"') = 0.62 V (SCE), compared to 0.49 V and 0.62 V in the case of the complex 2.[61 The pK, value of the aqua ligand in 3 is 8.6 compared to a pK, of 9.7 in 2.16] The structure of 3 is shown in Figure 1 .[81 The coordination about the Ru center is very similar to that in both [R~"OH,(tmen)(tpy)]~+ (tmen = N,N,N',N',-tetramethylethylenediamine)lgl and 2." Thus, incorporation of the strongly intercalating dppz ligand has not altered the electronic properties of the Rul'OH, functionality that are vital to the DNA cleavage reactivity.Complex 3 binds very strongly to DNA. We have determined the binding constants for a series of complexes related to 2 using an electrochemical method based on the cyclic voltammetric currents for the Ru"'/Ru" redox pairs of the complexes with and without DNA.1...