Two cyclometalated complexes of Rh(III), rac-[Rh(ppy)(2)chrysi](+) and rac-[Rh(ppy)(2)phi]+, have been synthesized and characterized with respect to their binding to DNA. The structure of rac-[Rh(ppy)(2)phi]Cl .H2O . CH2Cl2 has been determined by X-ray diffraction (monoclinic, P2(1)/c, Z = 4, a = 18.447(3) Angstrom, b = 9.770(1) Angstrom; c = 17.661(3) Angstrom, beta = 941821(11)degrees, V = 3172.0(8) Angstrom (3)) and reveals that the complex is a distorted octahedron with nearly planar ligands, similar in structure to the DNA mismatch recognition agent [Rh(bpy)(2)chrysi](3+). The 2-phenylpyridyl nitrogen atoms are shown to be in the axial positions, as a result of trans-directing effects. This tendency simplifies the synthesis and purification of such complexes by limiting the number of possible isomers generated. The abilities of [Rh(ppy)(2)chrysi](+) and [Rh(ppy)(2)phi](+) to bind and, with photoactivation, to cleave DNA have been demonstrated in assays on duplex DNA in the absence and presence of a single CC mismatch. [Rh(ppy)(2)chrysi](+) was shown upon photoactivation' to cleave DNA selectively at the base pair mismatch whereas [Rh(ppy)(2)phi](+) cleaves B-DNA nonspecifically. The reactivity of [Rh(ppy)(2)chrysi](+) was also compared to that of the known mismatch recognition agent [Rh(bpy)(2)chrysi](3+). Competitive photocleavage studies revealed that a 14-fold excess of [Rh(ppy)(2)chrysi](+) was required to achieve the same level of binding as that of [Rh(bpy)(2)chrysi](3+). However, the ratio of damage induced by [Rh(bpy)(2)chrysi](3+) to that induced by [Rh(ppy)(2)chrysi](+) is considerably greater than this value, indicating that decreased photoefficiency for the cyclometalated complex must contribute to its significantly attenuated photoreactivity. These cyclometalated intercalators provide the starting paints for the design of a new family of metal complexes targeted to DNA.