The reactivities toward biomolecules of a series of three dirhodium(II,II) complexes that possess an increasing number of accessible axial coordination sites are compared. In cis-[Rh-2(OAc)(2)(np)(2)](2+) (1; np = 1,8-naphthyridine) both axial sites are available for coordination, whereas for cis-[Rh-2(OAc)(2)(np)(pynp)](2+) (2; pynp = 2-(2-pyridyl)1,8-naphthyridine) and cis-[Rh-2(OAc)(2)(pynp)(2)](2+) (3) the bridging pynp ligand blocks one and two of the axial coordination sites in the complexes, respectively. The electronic absorption spectra of the complexes are consistent with strong metal-to-ligand charge transfer transitions at low energy and ligand-centered peaks localized on the np and/or pynp ligands in the UV and near-UV regions. Time-dependent density functional theory calculations were used to aid in the assignments. The three complexes exhibit metal-centered oxidations and reductions, localized on the aromatic ligands. The ability of the complexes to stabilize duplex DNA and to inhibit transcription in vitro is greatly affected by the availability of an open axial coordination site. The present work shows that open axial coordination sites on the dirhodium complexes are necessary for biological activity.