We report the synthesis and photochemical and biological characterization of Ru(II) complexes containing pi-expansive ligands derived from dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me(2)dppn) adorned with flanking aryl substituents. Late-stage Suzuki couplings produced Me(2)dppn ligands substituted at the 10 and 15 positions with phenyl (5), 2,4-dimethylphenyl (6), and 2,4-dimethoxyphenyl (7) groups. Complexes of the general formula [Ru(tpy)(L)(py)](PF6)(2)(8-10), where L = 4-7, were characterized and shown to have dual photochemotherapeutic (PCT) and photodynamic therapy (PDT) behavior. Quantum yields for photodissociation of monodentate pyridines from 8-10 were about 3 times higher than that of parent complex [Ru(tpy)(Me(2)dppn)(py)](PF6)(2) (1), whereas quantum yields for singlet oxygen (O-1(2)) production were similar to 10% lower than that of 1. Transient absorption spectroscopy indicates that 8-10 possess long excited state lifetimes (tau = 46-50 mu s), consistent with efficient O-1(2) production through population and subsequent decay of ligand-centered (3)pi pi* excited states. Complexes 8-10 displayed greater lipophilicity relative to 1 and association to DNA but do not intercalate between the duplex base pairs. Complexes 1 and 8-10 showed photoactivated toxicity in breast and prostate cancer cell lines with phototherapeutic indexes, PIs, as high as >56, where the majority of cell death was achieved 4 h after treatment with Ru(II) complexes and light. Flow cytometric data and rescue experiments were consistent with necrotic cell death mediated by the production of reactive oxygen species, especially O-1(2). Collectively, this study confirms that DNA intercalation by Ru(II) complexes with pi-expansive ligands is not required to achieve photoactivated cell death.