New Ru(ii) complex for dual photochemotherapy: release of cathepsin K inhibitor and 1O2 productionElectronic supplementary information (ESI) available. See DOI: 10.1039/c8dt00876k

• Main Authors: Rohrabaugh, Thomas N, Collins, Kelsey A, Xue, Congcong, White, Jessica K, Kodanko, Jeremy J, Turro, Claudia
• Format: Article
• Language: English
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c8dt00876k

A new complex, [Ru(tpy)(dppn)(Cbz-Leu-NHCH 2 CN)] 2+ ( 1 , tpy = 2,2′:6′,2′′-terpyridine, dppn = benzo[ i ]dipyrido[3,2- a :2′,3′- c ]phenazine) was synthesized and its photochemical properties were investigated. This complex undergoes photorelease of the Cbz-Leu-NHCH 2 CN ligand, a known cathepsin K inhibitor, with a quantum yield, Φ 450 , of 0.0012(4) in water ( λ irr = 450 nm). In addition, 1 sensitizes the production of singlet oxygen upon visible light irradiation with quantum yield, Φ Δ , of 0.64(3) in CH 3 OH. The photophysical properties of 1 were compared with those of [Ru(tpy)(bpy)(Cbz-Leu-NHCH 2 CN)] 2+ ( 2 , bpy = 2,2′-bipyridine), [Ru(tpy)(dppn)(CH 3 CN)] 2+ ( 3 ), and [Ru(tpy)(bpy)(CH 3 CN)] 2+ ( 4 ) to evaluate the effect of the release of the Cbz-Leu-NHCH 2 CN inhibitor relative to the CH 3 CN ligand, as well as the role of dppn as the bidentate ligand for 1 O 2 production instead of bpy. Nanosecond transient absorption spectroscopy confirms the formation of the long-lived dppn-centered 3 ππ* state in 1 and 3 with a maximum at ∼540 nm and τ ∼20 μs in deaerated acetonitrile. Complexes 1 and 3 are able to cause photoinduced damage to DNA ( λ irr ≥ 395 nm), whereas 2 and 4 do not photocleave DNA under similar experimental conditions. These results suggest that 1 is a promising agent for dual activity, both releasing a drug and producing singlet oxygen, and is poised to exhibit enhanced biological activity in phototochemotherapy upon irradiation with visible light. A new Ru( ii ) complex releases a cysteine protease inhibitor and produces cytotoxic 1 O 2 upon irradiation with visible light, making it potentially useful as a dual-action PDT agent.