New Ru(ii) complex for dual photochemotherapy: release of cathepsin K inhibitor and 1O2 production

摘要

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.