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

A new complex, [Ru(tpy)(dppn)(Cbz-Leu-NHCH2CN)]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-NHCH2CN ligand, a known cathepsin K inhibitor, with a quantum yield, Φ450, of 0.0012(4) in water (λirr = 450 nm). In addition, 1 sensitizes the production of singlet oxygen upon visible light irradiation with quantum yield, ΦΔ, of 0.64(3) in CH3OH. The photophysical properties of 1 were compared with those of [Ru(tpy)(bpy)(Cbz-Leu-NHCH2CN)]2+ (2, bpy = 2,2'-bipyridine), [Ru(tpy)(dppn)(CH3CN)]2+ (3), and [Ru(tpy)(bpy)(CH3CN)]2+ (4) to evaluate the effect of the release of the Cbz-Leu-NHCH2CN inhibitor relative to the CH3CN ligand, as well as the role of dppn as the bidentate ligand for 1O2 production instead of bpy. Nanosecond transient absorption spectroscopy confirms the formation of the long-lived dppn-centered 3ππ* 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 (λirr ≥ 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.