Sensitization of ruthenium nitrosyls to visible light via direct coordination of the dye resorufin: Trackable NO donors for light-triggered NO delivery to cellular targets

Three nitrosyl-dye conjugates, namely, [(Me(2)bpb)Ru(NO)(Resf)] (1-Resf), [(Me(2)bQb)Ru(NO)(Resf)] (2-Resf), and [((OMe)(2)bQb)Ru(NO)(Resf)] (3-Resf) have been synthesized via direct replacement of the chloride ligand of the parent {Ru-NO}(6) nitrosyls of the type [(R(2)byb)Ru(NO)(L)] with the anionic tricyclic dye resorufin (Resf). The structures of 1-Resf-3-Resf have been determined by X-ray crystallography. The dye is coordinated to the ruthenium centers of these conjugates via the phenolato-O atom and is trans to NO. Systematic red shift of the d(pi)(Ru) -> pi*(NO) transition of the parent nitrosyls [(R(2)byb)Ru(NO)(L)] due to changes in R and y in the equatorial tetradentate ligand R(2)byb(2-) results in its eventual merge with the intense absorption band of the dye around 500 nm in 3-Resf. Unlike the UV-sensitive parent [(R(2)byb)Ru(NO)(L)] nitrosyls, these dye-sensitized nitrosyls rapidly release NO when exposed to visible light (lambda >= 465 nm). Comparison of the photochemical parameters reveals that direct coordination of the light-harvesting chromophore to the ruthenium center in the present nitrosyls results in a significantly greater extent of sensitization to visible light compared to nitrosyls with appended chromophore (linked via alkyl chains). 1-Resf has been employed as a "trackable" NO donor to promote NO-induced apoptosis in MDA-MB-231 human breast cancer cells under the control of light. The results of this work demonstrate that (a) the d(pi)(Ru) -> pi*(NO) transition (photoband) of {Ru-NO}(6) nitrosyls can be tuned into visible range via careful alteration of the ligand frame(s) and (b) such nitrosyls can be significantly sensitized to visible light by directly ligating a light-harvesting chromophore to the ruthenium center. The potential of these photosensitive nitrosyl-dye conjugates as (i) biological tools to study the effects of NO in cellular environments and (ii) "trackable" NO donors in photodynamic therapy of malignancies (such as skin cancer) has been discussed.