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

Abstract

Three nitrosyl-dye conjugates, namely, [(Me 2bpb)Ru(NO)(Resf)] ( 1-Resf), [(Me 2bQb)Ru(NO)(Resf)] ( 2-Resf), and [((OMe) 2bQb)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 2byb)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 2byb)Ru(NO)(L)] due to changes in R and y in the equatorial tetradentate ligand R 2byb (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 2byb)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.

Multi-photon excitation in uncaging the small molecule bioregulator nitric oxide

“…For example, we and others have worked to design molecular species and larger constructs that are photoactive for NO release at longer excitation wavelengths in the visible [10,[18][19][20] and even in the NIR ranges [21]. However, doing so requires a compound that has appropriate absorption properties and reactivity when excited by longer wavelength light.…”

“…NO is also known to trigger cell apoptosis (programmed cell death) [9], and this property offers another potential therapeutic application in cancer therapy [10]. However, NO plays contradictory roles in regulating apoptosis and has been implicated in both tumour growth and suppression as dictated by local concentrations [9,[11][12][13].…”

Light-triggered nitric oxide delivery to malignant sites and infection

“…For example, when the dye resorufin (Resf; ε 600 = 105 000 M −1 cm −1 ) was attached directly to the Ru centre, No loss of viability was observed with these cells in the dark. However, when such cells were exposed to visible light (300 mW) for 1 min, the photoreleased NO promoted apoptosis within 6 h (as indicated by DNA fragmentation and cell wall blebbing; [42]). Complete loss of viability was noted within 24 h. These results demonstrate that selective NO delivery to malignant sites can be achieved with these designed NO donors under the control of light.…”

Synthesis, Characterization and Reaction of New Ruthenium Aromatic Thioamide Nitrosyls with some Nitrogen Donor Ligands

“…For example NO donors that are capable of releasing NO upon illumination could find use as antitumor agents in Photo Dynamic Theraphy (PDT). [3][4][5] Non heme iron nitrosyls such as sodium nitropruside Na 2 [Fe(CN) 5 4 ] are also known to release NO under photochemical condition Unfortunately release of NO from these NO donors is dependent on enzymatic reaction, heat or pH and hence target specificity is mostly precluded 6 . Release of auxiliary ligands from metal base NO donors like SNP also leads to deleterious side effect.…”