Reactivity of a nitrosyl ruthenium complex and its potential impact on the fate of DNA - An in vitro investigation.

The role of metal complexes on facing DNA has been a topic of major interest. However, metallonitrosyl compounds have been poorly investigated regarding their reactivities and interaction with DNA. A nitrosyl compound, cis-[Ru(bpy)(SO)(NO)](PF)(A), showed a variety of promising biological activities catching our attention. Here, we carried out a series of studies involving the interaction and damage of DNA mediated by the metal complex A and its final product after NO release, cis-[Ru(bpy)(SO)(HO](B). The fate of DNA with these metal complexes was investigated upon light or chemical stimuli using electrophoresis, electronic absorption spectroscopy, circular dichroism, size-exclusion resin, mass spectrometry, electron spin resonance (ESR) and viscometry. Since many biological disorders involve the production of oxidizing species, it is important to evaluate the reactivity of these compounds under such conditions as well. Indeed, the metal complex B exhibited important reactivity with HO enabling DNA degradation, with detection of an unusual oxygenated intermediate. ESR spectroscopy detected mainly the DMPO-OOH adduct, which only emerges if HO and O are present together. This result indicated HOO as a key radical likely involved in DNA damage as supported by agarose gel electrophoresis. Notably, the nitrosyl ruthenium complex did not show evidence of direct DNA damage. However, its aqua product should be carefully considered as potentially harmful to DNA deserving further in vivo studies to better address any genotoxicity.