The pH of HNO donation is modulated by ring substituents in Piloty's acid derivatives: azanone donors at biological pH

A group of Piloty's acid (N-hydroxybenzenesulfonamide) derivatives were synthesized and fully characterized in order to assess the rates and pH of HNO (azanone, nitroxyl) donation in aqueous media. The derivatives, with electron-withdrawing and -donating substituents include methyl, nitro, fluoro, tri-isopropyl, trifluoromethyl and methoxy groups. The most interesting modulation observed is the change in pH range in which the compounds are able to donate HNO. UV–visible kinetic measurements at different pH values were used to evaluate the decomposition rate of the donors. A novel technique based on electrochemical measurements using a Co-porphyrin sensor was used to assess the release of HNO as a function of pH, by direct measurement of [HNO]. The results were contrasted with DFT calculations in order to understand the electronic effects exerted by the ring substituents, which drastically modify the pH range of donation. For example, while Piloty's acid donates HNO from pH 9.3, the corresponding fluoro derivative starts donating at pH 4.0.

Graphical abstractA group of Piloty's acid (N-hydroxybenzenesulfonamide) derivatives were synthesized and characterized. A Co-porphyrin sensor was used to assess the release of HNO as a function of pH, by direct measurement of [HNO], showing a large change in the pH range at which the compounds start to donate HNO.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The decomposition rate of PA derivatives at different pH values is ca 10– 3–10– 4 s– 1. ► Novel electrochemical measurements were used to determine the pH of HNO donation. ► The pH of donation starts at − 1 to 10 depending on the substitution. ► DFT calculations allowed to understand the effects exerted by the ring substituents.