Development of Photoactivatable Nitroxyl (HNO) Donors Incorporating the (3‐Hydroxy‐2‐naphthalenyl)methyl Phototrigger

Yang Zhou; Ruth B. Cink; Zachary A. Fejedelem; M. Cather Simpson; Alexander J. Seed; Paul Sampson; Nicola E. Brasch

Index: 10.1002/ejoc.201800092

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Abstract

A new family of photoactivatable HNO donors of general structure RSO2NHO‐PT [where PT represents the (3‐hydroxy‐2‐naphthalenyl)methyl (3,2‐HMN) phototrigger] has been developed, which rapidly releases HNO. Photogeneration of HNO was demonstrated using the vitamin B12 derivative aquacobalamin as a trapping agent. The amount of sulfonate RSO2– produced was essentially the same as the amount of HNO released upon photolysis, providing a convenient method to indirectly quantify HNO release. Two competing pathways were also observed; a pathway involving O–N bond cleavage leading to release of a sulfonamide, and a pathway resulting in release of the parent Nhydroxysulfonamide RSO2NHOH (for HNO donors with Me‐ and Ph‐containing leaving groups only). Up to approximately 70 % of the HNO‐generating pathway was observed with the CF3‐containing leaving group, with HNO generation favored for small percentages of aqueous buffer in the acetonitrile/pH 7.00 phosphate buffer solvent mixture. Characterization of the photoproducts obtained from steady‐state irradiation by NMR spectroscopy showed that the desired HNO‐generating pathway was less favored for HNO donors with Me‐ and Ph‐containing leaving groups compared to the CF3‐containing leaving group, suggesting that the excellent CF3‐containing leaving group promotes HNO generation.