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Development of Photoactivatable Nitroxyl (HNO) Donors Incorporating the (3‐Hydroxy‐2‐naphthalenyl)methyl Phototrigger
Author(s) -
Zhou Yang,
Cink Ruth B.,
Fejedelem Zachary A.,
Cather Simpson M.,
Seed Alexander J.,
Sampson Paul,
Brasch Nicola E.
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800092
Subject(s) - chemistry , leaving group , acetonitrile , solvent , nitroxyl , aqueous solution , photodissociation , adduct , sulfonate , photochemistry , organic chemistry , catalysis , sodium
A new family of photoactivatable HNO donors of general structure RSO 2 NHO‐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 B 12 derivative aquacobalamin as a trapping agent. The amount of sulfonate RSO 2 – 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 N hydroxysulfonamide RSO 2 NHOH (for HNO donors with Me‐ and Ph‐containing leaving groups only). Up to approximately 70 % of the HNO‐generating pathway was observed with the CF 3 ‐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 CF 3 ‐containing leaving group, suggesting that the excellent CF 3 ‐containing leaving group promotes HNO generation.