Kinetic Study on the Reactivity of Azanone (HNO) toward Cyclic C-Nucleophiles

Azanone (HNO) is an elusive electrophilic reactive nitrogen species of growing pharmacological and biological significance. Here, we present a comparative kinetic study of HNO reactivity toward selected cyclic C-nucleophiles under aqueous conditions at pH 7.4. We applied the competition kinetics method, which is based on the use of a fluorescein-derived boronate probe FlBA and two parallel HNO reactions: with the studied scavenger or with O(2) (k = 1.8 × 10(4) M(−1)s(−1)). We determined the second-order rate constants of HNO reactions with 13 structurally diverse C-nucleophiles (k = 33–20,000 M(−1)s(−1)). The results show that the reactivity of HNO toward C-nucleophiles depends strongly on the structure of the scavenger. The data are supported with quantum mechanical calculations. A comprehensive discussion of the HNO reaction with C-nucleophiles is provided.