Kinetics of Azanone (HNO) Reactions with Thiols: Effect of pH

HNO (nitroxyl, IUPAC name azanone) is an electrophilic reactive nitrogen species of growing pharmacological and biological significance. Here, we present data on the pH-dependent kinetics of azanone reactions with the low molecular thiols glutathione and N-acetylcysteine, as well as with important serum proteins: bovine serum albumin and human serum albumin. The competition kinetics method used is based on two parallel HNO reactions: with RSH/RS(−) or with O(2). The results provide evidence that the reaction of azanone with the anionic form of thiols (RS(−)) is favored over reactions with the protonated form (RSH). The data are supported with quantum mechanical calculations. A comprehensive discussion of the HNO reaction with thiolates is provided.