The chemistry of nitroxyl (HNO) and implications in biology

Over the past century, HNO research has evolved from fundamental physical examinations to elucidation of interactions in atmospheric, industrial and bacterial processes. Most recently, the HNO literature has been primarily concerned with the pharmacological effects and potential physiological functions of HNO in mammalian systems. The chemistry of HNO is inordinately complicated for a triatomic molecule. Further, the rapid self-consumption of HNO through dehydrative dimerization impedes detection and necessitates in situ production. This review provides a detailed discussion of the most common donors of HNO and of the current understanding of the aqueous chemistry of HNO and the synthesis, consumption and reactivity of HNO in a cellular environment, as ascertained with these donors. Additionally, the consequences of the molecular interactions of HNO on physiology are described, and a comparison is made to NO in terms of cellular signaling and pharmacological potential.