The Chemistry of Nitroxyl-Releasing Compounds

Nitroxyl (HNO) demonstrates a diverse and unique biological profile compared to nitric oxide, a redox-related compound. Although numerous studies support the use of HNO as a therapeutic agent, the inherent chemical reactivity of HNO requires the use of donor molecules. Two general chemical strategies currently exist for HNO generation from nitrogen-containing molecules: (i) the disproportionation of hydroxylamine derivatives containing good leaving groups attached to the nitrogen atom and (ii) the decomposition of nitroso compounds (X-N = O, where X represents a good leaving group). This review summarizes the synthesis and structure, the HNO-releasing mechanisms, kinetics and by-product formation, and alternative reactions of six major groups of HNO donors: Angeli's salt, Piloty's acid and its derivatives, cyanamide, diazenium diolate-derived compounds, acyl nitroso compounds, and acyloxy nitroso compounds. A large body of work exists defining these six groups of HNO donors and the overall chemistry of each donor requires consideration in light of its ability to produce HNO. The increasing interest in HNO biology and the potential of HNO-based therapeutics presents exciting opportunities to further develop HNO donors as both research tools and potential treatments. Antioxid. Redox Signal. 14, 1637-1648.