Fifty Years of Diazeniumdiolate Research. From Laboratory Curiosity to Broad-Spectrum Biomedical Advances

[Image: see text] Here I show that a “pure” research project, seemingly totally lacking in practical application when it was first published, can years later spark a whole new scientific field with the potential to revolutionize clinical practice. A 1961 publication describing adducts of nitric oxide (NO) with certain nucleophiles attracted little notice at the time, but later work showing that the adducts could be hydrolyzed to regenerate the NO in bioactive form has provided the foundation for a host of biomedical applications. Crucial to the discovery of widely used tools for studying NO’s chemical biology as well as for the design of a variety of promising therapeutic advances has been the increasingly detailed understanding of the physicochemical properties of these “diazeniumdiolates” (also known as NONOates).