Synthesis of a generic diazeniumdiolate ion by reacting an amine with NO under basic conditions to produce an ion that can generate NO spontaneously at physiological pH. Such ions can be further derivatized to yield a neutral diazeniumdiolate molecule that is stable until the R3 protecting group is removed to regenerate the ion and, in the presence of hydrogen ion, release the NO.
We are now vigorously pursuing the hypothesis that this chemistry will serve as a basis for rationally designing innovations in the clinical arena. For a recent review, see Fifty years of diazeniumdiolate research. From laboratory curiosity to broad-spectrum biomedical advances.