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Basic Research in Diazeniumdiolate Chemistry

At the core of Dr. Keefer’s research effort was a program of basic organic chemistry investigations aimed at characterizing the fundamental physicochemical properties of a compound class known as the diazeniumdiolates (or NONOates). As illustrated in the scheme below, such compounds can serve as caged reservoirs of the multifaceted bioregulatory agent nitric oxide (NO). An increasingly refined understanding of the chemistry led to the design of prodrugs of NO that have proved useful in biomedical research. Compounds introduced to the literature by the Keefer group are now used world-wide.

See: Fifty years of diazeniumdiolate research. From laboratory curiosity to broad-spectrum biomedical advances.

Basic Research diagram

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.