Chemistry of the Nitric Oxide-Releasing Diazeniumdiolate (“Nitrosohydroxylamine”) Functional Group and Its Oxygen-Substituted Derivatives

Abstract

Joseph A. Hrabie received his entire education in the New York City public school system, including his Ph.D. degree in Chemistry (1981) under the guidance of Professor William F. Berkowitz at Queens College of the City University of New York. After postdoctoral research with Professor Herbert O. House at the Georgia Institute of Technology, he moved to the National Cancer Institute at Frederick and is currently a Senior Scientist with SAIC−Frederick, the primary NCI contractor at the site. In addition to many scientific publications, his continuing interest in nitric oxide chemistry has resulted in 15 U.S. patents. Larry K. Keefer received his B.A. degree from Oberlin College and his Ph.D. degree in Chemistry (1965) under the guidance of Professor Gloria G. Lyle at the University of New Hampshire. He held research positions at the Chicago Medical School and the University of Nebraska College of Medicine before coming to the National Cancer Institute in 1971. He and his colleagues in the NCI's Chemistry Section, Laboratory of Comparative Carcinogenesis, are intensively studying the chemistry and pharmacology of the diazeniumdiolates as nitric oxide sources for biomedical applications.This section contains a description of reactions that are used preparatively as well as those that do not

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

“…[16][17][18] The nanoparticles spontaneously release tunable levels of NO under aqueous conditions at physiological temperature and pH, and thus represent attractive vehicles for delivering NO. Nanoparticle delivery of NO has two main advantages over previously-developed small molecule NO donor systems (e.g., diazeniumdiolates, nitrosothiols, and metal-NO complexes 19,20 ). First, the rate of NO release is easily modulated as a function of nanoparticle size, composition, and/or surface hydrophobicity, thereby allowing for control over the duration of NO release.…”

Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia

“…Advantages of diazeniumdiolates over other NO donors include spontaneous NO release upon exposure to an aqueous environment, predictable rates of NO release, and a wide range of NO generation. [30,31] More specifically, we identified two distinctly different NO donors, 1-[2-(carboxylato) pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) and diazeniumdiolated poly (acrylonitrile) (PAN/NO), with short and long half-lives, respectively. [32,33] The aims for this study were three-fold: first, to evaluate the efficacy of these two markedly different diazeniumdiolate NO donors to prevent the development of neointimal hyperplasia; second, to evaluate two different delivery approaches, powder versus gel; and third, to evaluate the inflammatory response following application of these NO-donors.…”

Nitric oxide releasing-dendrimers: an overview

“…Nitric oxide release in these dendrimer-diazeniumdiolates derivatives occurs through a hydrolytic degradation mechanism, initiated by protonation at the amine nitrogen (Davies et al, 2001;Hrabie, Keefer, 2002;Keefer, 2011). Compound 1 and 7 ( Figure 3) were able to maintain the sustained-release of NO for more than 16 h, followed by 6 (~14h), being these values the longest observed among analogous compounds (dendrimers 2-5) and small alkyl diazeniumdiolates (Stasko, Schoenfisch, 2006).…”

“…All diazeniumdiolate derivative dendrimers (1-7, 10, 14-33 on Table I) release NO spontaneously under physiological conditions (pH 7.4, 37 ºC), yielding two moles of NO per mole of diazeniumdiolate ( Figure 7) (Davies et al, 2001;Hrabie, Keefer, 2002;Keefer, 2011).…”