| Although once known only as an environmental pollutant, recent research has demonstrated not only that nitric oxide (NO) is produced in vivo, but also that NO is a critical regulator of many fundamental biochemical processes including regulation of vasoconstriction and neurotransmission. Dialkylamino-based diazeniumdiolate salts are stable in the solid state, but release up to two equivalents of NO spontaneously when dissolved in aqueous solution under physiological conditions. These compounds have proven useful as research tools in a variety of applications requiring the controlled release of NO. In order to make diazeniumdiolates better pharmaceuticals, we have developed alkylated derivatives that are stable under physiological conditions, but release NO upon photolysis. During the course of this work, we also examined the aqueous photochemical decomposition of unsubstituted diazeniumdiolate salts. Nitroxyl (NO-/HNO), the one electron-reduced congener of NO, has recently been implicated as a potential heart failure therapeutic that increases both cardiac contractility and relaxation. Angeli's Salt (AS), is a diazeniumdiolate that releases nitroxyl (NO-/HNO) upon decomposition under physiological conditions. Because nearly all studies probing the fundamental chemistry and biochemistry of nitroxyl have utilized AS, we examined several other classes of compounds as potential nitroxyl donors. We have also begun to examine the mechanism by which nitroxyl enhances cardiac contractility and relaxation. |
