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Building a better trap: The use of iron dithiocarbamate complexes in the in vivo and ex vivo detection and quantification of nitric oxide

Posted on:2003-04-07Degree:Ph.DType:Dissertation
University:Dartmouth CollegeCandidate:Fecker, Jesse AlanFull Text:PDF
GTID:1464390011987220Subject:Chemistry
Abstract/Summary:
Nitric oxide is synthesized by living organisms and plays important roles in circulatory, neurological, and immune function. Nitric oxide can also play pathophysiological roles, depending on the amount of the molecule, the presence of other species and the redox environment of the tissue. For this reason, it is important to be able to accurately quantify NO levels. However, given the short half-life and generally low concentration of NO, it is difficult to measure its levels in different tissues of a living organism. One method of NO detection and quantification that has considerable potential involves trapping NO with an iron(II) dithiocarbamate complex and subsequently detecting the nitrosylated species by electron paramagnetic resonance (EPR) spectroscopy. This EPR method is capable of detecting NO in a live animal and has the potential for clinical applications.; This research has investigated NO detection by this technique, and addressed a number of questions about the chemistry of the dithiocarbamate ligands used in this method. Specifically, this research has examined the ability of other transition metals to bind to the dithiocarbamates, thereby interfering with NO detection, and the stability of the iron nitrosyl dithiocarbamates. Structurally related bisdithiocarbamates have also been investigated for improved NO detection properties. Finally, a novel modification of this method that involves covalently attaching the dithiocarbamate ligand to a solid resin support has been developed. Trapping NO by these derivatized solid supports may reduce the physiological effects of these NO traps, including possible toxicity, and may represent a means of extending this type of NO detection and quantification into the clinic.
Keywords/Search Tags:NO detection, Dithiocarbamate
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