Abstract/Details

Nitric oxide donors and superoxide probes: Synthesis and properties


2009 2009

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Abstract (summary)

This dissertation describes my Ph.D. work that focused on the synthesis and properties of “cyclic-SNO” as novel nitric oxide donors, the trityl derivatives as superoxide probes, and sugar nitric oxide donor conjugates as prodrugs.

In chapter 1, a new synthetic approach to cyclic-RSNO was established, and four such derivatives were synthesized. These compounds have strong vasodilatation effects making them potential novel NO donors. A kinetic mechanism to explain the NO-releasing property was proposed, and this hypothesis was well supported by the computational studies, EPR spectra and MS analyses. It should be addressed that the NO-releasing rate of these compounds was found to be 1st order and dependent on [H+].

In chapter 2, three new radical molecular probes were synthesized and characterized. They can specifically detect superoxide radicals by changes in intensity of the fluorescence spectrum or by EPR signals.

In chapter 3, a new class of fluorescence tagged glycosides (indolizine-3-yl-glycosides) were synthesized. The enzymatic glycosidation of these substrates caused the disappearance of fluorescence. These glycosides are novel probes in studying glycosidase.

In chapter 4, a new sialated diazeniumdiolate was synthesized as a prodrug of self-stable diazeniumdiolate NO donor. The self-stable prodrug could be triggered to release NO upon treatment of neuraminidase. Such a design provided a novel approach to selectively release NO where neuraminidase activity exists (e.g. influenza viruses).

In chapter 5, a new class of NO donor prodrugs were developed which had sugar and a 3-morphorlinosydnonimine (SIN-1) moieties. These prodrugs could release NO in the presence of glycosidases. Such NO prodrugs may be used as enzyme-activated NO donors in biomedical research.

In chapter 6, a new class of 9-phenyl-9H-fluorene-derivative radicals were synthesized and characterized by EPR to develop novel radical probes for high-sensitive measurement and imaging of oxygen and superoxide in biological systems using EPR. However, this class of novel radicals turned out to be unstable in the presence of oxygen and further structural modification will be needed.

Indexing (details)


Subject
Inorganic chemistry;
Pharmacy sciences
Classification
0488: Inorganic chemistry
0491: Pharmacy sciences
Identifier / keyword
Pure sciences; Electron paramagnetic resonance; Glycosidase; Nitric oxide donors; Superoxide probes
Title
Nitric oxide donors and superoxide probes: Synthesis and properties
Author
Lu, Dongning
Number of pages
188
Publication year
2009
Degree date
2009
School code
0168
Source
DAI-B 70/09, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109388572
Advisor
Wang, Peng George
University/institution
The Ohio State University
University location
United States -- Ohio
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3376077
ProQuest document ID
304987732
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304987732
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