Persistent Link:
http://hdl.handle.net/10150/321545
Title:
Reactivity and Mechanistic Aspects of NO and HNO Donors
Author:
Jorolan, Joel Hao
Issue Date:
2014
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Embargo:
Release 8-May-2016
Abstract:
Nitric oxide (NO) has been shown to both promote and inhibit tumor growth depending on its concentration. Ruthenium nitrosyl complexes have been suggested as catalytic NO donors. Catalysis may provide prolonged and elevated NO donation, which can lead to tumor regression. The mechanism of NO release and catalytic activity of [Ru(cyclam)(NO(Cl]²⁺ was explored. Spectroscopic (UV-vis, EPR, IR, mass spec) analysis validated the proposed ruthenium-based catalytic cycle. However, detection by chemiluminescence revealed that reduction of [Ru(cyclam)(NO)Cl]²⁺ does not lead to NO release. Crystallographic analysis showed that a dinitrogen dimer, [Cl(cyclam)Ru(μ-N₂)Ru(cyclam)Cl]²⁺ is formed upon reduction, which could explain the lack of NO release. Formation of the dinitrogen bridged dimer is supported by IR spectroelectrochemistry, which shows an N-N stretching frequency at 2050 cm⁻¹ following electrochemical reduction. HNO has recently emerged as an important pharmacological agent, but HNO can be autoxidized to a cytotoxic species. Despite extensive analysis, the identity of the autoxidation product remains unknown. HNO autoxidation is isoelectronic with the physiologically relevant reaction of NO and superoxide (O₂⁻) producing peroxynitrite (ONOO⁻). The reactivity of synthetic ONOO⁻ was compared to that of the products of autoxidation of HNO and nitroxyl (NO⁻) with a dual purpose in mind. The first was to compare the chemistry of HNO and NO⁻ autoxidation, while the second was to compare the chemistry of two preparations of ONOO⁻. Analysis indicates that aerobic decomposition of IPA/NO (Na[(CH₃)₂CHNHN(O)NO], sodium 1 (N isopropylamino)diazen-1-ium-1,2-diolate) in pH 13 provides a more reliable preparation of ONOO⁻ compared to the more common synthetic method. Furthermore, HNO autoxidation leads to an oxidant distinct from ONOO⁻, regardless of formation pathway.
Type:
text; Electronic Dissertation
Keywords:
Chemistry
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Miranda, Katrina

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleReactivity and Mechanistic Aspects of NO and HNO Donorsen_US
dc.creatorJorolan, Joel Haoen_US
dc.contributor.authorJorolan, Joel Haoen_US
dc.date.issued2014-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.releaseRelease 8-May-2016en_US
dc.description.abstractNitric oxide (NO) has been shown to both promote and inhibit tumor growth depending on its concentration. Ruthenium nitrosyl complexes have been suggested as catalytic NO donors. Catalysis may provide prolonged and elevated NO donation, which can lead to tumor regression. The mechanism of NO release and catalytic activity of [Ru(cyclam)(NO(Cl]²⁺ was explored. Spectroscopic (UV-vis, EPR, IR, mass spec) analysis validated the proposed ruthenium-based catalytic cycle. However, detection by chemiluminescence revealed that reduction of [Ru(cyclam)(NO)Cl]²⁺ does not lead to NO release. Crystallographic analysis showed that a dinitrogen dimer, [Cl(cyclam)Ru(μ-N₂)Ru(cyclam)Cl]²⁺ is formed upon reduction, which could explain the lack of NO release. Formation of the dinitrogen bridged dimer is supported by IR spectroelectrochemistry, which shows an N-N stretching frequency at 2050 cm⁻¹ following electrochemical reduction. HNO has recently emerged as an important pharmacological agent, but HNO can be autoxidized to a cytotoxic species. Despite extensive analysis, the identity of the autoxidation product remains unknown. HNO autoxidation is isoelectronic with the physiologically relevant reaction of NO and superoxide (O₂⁻) producing peroxynitrite (ONOO⁻). The reactivity of synthetic ONOO⁻ was compared to that of the products of autoxidation of HNO and nitroxyl (NO⁻) with a dual purpose in mind. The first was to compare the chemistry of HNO and NO⁻ autoxidation, while the second was to compare the chemistry of two preparations of ONOO⁻. Analysis indicates that aerobic decomposition of IPA/NO (Na[(CH₃)₂CHNHN(O)NO], sodium 1 (N isopropylamino)diazen-1-ium-1,2-diolate) in pH 13 provides a more reliable preparation of ONOO⁻ compared to the more common synthetic method. Furthermore, HNO autoxidation leads to an oxidant distinct from ONOO⁻, regardless of formation pathway.en_US
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectChemistryen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMiranda, Katrinaen_US
dc.contributor.committeememberMiranda, Katrinaen_US
dc.contributor.committeememberLichtenberger, Dennisen_US
dc.contributor.committeememberSaavedra, Scotten_US
dc.contributor.committeememberTomat, Elisaen_US
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