Nitric oxide reactions of bio-Inspired zinc and cobalt complexes

Chapter 1. Bioinorganic Chemistry of Nitric Oxide and of Some of Its Targets The redox-active nature of nitric oxide (NO) regulates the chemistry and roles of NO in biology. The interactions of NO with nitric oxide synthases, metallothioneins, and cobalamin-containing enzymes are discussed. Bioinspired small molecule models for metalloprotein active sites are introduced, and the ability of ligands to control the steric and electronic properties of coordinated metal centers is demonstrated. The bioinorganic chemistry of NO and its targets is described in the context of the investigations presented in this thesis. Chapter 2. Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn2+ with S-Nitrosothiols and Implications for Nitric Oxide Synthase Zinc thiolate complexes containing N2S tridendate ligands were prepared to investigate their reactivity toward reactive nitrogen species. This type of chemistry is proposed to occur at the zinc tetracysteine thiolate site of nitric oxide synthase (NOS). The complexes are unreactive toward nitric oxide in the absence of dioxygen, strongly indicating that NO cannot be the species directly responsible for S-nitrosothiol formation and loss of Zn2* at the NOS dimer interface in vivo. S-Nitrosothiol formation does occur upon exposure of zinc thiolate solutions to NO in the presence of air, however, or to NO2 or NOBF4, indicating that these reactive nitrogen/oxygen species are capable of generating the S-nitrosothiol. Interaction between simple Zn2+ salts and pre-formed S-nitrosothiols leads to decomposition of the -SNO moiety, resulting in release of gaseous NO and N20. The potential biological relevance of this chemistry is discussed. Chapter 3. Reactions of Organozinc Thiolates with Nitrosonium Ion: C-Nitroso Formation by Intramolecular Transnitrosation The organometallic species [ZnPAThEt] and [ZnPAThMes] are prepared, and their reactions with NOBF4 are characterized. The formation of C-nitrosoethane and C-nitrosomesitylene is confirmed, and structural characterization of C-nitrosomesitylene conclusively establishes the dimeric nature of the molecule in the solid state. An intramolecular transnitrosation reaction pathway for C-nitroso formation is proposed based on theoretical calculations. Chapter 4. Influence of Ligand Constraints on the Reactivity of Co(II) Complexes of Tetraazamacrocyclic Tropocoronand Ligands with Nitric Oxide Previous work on the reactivity of cobalt(II) complexes of tetraazamacrocyclic tropocoronand ligands with nitric oxide (NO) was extended to include the [Co(TC-5,5)] and [Co(TC-6,6)] derivatives. The cobalt mononitrosyl [Co(NO)(TC-5,5)] is isolated and structurally characterized from the reaction of [Co(TC-5,5)] and NO (g). In contrast, a {Co(NO) 2}'0 species is observed when [Co(TC-6,6)] is exposed to NO (g) and the nitrite complex [Co(NO2)(TC-6,6)] is structurally and spectroscopically characterized from reaction mixtures. The di(cobalt dinitrosyl) [Co2(NO) 4(TC-6,6)] is independently synthesized for spectroscopic comparison with reaction mixtures. This Chapter describes the first characterization of the dependence of cobalt(II) tropocoronand reactivity on linker chain length..

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2012

Author dc:creator

• Kozhukh, Julia, 1985-

Advisor dc:contributor.advisor

• Stephen J. Lippard.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/73360

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/73360