Nitric oxide reactions of bio-Inspired zinc and cobalt complexes
Author(s)
Kozhukh, Julia, 1985-
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Massachusetts Institute of Technology. Dept. of Chemistry.
Advisor
Stephen J. Lippard.
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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.. (cont.) Chapter 5. Reactivity of Tropocoronand-Bound Cobalt(III) Nitrite with Nitric Oxide as a Function of Polymethylene Linker Chain Length The studies on the dependence of cobalt(II) tropocoronand reactivity with nitric oxide (NO) on linker chain length, described in Chapter 4, were expanded to include the chemistry of the cobalt(III) nitrites [Co(NO2)(TC-n,n)] (n = 4 - 6) with NO. Complete conversion from the cobalt(III) nitrite to the cobalt mononitrosyl [Co(NO)(TC-4,4)] is demonstrated upon exposure to NO (g). In contrast, exposure of [Co(N0 2)(TC-5,5)] and [Co(N0 2)(TC-6,6)] to NO (g) results in conversion to a cobalt dinitrosyl adduct. This Chapter aims to broaden the field of cobalt(III) chemistry with NO. Chapter 6. Nitric Oxide Reactivity of Cobalt(III) Triflate and Cobalt(III) Thiolate Tropocoronand Complexes The reactivity of two cobalt(III) tropocoronands with NO (g) is described. [Co(TC-4,4)](OTf) undergoes reductive nitrosylation in the presence of NO (g), forming [Co(NO)(TC-4,4)], N20, and additional reactive species. The reaction releases one equivalent of protons for every equivalent of [Co(TC-4,4)](OTf) consumed. [Co(SC 6F5)(TC-4,4)] forms [Co(NO)(TC-4,4)] and the disulfide F5C6SSC6F5 in the presence of NO (g). We hypothesize that disulfide formation is followed by electrophilic aromatic substitution of F5C6S* onto the tropocoronand aromatic ring. Efforts to prepare substituted tropocoronand ligands and test the electrophilic aromatic substitution hypothesis are described. Chapter 7. Synthesis and Characterization of Mononuclear, Pseudotetrahedral Cobalt(III) Compounds The synthesis and characterization of two mononuclear cobalt(III) tropocoronand complexes, [Co(TC-5,5)](BF 4) and [Co(TC-6,6)](BPh 4), are reported. The cobalt(III) centers exist in rare pseudotetrahedral conformations, with twist angles of 650 and 740 for the [Co(TC-5,5]* and [Co(TC-6,6)]* species, respectively. Structural and electrochemical characteristics are compared with those of newly synthesized [Ga(TC-5,5)](GaCl4) and [Ga(TC-6,6)](GaCl 4) analogs.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2012. Vita. Cataloged from PDF version of thesis. Includes bibliographical references.
Date issued
2012Department
Massachusetts Institute of Technology. Department of ChemistryPublisher
Massachusetts Institute of Technology
Keywords
Chemistry.