Gas-Phase Reactivity Studies of Charged Quinoline Polyradicals by Using Distonic Ion Approach and Linear Quadrupole Ion Trap Mass Spectrometry, and Mechanistic Studies On Metal-Promoted Self-Assembly of Collagen Mimetic Peptides

Raghavendhar R Kotha, Purdue University

Abstract

Organic radicals have been of interest for several decades due to various applications in fields such as drug design, polymer science, organic materials and synthesis. While the chemical properties of many aromatic σ-type mono- and biradicals are known through theoretical and experimental research, limited experimental data are available for aromatic polyradicals due to difficulties in their generation and subsequent study in solution. This thesis focuses on the reactivities of such polyradicals in the gas phase. All gas-phase reactivity studies were performed using a Thermo Scientific linear quadrupole ion trap (LQIT) mass spectrometer equipped with a manifold for introduction of reagents. All radical precursors were introduced into the LQIT and protonated by using the atmospheric pressure chemical ionization (APCI) method. Radical sites were generated by using collision-activated dissociation (CAD) of protonated radical precursors with helium collision gas to cleave C-I, C-NO2, O-NO and/or O-CH3 bonds. After generation, the charged polyradicals were isolated in the ion trap and their reactivities toward dimethyl disulfide, cyclohexane and allyl iodide were examined to determine reaction efficiencies and reaction products. The reactivities of the tri- and tetraradicals were compared with those of corresponding mono- and biradicals. The reactivity of the studied triradicals is mainly controlled by the radicals’ electron affinity and the distortion energy of the meta-benzyne moiety in them. The triradicals with higher electron affinity and lower distortion energy reacted at higher efficiencies. All triradicals abstract three hydrogen atoms when allowed to react with cyclohexane, which demonstrates the presence of three radical sites. All triradicals formed ionized dimethyl disulfide of m/z 94 when allowed to react with dimethyl disulfide reagent, which was rationalized by initial proton transfer from the charged triradicals to neutral dimethyl disulfide, followed by hydrogen atom abstraction by the neutral triradicals from protonated dimethyl disulfide. The 2,4,6,8-tetraradical abstracts four hydrogen atoms from cyclohexane, which demonstrates the presence of four radical sites in this molecule, as expected. Along with hydrogen atom abstractions, the 2,4,6,8-tetraradical also reacts by hydride abstraction, for which a mechanism was proposed. Additionally, reactivity studies of three other tetraradicals, the 2,4,5,7-, 2,4,5,8- and 2,4,7,8- tetradehydroquinlinium cations, were carried out by using dimethyl disulfide and allyl iodide reagents. Preliminary data suggest that, with few exceptions, the reaction efficiencies of the all tetraradicals are lower than that of related mono- and triradicals, which may be attributed to strong radical-radical couplings present in the tetraradicals. A new class of charged quinoline based oxygen peribridged quinolinium cation was generated by using LQIT. These oxygen peribridged quinolinium cation was generated by using CAD to cleave an iodine atom and NO from protonated 4- iodo-5-nitroquinoline precursor. A similar approach was used to generate oxygen peribridged quinolinium mono- and biradicals from synthesized precursors. Gasphase reactivity studies of these oxygen peribridged mono- and biradicals toward dimethyl disulfide and allyl iodide reagents were carried out and the reactivities were compared with the corresponding mono- and biradicals without the oxygen ring. The reactivity data suggest that the oxygen ring significantly influences the reactivity of biradicals, while comparable reactivity was observed for monoradicals with and without the oxygen ring. Mimicking the self-assembly process of natural collagen is an interesting area of research for biomedical applications. One such design, based on a metaltrigger as a promoter for self-assembly of short collagen-mimetic peptides into functional biomaterials, is an attractive approach to address the inherent issues associated with the clinical use of natural collagen. In this approach, metal ions are allowed to interact with the chelating agents (ligands) of the peptides to promote self-assembly. Part of this thesis focuses on improving the understanding of the self-assembly mechanism by altering the ligands of the peptides. The number and type of ligands involved in the assembly process were shown to significantly influence the size and the morphology of the resulting materials. Self-assembly was controlled by limiting the number of ligands present in the peptide.

Degree

Ph.D.

Advisors

Kenttamaa, Purdue University.

Subject Area

Chemistry

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