Physical Sciences and Mathematics Commons^™

New Reactions Of Ring Strained Allyl Silanes, Elizabeth J. (Elizabeth Jane) Cummins

WWU Graduate School Collection

Herein, we report new allylation reactions using ring-strained allylalkoxysiletanes. These reactions can achieve high yield and have high chemoselectivity, as evidenced by carefully designed substrates. Based on previous evidence, we propose that the reaction proceeds through an exchange mechanism, where first the alkoxy group of the siletane exchanges with the hydroxyl group of the substrate, followed by coordination of the substrate carbonyl to the siletane, and then intramolecular allylation of the carbonyl.

Surface Plasmon Resonance Biosensors Based On High-Index Dielectric Metal-Insulator-Metal Structures, Sarah Clark

WWU Graduate School Collection

Surface Plasmon Resonance (SPR) is the phenomenon in which an incident electromagnetic wave couples to charge density oscillations on a metal surface.The resulting excitation, known as a surface plasmon polariton (SPP), will propagate along the metal-dielectric interface. SPR biosensors monitor protein binding interactions in real time, which lead to changes in the refractive index, thereby altering the SPP excitation conditions. Recently, we have designed a structure that supports guided-wave plasmon polariton modes (GW-PPMs), a novel type of plasmonic excitation that demonstrates increased propagation lengths compared to those of traditional SPPs in certain regions of phase space. Because it has been …

Driving Sortase-Mediated Ligations Using Metal-Coordinating Peptides, Sierra Reed

WWU Graduate School Collection

The versatility of sortase-mediated ligations as a protein modification technique has been well demonstrated, but the efficiency of these reactions suffers from inherent reversibility. Solutions to this issue have been reported, however these methods are accompanied by additional limitations of the sortase-mediated ligation (SML) strategy. A preferable methodology would include the smallest possible modification site without restricting the point of ligation. One promising solution to this issue is the expansion of the LPXTG SrtA recognition sequence to LPXTGGH, giving the excised fragment an N-terminal GGH motif. This minor alteration has been shown to allow complexation of the excised fragment with …

Lewis Acids In The Secondary Coordination Sphere For Kinetic Enhancement Toward Reduction Of Nitrite, Kyle T. Burns

WWU Graduate School Collection

Metal complexes utilizing the redox non-innocent pyridinediimine ligand scaffold have been shown to form ligand centered radicals. The reduction potential of the ligand-based redox sites is effectively uncoupled from the secondary coordination sphere, allowing for installation of bioinspired secondary sphere motifs to tune reactivity, without attenuating the reductive ability of the metal center. This thesis aims to explore the utility of this ligand design by installing various functionality, reminiscent of those found in Nature, into the secondary coordination sphere, such as Lewis acidic residues, polarized active sites, and allosteric docking sites. Installation of a pendant benzo-15-crown-5 ether moiety, capable of …

Development Of Regio- And Diastereoselective Samarium (Ii) Iodide Mediated Allylic Benzoate Reductions, Trevor Stockdale

WWU Graduate School Collection

Herein, we report a regio- and diastereoselective samarium mediated allylic benzoate reduction. The reaction can achieve high yields, regioselectivity, and diastereoselectivity, however there appear to be many factors influencing the outcome: proton sources, alkene geometry, chelating group length, relative stereocenter positioning, and stereocenter identity. These substrate parameters were looked at in-depth which ultimately led to several conclusions about optimized substrates. For instance, experiments indicate that the reaction proceeds through a bicyclic organosamarium species followed by intramolecular protonation from samarium bound water.

Structural Characterization Of A Human/Porcine Chimeric Fviii Construct And An Improved Human Factor Viii Model And Progress Towards Determination Of The Fviii C1 Domain In Complex With Inhibitory Antibodies, Ian Smith

WWU Graduate School Collection

Blood coagulation factor VIII (FVIII) is a non-enzymatic protein cofactor, which plays a crucial role in the formation of a stable blood clot. Absence or deficiency of FVIII results in the blood disorder hemophilia A, with symptoms including internal hemorrhaging and the inability to stop bleeding from open wounds. Treatment of hemophilia A relies on replacement of FVIII with blood, plasma, or protein concentrate infusions. Unfortunately, approximately 30% of patients receiving replacement FVIII generate pathologic anti-FVIII inhibitory antibodies, which both reduce the effectiveness of the FVIII therapeutic and increase the severity of hemophilia A symptoms.

This thesis reports the determination …

Improved Thermal And Mechanical Properties And Increased Miscibility Of Polybenzoxazine In Blends With Functionalized Thermoplastics And Particles, Emily A. Brown

WWU Graduate School Collection

The solubility, polymerization, and the macromolecular characterization of cured blends of BPA-based benzoxazine (BA-a) in end group tosylated poly(ethylene glycol) (mPEGOTs), polysulfone (PSUOTs), and poly(D,L-lactic acid) (PDLLAOTs) are studied and compared to their hydroxyl terminated analogues. The cure temperature for BA-a blends with tosylated polymers was reduced by ~60 °C compared to that of the pure BA-a. This confirms that the tosylated polymer is an accelerant for BA-a ring opening polymerization (ROP). There are two proposed mechanism for the production of free tosylate and cationic BA-a based initiators as a cure catalyst for BA-a ROP – where the former was …

A Chemoenzymatic Approach To The Synthesis Of Hemoglobin Oligomers, Johann Sigurjonsson

WWU Graduate School Collection

Polymerized hemoglobin (poly-Hb) molecules have been shown to have reduced toxicity compared to cell-free hemoglobins when transfused intravenously. Poly-Hbs are typically generated with non-specific crosslinking agents that yield a product that is polydisperse in molecular weight. We propose a chemoenzymatic approach to generate poly-Hb of defined molecular weight. The proposed method employs the site-specific ligation reaction of the sortase A enzyme from S. aureus. A Hb mutant previously developed in our lab has been “sortagged” – modified by adding either the sortase recognition sequence (LPXTG) to the C-terminus of the α-subunit or a tetraglycine motif (GGGG) to the N-terminus. …