Theses and Dissertations at Montana State University (MSU)
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Item When a lectin binds a sugar, and other sweet tales(Montana State University - Bozeman, College of Letters & Science, 2019) Bernhard, Samuel Pruitt; Chairperson, Graduate Committee: Mary J. Cloninger; Mackenzie S. Fricke was an author and Katharina Achazi, Paul Hillman, Willy Totten, Rainer Haag and Mary J. Cloningerwere co-authors of the article, 'The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized dendrimers' submitted to the journal 'Biomolecules Special Issue: Moving Forward with Dendrimers' which is contained within this dissertation.The current state of chemotherapy and cancer treatment leaves much to be desired. Treatment is generally non-specific and relies on high dosage to achieve therapeutically relevant concentrations at target sites. Glycopolymer-drug conjugates, featuring targeting molecules and therapeutic prodrug on a water-soluble polymeric scaffold, offer a solution to these contemporary problems. Here, the complexity of glycopolymer design is explored through the lens of a biologically significant carbohydrate-binding receptor. In particular, galectin-3 is a complex Beta-galactoside binding lectin that experiences altered expression in many cancer pathologies and is implicated in metastasis, angiogenesis and poor overall prognosis. Galectin-3 mediates undesired cancer promoting processes through carbohydrate binding and oligomerization. A more complete understanding of the role galectin-3 plays in cancer progression will guide development of methods in the therapeutic intervention of these processes. In the interest of understanding galectin-3 and using it as a targeted receptor, its binding characteristics have been assessed through fluorescence lifetime and dynamic light scattering measurements. Employment of carbohydrates and glycopolymers including mannose, lactose, and lactose functionalized poly(amidoamine) (PAMAM) dendrimers, dendritic polyglycerols (dPG), and linear polymers (LP) provided insight into the carbohydrate binding avidity of galectin-3 and its propensity to oligomerize or form micron scale aggregates. A relationship between scaffold size and receptor recruitment was observed, which sheds light into multivalent binding motifs initiated by these glycopolymers and establishes a threshold for minimum requisite lactose functionality on lactose functionalized dendritic polyglycerols. In vitro cell based glycopolymer studies with AlexaFluor 647 and lactose functionalized PAMAM dendrimers revealed size-dependent uptake and demonstrated that accumulation occurs within the lysosome. Cellular aggregation experiments revealed that lactose functionalized LPs and dPGs influence galectin-3 mediated homotypic cellular aggregation and, in fact, augment this aggregation through receptor recruitment and cross-linking. The results reported here have provided a more fundamental understanding of galectin-3 binding interactions and have laid the groundwork for optimized glycopolymer-drug conjugate design.Item The development of superresolution spectroscopic techniques and characterization of microscale exciton diffusion in organic semiconducting polymers(Montana State University - Bozeman, College of Letters & Science, 2018) Massaro, Eric Stephen; Chairperson, Graduate Committee: Erik Grumstrup; Andrew H. Hill and Erik M. Grumstrup were co-authors of the article, 'Superresolution structured pump-probe microscopy' in the journal 'ACS Photonics' which is contained within this thesis.; Andrew H. Hill, Casey L. Kennedy and Erik M. Grumstrup were co-authors of the article, 'Imaging theory of structured pump-probe microscopy' in the journal 'Optics Express' which is contained within this thesis.; Erik M. Grumstrup was a co-author of the article, 'Label-free saturated structured excitation microscopy' in the journal 'Photonics' which is contained within this thesis.; Erik M. Grumstrup was a co-author of the article, 'Exceptionally fast nanoscale exciton diffusion in donor-acceptor polymer thin films' which is contained within this thesis.; Erik M. Grumstrup was a co-author of the article, 'Toward direct imaging of sub-10 nm carrier diffusion lengths by differential detection pump-probe microscopy' which is contained within this thesis.Disordered semiconducting materials offer cost effective, solution processable alternatives to highly crystalline semiconducting materials for utilization in a variety of optoelectronic devices. However, characterization of these complex materials systems using bulk spectroscopic methods is heavily influenced by chemical and morphological heterogeneity inherent to the material. The experiments described in this thesis are designed to improve the fundamental understanding of the photophysical processes in disordered solution processed semiconducting materials by developing and utilizing high spatial resolution spectroscopic methods. Chapters 2-4 will outline the experimental and theoretical development of two superresolution spectroscopic techniques. First (chapters 2 & 3), structured pump-probe microscopy (SPPM) utilizes a structured excitation profile along with a diffraction limited probe pulse to achieve ~100 nm spatial resolution. Using SPPM it is also possible to collect time resolved spectroscopic data from a sub-diffraction limited volume. Second (chapter 4), label-free saturated structured excitation microscopy (LF-SSEM) is theoretically developed. LF-SSEM is experimentally similar to SPPM but exploits the saturation of the absorption process to achieve even greater resolution enhancement. Here, simulated LF-SSEM is shown to achieve ~33 nm spatial resolution. Chapter 5 demonstrates the utilization of PPM to investigate exciton transport in the organic semiconducting polymer (OSP), poly [N-9''-hepta-decanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT). Although OSPs have shown great promise for use in a variety of optoelectronic applications, much remains un-known about their excited state dynamics. The data reported here represents a significant contribution to the rapidly growing wealth of knowledge pertaining to OSP systems. Specifically, the microscale exciton diffusivity observed in PCDTBT thin films using PPM is found to reach 3.2 cm 2/s. Chapter 6 examines a technique in the early stages of development and optimization that is able to detect excited state carrier diffusion with increased sensitivity and accuracy compared to PPM. Differential detection pump-probe microscopy (DDPPM) uses two probe pulses to selectively eliminate the signal of carriers that have not diffused beyond the boundaries of the initial excitation. The experiments described within this dissertation are diverse, yet the common goal is to increase and improve the knowledge of photophysical properties in disordered semi-conducting materials. This goal takes two forms in the development of novel spectroscopic methodology and the characterization of complex materials using PPM. The singular result is the advancement of basic science pertaining to complex semiconducting materials systems.Item Subnanosecond emission from model DNA oligomers characterized through time-correlated single-photon counting spectroscopy(Montana State University - Bozeman, College of Letters & Science, 2017) Skowron, David John; Chairperson, Graduate Committee: Robert Walker; Yuyuan Zhang, Ashley A. Beckstead, Jacob M. Remington, Madison Strawn and Bern Kohler were co-authors of the article, 'Subnanosecond emission dynamics of AT DNA oligonucleotides' in the journal 'Journal of chemical physics and physical chemistry' which is contained within this thesis.Exposure of DNA to UV radiation creates electronic excited states that can decay to mutagenic photoproducts. Excited states can return to the electron ground state through deactivation pathways, preventing photochemical damage. Understanding has significantly advanced over the last decade through the applications of time-resolved techniques capable of picosecond and femtosecond time-resolution. While significant strides have been made towards understanding monomeric deactivation pathways, unraveling the complex photophysics of base multimers still presents a significant challenge. This report uses time-resolved fluorescence and ultrafast transient absorbance to analyze model DNA oligomers to understand how fundamental interactions between monomeric constituents influences the dynamics of base multimers. Model single- and double-stranded DNA oligomers were investigated using the time correlated single photon counting technique to address the uncertainty over how to compare results from time-resolved fluorescent and transient absorption techniques. Emission lifetimes ranging from 50 to 200 ps quantitatively agree with lifetimes measured from transient absorption experiments indicating emission observed on timescales greater than a few picoseconds is the result of excimer or charge recombination luminescence. In attempts to further characterize the time-resolved emission from model oligomers adenine oligomers consisting of 2 and 18 base constituents were examined in aqueous water and heavy water solutions. Differences in dynamics between the two oligomers revealed the average number of bases present within a stacked domain influence the dynamics of these systems. Lifetimes of the emission decays were assigned excimer-like states with various degrees of charge-transfer character. Finally, to further demonstrate the importance of base stacking domain length on the dynamics of these systems, time-resolved emission and absorption of the adenine dinucleotide and 18-mer where examined at temperatures ranging from 7 °C - 80 °C. It was observed that the kinetics between the oligomers was noticeably different at lower temperatures, but not at higher temperatures. It was concluded the domain length of the 18-mer was similar to the domain length of the dinucleotide at high temperatures, but not at low temperatures, demonstrating the domain length significant impacts theS photophysics of DNA.Item A study of polymeric platinum(II) compounds and Nanoscale materials(Montana State University - Bozeman, College of Letters & Science, 2004) Anderson, Bernard Marshall; Chairperson, Graduate Committee: Edwin H. Abbott; Lee H. Spangler (co-chair)The photophysical and structural properties of the tetra-u- pyrophosphitodiplatinate (2-) anion have been well studied in the past. One such analogue of this compound is a phosphorescent red compound of unknown structure. A new synthesis route has been was found for both the tetra-u- pyrophosphitodiplatinate (2-) and the red anionic compounds. By synthesizing the pyrophosphorus ligand outright and reacting that with tetrachloroplatinate (2-) either the tetra-u-pyrophosphitodiplatinate (2-) or the red anionic compounds can be synthesized depending on the amount of the phosphorus acid that is present. It was found from light scattering measurements and with the usage of 31P NMR spectroscopy that the red platinum(II) compound is structurally different than that of tetra-u-pyrophosphitodiplatinate (2-). A revised synthetic route was made for the synthesis of pyrophosphorus acid which was found to be an insoluble, highly reactive ligand. Reactions of pyrophosphorus acid with normal alcohols led to the formation of phosphorus acid and the corresponding monoalkylated phosphorus acid.Item The synthesis of glycodendrimers and their applications in carbohydrate-protein interactions and catalysis(Montana State University - Bozeman, College of Letters & Science, 2006) Morgan, Joel Ryan; Chairperson, Graduate Committee: Mary J. CloningerGlycodendrimers were synthesized for studies in carbohydrate-protein interactions, and from these studies we gained insight into the mechanism of some carbohydrate-protein interactions. First, the synthesis of tris-mannose cluster functionalized glycodendrimers of different sizes using a 'click chemistry' approach is described. The macromolecules were characterized using 1H and 13C NMR and MALDITOF MS. Next, a heterogeneous dendrimer functionalization strategy to control the presentation of the carbohydrate clusters around the dendrimer periphery is reported. Nacetyl galactosamine and phenyl azide heterogeneously functionalized PAMAM dendrimers were synthesized and used as macromonomers in a 'click chemistry' polymerization reaction. The dendritic polymer was designed as a lipid raft microdomain mimic.