Dissertation Defenses

Doctoral students who have an upcoming dissertation oral defense are posted here. So why not take this opportunity to learn about the research that our graduate students are doing!

Dissertation Defense for Holly Guevara


Department Contact Email: cindi.rohwer@unh.edu

Defense Title: Insights into the Ring-Opening Mechanism of Benzene Metabolism; an Investigation of the Oxidation of Model Oxepins by Cytochrome P450.

Defense Date and Time: 04/11/17 1:00 pm

Defense Location: Parsons Hall, Room W131

Defense Advisor: Professor Arthur Greenberg

Defense Abstract: Benzene is a known human carcinogen and environmental pollutant. The mechanism of its metabolism by cytochrome P450 is well understood. Initial oxidation of benzene produces benzene oxide/oxepin, valence tautomers in rapid equilibrium. Most metabolites of benzene are derived from benzene oxide and include phenol, catechols, quinones, and bioconjugates. A small number of ring-opened metabolites are derived from oxidation of oxepin. Muconaldehyde is one such metabolite; it is toxic and is known to react with glutathione and cross-link DNA. It is unclear how muconaldehyde is formed from oxepin. In the 1970’s Davies and Whitham postulated that oxepin is epoxidized by cytochrome P450 to form 2,8-dioxabicyclo[5.1.0]octa-3,5-diene (2,3-epoxyoxepin) that rapidly rearranges to form muconaldehyde. While Davies and Whitham were not able to observe the 2,3-epoxyoxepin intermediate, they used model compounds to generate ring opened products. Later, Greenberg et al demonstrated that dimethyldioxirane (DMDO) could epoxidize model oxepins at low temperature to form 2,3-epoxyoxepin intermediates; the intermediates were observed using low temperature NMR. Alternately, Golding proposed that oxepin was oxidized by consecutive one electron oxidations with cerium ammonium nitrate (CAN) to form a radical cation intermediate that ring-opened to form corresponding dicarbonyl compounds. It is still unclear which mechanism is utilized by cytochrome P450 to form ring-opened metabolites. The present study involves the synthesis of model oxepins 2,7-dimethyloxepin and 4,5-benzoxepin that are used in synthetic and enzymatic oxidation studies. The incubations with 2.7-dimethyloxepin did not produce ring-opened metabolites, but rather dimethylphenols. This is likely an application of the Curtin-Hammett principle where the dimethyl-1,6-benzene oxide tautomer is energetically accessible and the activation barrier for formation of phenol derived products is lower than that to produce ring opened compounds. Oxidation of 4,5-benzoxepin with DMDO produced 1H-2-benzopyran-1-carboxaldehyde, while oxidation with CAN gave a novel dimeric compound. The enzymatic oxidation of 4,5-benzoxepin revealed that the major oxidation pathway utilized by P450 is epoxidation of oxepin to a 2,3-epoxyoxepin; the major product observed was 1H-2-benzopyran-1-carboxaldehyde. This is the first time a 2,3-epoxyoxepin derivative has been shown as an intermediate in enzymatic oxidation and gives insight into the ring opening mechanism of benzene metabolism. A small amount of the dimeric compound was also observed, indicating a minor oxidation pathway of consecutive one electron oxidations. Much work has been done to fully characterize and identify the novel dimeric compound.


Dissertation Defense for Ben Brewer


Department Contact Email: stacy.hokinson@unh.edu

Defense Title: The Growth Effects and Uninteneded Consequences of State and Federal Policiesl

Defense Date and Time: 04/11/17 3:00 pm

Defense Location: Paul College Room 370N

Defense Advisor: Karen Conway

Defense Abstract: In this research, I examine the intended and unintended consequences of three types of policies currently under debate at the state and federal level: traffic safety laws, national health insurance reforms and state income tax benefits for the elderly. My first essay explores an unintended consequence of state seat belt laws. These laws mandate individuals must wear a seat belt with the presumed goal of reducing traffic fatalities, but the prevailing view is that they also reduce the number of organs available. I provide a conceptual model that reveals the law could either increase or decrease organ donation. Using state-level data from 1995-2014, I find evidence that while the law encourages seat belt use and reduces traffic fatalities, it does not decrease the overall supply of organs. Instead, the law increases the number of organs donated per traffic fatality, possibly due to the way the seat belt increases the protection of organs and/or changes the type of death an accident victim experiences. Mandatory seat belt laws therefore appear to be effective life-saving policies that do not impose a cost to those on organ transplantation wait lists.
My second essay explores the effect of a broader set of health policies at the federal level on the growth of health care expenditures. Using multiple structural break tests and annual data from 1960-2015, we estimate changes in the relationship between health expenditures and income in the US. We find evidence that this relationship changed in 1966 and 2010, two years of significant changes to national-level policies (Medicare/Medicaid and the Affordable Care Act/Great Recession). We cannot determine whether these changes increased or decreased health spending growth due to the lack of data around these dates in our sample. However, the policy changes that occur in the middle of our sample do not appear to have achieved their intended goal of slowing health spending growth.
I continue to focus on growth in my third essay by investigating the effects of state elderly income tax breaks on state economic growth. Offered on the basis of age and through favorable social security and pension income treatment, these tax breaks are championed by politicians as being beneficial to the state’s overall economy. We calculate the income tax benefit specific to being elderly and apply two alternative, commonly used empirical approaches to estimate the short and long run effects of these policies on state GDP growth. Despite politicians' justifications, we find no consistent evidence that these breaks improve economic growth, even for those directed at the higher income elderly.


Dissertation Defense for Kyle Rodriguez


Department Contact Email: cindi.rohwer@unh.edu


Defense Date and Time: 04/13/17 9:00 am

Defense Location: Kingsbury Hall, Room N111

Defense Advisor: Professor Samuel Pazicni

Defense Abstract: Heme proteins are responsible for a wide variety of functions throughout biology. These functions range from electron transfer, catalysis, small molecule sensing, and transport. While the primary coordination sphere of the heme cofactor predominately dictates function, the hydrogen-bonding rich, secondary coordination sphere heavily influences the reactivity of these proteins. To investigate these interactions, synthetic model complexes have been designed to provide insight on how these secondary coordination spheres effect the structure and function of these proteins. These models range from small molecule ligands to macromolecular polymers. This dissertation describes the design and synthesis of small molecule ligands and macromolecular polymer nanoparticles that incorporate aspects of the proteins’ secondary coordination spheres to help elucidate the role of these secondary interactions.
A series of novel intramolecular hydrogen-bond donor, thiophenolate derived ligands were designed in order to model the protein environment around the axial cysteinate in heme-thiolate proteins. The ligand design is based on 2-(acetylamino)thiophenol and 2,6-bis(acetylamino)thiophenol derivatives. While further work needs to be completed on the optimization of these syntheses, these models can provide a way to probe how the iron center is effected by secondary interactions through a small molecule ligand design.
Porphyrin-cored polymer nanoparticles (PCPNs) were synthesized and characterized as heme protein models. Created using novel collapsible porphyrin-cored star polymers (PCSPs) containing pendant groups susceptible to collapse chemistries, these systems afford model heme cofactors buried within similar macromolecular environments found in native proteins. Unlike traditional heme protein models, PCPNs offer tunable macromolecular backbones which can further incorporate secondary coordination sphere microenvironments around the porphyrin-core. Through reversible addition-fragmentation chain transfer (RAFT) polymerizations, these polymers were generated at high molecular weights similar to native proteins with uniformed chain lengths. PCPNs were formed through the photodimerization of 9-anthracenylmethyl methacrylate (AMMA) monomer units. Using orthogonally reactive pentafluorophenyl methacrylate (PFPMA) and 2-vinyl-4,4-dimethylazlactone (VDMA) monomers, post-polymerization modifications allowed for site-specific functionalization of the PCPNs. These modifications permit access to various microenvironments (hydrophobic, hydrophilic, hydrogen-bonding rich, etc.) to study their effects on heme iron reactivity.


Dissertation Defense for Kevin Weinman


Department Contact Email: larademarest@unh.edu


Defense Date and Time: 04/14/17 2:30 pm

Defense Location: Horton 422

Defense Advisor: Professor Kurk Dorsey

Defense Abstract: This dissertation studies the causes and effects of rapid and uncoordinated suburban growth in metropolitan Denver, Colorado after the Second World War. The region experienced sprawling, low-density residential development on its periphery despite a powerful wave of anti-growth sentiment and that swept the state in the sixties and seventies. This study argues that this resulted from the difficulties experienced by Coloradans in reconciling a number of their cherished ethics: individual freedom and the sanctity of property rights versus a nascent environmentalism, fervent pursuit of wealth and economic opportunity versus an enduring celebration of the state’s traditional ranching heritage and rural character, and a preference for local control versus a desire for more comprehensive regional solutions to the problems of growth.
The pace and type of suburban growth and development in metropolitan Denver emerged neither from intentional strategies nor a dominant development ethos. Instead, decades of indecisiveness and inaction at the state and county levels subjected the Denver metropolitan area to exogenous forces that filled the void. Outside corporate real estate developers privatized much of the process of the state’s suburban growth by acquiring large plots of ranchland in unincorporated areas, creating and controlling an unprecedented number of governmental entities called “special districts” to provide infrastructure and public services to their developments, and designing and building enormous communities that were cities in all but name. These “invisible suburbs” overwhelmed county, regional, and state efforts to integrate these new communities seamlessly into the metropolitan area. Privatized development carried socioeconomic, civic, financial, and environmental implications for the region and its residents.
This study focuses upon Denver’s southern suburbs, particularly those located in Douglas County, the nation’s fastest growing county during the late twentieth century. It analyzes state and local government records and reports, United States Census Bureau population and local government data, voting records, corporate publications, legal records and correspondence, and newspaper accounts to illustrate the efforts and struggles of the region’s residents and governments to contend with growth. It combines elements of business, environmental, public policy, and urban history to add to the historical literature of late-twentieth century American suburbanization.


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