Advances in Palladium-Catalyzed Allylation, Propargylation, and 1,3-Dienylation of Acetonitrile Pronucleophiles

Presented herein is the development and application of palladium-catalyzed methods for allylation, propargylation and 1,3-dienylation of acetonitrile pronucleophiles. The developed methods focus on optimizing both atom- and step-economy during product formation thus resulting in a minimal production of waste. Further, ligand-controlled regiodivergent strategies are also presented which provide efficient access to various functionalities through a change in reaction mechanism controlled by the denticity of the coordinating ligand. In regards to the developed methods for the propargylation and 1,3-dienylation of acetonitrile pronucleophiles, the presented work provides access to these functionalities using propargylic electrophiles that were rarely observed using previously known methods. In chapter 1, a brief review of commonly employed propargylation methods is presented which often occur under harsh reaction conditions or result in a large amount of byproduct formation. Further, few exceedingly difficult palladium-catalyzed propargylation strategies are also reported that overcome the large bias for the allenyl isomer or products arising from dinucleophilic addition. Alternatively, in chapter 2, we present our ligand-controlled regiodivergent strategy for the propargylation and 1,3-dienylation of acetonitrile pronucleophiles. Specifically, we report the first palladium-catalyzed coupling of a butadiene synthon to generate 1,3-dienylated products. Further, each method provides significant advantages over commonly employed strategies to access such functionalities such as optimizing step-economy and avoiding the necessity for prefunctionalized starting materials. In chapter 3 of this dissertation, we present our ongoing efforts to expand the substrate scope of the developed regiodivergent method to nitriles possessing a pKa 17. To achieve this goal, decarboxylative cross-coupling is employed to access the reactive intermediate in situ via irreversible decarboxylation thus generating CO2 as the only byproduct. Once again, selective propargylation or 1,3-dienylation is ligand-controlled and can occur though changing the ligand from monodentate to bidentate, respectively. Lastly, in chapter 4 we present a method for the in situ activation of allylic alcohols using CO2 for the allylation of nitroalkanes, nitriles, and aldehydes. The developed method provides several advantages over commonly employed allylation strategies: (a) avoids the pre-activation of allylic electrophiles for successful cross-coupling, (b) avoids the use of additives for allylic alcohol activation, and (c) generates base in situ for pronucleophile activation thus providing an atom-economic alternative for allylic cross-coupling

A Comparison of Macroepifauna Among Vegetated and Unvegetated Habitats in a South Florida Estuary Using a Passive Sampling Gear

We compared abundance, richness, diversity, and community structure of macroepifauna among the seagrasses Halodule wrightii, Thalassia testudinum, and Syringodium filiforme, and unvegetated substrate in Tarpon Bay, Caloosahatchee River estuary, Florida. Sampling was conducted using wire-mesh minnow traps deployed over fifty-six 24-h periods from Jan. 1999 to Jan. 2000. A total of 36, 35, 28, and 28 species were identified from Halodule, Thalassia, Syringodium, and unvegetated samples, respectively. The gastropod Nassarius vibex was the most abundant species from Halodule and unvegetated substrate, whereas the pinfish (Lagodon rhomboides) was the most abundant species from Thalassia and Syringodium. Abundance of these codominant species varied seasonally throughout the study. For all taxa combined and for codominants, each seagrass contained greater averages than unvegetated substrate in each season. Seagrasses typically had higher average species richness and diversity than unvegetated substrate in each season. Results indicate that Tarpon Bay typifies subtropical estuaries in that its epifaunal community is dominated by few species, faunal abundances vary seasonally, and more organisms are found in seagrasses than in unvegetated areas. Our results serve as a foundation to compare against future research in an understudied system

Pollen from multiple sunflower cultivars and species reduces a common bumblebee gut pathogen

Pathogens are one of the factors driving pollinator declines. Diet can play an important role in mediating pollinator health and resistance to pathogens. Sunflower pollen (Helianthus annuus) dramatically reduced a gut pathogen (Crithidia bombi) of Bombus impatiens previously, but the breadth of this effect was unknown. We tested whether pollen from nine H. annuus cultivars, four wild H. annuus populations, H. petiolarus, H. argophyllus and two Solidago spp., reduced Crithidia in B. impatiens compared to mixed wildflower pollen and buckwheat pollen (Fagopyrum esculentum) as controls. We also compared hand- and honeybee-collected pollen (which contains nectar) to assess whether diet effects on pathogens were due to pollen or nectar. All Helianthus and Solidago pollen reduced Crithidia by 20–40-fold compared to buckwheat pollen, and all but three taxa reduced Crithidia compared to wildflower pollen. We found no consistent differences between hand- and bee-collected pollen, suggesting that pollen alone can reduce Crithidia infection. Our results indicate an important role of pollen diet for bee health and potentially broad options within the Asteraceae for pollinator plantings to manage bee disease

Deglacial laminated facies on the NW European continental margin: The hydrographic significance of British-Irish Ice Sheet deglaciation and Fleuve Manche paleoriver discharges

[1] We have compiled results obtained from four high sedimentation rate hemipelagic sequences from the Celtic sector of the NW European margin ( NE Atlantic) to investigate the paleoceanographic and paleoclimatic evolution of the area over the last few climatic cycles. We focus on periods characteristic of deglacial transitions. We adopt a multiproxy sedimentological, geochemical, and micropaleontological approach, applying a sampling resolution down to ten microns for specific intervals. The investigation demonstrates the relationships between the Bay of Biscay hydrography and the glacial/deglacial history of both the proximal British-Irish Ice Sheet (BIIS) and the western European continent. We identify recurrent phases of laminae deposition concurrent with major BIIS deglacial episodes in all the studied cores. Evidence for abrupt freshwater discharges into the open ocean highlights the influence of such events at a regional scale. We discuss their impact at a global scale considering the present and past key location of the Bay of Biscay versus the Atlantic Meridional Overturning Circulation (AMOC)

Photocatalytic Aminodecarboxylation of Carboxylic Acids

Aminodecarboxylation of unactivated alkyl carboxylic acids has been accomplished utilizing an organic photocatalyst. This operationally simple reaction utilizes readily available carboxylic acids to chemoselectively generate reactive alkyl intermediates that are not accessible via conventional two-electron pathways. The organic radical intermediates are efficiently trapped with electrophilic diazo compounds to provide aminated alkanes.Division of Chemistry. Grant Number: 146517

Critical Role of Nrf2 in Experimental Ischemic Stroke

Ischemic stroke is one of the leading causes of death and long-term disability worldwide; however, effective clinical approaches are still limited. The transcriptional factor Nrf2 is a master regulator in cellular and organismal defense against endogenous and exogenous stressors by coordinating basal and stress-inducible activation of multiple cytoprotective genes. The Nrf2 network not only tightly controls redox homeostasis but also regulates multiple intermediary metabolic processes. Therefore, targeting Nrf2 has emerged as an attractive therapeutic strategy for the prevention and treatment of CNS diseases including stroke. Here, the current understanding of the Nrf2 regulatory network is critically examined to present evidence for the contribution of Nrf2 pathway in rodent ischemic stroke models. This review outlines the literature for Nrf2 studies in preclinical stroke and focuses on the in vivo evidence for the role of Nrf2 in primary and secondary brain injuries. The dynamic change and functional importance of Nrf2 signaling, as well as Nrf2 targeted intervention, are revealed in permanent, transient, and global cerebral ischemia models. In addition, key considerations, pitfalls, and future potentials for Nrf2 studies in preclinical stroke investigation are discussed

Two separate functions of class II (Ia) molecules: T-cell stimulation and B-cell excitation.

We have evaluated the role of major histocompatibility complex-encoded class II (Ia) molecules as transmembrane signaling receptors in the T helper cell-dependent activation of B lymphocytes. For these studies, we utilized the murine B-cell lymphoma CH12, which expresses both I-A and I-E class II molecules. In addition, CH12 cells carry IgM of known antigen specificity and require both specific antigen and Ia-restricted T-cell help for the induction of antibody secretion. In this respect, they resemble normal resting B cells. We have studied the ability of antigen-specific or alloreactive T helper cells reactive with either the I-A or the I-E molecules on CH12 to be activated and their ability to stimulate antibody production by CH12. The results show that, although CH12 cells present antigen to T helper cells that interact with either the I-A or the I-E molecules, CH12 cells are stimulated to secrete antibody only by T helper cells reactive with their I-E molecules. Our data demonstrate that class II molecules are transducers of signals for B-cell excitation in addition to serving a restricting function for helper T-cell stimulation. Moreover, the data demonstrate that these two functions, T-cell stimulation and B-cell excitation, are discrete and need not be expressed by the same Ia molecule