Catalytic Enantioselective Carbon–Oxygen Bond Formation: Phosphine-Catalyzed Synthesis of Benzylic Ethers via the Oxidation of Benzylic C–H Bonds

Benzylic alcohols and ethers are common subunits in bioactive molecules, as well as useful intermediates in organic chemistry. In this Communication, we describe a new approach to the enantioselective synthesis of benzylic ethers through the chiral phosphine-catalyzed coupling of two readily available partners, γ-aryl-substituted alkynoates and alcohols, under mild conditions. In this process, the alkynoate partner undergoes an internal redox reaction. Specifically, the benzylic position is oxidized with good enantioselectivity, and the alkyne is reduced to the alkene

ALGAL TOXICITY AND FORMATION OF HALOGENATED ORGANIC COMPOUNDS IN BALLAST WATER AFTER OXIDATIVE TREATMENT

Ballast water plays a vital role in the stabilization and operations of modern ships, and it is estimated that 3 to 5 billion tons of ballast water are transferred around the world each year. However, the discharge of ballast water has led to the release of non-indigenous species, and costly and ecologically damaging biological invasions. To combat this serious problem, ballast water discharge is now regulated and ballast water management systems (BWMS) have been developed to meet required discharge limits for the release of live organisms. The most common BWMS rely on chlorination of ballast water to kill planktonic organisms but also result in the formation of disinfection by-products (DBPs) and the potential for aquatic toxicity. The research in this thesis was conducted to advance the understanding of treated ballast water toxicity, and to document the formation of higher molecular weight DBPs using ultrahigh resolution mass spectrometry. Research was conducted with commercial BWMS that were based on either direct chlorination (Ch. 2 & 3) or in-situ electrochlorination (Ch. 2 & 4). Ballast water treatment was conducted in estuarine waters of the Port of Baltimore (Patapsco River, Maryland). In Chapter 2, I tested the algal toxicity of discharged ballast water from four BWMS at the time of discharge and monthly thereafter, showing the longevity of the toxic effect of treated water on micro algae. In Chapters 3 and 4, I used ultrahigh resolution mass spectrometry to identify the molecular composition of dissolved organic matter (DOM) and halogenated DBPs after oxidative treatment of ballast water. By comparing samples before and after direct chlorination, I was able to document the changes in dissolved organic matter and the formation of numerous halogenated DBPs (Ch. 3). In Chapter 4, I was able to document the change in brominated DBPs after a period of 92 days, showing the relative persistence of dibrominated compounds. This work together demonstrates that use of traditional water treatment to solve one environmental problem may, in fact, cause other unintended consequences to aquatic ecosystems

Degree of free fatty acid saturation influences chocolate rejection in human assessors

In foods, free fatty acids (FFA) traditionally have been viewed as contributing an odor, yet evidence has accumulated that FFA also contribute a unique taste (“oleogustus”). However, minimal work has been conducted using actual foods to test the contribution of FFA to taste preferences. We chose to investigate flavor, taste, and aroma contributions of added FFA in chocolate, as some commercial manufacturers already use lipolysis of triglycerides to generate unique profiles. We hypothesized small added concentrations of FFA would increase preferences for chocolate while higher added concentrations would decrease preferences. We also hypothesized a saturated fatty acid (stearic C18) would have a lesser effect than a monounsaturated (oleic C18:1), which would have a lesser effect than a polyunsaturated (linoleic C18:2) fatty acid. For each, paired preference tests were conducted for 10 concentrations (0.04% to 2.25%) of added FFA compared to control chocolate without added FFAs. Stearic acid was tested for flavor (tasting, nares open), while the unsaturated fatty acids were tested for both aroma (orthonasal only, no tasting) and taste (tasting with nares blocked to eliminate retronasal odor). We found no preference for any added FFA chocolate; however, rejection was observed independently for both taste and aroma of unsaturated fatty acids, with linoleic acid reaching rejection at lower concentrations than oleic acid. These data indicate degree of unsaturation influences rejection of both FFA aroma and taste in chocolate. Thus, alterations of FFA profiles in foods should be approached cautiously to avoid shifting concentrations of unsaturated fatty acids to hedonically unacceptable levels

Single-kernel ionomic profiles are highly heritable indicators of genetic and environmental influences on elemental accumulation in maize grain (Zea mays)

Peer reviewedPublisher PD

Biphenyl-Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

Because of the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. Introduced herein is a new family of chiral nucleophilic catalysts, biphenyl-derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation. A range of one-carbon coupling partners can be employed, thereby generating cyclopentenes which bear a fully substituted stereocenter [either all-carbon or heteroatom-substituted (sulfur and phosphorus)]. Stereocenters at the other four positions of the cyclopentane ring can also be introduced with good stereoselectivity. An initial mechanistic study indicates that phosphine addition to the electrophilic four-carbon coupling partner is not the turnover-limiting step of the catalytic cycle

Dynamics of Cortical Degeneration Over a Decade in Huntington's Disease

BACKGROUND: Characterizing changing brain structure in neurodegeneration is fundamental to understanding longterm effects of pathology and ultimately providing therapeutic targets. It is well established that Huntington’s disease (HD) gene carriers undergo progressive brain changes during the course of disease, yet the long-term trajectory of cortical atrophy is not well defined. Given that genetic therapies currently tested in HD are primarily expected to target the cortex, understanding atrophy across this region is essential. METHODS: Capitalizing on a unique longitudinal dataset with a minimum of 3 and maximum of 7 brain scans from 49 HD gene carriers and 49 age-matched control subjects, we implemented a novel dynamical systems approach to infer patterns of regional neurodegeneration over 10 years. We use Bayesian hierarchical modeling to map participant- and group-level trajectories of atrophy spatially and temporally, additionally relating atrophy to the genetic marker of HD (CAG-repeat length) and motor and cognitive symptoms. RESULTS: We show, for the first time, that neurodegenerative changes exhibit complex temporal dynamics with substantial regional variation around the point of clinical diagnosis. Although widespread group differences were seen across the cortex, the occipital and parietal regions undergo the greatest rate of cortical atrophy. We have established links between atrophy and genetic markers of HD while demonstrating that specific cortical changes predict decline in motor and cognitive performance. CONCLUSIONS: HD gene carriers display regional variability in the spatial pattern of cortical atrophy, which relates to genetic factors and motor and cognitive symptoms. Our findings indicate a complex pattern of neuronal loss, which enables greater characterization of HD progression

A Versatile Approach to Ullmann C−N Couplings at Room Temperature: New Families of Nucleophiles and Electrophiles for Photoinduced, Copper-Catalyzed Processes

The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C−N bond formation to occur under unusually mild conditions. In this study, we substantially expand the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C−N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups

Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis

<p>Abstract</p> <p>Background</p> <p>Vitamin D insufficiency is common in hospitalized patients. Recent evidence suggests that vitamin D may enhance the innate immune response by induction of cathelicidin (LL-37), an endogenous antimicrobial peptide produced by macrophages and neutrophils. Thus, the relationship between vitamin D status and LL-37 production may be of importance for host immunity, but little data is available on this subject, especially in the setting of human sepsis syndrome and other critical illness.</p> <p>Methods</p> <p>Plasma concentrations of 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (DBP) and LL-37 in critically ill adult subjects admitted to intensive care units (ICUs) with sepsis and without sepsis were compared to healthy controls.</p> <p>Results</p> <p>Critically ill subjects had significantly lower plasma 25(OH)D concentrations compared to healthy controls. Mean plasma LL-37 levels were significantly lower in critically ill subjects compared to healthy controls. Vitamin D binding protein levels in plasma were significantly lower in critically ill subjects with sepsis compared to critically ill subjects without sepsis. There was a significant positive association between circulating 25(OH)D and LL-37 levels.</p> <p>Conclusion</p> <p>This study demonstrates an association between critical illness and lower 25(OH)D and DBP levels in critically ill patients as compared to healthy controls. It also establishes a positive association between vitamin D status and plasma LL-37, which suggests that systemic LL-37 levels may be regulated by vitamin D status. Optimal vitamin D status may be important for innate immunity especially in the setting of sepsis. Further invention studies to examine this association are warranted.</p

Association of the Joint Effect of Menopause and Hormone Replacement Therapy and Cancer in African American Women: The Jackson Heart Study

Cancer is the second leading cause of death in the US and in Mississippi. Breast cancer (BC) is the most common cancer among women, and the underlying pathophysiology remains unknown, especially among African American (AA) women. The study purpose was to examine the joint effect of menopause status (MS) and hormone replacement therapy (HRT) on the association with cancers, particularly BC using data from the Jackson Heart Study. The analytic sample consisted of 3202 women between 35 and 84 years of which 73.7% and 22.6% were postmenopausal and on HRT, respectively. There were a total of 190 prevalent cancer cases (5.9%) in the sample with 22.6% breast cancer cases. Menopause (p < 0.0001), but not HRT (p = 0.6402), was independently associated with cancer. Similar results were obtained for BC. BC, cancer, hypertension, type 2 diabetes, prevalent cardiovascular disease, physical activity and certain dietary practices were all significantly associated with the joint effect of menopause and HRT in the unadjusted analyses. The family history of cancer was the only covariate that was significantly associated with cancer in the age-adjusted models. In examining the association of cancer and the joint effect of menopause and HRT, AA women who were menopausal and were not on HRT had a 1.97 (95% CI: 1.15, 3.38) times odds of having cancer compared to pre-menopausal women after adjusting for age; which was attenuated after further adjusting for family history of cancer. Given that the cancer and BC cases were small and key significant associations were attenuated after adjusting for the above mentioned covariates, these findings warrant further investigation in studies with larger sample sizes of cancer (and BC) cases

Usage of NASA's Near Real-Time Solar and Meteorological Data for Monitoring Building Energy Systems Using RETScreen International's Performance Analysis Module

This paper describes building energy system production and usage monitoring using examples from the new RETScreen Performance Analysis Module, called RETScreen Plus. The module uses daily meteorological (i.e., temperature, humidity, wind and solar, etc.) over a period of time to derive a building system function that is used to monitor building performance. The new module can also be used to target building systems with enhanced technologies. If daily ambient meteorological and solar information are not available, these are obtained over the internet from NASA's near-term data products that provide global meteorological and solar information within 3-6 days of real-time. The accuracy of the NASA data are shown to be excellent for this purpose enabling RETScreen Plus to easily detect changes in the system function and efficiency. This is shown by several examples, one of which is a new building at the NASA Langley Research Center that uses solar panels to provide electrical energy for building energy and excess energy for other uses. The system shows steady performance within the uncertainties of the input data. The other example involves assessing the reduction in energy usage by an apartment building in Sweden before and after an energy efficiency upgrade. In this case, savings up to 16% are shown