Development and application of metal-catalyzed diamination reactions, The

2014 Fall.Includes bibliographical references.Nitrogen-rich molecules are of great interest in chemistry and incorporation of nitrogen into molecules is an on-going active field of study. In particular, vicinal diamines are important functional moieties that are found throughout biologically active molecules and natural products as well as highly effective chiral control agents in organic synthesis. There has been much effort directed toward the efficient synthesis of vicinal diamines; however the development of a direct route has proven to be challenging. This dissertation discusses the application of diamination products from existing methods to synthesize biologically active motifs, as well as the development of new metal-catalyzed diamination methods for the synthesis of biologically interesting motifs from readily available starting materials. The β, γ-diamino acid motif is an area of active research because of its prevalence in biologically active molecules and its use in peptide library syntheses. Cyclization of β, γ-diamino acids give the closely related 4-aminopyrrolidinones. These five-membered amino lactams have been reported to potentiate insulin activity when incorporated into hypoglycemic peptide analogues and made the analogues more stable towards physiological degradation. Current methods for the synthesis of these compounds require multi-step procedures and rely heavily on commercially available amino acids as starting materials, thus limiting the structural variability for biological studies. Using a diamination method discovered in our lab, 4-aminopyrrolidinones were efficiently synthesized in 40% overall yield, over five steps from readily available terminal olefins or conjugated dienes, providing a comparable process in the synthesis of these compounds. As part of our ongoing efforts to study the mechanism of metal-catalyzed diaminations using diaziridinone as nitrogen source, it was found that regioselectivity in the diamination of conjugated dienes could be controlled using Cu(I) as catalyst and varying reaction conditions. An alternative nitrogen source, thiadiaziridine 1,1-dioxide, which has shown to display interesting reactivity, was chosen to further investigate the Cu(I)-catalyzed regioselective diamination. Upon varying reaction conditions with Cu(I) catalysts, regioselective diamination occurred for various conjugated dienes and allowed direct access to a range of diverse cyclic sulfamides which have interesting biological potential. With the racemic synthesis of cyclic sulfamides, it was of interest to obtain these compounds asymmetrically, as their biological properties are of value and current methods for their asymmetric synthesis do not allow much variation in substitution patterns. Using Pd2(dba)3 and a chiral phosphoramidite ligand, a variety of chiral cyclic sulfamides were synthesized in moderate to high yields and with ee's greater than 90%, providing direct access to these valuable compounds in one step from readily available conjugated diene substrates. Lastly, N,N-Di-tert-butyl thiadiaziridine 1,1-dioxide has been found to be a versatile reagent for interesting reactivity. Other uses of this reagent include the Pd(II)-catalyzed terminal diamination of conjugated dienes, diamination of allenes, and the Pd-catalyzed oxidation of alcohols to form α, β-unsaturated compounds

Seagrass can mitigate negative ocean acidification effects on calcifying algae

The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm structure and experimental assistance.info:eu-repo/semantics/publishedVersio

Micro-finance, women’s empowerment and fertility decline in Bangladesh: How important was women’s agency?

As Nobel Prize winner Amartya Sen has argued “[Bangladesh’s development achievements have] important lessons for other countries across the globe, [in particular a focus on] reducing gender inequality”. A major avenue through which this emphasis has been manifest lies, according to this narrative, in enhancements to women’s agency for instrumental and intrinsic reasons particularly through innovations in family planning and microfinance. The “Bangladesh paradox” of improved wellbeing despite low economic growth over the last four decades is claimed as a paradigmatic case of the spread of both modern family planning programmes and microfinance leading to women’s empowerment and fertility reduction. In this paper we show that the links between microfinance, empowerment and fertility reduction, are fraught with problems, and far from robust; hence the claimed causal links between microfinance and family planning via women’s empowerment needs to be further reconsidered

Predicting Responses of Geo-ecological Carbonate Reef Systems to Climate Change: A Conceptual Model and Review

[Chapter Abstract] 230Coral reefs provide critical ecological and geomorphic (e.g. sediment production for reef-fronted shoreline maintenance) services, which interact in complex and dynamic ways. These services are under threat from climate change, requiring dynamic modelling approaches that predict how reef systems will respond to different future climate scenarios. Carbonate budgets, which estimate net reef calcium carbonate production, provide a comprehensive ‘snap-shot’ assessment of reef accretionary potential and reef stability. These budgets, however, were not intended to account for the full suite of processes that maintain coral reef services or to provide predictive capacity on longer timescales (decadal to centennial). To respond to the dual challenges of enhancing carbonate budget assessments and advancing their predictive capacity, we applied a novel model elicitation and review method to create a qualitative geo-ecological carbonate reef system model that links geomorphic, ecological and physical processes. Our approach conceptualizes relationships between net carbonate production, sediment transport and landform stability, and rates knowledge confidence to reveal major knowledge gaps and critical future research pathways. The model provides a blueprint for future coral reef research that aims to quantify net carbonate production and sediment dynamics, improving our capacity to predict responses of reefs and reef-fronted shorelines to future climate change.https://nsuworks.nova.edu/occ_facbooks/1116/thumbnail.jp

Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review

Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access) between environmental drivers/exposures and disease detection. Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g. person-to-person vs environment-to-person), and linking weather data to individual cases longitudinally

Inter-assessor reliability of practice based biomechanical assessment of the foot and ankle

Background There is no consensus on which protocols should be used to assess foot and lower limb biomechanics in clinical practice. The reliability of many assessments has been questioned by previous research. The aim of this investigation was to (i) identify (through consensus) what biomechanical examinations are used in clinical practice and (ii) evaluate the inter-assessor reliability of some of these examinations. Methods Part1: Using a modified Delphi technique 12 podiatrists derived consensus on the biomechanical examinations used in clinical practice. Part 2: Eleven podiatrists assessed 6 participants using a subset of the assessment protocol derived in Part 1. Examinations were compared between assessors. Results Clinicians choose to estimate rather than quantitatively measure foot position and motion. Poor inter-assessor reliability was recorded for all examinations. Intra-class correlation coefficient values (ICC) for relaxed calcaneal stance position were less than 0.23 and were less than 0.14 for neutral calcaneal stance position. For the examination of ankle joint dorsiflexion, ICC values suggest moderate reliability (less than 0.61). The results of a random effects ANOVA highlight that participant (up to 5.7°), assessor (up to 5.8°) and random (upto 5.7°) error all contribute to the total error (up to 9.5° for relaxed calcaneal stance position, up to 10.7° for the examination of ankle joint dorsiflexion). Kappa Fleiss values for categorisation of first ray position and mobility were less than 0.05 and for limb length assessment less than 0.02, indicating slight agreement. Conclusion Static biomechanical assessment of the foot, leg and lower limb is an important protocol in clinical practice, but the key examinations used to make inferences about dynamic foot function and to determine orthotic prescription are unreliable

Catalytic Asymmetric Synthesis of Cyclic Sulfamides from Conjugated Dienes

This paper describes the catalytic asymmetric diamination of alkyl dienes using <i>N</i>,<i>N</i>′-di-<i>tert</i>-butylthiadiaziridine 1,1-dioxide in the presence of Pd(0) and a chiral phosphoramidite ligand to give cyclic sulfamides in high yield and high ee. The diamination is also amenable to gram scale