Net Intermolecular Silyloxypyrone-Based (5+2) Cycloadditions Utilizing Amides as Enabling and Cleavable Tethers.

Silyloxypyrone-based (5+2) cycloadditions were facilitated by amides that allowed for increased reactivity and a pathway for cleaving the tether to afford net intermolecular cycloadducts. Various amides underwent facile cycloaddition, and several experiments revealed steric and electronic factors that accelerate the reaction. tert-Butyl amides reacted faster than less hindered variants in multiple cases. In the case of dearomative oxidopyrylium-indole (5+2) cycloadditions, an amine-based tether was ineffective, whereas amides enabled this powerful transformation. Theoretical calculations evidenced a concerted asynchronous reaction in which the amide facilitates a conformational driving force enabling cycloaddition. Finally, a one-pot acylation/(5+2) cycloaddition/nucleophilic lactam opening and other examples of tosyl lactam opening of a modified cycloadduct were demonstrated.

Experimental and Theoretical Investigation of the Synchronicity of Ambident Silyloxypyrone-Based (5 + 2) Cycloadditions.

The reaction pathway of silyloxypyrone-based (5 + 2) cycloadditions was determined to be extremely dependent on the nature of the dipolarophile. Neutral alkenes were the least reactive, whereas both electron-deficient and electron-rich dipolarophiles were more reactive, thus providing evidence for ambident oxidopyrylium intermediates. Qualitative rate studies, Hammett linear free energy relationships, and theoretical calculations combined to provide evidence for a spectrum of reactivity that passes through the borderlands of concerted and stepwise.

COVID-19 and finance scholarship: A systematic and bibliometric analysis.

COVID-19 has posed unprecedented challenges to global finances because of its unparalleled global scope, with both concomitant shocks as well as the likely altering of risk assessments and forecasts for the foreseeable future. As the effects of COVID-19 on financial markets and institutions have been widely addressed by various literature, we systematically synthesize this literature. Through a comprehensive search process, we extract and review 818 articles. Appling bibliometric methods, we explore the trends among various research constituents involved in the field. Using multi-dimensional scaling, we identify the intellectual structure of research in the domain and outline four distinct themes. We also identify the evolution and shifts in research within the short span of three years since the inception of COVID-19. Through detailed content analysis, various future research directions are proposed.

COVID-19 social distancing measures and economic growth: Distinguishing short- and long-term effects.

Social distancing policies have been criticized for their adverse effect on economies. However, we evidence that while they have a short-run adverse effect, they also have a long-run recovery effect on economic growth. Utilizing quarterly gross domestic product (GDP) growth rate data from OECD member states, we find that the medium-term recovery effect of stringent social distancing policies on economic growth is three times higher the short-term adverse effect. We additionally investigate social distancing measures with sub-components of GDP, as well as the conditioning roles of institutional factors.

Small-Mammal Shooting as a Conduit for Lead Exposure in Avian Scavengers.

Lead (Pb) exposure is a widespread wildlife conservation threat. Although commonly associated with Pb-based ammunition from big-game hunting, small mammals (e.g., ground squirrels) shot for recreational or pest-management purposes represent a potentially important Pb vector in agricultural regions. We measured the responses of avian scavengers to pest-shooting events and examined their Pb exposure through consumption of shot mammals. There were 3.4-fold more avian scavengers at shooting fields relative to those at fields with no recent shooting, and avian scavengers spent 1.8-fold more time feeding after recent shooting events. We isotopically labeled shot ground squirrels in the field with an enriched 15N isotope tracer; 6% of avian scavengers sampled within a 39 km radius reflected this tracer in their blood. However, 33% of the avian scavengers within the average foraging dispersal distance of nests (0.6-3.7 km) were labeled, demonstrating the importance of these shooting fields as a source of food for birds nesting in close proximity. Additionally, Pb concentrations in 48% of avian scavengers exceeded subclinical poisoning benchmarks for sensitive species (0.03-0.20 µg/g w/w), and those birds exhibited reduced δ-aminolevulinic acid dehydratase activity, indicating a biochemical effect of Pb. The use of shooting to manage small mammal pests is a common practice globally. Efforts that can reduce the use of Pb-based ammunition may lessen the negative physiological effects of Pb exposure on avian scavengers.

Co-movement of COVID-19 and Bitcoin: Evidence from wavelet coherence analysis.

We apply wavelet methods to daily data of COVID-19 world deaths and daily Bitcoin prices from 31th December 2019 to 29th April 2020. We find, especially for the period post April 5, that levels of COVID-19 caused a rise in Bitcoin prices. We contribute to the fast-growing body of work on the financial impacts of COVID-19, as well as to ongoing consideration of whether Bitcoin is a safe haven investment. Our results should be of great interest to both scholars and policy makers, as well as investment professionals interested in the financial implications of both COVID-19 and cryptocurrencies.

Co-movements and spillovers of oil and renewable firms under extreme conditions: New evidence from negative WTI prices during COVID-19.

We test for the existence of volatility spillovers and co-movements among energy-focused corporations during the outbreak of the COVID-19 pandemic, inclusive of the April 2020 events where West Texas Intermediate (WTI) oil future prices became negative. Employing the spillover index approach of Diebold and Yilmaz (2012); as well as developing a DCC-FIGARCH conditional correlation framework and using estimated spillover indices built on a generalised vector autoregressive framework in which forecast-error variance decompositions are invariant to the variable ordering, we examine the sectoral transmission mechanisms of volatility shocks and contagion throughout the energy sector. Among several results, we find positive and economically meaningful spillovers from falling oil prices to both renewable energy and coal markets. However, this result is only found for the narrow portion of our sample surrounding the negative WTI event. We interpret our results being directly attributed to a sharp drop in global oil, gas and coal demand, rather than because of a sudden increase in oil supply. While investors observed the US fracking industry losing market share to coal, they also viewed renewables as more reliable mechanism to generate long-term, stable and low-cost supply.

Did Congress trade ahead? Considering the reaction of US industries to COVID-19.

During the ongoing COVID-19 pandemic in the US, there has been considerable media attention regarding several US legislators who traded stocks in late January through February 2020. The concern is that these legislators traded in anticipation of COVID-19 having a major impact on the financial markets, while publicly suggesting otherwise. We consider whether these legislator trades were in a time window, and of a nature, that would be consistent with trading ahead of the market. Towards this end, we assess the reactions of US industries to sudden COVID-related news announcements, concomitantly with an analysis of levels of investor attention to COVID. Results suggest that, at an industry-level, for legislator trading to be "ahead of the market" it needed to have been done prior to February 26, and involving the 15 industries we identify as having abnormal returns, especially medical and pharmaceutical products (positive); restaurants, hotels, and motels (negative); as well as services and utilities. These criteria are met by many of the legislator trades. Our results help to both parameterize concerns about this case of legislator trading; as well as provide insight into the reactions and expectations of investors toward COVID-19.

COVID-19 and finance: Agendas for future research.

This paper highlights the enormous economic and social impact of COVID-19 with respect to articles that have either prognosticated such a large-scale event, and its economic consequences, or have assessed the impacts of other epidemics and pandemics. A consideration of possible impacts of COVID-19 on financial markets and institutions, either directly or indirectly, is briefly outlined by drawing on a variety of literatures. A consideration of the characteristics of COVID-19, along with what research suggests have been the impacts of other past events that in some ways roughly parallel COVID-19, points toward avenues of future investigation.

Additive manufacturing of platinum group element (PGE) reference materials with a silica matrix.

RATIONALE: The microanalytical community has an outstanding need for platinum group element (PGE) reference materials, particularly for trace element analysis by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). National Institute of Standards and Technology (NIST) glasses contain Rh, Pd, and Pt, but lack Ru, Os, and Ir. Synthesis of silicate PGE standards has proven difficult due the tendency of PGEs to form metallic nuggets. METHODS: Additive manufacturing methods were used to produce PGE standards with a silica matrix. Monodispersed submicron PGE-doped Stöber particles were used as feedstock materials for electrophoretic deposition (EPD). Two-cm-sized samples produced by EPD were subsequently densified by thermal processing. The homogeneity of PGEs was tested using LA-ICPMS and concentrations were measured by laser ablation and solution ICPMS. RESULTS: The PGE concentrations ranged from 0.5 to 3 µg/g. The inhomogeneity was at the 3% RSD level for Ru, Rh, Ir, and Os throughout and 5% for Pt and Pd in the interior of the samples. Based on LA-ICPMS analyses, the interiors of the two samples have near identical concentrations in PGEs. CONCLUSIONS: The samples fabricated in this study represent the most complete and homogeneous PGE standards produced with a silicate matrix. The ability to produce multiple samples with the same composition provides opportunities for validating methods, monitoring long-term reproducibility, and facilitating interlaboratory comparisons.

Investigation of Transfer Group, Tether Proximity, and Alkene Substitution for Intramolecular Silyloxypyrone-Based [5 + 2] Cycloadditions.

Systematic investigation of intramolecular silyloxypyrone-based [5 + 2] cycloadditions revealed three significant factors impacting conversion to cycloadduct: (1) the silyl transfer group has a substantial influence on the rate of reaction, and the robust t-butyldiphenylsilyl group was found to be more effective overall than the conventional t-butyldimethylsilyl group; (2) α,ß-unsaturated esters were generally more reactive than terminal olefins and afforded appreciable quantity of cycloadduct even at room temperature; and (3) the proximity of the tether to the silyl transfer group revealed a critical alignment trend between the pyrone and the alkene. Taken together, these investigations provided insight regarding the steric and electronic parameters that impact the scope and limitation of these reactions.

Oxidopyrylium-Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C3) Sequences: Scope, Limitation, and Computational Investigations.

Oxidopyrylium-alkene [5 + 2] cycloaddition conjugate addition cascade (C3) sequences are described. Intramolecular cycloadditions involving terminal alkenes, enals, and enones were investigated. Substrates with tethers of varying lengths delivered five- and six-membered carbocycles and heterocycles thus demonstrating the scope and limitation of the cycloaddition-conjugate addition cascade. Several experiments and theoretical calculations provide evidence for the proposed mechanistic pathway.

Investigation of oxidopyrylium-alkene [5+2] cycloaddition conjugate addition cascade (C3) sequences.

Novel oxidopyrylium-alkene [5+2] cycloaddition conjugate addition cascade (C(3)) sequences are described. Various acetoxypyranone-alkenes with pendant nucleophiles undergo [5+2] cycloaddition followed by conjugate addition from the concave face of the intermediate pyranone toward bridged, tetracyclic ethers. In several cases, 3 new rings, 4 new bonds, and 6 new contiguous stereocenters are constructed with excellent diastereoselectivity. Finally, an asynchronous concerted reaction pathway is proposed to explain the high diastereoselectivity of the oxidopyrylium-alkene [5+2] C(3).

Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity.

A series of 9-alkylaminoacridines were synthesized and evaluated for activity against two strains of methicillin-resistant and one strain of methicillin-sensitive Staphylococcus aureus. Results are presented that show a clear structure activity relationship between the N-alkyl chain length and antibacterial activity with peak MIC99 values of 2-3 µM for alkyl chains ranging from 10 to 14 carbons in length. Although prior work has linked the function of acridine-based compounds to intercalation and topoisomerase inhibition, the present results show that 9-alkylaminoacridines likely function as amphiphilic membrane-active disruptors potentially in a similar manner as quaternary ammonium antimicrobials.

Multidimensional reaction screening for photochemical transformations as a tool for discovering new chemotypes.

We have developed an automated photochemical microfluidics platform that integrates a 1 kW high-pressure Hg vapor lamp and allows for analytical pulse flow or preparative continuous flow reactions. Herein, we will discuss the use of this platform toward the discovery of new chemotypes through multidimensional reaction screening. We will highlight the ability to discretely control wavelengths with optical filters, allowing for control of reaction outcomes.

Unique reactivity of anti- and syn-acetoxypyranones en route to oxidopyrylium intermediates leading to a cascade process.

Unique reactivity of anti- and syn-acetoxypyranones was observed in oxidopyrylium-alkene [5 + 2] cycloadditions. The subtle interplay between the corresponding acetoxypyranone conformation and steric bulk of tertiary amine bases causes syn-acetoxypyranones to undergo [5 + 2] cycloaddition appreciably faster than anti-acetoxypyranones. Additionally, the efficiency of a cascade process that afforded a novel tetracyclic lactol was determined to be dependent on the relative stereochemistry of each diastereomer, the amine base utilized, and the addition of water.

Synthesis and in silico screening of a library of ß-carboline-containing compounds.

The synthesis of a library of tetrahydro-ß-carboline-containing compounds in milligram quantities is described. Among the unique heterocyclic frameworks are twelve tetrahydroindolizinoindoles, six tetrahydrocyclobutanindoloquinolizinones and three tetrahydrocyclopentenoneindolizinoindolones. These compounds were selected from a virtual combinatorial library of 11,478 compounds. Physical chemical properties were calculated and most of them are in accordance with Lipinski's rules. Virtual docking and ligand-based target evaluations were performed for the ß-carboline library compounds and selected synthetic intermediates to assess the therapeutic potential of these small organic molecules. These compounds have been deposited into the NIH Molecular Repository (MLSMR) and may target proteins such as histone deacetylase 4, endothelial nitric oxide synthase, 5-hydroxytryptamine receptor 6 and mitogen-activated protein kinase 1. These in silico screening results aim to add value to the ß-carboline library of compounds for those interested in probes of these targets.

Synthesis and reactivity of bicyclo[3.2.1]octanoid-derived cyclopropanes.

Photochemical oxa-di-π-methane rearrangement of bicyclo[3.2.1]octanoid scaffolds affords multifunctional, donor-acceptor cyclopropanes. A related photochemical reaction of an iminium ether substrate uncovered an unprecedented aza-di-π-methane rearrangement of a ß,γ-unsaturated iminium. Donor-acceptor cyclopropanes have been evaluated as substrates for reactions generating several new chemotypes.

Synthesis and cancer cell cytotoxicity of substituted xanthenes.

A series of substituted xanthenes was synthesized and screened for activity using DU-145, MCF-7, and HeLa cancer cell growth inhibition assays. The most potent compound, 9 g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3-carboxamide), was found to inhibit cancer cell growth with IC(50) values ranging from 36 to 50 microM across all three cancer cell lines. Structure-activity relationship (SAR) data is presented that indicates additional gains in potency may be realized through further derivatization of the compounds (e.g., the incorporation of a 7-fluoro substituent to 9 g). Results are also presented that suggest the compounds function through a unique mechanism of action as compared to that of related acridine and xanthone anticancer agents (which have been shown to intercalate into DNA and inhibit topoisomerase II activity). A structural comparison of these compounds suggests the differences in function may be due to the structure of the xanthene heterocycle which adopts a nonplanar conformation about the pyran ring.

Reaction discovery using microfluidic-based multidimensional screening of polycyclic iminium ethers.

Polycyclic iminium ethers are ambident electrophilic intermediates that react with a range of nucleophiles in a highly condition-dependent manner to afford densely functionalized lactams. In an effort to expand the scope of reactivity and assist in the generation of new chemotypes from these intermediates, several iminium ethers were subjected to reaction screening using an automated microfluidics reaction platform. Application of this approach led to the discovery of several interesting reaction pathways involving the iminium ether intermediates that will be described.