Published descriptions of the specific lines of research leading to the discovery of therapeutically important medicines, especially major new class medicines, have long provided value to the ...biopharmaceutical community as models of success, often influencing the strategies and methods of subsequent drug research. Quinolone antibacterials represent one of medicine's most important classes of anti-infective agents; yet in contrast to many other classes of anti-infectives, astonishingly few details concerning the origin of the class or the rationale leading to the selection of the first clinical agent, nalidixic acid, were ever published by the discoverers. Moreover, earlier disclosures of an independent discovery of the quinolone class of antibacterials have been almost entirely overlooked by the scientific literature. This review brings together all the available information from primary literature sources relating to both discoveries and provides for the first time a much fuller, if still partially speculative, story of the earliest years of this important class of drugs.
Given its many distinct characteristics, electrochemistry represents an attractive approach to meet the prevailing trends in organic synthesis. In particular, electrocatalysisa process that ...integrates electrochemistry and small-molecule catalysishas the potential to substantially improve the scope of synthetic electrochemistry and provide a wide range of useful transformations. Recently, we have demonstrated new catalytic approaches that combine electrochemistry and redox-metal catalysis for the oxidative difunctionalization of alkenes to access a diverse array of vicinally functionalized structures. This Perspective details our design principles underpinning the development of electrochemical diazidation, dichlorination, and halotrifluoromethylation of alkenes, which were built on foundational work by others in the areas of synthetic electrochemistry, radical chemistry, and transition-metal catalysis. The introduction of redox-active Mn catalysts allows the generation of radical intermediates from readily available reagents at low potentials under mild conditions. These transition metals also impart selectivity control over the alkene functionalization processes by functioning as radical group transfer agents. As such, our electrocatalytic difunctionalization reactions exhibit excellent chemoselectivity, broad substrate scope, and high functional group compatibility. Specifically, anodically coupled electrolysis, an approach that pairs two single-electron oxidation events in a parallel manner, enables the development of regio- and chemoselective heterodifunctionalization of alkenes. The products of the new transformations we describe in this Perspective represent pertinent structures in numerous medicinally relevant compounds. We anticipate that the design parameters presented here are general and will provide a platform for the development of electrocatalytic systems for other challenging organic redox transformations.
One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, ...and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention.
One-carbon metabolism supports biosynthesis, amino acid homeostasis, epigenetic maintenance, and redox defense. Ducker and Rabinowitz review this metabolism, from the biochemical basics of folate to organismal physiology, with an emphasis on recent advances in understanding one-carbon metabolic cycles, compartmentalization, and pathway activity both in normal physiology and in human disease.
Gas physisorption is an experimental technique based on equilibrium Van der Waals interactions between gas molecules and solid particles, that quantifies the specific surface area (SSA), pore size ...distribution (PSD), and pore volume of solids and powders. The performance of catalysts, absorbents, chromatography column materials, and polymer resins depends on these morphological properties. Here we introduce the basic principles and procedures of physical adsorption, especially nitrogen physisorption, as a guide to students and researchers unfamiliar with the field. The Brunauer‐Emmett‐Teller theory (BET) is a common approach to estimate SSA that extends the Langmuir monolayer molecular adsorption model to multilayer layers. It relies on an equilibrium adsorption isotherm, measured at the normal boiling point of the adsorbate, eg, 77 K or 87 K for N2 and Ar, respectively. Web of Science indexed 45 400 articles in 2016 and 2017 that mentioned N2 adsorption porosimetry—BET and BJH (Barrett‐Joyner‐Halenda) keywords. The VOSViewer bibliometric tool grouped these articles into four research clusters: adsorption, activated carbon in aqueous solutions for removal of heavy metal ions; synthesis of nanoparticles and composites; catalysts performance in oxidation and reduction processes; and photocatalytic degradation with TiO2. According to the literature, the accuracy of the density function theory (DFT) method is higher than with the BJH theory and it is more reliable.
We report a Mn-catalyzed electrochemical dichlorination of alkenes with MgCl2 as the chlorine source. This method provides operationally simple, sustainable, and efficient access to a variety of ...vicinally dichlorinated compounds. In particular, alkenes with oxidatively labile functional groups, such as alcohols, aldehydes, sulfides, and amines, were transformed into the desired vicinal dichlorides with high chemoselectivity. Mechanistic data are consistent with metal-mediated Cl atom transfer as the predominant pathway enabling dual C–Cl bond formation and contradict an alternative pathway involving electrochemical evolution of chlorine gas followed by Cl2-mediated electrophilic dichlorination.
This paper reviews findings on the anisotropy of the grain boundary energies. After introducing the basic concepts, there is a discussion of fundamental models used to understand and predict grain ...boundary energy anisotropy. Experimental methods for measuring the grain boundary energy anisotropy, all of which involve application of the Herring equation, are then briefly described. The next section reviews and compares the results of measurements and model calculations with the goal of identifying generally applicable characteristics. This is followed by a brief discussion of the role of grain boundary energies in nucleating discontinuous transitions in grain boundary structure and chemistry, known as complexion transitions. The review ends with some questions to be addressed by future research and a summary of what is known about grain boundary energy anisotropy.
Vicinal diamines are a common structural motif in bioactive natural products, therapeutic agents, and molecular catalysts, motivating the continuing development of efficient, selective, and ...sustainable technologies for their preparation. We report an operationally simple and environmentally friendly protocol that converts alkenes and sodium azide—both readily available feedstocks—to 1,2-diazides. Powered by electricity and catalyzed by Earth-abundant manganese, this transformation proceeds under mild conditions and exhibits exceptional substrate generality and functional group compatibility. Using standard protocols, the resultant 1,2-diazides can be smoothly reduced to vicinal diamines in a single step, with high chemoselectivity. Mechanistic studies are consistent with metal-mediated azidyl radical transfer as the predominant pathway, enabling dual carbon-nitrogen bond formation.
Abstract
Consumers regularly encounter cues of contagious disease in daily life—a commuter sneezes on the train, a colleague blows their nose in a meeting, or they read recent headlines about the ...dangerous spread of a disease. Research has overwhelmingly argued that the dominant response to these cues is disgust—an emotion that leads to a desire to reject and avoid potential contamination. We argue, however, that contagious disease cues can also elicit fear. Across four experiments and two large empirical data analyses of the presence of contagious disease on actual consumption behavior, we find that cues of contagious disease increase both fear and disgust, and these emotions together form a unique behavioral tendency with respect to consumer behavior. Relative to either emotion alone, disgust and fear increase preference for more-familiar products asymmetrically over less-familiar ones. These results contribute theoretically to research on complex emotional states and the behavioral tendencies of emotions, document a systematic and consequential impact of contagious disease cues on real consumption behavior, and have significant practical implications for marketers.
Metal–organic frameworks (MOFs), constructed from organic linkers and inorganic building blocks, are well-known for their high crystallinity, high surface areas, and high component tunability. The ...stability of MOFs is a key prerequisite for their potential practical applications in areas including storage, separation, catalysis, and biomedicine since it is essential to guarantee the framework integrity during utilization. However, MOFs are prone to destruction under external stimuli, considerably hampering their commercialization. In this Review, we provide an overview of the situations where MOFs undergo destruction due to external stimuli such as chemical, thermal, photolytic, radiolytic, electronic, and mechanical factors and offer guidelines to avoid unwanted degradation happened to the framework. Furthermore, we discuss possible destruction mechanisms and their varying derived products. In particular, we highlight cases that utilize MOF instability to fabricate varying materials including hierarchically porous MOFs, monolayer MOF nanosheets, amorphous MOF liquids and glasses, polymers, metal nanoparticles, metal carbide nanoparticles, and carbon materials. Finally, we provide a perspective on the utilization of MOF destruction to develop advanced materials with a superior hierarchy for various applications.
The application of neuroimaging methods to product marketing - neuromarketing - has recently gained considerable popularity. We propose that there are two main reasons for this trend. First, the ...possibility that neuroimaging will become cheaper and faster than other marketing methods; and second, the hope that neuroimaging will provide marketers with information that is not obtainable through conventional marketing methods. Although neuroimaging is unlikely to be cheaper than other tools in the near future, there is growing evidence that it may provide hidden information about the consumer experience. The most promising application of neuroimaging methods to marketing may come before a product is even released - when it is just an idea being developed.