ResearchFlow: Understanding the Knowledge Flow between Academia and Industry

Understanding, monitoring, and predicting the flow of knowledge between academia and industry is of critical importance for a variety of stakeholders, including governments, funding bodies, researchers, investors, and companies. To this purpose, we introduce ResearchFlow, an approach that integrates semantic technologies and machine learning to quantifying the diachronic behaviour of research topics across academia and industry. ResearchFlow exploits the novel Academia/Industry DynAmics (AIDA) Knowledge Graph in order to characterize each topic according to the frequency in time of the related i) publications from academia, ii) publications from industry, iii) patents from academia, and iv) patents from industry. This representation is then used to produce several analytics regarding the academia/industry knowledge flow and to forecast the impact of research topics on industry. We applied ResearchFlow to a dataset of 3.5M papers and 2M patents in Computer Science and highlighted several interesting patterns. We found that 89.8% of the topics first emerge in academic publications, which typically precede industrial publications by about 5.6 years and industrial patents by about 6.6 years. However this does not mean that academia always dictates the research agenda. In fact, our analysis also shows that industrial trends tend to influence academia more than academic trends affect industry. We evaluated ResearchFlow on the task of forecasting the impact of research topics on the industrial sector and found that its granular characterization of topics improves significantly the performance with respect to alternative solutions

Enantioselective, intermolecular benzylic C–H amination catalysed by an engineered iron-haem enzyme

C–H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C–H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C–H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C–H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C–H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor

Metal-catalysed azidation of tertiary C–H bonds suitable for late-stage functionalization

Some enzymes are able to selectively oxidize unactivated aliphatic C-H bonds to form alcohols; however biological systems do not possess enzymes that are able to catalyze the analogous amination of a C-H bond.(1,2) The absence of such chemistry is limiting because nitrogen-containing groups are found in therapeutic agents and clinically useful natural products. In one prominent example, the conversion of the ketone of erythromycin to the –N(Me)CH(2)– group in azithromycin leads to a compound that can be dosed once daily with a shorter length of treatment.(3,4) For such reasons, synthetic chemists are very interested in identifying catalysts that can directly convert C-H bonds to C-N bonds. Most currently used catalysts for C-H bond amination are ill suited for the functionalization of complex molecules, because they require excess substrate or directing groups, harsh reaction conditions, weak or acidic C-H bonds, or reagents containing specialized groups on the nitrogen atom.(5-14) Among C-H bond amination reactions, those forming a carbon-nitrogen bond at a tertiary alkyl group would be particularly valuable, because this linkage is difficult to generate enzymatically from ketone or alcohol precursors.(15) In this manuscript, we report a mild, selective, iron-catalyzed azidation of tertiary C-H bonds with substrate as limiting reagent. The reaction tolerates aqueous environments and is suitable for “late-stage” functionalization of complex structures. Moreover, this azidation creates the ability to install a range of nitrogen functional groups, including those from bio-orthogonal Huisgen “click” cycloadditions and the Staudinger ligation.(16-19) For these reasons, we anticipate this methodology will create opportunities to easily modify natural products, their precursors, and their derivatives to analogs that contain distinct polarity and charge from nitrogen-containing groups. It could also be used to help identify targets of biologically active molecules by creating a point of attachment, for example to fluorescent tags or ‘handles’ for affinity chromatography, directly onto complex molecular structures

Dosage delivery of sensitive reagents enables glove-box-free synthesis

Contemporary organic chemists employ a broad range of catalytic and stoichiometric methods to construct molecules for applications in the material sciences, and as pharmaceuticals, agrochemicals, and sensors. The utility of a synthetic method may be greatly reduced if it relies on a glove box to enable the use of air- and moisture-sensitive reagents or catalysts. Furthermore, many synthetic chemistry laboratories have numerous containers of partially used reagents that have been spoiled by exposure to the ambient atmosphere. This is exceptionally wasteful from both an environmental and a cost perspective. Here we report an encapsulation method for stabilizing and storing air- and moisture-sensitive compounds. We demonstrate this approach in three contexts, by describing single-use capsules that contain all of the reagents (catalysts, ligands, and bases) necessary for the glove-box-free palladium-catalysed carbon-fluorine, carbon-nitrogen, and carbon-carbon bond-forming reactions. This strategy should reduce the number of error-prone, tedious and time-consuming weighing procedures required for such syntheses and should be applicable to a wide range of reagents, catalysts, and substrate combinations.National Science Foundation (U.S.) (Pre-doctoral fellowship (1122374))National Institutes of Health (U.S.) (Postdoctoral fellowship (1F32GM108092-01A1))National Institutes of Health (U.S.) (Award number R01GM46059