Kinetics of a dual nickel and iridium photocatalysed cross-coupling

Over the past decade, photoredox catalysis has developed into an important tool for synthetic chemists. Of particular importance has been the dual photoredox/nickel catalysis technique pioneered by the Doyle, MacMillan and Molander groups in 2014. While there has been much development of the synthetic applications of these techniques, in both industrial and academic settings, the mechanisms of this type of reaction remain poorly understood and few bulk-reaction kinetic studies have been conducted. This work takes the silane-mediated bromide-bromide sp2-sp3 cross-coupling developed by the MacMillan group in 2016 as a case study to probe the mechanism, both of this particular transformation and as representative of the class of reactions as a whole. In order to study this reaction, an in situ illumination 19F NMR spectroscopy (LED-NMR) apparatus was constructed in-house. Systematic variation of the reaction conditions allowed for the impact of each of the reaction components on the kinetics of the system to be observed. Four components (light, aryl bromide, nickel, and iridium photocatalyst) were found to control the rate of aryl bromide consumption, but not the product selectivity, while two components (silane and alkyl bromide), control the product selectivity, but not the rate. One particularly important outcome of this monitoring was the direct observation of a key aryl-Ni(II) intermediate that is the major resting state of the nickel catalyst throughout the cycle. Subsequent 13C isotope labelling studies demonstrated that this complex undergoes Ir-photocatalysed conversion to products in competition with degenerate release of aryl bromide. The experimental observations enabled development of a minimal kinetic model which allows simulation of the reaction evolution. This model provides useful insights for optimisation of these processes in the laboratory, as well as providing a framework for evaluating the validity of existing, and future, mechanistic proposals

Kinetics of a Ni/Ir-Photocatalyzed Coupling of ArBr with RBr: Intermediacy of ArNi^II(L)Br and Rate/Selectivity Factors

[Image: see text] The Ni/Ir-photocatalyzed coupling of an aryl bromide (ArBr) with an alkyl bromide (RBr) has been analyzed using in situ LED-(19)F NMR spectroscopy. Four components (light, [ArBr], [Ni], [Ir]) are found to control the rate of ArBr consumption, but not the product selectivity, while two components ([(TMS)(3)SiH], [RBr]) independently control the product selectivity, but not the rate. A major resting state of nickel has been identified as ArNi(II)(L)Br, and (13)C-isotopic entrainment is used to show that the complex undergoes Ir-photocatalyzed conversion to products (Ar-R, Ar-H, Ar-solvent) in competition with the release of ArBr. A range of competing absorption and quenching effects lead to complex correlations between the Ir and Ni catalyst loadings and the reaction rate. Differences in the Ir/Ni Beer–Lambert absorption profiles allow the rate to be increased by the use of a shorter-wavelength light source without compromising the selectivity. A minimal kinetic model for the process allows simulation of the reaction and provides insights for optimization of these processes in the laboratory

Reversibly tuning the viscosity of peptide-based solutions using visible light

Light can be used to design stimuli–responsive systems. We induce transient changes in the assembly of a low molecular weight gelator solution using a merocyanine photoacid. Through our approach, reversible viscosity changes can be achieved via irradiation, delivering systems where flow can be controlled non-invasively on demand

Effect of SARS-CoV-2 proteins on vascular permeability.

Severe acute respiratory syndrome (SARS)-CoV-2 infection leads to severe disease associated with cytokine storm, vascular dysfunction, coagulation, and progressive lung damage. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. Whereas most proteins induced significant changes in endothelial permeability, nsp2, nsp5_c145a (catalytic dead mutant of nsp5), and nsp7 also reduced CD31, and increased von Willebrand factor expression and IL-6, suggesting endothelial dysfunction. Using propagation-based analysis of a protein–protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects. We further applied our PPI model to identify the role of each SARS-CoV-2 protein in other tissues affected by coronavirus disease (COVID-19). While vali-dating the PPI network model, we found that the tight junction (TJ) proteins cadherin-5, ZO-1, and β-catenin are affected by nsp2, nsp5_c145a, and nsp7 consistent with the model prediction. Overall, this work identifies the SARS-CoV-2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID-1

The Fifth Dimension in Socio-Scientific Reasoning: Promoting Decision-Making about Socio-Scientific Issues in a Community

Making informed decisions about socio-scientific issues requires socio-scientific reasoning, which is highly challenging for students. This construct has four dimensions, including recognizing complexity, analyzing multiple perspectives, appreciating the need for ongoing inquiry, and employing skepticism. To support its development, we integrated established principles for designing socio-scientific issues learning environments with the Knowledge Community of Inquiry model. A design-based research study was conducted with two iterations, involving 85 eighth graders, to examine the effectiveness of the integrative approach in supporting students’ socio-scientific reasoning and decision-making. The web-based unit “Asthma in the Community” was adapted and enacted with the students. In the first iteration, the socio-scientific approach was applied, and in the second iteration, the unit was redesigned with features from the Knowledge Community of Inquiry approach. Results showed that all students who participated in the second iteration developed socio-scientific reasoning, made better evidence-based decisions than those in the first iteration, and expressed an understanding of decision-making processes in a community, which is suggested as new, fifth dimension of socio-scientific reasoning. This fifth dimension is suggested as essential for coping with decision-making in socio-scientific issues in the networked society, and the study suggests how to design learning environments that can support its development

Comment on "Network Motifs: Simple Building Blocks of Complex Networks" and "Superfamilies of Evolved and Designed Networks"

Comment on "Network Motifs: Simple Building Blocks of Complex Networks" and "Superfamilies of Evolved and Designed Networks" Motifs could just be a by-product of network generation without the need for functional selection (for GRNs evolutionary mechanisms like gene duplication etc.)