The reaction of vinylazides with alkenyldiazo compounds in the presence of Cu(CH3CN)4BF4 provided cyclopentene derivatives with retention of the azide functionality. This process likely involves a ...sequence comprising: 1) decomposition of the diazo component with generation of a copper alkenylcarbene species; 2) stepwise regioselective 3+2 cycloaddition; 3) allylic azide rearrangement. This method is compatible with a broad range of substrates. We also show that the azide‐containing cycloadducts can be efficiently converted into the corresponding amine and triazole derivatives.
2×(vinyl)=3+2: A copper‐promoted reaction of vinylazides and vinyldiazo compounds provides a convenient route to azide‐containing cyclopent‐1‐ene‐carboxylic acid derivatives. This transformation likely involves the initial generation of a copper alkenylcarbene species, which then undergoes a 3+2 cycloaddition/allylic azide rearrangement sequence. Further elaboration of the azide functional group allows the synthesis of new nitrogen‐containing carbocycles.
•Immunogenicity of infliximab and adalimumab is a problem causing loss of response.•Monitoring of anti-drug antibodies is recommended in clinical guidelines.•Quantitative point-of-care tests for ...anti-drug antibodies determination are being developed.•We performed the first comparison between a quantitative rapid method and ELISA kits.•Different clinical decisions could be chosen depending on the method used.
Adalimumab (ADL), infliximab (IFX) and their biosimilars are widely used biological drugs. Some patients, however, generate neutralizing antibodies that hamper the effectiveness of these drugs. Evidence shows therapeutic drug monitoring of serum levels ADL/IFX and anti-drug antibodies (ADA) is useful to improve treatment effectiveness. We evaluated a new rapid quantitative method, Quantum Blue (QB), for determining serum anti-ADL and anti-IFX antibodies (Research Use Only labelling) by comparing it with two established ELISA kits, Promonitor (PM) and Lisa-Tracker (LT).
Eighty samples (40 for each drug type) were analysed. Percentage of agreement and kappa statistic were used to compare positive/negative ADA results. Clinical implications for drug treatment in the patients with discordant results were evaluated. The Chi-square test was used to analyze differences for ADA detection in patients with disease flare and without concomitant immunosuppressant treatment.
Agreement exceeded 80 % among anti-ADL methods. Although LT ELISA showed a lower capacity in detecting anti-ADL antibodies, discrepancies were found for levels close to the cut-off concentration, thus having minimal impact on clinical decisions. Conversely, QB anti-IFX displayed low agreement with PM and LT ELISA kits (67.5 % and 50 %, respectively), and was unable to detect high levels of antibodies, therefore having major clinical implications. Agreement between PM and LT ELISA anti-IFX kits was 82.5 % with all discordant results being undetected for PM and slightly positive for LT.
QB anti-ADL shows similar performance to ELISA kits while QB anti-IFX needs further improvements to achieve reliable antibody detection.
In plant cells, as in most eukaryotic organisms, peroxisomes are probably the major sites of intracellular H
O
production, as a result of their essentially oxidative type of metabolism. In recent ...years, it has become increasingly clear that peroxisomes carry out essential functions in eukaryotic cells. The generation of the important messenger molecule hydrogen peroxide (H
O
) by animal and plant peroxisomes and the presence of catalase in these organelles has been known for many years, but the generation of superoxide radicals (O
) and the occurrence of the metalloenzyme superoxide dismutase was reported for the first time in peroxisomes from plant origin. Further research showed the presence in plant peroxisomes of a complex battery of antioxidant systems apart from catalase. The evidence available of reactive oxygen species (ROS) production in peroxisomes is presented, and the different antioxidant systems characterized in these organelles and their possible functions are described. Peroxisomes appear to have a ROS-mediated role in abiotic stress situations induced by the heavy metal cadmium (Cd) and the xenobiotic 2,4-D, and also in the oxidative reactions of leaf senescence. The toxicity of Cd and 2,4-D has an effect on the ROS metabolism and speed of movement (dynamics) of peroxisomes. The regulation of ROS production in peroxisomes can take place by post-translational modifications of those proteins involved in their production and/or scavenging. In recent years, different studies have been carried out on the proteome of ROS metabolism in peroxisomes. Diverse evidence obtained indicates that peroxisomes are an important cellular source of different signaling molecules, including ROS, involved in distinct processes of high physiological importance, and might play an important role in the maintenance of cellular redox homeostasis.
Ba'zinc'ga! A zinc‐catalyzed sequence involving a cyclization with a subsequent CO, CN, or CC bond formation enables the preparation of a variety of valuable furfuryl ethers (with alcohols) and ...unsymmetrically substituted triarylmethane derivatives (with azoles or arenes). ZnCl2 serves as the catalyst.
The reaction of nitriles with alkenyldiazo compounds in the presence of gold catalysts provides functionalized pyrrole derivatives in moderate to high yields. This formal 3+2 cyclization reaction ...takes place with complete regioselectivity. The observed regiochemical outcome suggests the attack of the nitrile to the terminal position of the alkenylgold carbenoid (vinylogous reactivity). A broad range of nitriles (including those bearing functional groups) is compatible with this cyclization reaction.
Allylsilanes have long been recognized as valuable building blocks for organic synthesis. A zinc‐catalyzed reaction of cyclopropenes and hydrosilanes provides a convenient route to these versatile ...unsaturated organosilanes. In this transformation, ZnBr2 serves as an efficient catalyst, allowing the generation of a zinc vinyl carbenoid intermediate, which is subsequently involved in a Si−H bond insertion. The process shows broad scope, and is amenable to substituted and functionalized cyclopropenes or the functionalization of polysiloxanes. Moreover, zinc‐catalyzed carbene insertion into a Ge−H bond is reported for the first time.
Unsaturated organosilanes: Allylsilanes were produced by regioselective and atom‐economical zinc‐catalyzed reactions of cyclopropene and hydrosilane molecules. Insertion of a zinc vinyl carbenoid species into the Si−H bond is posited. The method extends to germanium analogues and an array of cyclopropene and oligomeric siloxanes.
The awake prone positioning strategy for patients with acute respiratory distress syndrome is a safe, simple and cost-effective technique used to improve hypoxaemia. We aimed to evaluate intubation ...and mortality risk in patients with coronavirus disease 2019 (COVID-19) who underwent awake prone positioning during hospitalisation.
In this retrospective, multicentre observational study conducted between 1 May 2020 and 12 June 2020 in 27 hospitals in Mexico and Ecuador, nonintubated patients with COVID-19 managed with awake prone or awake supine positioning were included to evaluate intubation and mortality risk through logistic regression models; multivariable and centre adjustment, propensity score analyses, and E-values were calculated to limit confounding.
827 nonintubated patients with COVID-19 in the awake prone (n=505) and awake supine (n=322) groups were included for analysis. Fewer patients in the awake prone group required endotracheal intubation (23.6%
40.4%) or died (19.8%
37.3%). Awake prone positioning was a protective factor for intubation even after multivariable adjustment (OR 0.35, 95% CI 0.24-0.52; p<0.0001, E=2.12), which prevailed after propensity score analysis (OR 0.41, 95% CI 0.27-0.62; p<0.0001, E=1.86) and mortality (adjusted OR 0.38, 95% CI 0.26-0.55; p<0.0001, E=2.03). The main variables associated with intubation among awake prone patients were increasing age, lower baseline peripheral arterial oxygen saturation/inspiratory oxygen fraction ratio (
/
) and management with a nonrebreather mask.
Awake prone positioning in hospitalised nonintubated patients with COVID-19 is associated with a lower risk of intubation and mortality.
The synthesis of uncommon bifunctional allylic derivatives bearing a silane and an alcohol within the same allylic framework is reported. This method relies on the coupling of hydrosilanes with ...substituted and functionalized cyclopropenes, which deliver the allyl fragment. Rhodium(II) catalysts provide regioselective access to vinyl carbene intermediates, which easily undergo Si−H bond insertions. The transformation occurs with complete atom economy and shows a remarkably broad scope, including a intramolecular version for the synthesis of cyclic O−Si‐linked compounds as well as the synthesis of the corresponding allyl amines.
Synthesis of uncommon bifunctional allylic derivatives bearing a silane and an alcohol within the same allylic system is reported. The method relies on the use of hydrosilanes and adequately functionalized cyclopropenes, which deliver the allyl fragment via regioselective generation of a RhII vinyl carbene intermediate. The method shows a remarkably broad scope, including an intramolecular version for the synthesis of cyclic siloxanes or extension to allylic amines.
The zinc‐catalyzed reaction of cyclopropenes with alkenes leading to vinylcyclopropane derivatives is reported. A broad range of alkenes (including highly substituted or functionalized alkenes) is ...compatible with this protocol. On the basis of trapping experiments and computational studies, this cyclopropanation reaction is proposed to proceed through initial formation of an electrophilic zinc vinyl carbenoid intermediate, which may be involved in a concerted cyclopropanation reaction. The reported protocol represents an unprecedented and simple strategy for the catalytic generation of zinc vinyl carbenoids, which are promising intermediates in organic synthesis.
Open and close! The title reaction provides a convenient and general route to relevant vinylcyclopropane derivatives. Mechanistic studies support the participation of a zinc vinylcarbene intermediate, which may be subsequently involved in a concerted cyclopropanation reaction. This method represents a step towards identifying suitable precursors for the catalytic generation of zinc carbenoids.
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