α-Bromoacetate as a Mild and Safe Brominating Agent in the Light-Driven Vicinal Dibromination of Unactivated Alkenes and Alkynes.

Light-induced vicinal dibromination of unactivated alkenes and alkynes has been demonstrated by using methyl α-bromoacetate as a mild brominating agent. A near-visible light (370 nm) light-emitting diode (LED) mediates this simple dibromination reaction under mild conditions with the inexpensive and nontoxic α-bromoacetate. The reaction proceeds well with both terminal and internal alkenes and alkynes and those contained in N/O-heterocycles, indicating its versatility in synthesizing dibrominated organic compounds.

Iron-Mediated Dialkylation of Alkenylarenes with Benzyl Bromides.

We disclose a method for the dibenzylation of alkenylarenes with benzyl bromides using iron powder. This reaction generates branched alkyl scaffolds adorned with functionalized aryl rings through the formation of two new C(sp3)-C(sp3) bonds at the vicinal carbons of alkenes. This protocol tolerates electron-rich, electron-neutral, and electron-poor benzyl bromides and alkenylarenes. Mechanistic studies suggest the formation of benzylic radical intermediates as a result of single-electron transfer from the iron, which is intercepted by alkenylarenes.

Ni-Catalyzed Linearizable Cyclization/Coupling with Detachable Silicon-Oxygen Linker: Access to 1,2-Oxasilolanes, 3-Hydroxysilanes and 4-Arylalkanols.

We disclose a Ni-catalyzed cyclization/alkylmetal interception reaction in which products are readily linearized to permit regiodefined alkene dicarbofunctionalization. This method offers a convenient route to access 1,2-oxasilolane heterocycles, 3-hydroxysilanes and 4-arylalkanols with the formation of C(sp3)-C(sp3) bonds at primary and secondary alkyl carbon centers. In this reaction, a silicon-oxygen (Si-O) bond functions as a detachable linker that can be delinked with several hydride, alkyl, aryl and vinyl nucleophiles to create profusely functionalized 3-hydroxysilanes. A silicon motif in the cyclic C(sp3)-Si-O construct in 1,2-oxasilolane heterocycles can also be selectively deleted by Pd-catalyzed hydrodesilylation affording Si-ablated linear alcohol products reminiscent of vicinal ethylene dicarbofunctionalization with C(sp3) and C(sp2) carbon sources.

Photosensitized O2 enables intermolecular alkene cyclopropanation by active methylene compounds.

Cyclopropanes are key features in many preclinical, clinical, and commercial drugs, as well as natural products. The most prolific technique for their synthesis is the metal-catalyzed reaction of an alkene with a diazoalkane, a highly energetic reagent requiring stringent safety precautions. Discovery of alternative innocuous reagents remains an ongoing challenge. Herein, we report a simple photoredox-catalyzed intermolecular cyclopropanation of unactivated alkenes with active methylene compounds. The reaction proceeds in neutral solvent under air or dioxygen (O2) with a photoredox catalyst excited by blue light-emitting diode light and an iodine co-catalyst that is either added as molecular iodine or generated in situ from alkyl iodides. Mechanistic investigations indicate that photosensitized O2 plays a vital role in the generation of carbon-centered radicals for both the addition of active methylene compounds to alkenes and the ring closure.

Nickel-Catalyzed Alkene Difunctionalization as a Method for Polymerization.

Alkene dicarbofunctionalization is a rapidly emerging tool for complex molecule synthesis that installs two carbon fragments regioselectively across an alkene. This method has the potential to engineer stereodefined polymers, yet the application of difunctionalization reactions to polymer synthesis remains unexplored. Herein, we describe the first example of a Ni-catalyzed difunctionalization of alkenes with arylboronic esters and aryl bromides innate to the alkene. The polymerization reaction proceeds regioselectively with the addition of the aryl bromide to the terminal alkenyl carbon and arylboronic ester to the internal benzylic carbon. The resultant poly[arylene-α-(aryl)ethylene]s comprise aryl groups installed at regular intervals along the polymer backbone through chain propagation in two directions. Polymers with molecular weights generally ranging from 30 to 175 kDa were obtained after successful fractionation from oligomeric species. Thermal analysis of the poly[arylene α-(aryl)ethylene]s revealed stability up to ∼399 °C, with a Tg of 90 °C, both of which are similar in value to poly(styrene)s and poly(phenylene methylene)s.

Nickel-Catalyzed Regioselective Intermolecular Dialkylation of Alkenylarenes: Generation of Two Vicinal C(sp3 )-C(sp3 ) Bonds Across Alkenes.

We disclose a Ni-catalyzed regioselective dialkylation reaction of alkenylarenes with α-halocarbonyls and alkylzinc reagents. The reaction produces γ-arylated alkanecarbonyl compounds with the generation of two new C(sp3 )-C(sp3 ) bonds at the vicinal carbons of alkenes. This reaction is effective for the use of primary, secondary and tertiary α-halocarboxylic esters, amides and ketones in conjunction with primary and secondary alkylzinc reagents as the sources of two C(sp3 ) carbons for the dialkylation of terminal and cyclic internal alkenes.

Pd-Catalyzed 1,3-Alkenylarylation of Skipped Diene via Metal Migration.

We disclose a palladium-catalyzed difunctionalization of skipped diene with alkenyl triflates and arylboronic acids to produce 1,3-alkenylarylated products. The reaction proceeded efficiently with Pd(acac)2 as a catalyst and CsF as a base for a wide range of electron-deficient and electron-rich arylboronic acids as well as oxygen-heterocyclic, sterically hindered, and complex natural product-derived alkenyl triflates bearing various functional groups. The reaction produced 3-aryl-5-alkenylcyclohexene derivatives with 1,3-syn-disubstituted stereochemistry.

The color of aerosol particles.

Digital in-line holography (DIH) is an established method to image small particles in a manner where image reconstruction is performed computationally post-measurement. This ability renders it ideal for aerosol characterization, where particle collection or confinement is often difficult, if not impossible. Conventional DIH provides a gray-scale image akin to a particle's silhouette, and while it gives the particle size and shape, there is little information about the particle material. Based on the recognition that the spectral reflectance of a surface is partly determined by the material, we demonstrate a method to image free-flowing particles with DIH in color with the eventual aim to differentiate materials based on the observed color. Holograms formed by the weak backscattered light from individual particles illuminated by red, green, and blue lasers are recorded by a color sensor. Images are reconstructed from the holograms and then layered to form a color image, the color content of which is quantified by chromaticity analysis to establish a representative signature. A variety of mineral dust aerosols are studied where the different signatures suggest the possibility to differentiate particle material. The ability of the method to resolve the inhomogeneous composition within a single particle in some cases is shown as well.

Ni-Catalyzed Regioselective Reductive 1,3-Dialkenylation of Alkenes.

Dicarbofunctionalization is an important efficient synthetic technique for adding two chemical moieties across an alkene. Here, a novel method of reductive dicarbofunctionalization has been developed using a single alkenyl triflate as the electrophile, combined with an unactivated alkene. The reaction does not require an external auxiliary and proceeds with complete regioselectivity.

Cu-Catalyzed Cyclization/Coupling of Alkenyl Aldimines with Arylzinc Reagents: Access to Indole-3-diarylmethanes.

We report a Cu(II)-catalyzed cyclization/coupling of alkenyl aldimines with arylzinc reagents to create indole-3-diarylmethane derivatives (Sapkota et al. ChemRxiv 2022, DOI: 10.26434/chemrxiv-2022-d6qn). The current reaction provides a unified modular route from readily available starting materials to indole-3-diarylmethanes in which all three arene cores can be decorated with differential functional substitutions on demand. Since the cyclization/coupling of alkenyl aldimines is unknown to date, the current method widens the scope with regard to both the substrate and product diversity for this class of reaction.

Utility of plasma NGAL for the diagnosis of AKI following cardiac surgery requiring cardiopulmonary bypass: a systematic review and meta-analysis.

The objective of this study was to assess the diagnostic value of plasma neutrophil gelatinase-associated lipocalin (pNGAL) for the early diagnosis of acute kidney injury (AKI) in adult patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Electronic databases and other resources were systematically searched for relevant studies. Risk of bias was assessed using the Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Studies were assigned to a sub-group based on the timing of the pNGAL sample in relation to the cessation of CPB. These were < 4 h, 4-8 h, 12 h or 24 h post-cessation of CPB. Summary values for sensitivity and specificity were estimated using the hierarchical summary receiver operator characteristic (ROC) curve model. A random-effects meta-analysis of each pair of sensitivity and specificity estimates from each included study was performed. In total, 3131 patients from 16 studies were included. When taken at 4-8 h following CPB, pNGAL had superior performance for the diagnosis of AKI in the defined population when compared to earlier and later time points. Prediction regions and confidence intervals, however, demonstrated significant variability in pooled estimates of sensitivity and specificity. This is likely due to population and study design heterogeneity, lack of standardisation of assays and thresholds, and inability to distinguish the different molecular forms of NGAL. In conclusion, the diagnostic utility of pNGAL in this clinical setting is inconclusive and large individual studies of representative populations of cardiac surgery patients using assays that specifically detect NGAL in its monomeric form are required.

C-H Bond Functionalization under Electrochemical Flow Conditions.

Electrochemical C-H functionalization is a rapidly growing area of interest in organic synthesis. To achieve maximum atom economy, the flow electrolysis process is more sustainable. This allows shorter reaction times, safer working environments, and better selectivities. Using this technology, the problem of overoxidation can be reduced and less emergence of side products or no side products are possible. Flow electro-reactors provide high surface-to-volume ratios and contain electrodes that are closely spaced where the diffusion layers overlap to give the desired product, electrochemical processes can now be managed without the need for a deliberately added supporting electrolyte. Considering the importance of flow electrochemical C-H functionalization, a comprehensive review is presented. Herein, we summarize flow electrolysis for the construction of C-C and C-X (X=O, N, S, and I) bonds formation. Also, benzylic oxidation and access to biologically active molecules are discussed.

Backscatter multiple wavelength digital holography for color micro-particle imaging.

This work applies digital holography to image stationary micro-particles in color. The approach involves a Michelson interferometer to mix reference light with the weak intensity light backscattered from a distribution of particles. To enable color images, three wavelengths are used, 430, 532, and 633 nm, as primary light sources. Three separate backscattered holograms are recorded simultaneously, one for each wavelength, which are resolved without spectral cross talk using a three-CMOS prism sensor. Fresnel diffraction theory is used to render monochrome images from each hologram. The images are then combined via additive color mixing with red, green, and blue as the primary colors. The result is a color image similar in appearance to that obtained with a conventional microscope in white-light epi-illumination mode. A variety of colored polyethylene micro-spheres and nonspherical dust particles demonstrate the feasibility of the approach and illustrate the effect of simple speckle-noise suppression and white balance methods. Finally, a chromaticity analysis is applied that is capable of differentiating particles of different colors in a quantitative and objective manner.

Comparative Evaluation of Two NGAL Automated Immunoassays in Urine and Plasma.

BACKGROUND: Acute kidney injury (AKI), a frequent and serious complication of hospitalized patients, is associated with increased mortality and morbidity. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early identification of AKI. We report a comparative laboratory verification of the Abbott Diagnostics (ARCHITECT® urine NGAL) and BioPorto Diagnostics (NGAL TestTM) assays including an assessment of the Abbott assay's performance in EDTA plasma. METHODS: Intra-/interbatch imprecision, linearity, recovery, and limit of quantitation (LoQ) were assessed and an interassay comparison performed (n = 51). Between-laboratory agreement was assessed against other laboratories using the Abbott (n = 48) and BioPorto (n = 94) assays. Plasma NGAL (pNGAL) levels were measured in non-AKI patients with a range of estimated glomerular filtration rates (n = 80). RESULTS: Coefficients of variation (CVs) for intra- and interbatch imprecision were 0.7%-12.4% and 1.9%-27.5% for the BioPorto assay, respectively, and 1.4%-6.3%/3.4%-6.8%, respectively, for the Abbott assay. The BioPorto assay exhibited a higher LoQ (27.5 ng/mL vs 1.2 ng/mL). Both assays were linear over the range 5-6000 ng/mL. Recovery of recombinant NGAL was 113.1 ± 7.1% and 96.5 ± 7.8% for the Abbott and BioPorto assays, respectively. On average, the Abbott assay gave results 9.2% lower than the BioPorto assay. Mean differences of 0.2% (Abbott) and 20.2% (BioPorto) were observed in the between-laboratory comparison. In patients without AKI, pNGAL levels were inversely proportional to eGFR. CONCLUSIONS: Performance of the Abbott and BioPorto assays was similar although the latter performed less well at lower NGAL concentrations. The Abbott assay tended to yield lower results, exhibited a lower LoQ and over-recovered NGAL. Although only Conformité Européenne-marked and marketed for use in urine, the Abbott assay demonstrated equivalent performance to the BioPorto assay with EDTA plasma.

Ni-Catalyzed Regio- and Stereoselective Alkylarylation of Unactivated Alkenes in γ,δ-Alkenylketimines.

We disclose a Ni-catalyzed vicinal alkylarylation of unactivated alkenes in γ,δ-alkenylketimines with aryl halides and alkylzinc reagents. The reaction produces γ-C(sp3)-branched δ-arylketones with the construction of two new C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. Electron-deficient alkenes play crucial dual roles as ligands to stabilize reaction intermediates and to increase catalytic rates for the formation of C(sp3)-C(sp3) bonds. This alkene alkylarylation reaction is also effective for secondary alkylzinc reagents and internal alkenes, and proceeds with a complete regio- and stereocontrol, affording products with up to three contiguous all-carbon all-cis secondary stereocenters.

Balanced forced-diuresis as a renal protective approach in cardiac surgery: Secondary outcomes of electrolyte changes.

OBJECTIVES: Forced-diuresis during cardiopulmonary bypass (CPB) can be associated with significant electrolyte shifts. This study reports on the serum electrolyte changes during balanced forced-diuresis with the RenalGuard® system (RG) during CPB. METHODS: Patients at risk of acute kidney injury (AKI)-(history of diabetes &/or anaemia, e-GFR 20-60 ml/min/1.73 m2 , anticipated CPB time >120 min, Log EuroScore >5)-were randomized to either RG (study group) or managed as per current practice (control group). RESULTS: The use of RG reduced AKI rate (10% for RG and 20.9% in control, p = .03). Mean urine output was significantly higher in the RG group during surgery (2366 ± 877 ml vs. 765 ± 549 ml, p < .001). The serum potassium levels were maintained between 3.96 and 4.97 mmol/L for the RG group and 4.02 and 5.23 mmol/L for the controls. Median potassium supplemental dose was 60 (0-220) mmol (RG group) as compared to 30 (0-190) mmol for control group over first 24 h (p < .001). On Day 1 post-op, there were no significant differences in the serum sodium, potassium, calcium, magnesium, phosphate, and chloride levels between the two groups. Otherwise, postoperative clinical recovery was also similar. CONCLUSIONS: Balanced forced-diuresis with the RG reduced AKI rates after on-pump cardiac surgery compared to controls. Although the RG group required higher doses of IV potassium replacement in the postoperative period, normal serum levels of potassium were maintained by appropriate intravenous potassium supplementation and the clinical outcomes between groups were similar.

Transition Metal (Ni, Cu, Pd)-Catalyzed Alkene Dicarbofunctionalization Reactions.

Recently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of alkene difunctionalization with two carbon sources, emerged as a formidable reaction with immense promise to synthesize complex molecules expeditiously from simple chemicals. This reaction is generally achieved with transition metals (TMs) through interception by carbon sources of an alkylmetal [ß-H-C(sp3)-[M]] species, a key intermediate prone to undergo rapid ß-H elimination. Related prior reports, since Paolo Chiusoli and Catellani's work in 1982 [ Tetrahedron Lett. 1982, 23, 4517], have used bicyclic and disubstituted terminal alkenes, wherein ß-H elimination is avoided by geometric restriction or complete lack of ß-H's. With reasoning that ß-H-C(sp3)-[M] intermediates could be rendered amenable to interception with the use of first row late TMs and formation of coordination-assisted transient metallacycles, these two strategies were implemented to address the ß-H elimination problem in alkene dicarbofunctionalization reactions.Because first row late TMs catalyze C(sp3)-C(sp3) coupling, Cu and Ni were anticipated to impart sufficient stability to ß-H-C(sp3)-[M] intermediates, generated catalytically upon alkene carbometalation, for their subsequent interception by carbon electrophiles/nucleophiles in three-component reactions. Additionally, such an innate property could enable alkene difunctionalization with carbon coupling partners through entropically driven cyclization/coupling reactions. The cyclometalation concept to stabilize intractable ß-H-C(sp3)-[M] intermediates was hypothesized when three-component reactions were performed. The idea of cyclometalation to curtail ß-H elimination is founded upon Whitesides's [ J. Am. Chem. Soc. 1976, 98, 6521] observation that metallacycles undergo ß-H elimination much slower than acyclic alkylmetals.In this Account, examples of alkene dicarbofunctionalization reactions demonstrate that Cu and Ni catalysts could enable cyclization/coupling of alkenylzinc reagents, alkyl halides, and aryl halides to afford complex carbo- and heterocycles. In addition, forming coordination-assisted transient nickellacycles enabled regioselective performance of three-component dicarbofunctionalization of various alkenyl compounds. In situ reaction of [M]-H with alkenes generated after ß-H elimination induced an unprecedented metallacycle contraction process, in which six-membered metal-containing rings shrank to five-membered cycles, allowing creation of new carbon-carbon bonds at allylic (1,3) positions. Applications of these regioselective alkene dicarbofunctionalization reactions are discussed.

Ni-Catalyzed Arylbenzylation of Alkenylarenes: Kinetic Studies Reveal Autocatalysis by ZnX2 *.

We report a Ni-catalyzed regioselective arylbenzylation of alkenylarenes with benzyl halides and arylzinc reagents. The reaction furnishes differently substituted 1,1,3-triarylpropyl structures that are reminiscent of the cores of oligoresveratrol natural products. The reaction is also compatible for the coupling of internal alkenes, secondary benzyl halides and variously substituted arylzinc reagents. Kinetic studies reveal that the reaction proceeds with a rate-limiting single-electron-transfer process and is autocatalyzed by in-situ-generated ZnX2 . The reaction rate is amplified by a factor of three through autocatalysis upon addition of ZnX2 .

Balanced forced-diuresis compared to control as a reno-protective approach in cardiac surgery: secondary outcome of a randomized controlled trial, assessment of neutrophil gelatinase-associated lipocalin levels.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20-60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points. RESULTS: Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14-4.27, p = 0.02). CONCLUSIONS: Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946 .