Mechanism of the Nickel-Catalyzed Electrosynthesis of Ketones by Heterocoupling of Acyl and Benzyl Halides

Summary.  The mechanism of the nickel-catalyzed electrosynthesis of ketones by heterocoupling of phenacyl chloride and benzyl bromide has been investigated by fast scan rate cyclic voltammetry with [Ni(bpy)²⁺ ₃](BF₄ ⁻)₂ as the catalytic precursor (bpy = 2,2{−}{ bipyridine}). The key step is an oxidative addition of Ni⁰(bpy) (electrogenerated by reduction of the Ni(II) precursor) to PhCH₂Br whose rate constant is found to be 10 times higher than that of PhCH₂COCl. The complex PhCH₂Ni^IIBr(bpy) formed in the oxidative addition is reduced at the potential of the Ni^II/Ni⁰ reduction by a two-electron process which affords an anionic complex PhCH₂Ni⁰(bpy)⁻ able to react with PhCH₂COCl to generate eventually the homocoupling product PhCH₂COCH₂Ph. The formation of the homocoupling product PhCH₂COCOCH₂Ph is prevented because of the too slow oxidative addition of Ni⁰(bpy) to PhCH₂COCl compared to PhCH₂Br. The formation of the homocoupling product PhCH₂CH₂Ph is also prevented because PhCH₂Ni⁰(bpy)⁻ does not react with PhCH₂Br. This explains why the electrosynthesis of the ketone can be performed selectively in a one-pot procedure, starting from an equal mixture of PhCH₂COCl and PhCH₂Br and a nickel catalyst ligated by the bpy ligand. Received June 27, 2000. Accepted July 11, 2000     

Synthesis,Characterization and Antimicrobial Activity of Zinc Oxide Nanoparticles against Selected Waterborne Bacterial and Yeast Pathogens

The disinfection of wastewater using nanoparticles (NPs) has become a focal area of research in water treatment. In this study, zinc oxide (ZnO) NPs were synthesized using the microwave heating crystallization technique and characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). Qualitative well diffusion and quantitative minimum inhibitory concentration (MIC) tests were conducted to determine the antimicrobial activity of ZnO NPs against selected waterborne pathogenic microbes. FTIR spectral studies confirmed that the binding of urea with Zn occurs through Zn–O stretching. XRD confirmed the crystallized identity in a hexagonal ZnO wurtzite-type structure. The formation of zones of inhibition and low MIC values in the antimicrobial analysis were indicative of the effective antimicrobial activity of zinc oxide nanoparticles against the test microorganisms. The application of metallic nanoparticles in water treatment could curb the spread of waterborne microbial diseases.     

Rate and mechanism of the reaction of alkenes with aryl palladium complexes ligated by a bidentate P,P ligand in Heck reactions

The regioselectivity of the Heck reaction is supposed to be highly affected by the electronic properties of the alkene and the ionic or neutral character of the aryl palladium(II) complexes involved in the reaction with alkenes. In Heck reactions performed in dmf, [Pd(dppp){dppp(O)}Ph](+) (dppp=1,2-bis(diphenylphosphino)propane) is generated in the oxidative addition of PhI with [Pd(0)(dppp)(OAc)](-) formed in situ from Pd(OAc)(2) associated to two equivalents of dppp. [Pd(dppp){dppp(O)}Ph](+) is not very reactive with alkenes (styrene or methyl acrylate); however, it reacts with iodide ions (released in the catalytic reactions) to give [Pd(dppp)IPh] and with acetate ions (used as base) to give [Pd(dppp)(OAc)Ph]. [Pd(dppp)(OAc)Ph] reacts with styrene and methyl acrylate exclusively by an ionic mechanism, that is, via the cationic complex [Pd(dppp)(dmf)Ph](+) formed by dissociation of the acetate ion. The reaction of [Pd(dppp)IPh] is more complex and substrate dependent. It reacts with styrene exclusively by the ionic mechanism via [Pd(dppp)(dmf)Ph](+). [Pd(dppp)IPh] (neutral mechanism) and [Pd(dppp)(dmf)Ph](+) (ionic mechanism) react in parallel with methyl acrylate. [Pd(dppp)(dmf)Ph](+) is more reactive than [Pd(dppp)IPh] but is always generated at lower concentration.     

Three Roles for the Fluoride Ion in Palladium‐Catalyzed Hiyama Reactions: Transmetalation of [ArPdFL2] by Ar′Si(OR)3

From the kinetic data on the transmetalation/reductive elimination in fluoride‐promoted Hiyama reactions, obtained using electrochemical techniques, it has been established that fluoride ions play three roles. F^? reacts with trans‐[ArPdBrL₂] (L=PPh₃) to form trans‐[ArPdFL₂], which reacts with Ar′Si(OMe)₃ in the rate‐determining transmetalation, whereas trans‐[ArPdBrL₂] does not react with Ar′Si(OMe)₃. F^? reacts with Ar′Si(OMe)₃ to deliver the unreactive silicate Ar′SiF(OMe)₃^?, thus leading to two antagonistic kinetic effects. In addition, F^? catalyzes the reductive elimination from intermediate trans‐[ArPdAr′L₂].     

On the Triple Role of Fluoride Ions in Palladium‐Catalyzed Stille Reactions

The mechanism of Stille reactions (cross‐coupling of ArX with Ar′SnnBu₃) performed in the presence of fluoride ions is established. A triple role for fluoride ions is identified from kinetic data on the rate of the reactions of trans‐[ArPdBr(PPh₃)₂] (Ar=Ph, p‐(CN)C₆H₄) with Ar′SnBu₃ (Ar′=2‐thiophenyl) in the presence of fluoride ions. Fluoride ions promote the rate‐determining transmetallation by formation of trans‐[ArPdF(PPh₃)₂], which reacts with Ar′SnBu₃ (Ar′=Ph, 2‐thiophenyl) at room temperature, in contrast to trans‐[ArPdBr(PPh₃)₂], which is unreactive. However, the concentration ratio [F^?]/[Ar′SnBu₃] must not be too high, because of the formation of unreactive anionic stannate [Ar′Sn(F)Bu₃]^?. This rationalises the two kinetically antagonistic roles exerted by the fluoride ions that are observed experimentally, and is found to be in agreement with the kinetic law. In addition, fluoride ions promote reductive elimination from trans‐[ArPdAr′(PPh₃)₂] generated in the transmetallation step.     

Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus

There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that was previously demonstrated to be active against Influenza A virus, were evaluated against SARS-CoV-2. Intrinsic fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated naproxen binding to the nucleoprotein of SARS-Cov-2 as predicted by molecular modeling. Naproxen impeded recombinant N oligomerization and inhibited viral replication in infected cells. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen specifically inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2-induced damage. No inhibition of viral replication was observed with paracetamol or the COX-2 inhibitor celecoxib. Thus, among the NSAID tested, only naproxen combined antiviral and anti-inflammatory properties. Naproxen addition to the standard of care could be beneficial in a clinical setting, as tested in an ongoing clinical study.     

Muon level-crossing resonance in Si∶Al

A systematic investigation of five sherds from the Celtic oppidum of Manching by refiring in different atmospheres is presented. The data are part of an extended and general study of Celtic ceramics in early Europe.     

Mexoryr SX Protects Against Solar-Simulated UVR-lnduced Photocarcinogenesis in Mice

Abstract— The aim of this study was to determine, for regulatory purposes, the potential of MexoryP SX, a broad UVA absorber that also absorbs to some extent in the UVB, to modify the UV radiation (UVR)-induced murine skin tumor development and growth. Skh-hrl mice were exposed to solar-simulated UVR 5 days per week for 40 weeks. Two control groups were irradiated without topical application, three groups received a sunscreen preparation containing either the UVA absorber, MexoryP SX at 5 or 10% concentration, or a filter that absorbs principally in the UVB, 2-ethylhexyl-p-methoxycinna-mate (2-EHMC) at 5% concentration, introduced as a comparator test article. Sunscreen application was performed before UVR exposure 3 days per week and after UVR exposure on the other 2 days (consistent with the design of a standard photocarcinogenesis safety test). Two different weekly UVR doses were administrated: the lower dose was given to one group of unprotected animals, whereas the higher dose was administrated to the other unprotected group and to the three sunscreen-treated groups. The two UVR control groups demonstrated a UVR-dependent response for cumulative tumor prevalence, tumor yield and median latent period. Neither concentration of Mexoryl SX increased the probability of tumor development; consistent with the principles for safety testing, this provides evidence in that it is safe for use in sunlight. Although this study was explicitly designed as a safety test, the results also provide some clues about the efficacy of MexoryP SX in decreasing the probability of tumor development. Topical administration of Mexoryl* SX, at both concentrations, resulted in a 6 week delay in the median latent period compared to high UVR controls, whereas 5% 2-EHMC delayed the median latent periods only by 2 weeks. Tumor prevalence and yield show the same efficacy differences between the two sunscreen ingredients. Tumor protection factors were calculated from these results and found to be equal to 2.4 for the two preparations containing Mexoryl* SX and to 1.3 for the 5% 2-EHMC preparation.     

p53 Mutations in Hairless SKH-hr1 Mouse Skin Tumors Induced by a Solar Simulator

In this study, we investigated whether the spectrum of p53 mutations in skin tumors induced in hairless SKH-hr1 mice by a solar simulator (290–400 nm) are similar to those found in skin tumors induced in C3H mice by UV radiation from unfiltered (250–400 nm) and Kodacelfiltered (290–400 nm) FS40 sunlamps. Analysis of tumor DNA for p53 mutations revealed that 14 of 16 (87.5%) SkH-hr1 skin tumors induced by the solar simulator contained mutations. Single C → T transitions at dipyrimidine sequences located on the nontranscribed DNA strand were the most predominant type of p53 mutation. Remarkably, 52% of all p53 mutations in solar simulator-induced SKH-hr1 skin tumors occurred at codon 270, which is also a hotspot in C3H skin tumors induced by unfiltered and Kodacel-filtered FS40 sunlamps. However, T → G transversions, which are hallmarks of UVA-induced mutations, were not detected in any of the solar simulator-induced skin tumors analyzed. These results demonstrate that the p53 mutation spectra seen in solar simulator-induced SKH-hr1 skin tumors are similar to those present in unfiltered and Kodacel-filtered FS40 sunlamp-induced C3H skin tumors. In addition, our data indicate that the UVA present in solar simulator radiation does not play a role in the induction of p53 mutations that contribute to skin cancer development.