Asymmetric hetero Diels-Alder as an access to carbacephams.

A short and efficient asymmetric synthesis of the (6R,7S)-7-tert-butoxycarbonylamino-2-ketocarbacepham is described. The key step involves the hetero Diels-Alder reaction of the benzylimine derived from the enantiomer of Garner's aldehyde with Danishefsky's diene.     

Fluorimetric determination of the fungicide benomyl after solvolysis

A simple spectrofluorimetric method for the determination of the fungicide benomyl in grapes is described. Benomyl is rapidly solvolysed in organic solvents to give the highly fluorescent metabolite carbendazim. Solvent effects on the spectral shape and their influence on analytical performance are studied. DMF was found to be the best solvent. The method is sensitive to 12 ng/ml benomyl, and has an RSD at the 0.5 g/ml level of 2.2%. The method is suitable for determining benomyl in spiked grapes, with recoveries in the range 97 to 104%.     

Indirect spectrophotometric determination of cyanide

A spectrophotometric method for cyanide based on its inhibition of the colour formation reaction between nickel(II) and 3-(4,5-dimethyl-2-thiazolylazo)-2,6-dihydroxybenzoic acid has been developed, and allows the determination of down to 0.1 g of cyanide. Most of the interferences can be avoided by displacement of the hydrogen cyanide using an arsine generator.     

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT in vitro. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).     

Ambiphilic boryl groups in a neutral Ni(ii) complex: a new activation mode of H2

The concept of metal–ligand cooperation opens new avenues for the design of catalytic systems that may offer alternative reactivity patterns to the existing ones. Investigations of this concept with ligands bearing a boron center in their skeleton established mechanistic pathways for the activation of small molecules in which the boron atom usually performs as an electrophile. Here, we show how this electrophilic behavior can be modified by the ligand trans to the boron center, evincing its ambiphilic nature. Treatment of diphosphinoboryl (PBP) nickel–methyl complex 1 with bis(catecholato)diboron (B₂Cat₂) allows for the synthesis of nickel(ii) bis-boryl complex 3 that promotes the clean and reversible heterolytic cleavage of dihydrogen leading to the formation of dihydroborate nickel complex 4. Density functional theory analysis of this reaction revealed that the heterolytic activation of H₂ is facilitated by the cooperation of both boryl moieties and the metal atom in a concerted mechanism that involves a Ni(ii)/Ni(0)/Ni(ii) process. Contrary to 1, the boron atom from the PBP ligand in 3 behaves as a nucleophile, accepting a formally protic hydrogen, whereas the catecholboryl moiety acts as an electrophile, receiving the attack from the hydride-like fragment. This manifests the dramatic change in the electronic properties of a ligand by tuning the substituent trans to it and constitutes an unprecedented cooperative mechanism that involves two boryl ligands in the same molecule operating differently, one as a Lewis acid and the other one as a Lewis base, in cooperation with the metal. In addition, reactivity towards different nucleophiles such as amines or ammonia confirmed the electrophilic nature of the Bcat moiety, allowing the formation of aminoboranes.

A bis(boryl)nickel complex promotes the facile and reversible activation of H₂ through a cooperative mechanism that involves the metal and both boryl moieties in a concerted five-center process.     

Reactivity of 2-deoxy-2-iodoglycosyl isothiocyanates with O-, S-, and N-nucleophiles. Synthesis of glycopyranoso-fused thiazoles

The reactivity of 2-deoxy-2-iodoglycosyl isothiocyanates toward O- and S-nucleophiles gives an easy access to 2-deoxy-2-iodoglycopyranosyl thiocarbamates and dithiocarbamates. Internal nucleophilic displacement of the iodine by the sulfur atom in these compounds allows the preparation of glycopyranoso[1,2-d]-1,3-thiazoles and glycopyranoso[1,2-d]-1,3-thiazolidin-2-one or -2-thione. Reaction with amines or polyamines as N-nucleophiles led directly to 2-aminoglycopyranoso[1,2-d]-1,3-thiazoles without isolation of the intermediate thioureas. Methyl 2-deoxy-2-iodoglycopyranosyl thiocarbamates also allow the synthesis of 2-deoxyglycopyranosyl thiocarbamates or 2-deoxy-2-iodoglycopyranosyl carbamates.     

Electrochemical reaction of lithium with nanosized vanadium antimonate

Nanometric vanadium antimonate, VSbO₄, was prepared by mechanical milling from Sb₂O₃ and V₂O₅ and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Mossbaüer spectroscopy (MS) and X-ray photoelectron spectroscopy (XPS) techniques. Its reactivity towards lithium was examined by testing Li/VSbO₄ cells under galvanostatic and potentiostatic regimes. The amount of Li inserted was found to be consistent with a two-step process involving the reactions (i) VSbO₄+8 Li→Sb+V+4 Li₂O and (ii) Sb+3 Li→Li₃Sb, the former being virtually irreversible and the latter reversible as suggested by the shape of the anodic and cathodic curves. Ex situ XPS measurements of the discharged and charged electrode provided direct evidence of the formation of alloyed Sb and confirmed the results of the potentiostatic curves regarding the irreversible or reversible character of the previous reactions. The Li/VSbO₄ cell exhibited acceptable electrochemical performance, which surpassed that of other Sb-based compounds as the likely result of the formation of V and its associated enhanced electrode conductivity.     

Determination of volatile corrosion inhibitors by capillary electrophoresis

In this work, a capillary electrophoresis (CE) method using indirect UV detection (214nm) for the simultaneous determination of monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), diethylethanolamine (DEEA), monocyclohexylamine (MCHA) and dicyclohexylamine (DCHA) in water/ethanol extracts of wrapping materials containing volatile corrosion inhibitors (VCIs) was described. A running buffer consisting of 0.010 molL(-1) imidazole, 0.010 molL(-1) 2-hydroxyisobutyric acid (HIBA) and 0.010 molL(-1) 18-crown-6 ether enabled separation of the analytes in less than 7 min. A few method validation parameters were determined revealing good migration time repeatability (<0.7% RSD) and area repeatability (< 1.8% RSD). Limits of detection were in the range of 0.52-1.54 mg L(-1). Recovery values were in the range of 94.8-100.9%. The methodology was successfully applied to the analysis of three commercial products (VCI treated paper, foam and plastic). The concentration of amines in these materials varied from 0.050 to 22.3% (w/w).     

Highly stereoselective syntheses of syn- and anti-1,2-amino alcohols

The reduction of N-protected amino ketones can be carried stereoselectively to produce either the syn- or anti-amino alcohol diastereomer. Carbamate-protected amino ketones can be reduced predictably and selectively to anti-amino alcohols with LiAlH(O-t-Bu)3 in ethanol at -78 degrees C. N-Trityl-protected amino ketones can be reduced selectively to syn-amino alcohols with LiAlH(O-t-Bu)3 in THF at -5 degrees C.