A novel approach toward the synthesis of strigolactones through intramolecular [2+2] cycloaddition of ketenes and ketene-iminiums to olefins. Application to the asymmetric synthesis of GR-24

An intramolecular [2+2] cycloaddition of ketenes and ketene-iminium was developed for the preparation of GR-24, a synthetic analogue of the family of strigolactone plant hormones. Excellent levels of regioselectivity and of chiral induction were obtained using a bulky chiral amine for the formation of the cyclobutanone and a subsequent regioselective Baeyer-Villiger afforded the tricyclic lactone core of (+)-GR-24.     

Gold(I)/Gold(III) Catalysis that Merges Oxidative Addition and π‐Alkene Activation

Heteroarylation of alkenes with aryl iodides was efficiently achieved with a (MeDalphos)AuCl complex through Au^I/Au^III catalysis. The possibility to combine oxidative addition of aryl iodides and π‐activation of alkenes at gold is demonstrated for the first time. The reaction is robust and general (>30 examples including internal alkenes, 5‐, 6‐, and 7‐membered rings). It is regioselective and leads exclusively to trans addition products. The (P,N) gold complex is most efficient with electron‐rich aryl substrates, which are troublesome with alternative photoredox/oxidative approaches. In addition, it provides a very unusual switch in regioselectivity from 5‐exo to 6‐endo cyclization between the Z and E isomers of internal alkenols.     

Nucleophile addition of reduced glutathione on 2-methyl-2-nitroso compound: A combined electron paramagnetic resonance spectroscopy and electrospray tandem mass spectrometry study

Mass spectrometry (MS) was used in conjunction with electron paramagnetic resonance (EPR) to characterize products arising from reactions between reduced glutathione (GSH) and 2-methyl 2-nitroso propane (MNP) in an oxidative medium, to evaluate the reactivity of this tripeptide as a nucleophile toward a nitroso compound. Depending on the experimental conditions, different radical species could be detected by EPR, which allowed some structural assumptions. These samples were then submitted to electrospray ionization, in both positive and negative ion modes, for structural elucidation in tandem mass spectrometry. Although the primary nitroxide products could not be detected in MS, structurally related compounds such as hydroxylamine and O-methyl hydroxylamine could be fully characterized. In the absence of light, a S-adduct was formed via a Forrester-Hepburn reaction, that is, a nucleophile addition of MNP onto the thiol function in reduced glutathione to yield a hydroxylamine intermediate, further oxidized into nitroxide. In contrast, irradiating the reaction medium with visible light could allow an inverted spin trapping reaction to take place, involving the oxidation of both MNP and GSH before the nucleophilic addition of the sulfenic acid function onto the nitrogen of MNP, yielding a so-called O-adduct. It was also found that dilution of the reaction medium with methanol for the purpose of electrospray ionization could allow nitroxides to be indirectly observed either as hydroxylamine or O-methyl hydroxylamine species.     

Reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro: a model to study hypersensitivity to UV light

Xeroderma pigmentosum (XP) is a rare, recessive, photosensitive and cancer-prone syndrome, the biochemical hallmark of which is a defect in nucleotide excision repair of ultraviolet (UV)-induced mutagenic lesions. After isolation and amplification of several strains of XP-C keratinocytes and fibroblasts, a three-dimensional skin model in vitro comprising both epidermis and a dermal equivalent could be obtained. XP dermal tissues and XP epidermis displayed specific morphological and biochemical characteristics compared with tissues obtained with normal cells. One of the major features was the formation of epidermal invaginations into the dermal equivalent. After UV-B exposure, and contrary to repair of DNA lesions in normal cells, the XP model displayed repair deficiency with long-lasting persistence of UV-induced DNA damage and p53 positive nuclei. Recent data obtained after genetic correction leading to functional XPC gene in keratinocytes and fibroblasts revealed that several abnormal features could be normalized. In conclusion, reconstruction of XP skin in vitro provides a very promising system to study genetic hyperphotosensitivity and opens a rational perspective to XP tissue therapy.     

Trennung des Eisens von Cer durch Verteilen zwischen zwei L?sungsmitteln

Zusammenfassung Eisen und Cer lassen sich in Gegenwart von Ammoniumthiocyanat in salzsaurer Lösung durch Ausschütteln mit Äther + Tetrahydrofuran quantitativ trennen. Die Trennung ist in 8–10 min durchzuführen.     

New highlights in the synthesis and reactivity of 1,4-dihydropyrazine derivatives

In the course of our investigations on the synthesis of original nitrogen heterocyclic derivatives, we were interested in the synthesis and study of original 1,4-dihydropyrazine rings. To this aim the desired bisvinylphosphate derivative was prepared from N-Boc piperazine-2,5-dione and then was engaged in palladium catalyzed reactions (reduction, Suzuki and Stille cross-coupling reactions). The 1,4-dihydropyrazine and the corresponding 2,5-disubstituted derivatives were obtained in fair to good yields and were then functionalized under anionic conditions. Aromatization into 1,4-pyrazines was investigated in a second stage.     

Cytotoxic and Photocytotoxic Effects of Cercosporin on Human Tumor Cell Lines

Cercosporin is a naturally occurring perylenequinone. Although other perylenequinones have been extensively studied as photosensitizers in photodynamic therapy of cancer (PDT), cercosporin has been studied in this light only within the remits of phytopathology. Herein, we investigated the photocytotoxicity of cercosporin against two glioblastoma multiforme (T98G and U87) and one breast adenocarcinoma (MCF7) human cell lines. Cercosporin was found to be a potent singlet oxygen producer upon 532 nm excitation, while its cell loading was similar for MCF7 and U87, but approximately threefold higher for T98G cells. The subcellular localization of cercosporin was in all cases in both mitochondria and the endoplasmic reticulum. Light irradiation of cercosporin‐incubated cells around 450 nm showed that T98G cells were more susceptible to cercosporin PDT, mainly due to their higher cercosporin uptake. Metabolic studies before and 1 h following cercosporin PDT showed that cercosporin PDT instigated a bioenergetic collapse in both the respiratory and glycolytic activities of all cell lines. In the dark, cercosporin exhibited a synergistic cytotoxicity with copper only in the most respiratory cell lines (MCF7 and T98G). Cercosporin is a potent photosensitizer, but with a short activation wavelength, mostly suitable for superficial PDT treatments, especially when it is necessary to avoid perforations.     

Accuracy evaluation of an optical lattice clock with bosonic atoms

We report what we believe to be the first accuracy evaluation of an optical lattice clock based on the S01-->P03 transition of an alkaline earth boson, namely, Sr88 atoms. This transition has been enabled by using a static coupling magnetic field. The clock frequency is determined to be 429228066418009(32)Hz. The isotopic shift between Sr87 and Sr88 is 62188135Hz with fractional uncertainty 5x10(-7). We discuss the necessary conditions to reach a clock accuracy of 10(-17) or less by using this scheme.     

Simultaneous determination of inorganic mercury,methylmercury, and total mercury concentrations in cryogenic fresh-frozen and freeze-dried biological reference materials

Two speciated isotope dilution (SID) approaches consisting of a single-spike (SS) method and a double-spike (DS) method including a reaction/transformation model for the correction of inadvertent transformations affecting mercury species were compared in terms of accuracy, method performance, and robustness for the simultaneous determination of methylmercury (MeHg), inorganic mercury (iHg), and total mercury (HgT) concentrations in five biological Standard Reference Materials (SRMs). The SRMs consisted of oyster and mussel tissue materials displaying different mercury species concentration levels and different textural/matrix properties including freeze-dried (FD) materials (SRMs 1566b, 2976, and 2977) and cryogenically prepared and stored fresh-frozen (FF) materials (SRMs 1974a, 1974b). Each sample was spiked with (201)iHg (Oak Ridge National Laboratory, ORNL) and Me(202)Hg (Institute for Reference Materials and Measurements. IRMM-670) solutions and analyzed using alkaline microwave digestion, ethylation, and gas chromatography inductively coupled plasma mass spectrometry (GC/ICP-MS). The results obtained by the SS-SID method suggested that FF and FD materials are not always commutable for the simultaneous determination of iHg, MeHg, and HgT, due to potential transformation reactions resulting probably from the methodology and/or from the textural/matrix properties of the materials. These transformations can occasionally significantly affect mercury species concentration results obtained by SS-SID, depending on the species investigated and the materials considered. The results obtained by the DS-SID method indicated that the two classes of materials were commutable. The simultaneous and corrected concentrations of iHg, MeHg, and HgT obtained by this technique were not found to be statistically different form the certified and reference concentration together with their expanded uncertainty budgets for the five SRMs investigated, exemplifying the robustness, the accuracy, and the improved commutability of this method compared to SS-SID measurements.