Deoxygenative perfluoroalkylthiolation of carboxylic acids with benzothiazolium reagents

Deoxygenative perfluoroalkylthiolation reactions of readily available carboxylic acid derivatives have been developed using a series of 2-(perfluoroalkylthio)benzothiazolium (BT-SRF) reagents as convenient sources of perfluoroalkylthiolate anions. This method avoids pre-activation of the substrates and delivers rarely reported perfluoroalkyl thioesters featuring SRF groups up to C6F13. A survey of carboxylic acid substrates with the pentafluoroethylthiolating reagent BT-SC2F5 also revealed the generality of the approach as a method for accessing underexplored fluorinated compounds

Pulmonary adenocarcinomas presenting as ground-glass opacities on multidetector CT: three-dimensional computer-assisted analysis of growth pattern and doubling time

We aimed to evaluate the growth pattern and doubling time (DT) of pulmonary adenocarcinomas exhibiting ground-glass opacities (GGOs) on multidetector computed tomography (CT). METHODS The growth pattern and DT of 22 pulmonary adenocarcinomas exhibiting GGOs were retrospectively analyzed using three-dimensional semiautomatic software. Analysis of each lesion was based on calculations of volume and mass changes and their respective DTs throughout CT follow- up. Three-dimensional segmentation was performed by a single radiologist on each CT scan. The same observer and another radiologist independently repeated the segmentation at the baseline and the last CT scan to determine the variability of the measurements. The relationships among DTs, histopathology, and initial CT features of the lesions were also analyzed. RESULTS Pulmonary adenocarcinomas presenting as GGOs exhibited different growth patterns: some lesions grew rapidly and some grew slowly, whereas others alternated between periods of growth, stability, or shrinkage. A significant increase in volume and mass that exceeded the coefficient of repeatability of interobserver variability was observed in 72.7% and 84.2% of GGOs, respectively. The volume-DTs and mass-DTs were heterogeneous throughout the follow-up CT scan (range, -4293 to 21928 and -3113 to 17020 days, respectively), and their intra- and interobserver variabilities were moderately high. The volume-DTs and mass-DTs were not correlated with the initial CT features of GGOs; however, they were significantly shorter in invasive adenocarcinomas (P = 0.002 and P = 0.001, respectively). CONCLUSION Pulmonary adenocarcinomas exhibiting GGOs show heterogeneous growth patterns with a trend toward a progressive increase in size. DTs may be useful for predicting tumor aggressiveness

Silver-Catalyzed Nucleophilic Deoxydifluoromethylthiolation of Activated Aliphatic Alcohols with BT−SCF2H

Deoxygenative conversion of alcohols into difluoromethylthioethers is reported using 2-((difluoromethyl)thio)-3-methylbenzo[d]thiazol-3-ium triflate (BT−SCF2H) as a source of −SCF2H anions. The presence of silver(I) triflate as a catalyst was found to be crucial for stabilizing the in situ-generated anion, while the concomitant formation of a reactive 2-(alkoxy)benzothiazolium electrophile likely ensures a fast onward substitution reaction, avoiding the build-up of −SCF2H. To the best of our knowledge, this process represents the first report of a direct nucleophilic substitution reaction with −SCF2H and delivers products containing the medicinally relevant difluoromethylthio motif in a single step from widely available alcohols

Synthese und Bewertung neuer Reagenzien für die Organofluorchemie

In this thesis, novel synthetic approaches to introduce fluorinated functional groups were investigated. Expanding upon the work previously carried out by our group, the reagents BT-SCF2H and BT-SeCF2H were introduced, and their reactivity toward alcohols and acids was investigated. A wide scope of carboxylic acids, both aliphatic and aromatic, were successfully converted into the corresponding difluoromethylthio- and -seleno esters under mild conditions in good to excellent yields, representing the first method to access these valuable compounds directly from carboxylic acids through a nucleophilic reaction. As suggested by computational calculations, the mechanism likely proceeds through an unusual 4-membered TS, with no release of the free unstable anion. The difluoromethylchalcogenation of alcohols proved to be more challenging that the corresponding trifluoromethylchalcogenation previously published by our group, owing to the lower stability of partially fluorinated anions. Whilst the reaction proceeds without any additive with BT-SeCF2H, the yields are low with all but the most activated substrates. The addition of silver triflate proved to be the key to enabling this valuable transformation, increasing the yield, and expanding the alcohol scope with BT-SeCF2H, and enabling the difluoromethylthiolation of benzylic alcohols altogether.In dieser Arbeit wurden neue synthetische Ansätze zur Einführung fluorierter funktioneller Gruppen untersucht. In Erweiterung der zuvor von unserer Gruppe durchgeführten Arbeiten wurden die Reagenzien BT-SCF2H und BT-SeCF2H eingeführt und ihre Reaktivität gegenüber Alkoholen und Säuren untersucht. Eine Vielzahl von Carbonsäuren, sowohl aliphatische als auch aromatische, wurden unter milden Bedingungen erfolgreich in die entsprechenden Difluormethylthio- und -selenoester umgewandelt, und zwar in guten bis ausgezeichneten Ausbeuten. Wie aus Berechnungen hervorgeht, läuft der Mechanismus wahrscheinlich über einen ungewöhnlichen 4-gliedrigen TS ab, wobei das freie instabile Anion nicht freigesetzt wird. Die Difluormethylchalcogenierung von Alkoholen erwies sich aufgrund der geringeren Stabilität der teilfluorierten Anionen als schwieriger als die entsprechende Trifluormethylchalcogenierung, die unsere Gruppe zuvor veröffentlicht hatte. Während die Reaktion mit BT-SeCF2H ohne jeglichen Zusatz abläuft, sind die Ausbeuten bei allen außer den am stärksten aktivierten Substraten gering. Die Zugabe von Silbertriflat erwies sich als Schlüssel zur Ermöglichung dieser wertvollen Umwandlung, zur Erhöhung der Ausbeute und zur Erweiterung des Alkoholbereichs mit BT-SeCF2H, und ermöglichte die Difluormethylthiolierung von Benzylalkoholen insgesamt

Multi-port converters in smart grids: Protection selectivity

Requests for high quality and continuity of supply have led to the study of DC micro-grids. The realization of these networks would allow exploitation of DC advantages, but it would also create fault clearance and selectivity problems because semi-conductors suffer over-currents and over-voltages. The use of traditional DC circuit breakers is often not acceptable. As an alternative, static switches can be installed to solve these problems, in spite of increases in power loss. In this work, a multi-port converter is proposed to solve the aforementioned problems. In addition, it is able to manage power flows and AC and DC I/O, improve stability, and decouple port voltages

Deoxygenative nucleophilic difluoromethylselenylation of carboxylic acids and alcohols with BT-SeCF2H

The benzothiazolium salt BT-SeCF2H is introduced as an efficient nucleophilic reagent for transferring difluoromethylselenyl groups onto organic molecules. SeCF2H-Containing selenoesters could be prepared upon deoxygenative substitution of readily available carboxylic acids, while silver catalysis allowed for efficient formation of (difluoromethyl)selenoethers, including the established electrophilic reagent BnSeCF2H, directly from simple alcohols. To the best of our knowledge, these deoxygenative reactions represent the first reported nucleophilic difluoromethylselenylation processes and thus open up new approaches to prepare valuable fluorinated compounds

Effect of the 3D Artificial Nichoid on the Morphology and Mechanobiological Response of Mesenchymal Stem Cells Cultured In Vitro

Stem cell fate and behavior are affected by the bidirectional communication of cells and their local microenvironment (the stem cell niche), which includes biochemical cues, as well as physical and mechanical factors. Stem cells are normally cultured in conventional two-dimensional monolayer, with a mechanical environment very different from the physiological one. Here, we compare culture of rat mesenchymal stem cells on flat culture supports and in the “Nichoid”, an innovative three-dimensional substrate micro-engineered to recapitulate the architecture of the physiological niche in vitro. Two versions of the culture substrates Nichoid (single-layered or “2D Nichoid” and multi-layered or “3D Nichoid”) were fabricated via two-photon laser polymerization in a biocompatible hybrid organic-inorganic photoresist (SZ2080). Mesenchymal stem cells, isolated from rat bone marrow, were seeded on flat substrates and on 2D and 3D Nichoid substrates and maintained in culture up to 2 weeks. During cell culture, we evaluated cell morphology, proliferation, cell motility and the expression of a panel of 89 mesenchymal stem cells’ specific genes, as well as intracellular structures organization. Our results show that mesenchymal stem cells adhered and grew in the 3D Nichoid with a comparable proliferation rate as compared to flat substrates. After seeding on flat substrates, cells displayed large and spread nucleus and cytoplasm, while cells cultured in the 3D Nichoid were spatially organized in three dimensions, with smaller and spherical nuclei. Gene expression analysis revealed the upregulation of genes related to stemness and to mesenchymal stem cells’ features in Nichoid-cultured cells, as compared to flat substrates. The observed changes in cytoskeletal organization of cells cultured on 3D Nichoids were also responsible for a different localization of the mechanotransducer transcription factor YAP, with an increase of the cytoplasmic retention in cells cultured in the 3D Nichoid. This difference could be explained by alterations in the import of transcription factors inside the nucleus due to the observed decrease of mean nuclear pore diameter, by transmission electron microscopy. Our data show that 3D distribution of cell volume has a profound effect on mesenchymal stem cells structure and on their mechanobiological response, and highlight the potential use of the 3D Nichoid substrate to strengthen the potential effects of MSC in vitro and in vivo