Total (Czechia)

Abstract We report an efficient and scalable synthesis of azidotrifluoromethane (CF 3 N 3 ) and longer perfluorocarbon‐chain analogues (R F N 3 ; R F =C 2 F 5 , n C 3 F 7 , n C 8 F 17 ), which enables the direct insertion of CF 3 and perfluoroalkyl groups into triazole ring systems. The azidoperfluoroalkanes show good reactivity with terminal alkynes in copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC), giving access to rare and stable N ‐perfluoroalkyl triazoles. Azidoperfluoroalkanes are thermally stable and the efficiency of their preparation should be attractive for discovery programs.

Fluoroalkylation reagents based on hypervalent iodine are widely used to transfer fluoroalkyl moieties to various nucleophiles. However, the transferred groups have so far been limited to simple structural motifs. We herein report a reagent featuring a secondary amine that can be converted to amide, sulfonamide, and tertiary amine derivatives in one step. The resulting reagents bear manifold functional groups, many of which would not be compatible with the original synthetic pathway. Exploiting this structural versatility and the known high reactivity toward thiols, the new-generation reagents were used in bioconjugation with an artificial retro-aldolase, containing an exposed cysteine and a reactive catalytic lysine. Whereas commercial reagents based on maleimide and iodoacetamide labeled both sites, the iodanes exclusively modified the cysteine residue. The study thus demonstrates that modular fluoroalkylation reagents can be used as tools for cysteine-selective bioconjugation.

Tetrafluoroalkyl bromides are metalated with equimolar iPrMgCl·LiCl (Turbo Grignard) to form organomagnesium compounds which are stable at low temperatures and react with various electrophiles (aldehydes, ketones, CO2, cyclic sulfate and sulfamidate, N-sulfonylimines, nitrone, chlorophosphate, nonaflyl azide) to afford novel functionalized tetrafluoroethylene-containing products. Ease of operation, excellent selectivity, high nucleophilicity, and enhanced stability of the reactive species together with a broad substrate scope comprise a highly attractive nucleophilic tetrafluoroethylation protocol affording unique synthetic building blocks.

OBJECTIVES: Bee products have been studied extensively for their healing properties and have become part of cosmetic preparations and folk medicine. The major objective of this study was to examine the presence of antimicrobials in various bee products. DESIGN: Propolis, honeycomb lids, pollen, honeycombs, and honey were screened for antimicrobial compounds. Viridans streptococci were used as indicator strains. Ethanol extracts were applied onto paper disks, dried, and put on the surface of nutrient agar plates with the overlay containing viridans streptococci. The plates were then incubated and evaluated the next day for the presence of inhibition zones. The size of the inhibition zone represented a quantitative measure of antimicrobial activity in a sample. Thin-layer chromatography was used for separation of compounds in the samples and biodetection-an overlay with indicator strain-identified the antimicrobial compounds by formation of inhibition zones. RESULTS: Ethanol extracts of propolis and honeycomb lids, as well as honey containing honeycomb lids contained a mixture of antimicrobial compounds in various amounts. Thin-layer chromatography experiments with two different solvent systems differing in polarity suggested that major antimicrobials present in the samples prepared from honeycomb lids, honeycombs, pollen, and propolis have similar properties. These active compounds were not extremely hydrophobic. CONCLUSIONS: Extracts from the tested samples of bee products exhibited antimicrobial properties at various levels depending on the sample and bacterial species used for testing. Using chromatographic techniques, we demonstrated similar properties of the active compounds in various active samples. In conclusion, our results suggest that honey containing honeycomb lids may be a beneficial food supplement because of the presence of antibacterial compounds.

Tetrafluoroethylene-containing azides are accessed in two steps (one pot) from tetrafluoroalkyl bromides by metalation and reaction with electrophilic azides. Subsequent copper(i)-catalyzed azide-alkyne cycloaddition afforded N-tetrafluoroethyl and N-tetrafluoroethylene 4-substituted 1,2,3-triazoles. In addition, the protocol for the synthesis of 4,5-disubstituted 1,2,3-triazoles is presented.

-iodanes and their hydrochloride salts was prepared and used in a combination with sodium ascorbate in buffer or aqueous methanol mixtures for radical fluoroalkylation of a range of substituted indoles, pyrroles, tryptophan or its derivatives, and Trp residues in peptides. As demonstrated on several peptides, the aromatic amino acid residues of Trp, Tyr, Phe, and His are targeted with high selectivity to Trp. The functionalization method is biocompatible, mild, rapid, and transition-metal-free. The proteins myoglobin, ubiquitin, and human carbonic anhydrase I were also successfully functionalized.

Covalent labeling of proteins in combination with mass spectrometry has been established as a complementary technique to classical structural methods, such as X-ray, NMR, or cryogenic electron microscopy (Cryo-EM), used for protein structure determination. Although the current covalent labeling techniques enable the protein solvent accessible areas with sufficient spatial resolution to be monitored, there is still high demand for alternative, less complicated, and inexpensive approaches. Here, we introduce a new covalent labeling method based on fast fluoroalkylation of proteins (FFAP). FFAP uses fluoroalkyl radicals formed by reductive decomposition of Togni reagents with ascorbic acid to label proteins on a time scale of seconds. The feasibility of FFAP to effectively label proteins was demonstrated by monitoring the differential amino acids modification of native horse heart apomyoglobin/holomyoglobin and the human haptoglobin-hemoglobin complex. The obtained data confirmed the Togni reagent-mediated FFAP is an advantageous alternative method for covalent labeling in applications such as protein footprinting and epitope mapping of proteins (and their complexes) in general. Data are accessible via the ProteomeXchange server with the data set identifier PXD027310.

Azidodifluoromethane was prepared in 65 % yield from chlorodifluoromethane by a two‐step synthesis using tributyl(difluoromethyl)ammonium chloride as an intermediate. The resulting azide was used in Huisgen azide‐alkyne reactions and ketone [3+2] cycloadditions to access novel N ‐difluoromethyl‐1,2,3‐triazoles.

Abstract Trifluoromethylated and fluoroalkylated cyclic λ 3 ‐iodanes and their acyclic salts were used for visible light‐driven fluoroalkylation of tryptophan and tryptophan‐containing peptides in aqueous media. In comparison to previously reported fluoroalkylation using similar reagents and sodium ascorbate as reductant, the photochemical process did not require any additive or catalyst and was more selective for Trp versus other aromatic amino acids due to the gradual production of fluoroalkyl radicals over the whole irradiation period. However, in the presence of Cys residues, both methods were not selective and cysteine sulfhydryl groups were fluoroalkylated in side reactions. Spectroscopic and photochemical investigations as well as quantum chemical calculations provided insight into the reaction mechanism. The process was found to be photoinduced involving the formation of fluoroalkyl radical from the excited state of λ 3 ‐iodane.

We report herein a simple alternative method for the asymmetric transfer hydrogenation (ATH) of 1‐aryl‐3,4‐dihydroisoquinolines (1‐Ar‐DHIQs) that are known to be challenging substrates owing to their poor reactivity. The hydrogenation protocol employs the readily available Cp*Ir(TsDPEN) {where Cp* = pentamethylcyclopentadienyl and TsDPEN = ( S , S )‐HNCHPhCHPhNTs 2– } catalytic complex, 2‐propanol and HCOOH/triethylamine mixture as the solvent and hydrogen donor, and anhydrous phosphoric acid as an inexpensive additive. The series of examined substrates shows a favorable tolerance to various functional groups. Unlike 1‐alkyl‐DHIQs, where the enantiomeric excess ( ee ) starkly changes during the course of hydrogenation, 1‐Ar‐DHIQs exhibit a constant ee value, which makes the method practical and useful for the production of fine chemicals containing the 1,2,3,4‐tetrahydroisoquinoline motif.

Abstract We report an efficient and scalable synthesis of azidotrifluoromethane (CF 3 N 3 ) and longer perfluorocarbon‐chain analogues (R F N 3 ; R F =C 2 F 5 , n C 3 F 7 , n C 8 F 17 ), which enables the direct insertion of CF 3 and perfluoroalkyl groups into triazole ring systems. The azidoperfluoroalkanes show good reactivity with terminal alkynes in copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC), giving access to rare and stable N ‐perfluoroalkyl triazoles. Azidoperfluoroalkanes are thermally stable and the efficiency of their preparation should be attractive for discovery programs.

A new fluorinated azidoethane─1-azido-1,1,2,2-tetrafluoroethane─was prepared in quantitative yield by the addition of an azide anion to tetrafluoroethylene in a protic medium. The title azide was shown to be thermally stable and insensitive to impact. Copper(I)-catalyzed [3 + 2] cycloaddition with alkynes afforded 4-substituted N-tetrafluoroethyl-1,2,3-triazoles which underwent rhodium(II)-catalyzed transannulation with nitriles to novel N-tetrafluoroethylimidazoles or the reaction with triflic acid to enamido triflates. [3 + 2] Cycloaddition of the title azide with primary amines afforded novel 5-difluoromethyl tetrazoles.

Disuccinimidyl dibutyric urea (DSBU) is a mass spectrometry (MS)-cleavable cross-linker that has multiple applications in structural biology, ranging from isolated protein complexes to comprehensive system-wide interactomics. DSBU facilitates a rapid and reliable identification of cross-links through the dissociation of its urea group in the gas phase. In this study, we further advance the structural capabilities of DSBU by remodeling the urea group into an imide, thus introducing a novel class of cross-linkers. This modification preserves the MS cleavability of the amide bond, granted by the two acyl groups of the imide function. The central nitrogen atom enables the introduction of affinity purification tags. Here, we introduce disuccinimidyl disuccinic imide (DSSI) as a prototype of this class of cross-linkers. It features a phosphonate handle for immobilized metal ion affinity chromatography enrichment. We detail DSSI synthesis and describe its behavior in solution and in the gas phase while cross-linking isolated proteins and human cell lysates. DSSI and DSBU cross-links are compared at the same enrichment depth to bridge these two cross-linker classes. We validate DSSI cross-links by mapping them in high-resolution structures of large protein assemblies. The cross-links observed yield insights into the morphology of intrinsically disordered proteins and their complexes. The DSSI linker might spearhead a novel class of MS-cleavable and enrichable cross-linkers.

A method called, sigma-consensus, is proposed to eliminate the need for a user-defined inlier-outlier threshold in RANSAC. Instead of estimating the noise sigma, it is marginalized over a range of noise scales. The optimized model is obtained by weighted least-squares fitting where the weights come from the marginalization over sigma of the point likelihoods of being inliers. A new quality function is proposed not requiring sigma and, thus, a set of inliers to determine the model quality. Also, a new termination criterion for RANSAC is built on the proposed marginalization approach. Applying sigma-consensus, MAGSAC is proposed with no need for a user-defined sigma and improving the accuracy of robust estimation significantly. It is superior to the state-of-the-art in terms of geometric accuracy on publicly available real-world datasets for epipolar geometry (F and E) and homography estimation. In addition, applying sigma-consensus only once as a post-processing step to the RANSAC output always improved the model quality on a wide range of vision problems without noticeable deterioration in processing time, adding a few milliseconds.

As a result of steadily increasing traffic load on the roads in the Czech Republic, we should be focused on the innovative technical solutions, which will lead to extending the life time of asphalt pavements. One of these ways could be the future use of bitumen with a higher degree of polymer modification. This paper discusses experience with comparison of new highly polymer modified asphalt binder type with conventional polymer modified asphalt binder and unmodified binder with penetration grade 50/70. There are compared the results of various types laboratory tests of asphalt binders, as well as the results of asphalt mixtures laboratory tests. The paper also mentions the experience with workability and compactability of asphalt mixture with highly polymer modified asphalt binder during the realization of the experimental reference road section by the Skanska company in the Czech Republic.

Triboluminescence is a fascinating phenomenon that can engage students’ interest in chemistry. However, safe, cost-effective, and accessible laboratory experiments featuring highly triboluminescent substances are limited. To bridge this gap, we present a simple, rapid, semimicro test tube preparation of the visually engaging manganese complex [MnBr2(Ph3PO)2], conducted by high school students. During the laboratory session, students practice various laboratory skills, including handling semimicro quantities of substances, ascertaining the melting point, and recrystallizing the synthesized complex. They also investigate the complex’s triboluminescent, fluorescent, and magnetic properties through straightforward and illustrative experiments. Furthermore, this laboratory activity has been successfully implemented in an undergraduate chemistry didactics course for chemistry educators. The experiment’s simplicity, combined with the safety of starting materials and use of nontoxic solvents, makes it an optimal choice for a variety of educational environments, such as high school and university laboratory sessions, science clubs, and public science outreach activities.

20. yüzyılın son çeyreğinden itibaren dünya ölçeğinde yaşanan değişimler; devlet-toplum ilişkileri, demokrasi ve yerel yönetim gibi kavramları ve bunların birbirleriyle olan ilişkilerini yeniden tanımlamıştır. Vatandaşların kamu hizmetlerinden beklentileri çeşitlenmiş, kamu yönetiminin daha kaliteli hizmet sunması için yeni gerekçeler oluşmuştur. Kamu kurumlarının bu beklentileri karşılayabilmek ve hizmetlerini en etkin seviyeye ulaştırabilmek için Toplam Kalite Yönetimi’nden (TKY) faydalanmaları önem kazanmıştır. Dolayısıyla yerel yönetimler ve onun en önemli unsuru olan belediyeler önemli bir aktör haline gelmiştir. Bu çalışmanın amacı, bir yönetim yaklaşımı olan TKY’nin belediyelerde uygulama alanlarını ve sonuçlarını çok yönlü değerlendirmektir. Çalışmanın kapsamını Şişli, Üsküdar ve Pendik Belediyeleri’ndeki TKY uygulama süreçleri oluşturmaktadır. Araştırmada kalitatif (nitel) araştırma yöntemi uygulanmıştır. Elde edilen verilerle belediyelerdeki TKY uygulamalarının analizi yapılarak genel bir değerlendirmeye gidilmiştir. Araştırmanın verileri Yüksek Öğretim Kurumu (YÖK) ulusal tez merkezi veri tabanında yer alan tezlerden elde edilmiştir. Çalışma sonucunda belediyelerde TKY uygulamalarının istenilen düzeyde olmasa da genel olarak başarılı bir şekilde gerçekleştirildiği görülmüştür.

The purpose of this study was to develop a standardized assessment (LDUKES) that measures an individual's reported use of judgment in relation to fall risk. Fifty-three participants from 7 different senior care facilities completed an assessment that was created by researchers. Researchers found that participants' responses indicated a statistically significant inverse correlation ( P < .05) between whether the participant had fallen and his or her perceived risk of falling. This relationship indicates that those who reported falling thought that they were at a lower risk of falling in the future. In addition, when comparing fall history (A3) with physical characteristics (section C) using an independent-samples t test, a significance was found between individuals who reported falls or stumbles and individuals who did not report falls ( P < .05). Further research using the LDUKES assessment is recommended to identify the ability to effectively assess judgment related to fall risk.

Selective and irreversible labeling of a cysteine present in artificial retro-aldolase is achieved by employing modular tetrafluoroalkylation reagents based on hypervalent iodine. Unlike commonly used maleimide or iodoacetamide reagents, the fluoroalkyl-transfer λ3-iodanes leave the enzyme's active center, a nucleophilic lysine, intact. Many different functional moieties or dyes can be fused to the reagents in one step, making the method an attractive and robust approach for the derivatization of biomolecules. More information can be found in the Communication by P. Beier, D. Hilvert, A. Togni, et al. on page 6490 ff.

The authors deal with the postoperative dioptric deviation from the calculated optic potency of the emetropic intraocular lens, using formulae SRK II, SRK/T and Holladay's formula. Within the range +/- 1.5 D the deviation varied in 84% of the operated eyes where the intraocular lens was assessed according to formula SRK II; in 76% when formula SRK/T was used and in 74% when Holladay's formula was used. The authors give also an account of possible sources of errors during measurement, calculation and evaluation of results.