1,721,007 research outputs found
NMR spectroscopy: a versatile tool for the investigation of organic reaction mechanisms and metabolomics analyses
Full text linkOlefin metathesis has become a powerful tool for the formation of carbon-carbon bonds and, therefore, for the synthesis of a number of molecules. This progress was recognized in 2005 with the award of NOBEL Prize in Chemistry to Yves Chauvin, Robert Grubbs and Richard Schrock for their work in this area. While the series of [2+2]cycloadditions and retro[2+2]cycloadditions that make up the pathways of ruthenium-catalysed metathesis reactions is wellestablished, the exploration of mechanistic aspects of alkene metathesis is going on. At first, we reported the tetramerization of (E)-2,4-dimethoxycinnamic acid ω-undecenyl ester with ethereal BF3. The reaction gave three stereoisomers 1a, 1b, and 1c, which were assigned as the chair, cone, and 1,2-alternate conformations, respectively. Undecenyl resorc[4]arene 1a, which featured the simplest pattern of substituent, was submitted to olefin metathesis using the second generation Grubbs complex as the catalyst. Depending on the reaction conditions, different products were isolated: a bicyclic alkene 2a, a linear dimer 3a, and a cross-linked homopolymer P1a. Moreover, we detected for the first time the formation of a ruthenium-carbene resorc[4]arene complex during the metathesis reaction of resorc[4]arene olefin 2a with the first generation Grubbs catalyst in CDCl3. We developed an NMR analytical protocol which proved capable of yielding both qualitative and quantitative information. In the first case, we were able to identify the complex 3a[Ru] as a key intermediate in the ROM-CM sequence of reactions, giving us a definitive proof of the previously hypothesized mechanism. As a further feedback of the pathway, we performed a quantitative analysis using benzene in the place of CDCl3, due to the poor stability of the catalyst in such a solvent. The reaction allowed the isolation of decomposition products of the ruthenium-carbene-resorc[4]arene complex 2a[Ru] such as compound 4a, which, due to the presence of still reactive alkene functions, proved to behave as propagating alkylidene species leading to further decomposition products.Metabolomics provides a direct measure of the state of the cell or biological system, where changes in the metabolome capture how the system responds to environmental or genetic stress. Specifically, a drug or an active chemical lead would be expected to perturb the
metabolome of a cell or tissue upon treatment. The two leading analytical approaches to metabolomics are mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. In particular, NMR technique accounts for high reproducibility, quantitative determination of a wide dynamic range, and the capability to determine the structure of unknown metabolites. Cells of high-grade tumors, including medulloblastoma (MB) and glioblastoma (GBM), must similarly balance energy metabolism with the need to synthesize the macromolecules essential for tumor growth. Cells with large ATP requirements are likely to be disadvantaged by aerobic glycolysis because glycolysis generates less ATP per molecule of glucose than oxidative phosphorylation. Proliferating cells, however, may use aerobic glycolysis to satisfy the competing needs for both energy generation and the accumulation of biomass. Recently, it has been demonstrated that Sonic Hedgehog (SHH) pathway activation in granule cell progenitors (GCPs), responsible of MB development, induces transcription of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), two key gatekeepers of glycolysis. The process is mediated by the canonical activation of the GLI transcription factors and causes a robust increase of extracellular lactate concentration.
Glabrescione B (GlaB), an isoflavone naturally found in the seeds of Derris glabrescens (Leguminosae), turned out to be an efficient inhibitor of the growth of HH/GLI-dependent tumors and cancer stem cells in vitro and in vivo. Here, we reported the GlaB activity on
both human MB DAOY and murine glioma GL261 cell models in vitro and in vivo. In order to evaluate how the GlaB-treatment affects cell metabolism as a consequence of GLI1 inhibition, untargeted NMR metabolomics analyses of cellular lysates and conditioned media were performed in both cell lines. For this purpose, a simple, fast, and reproducible sample preparation protocol was developed. To reduce bias in the interpretation of the experiments, it was decided to produce from five to seven biological replicates for each treated and untreated group. The 1D 1H NMR spectra were acquired to determine the metabolic fingerprints of the treated and untreated cancer cells. Notably, the NMR metabolomics approach revealed a typical endo-metabolic phenotype of the cells under investigation. Both the exo- and endo-metabolome of the DAOY and GL261 cell lines resulted to be completely changed after 24 h and 48 h of GlaB administration, respectively. The levels of most metabolites decreased after treatment, consistently with possible apoptosis phenomenon
Inorganic gold and polymeric poly(lactide-co-glycolide) nanoparticles as novel strategies to ameliorate the biological properties of antimicrobial peptides
No full textCationic antimicrobial peptides (AMPs) are an interesting class of gene-encoded molecules endowed with a broad-spectrum of anti-infective activity and immunomodulatory properties. They represent promising candidates for the development of new antibiotics, mainly due to their membrane-perturbing mechanism of action that very rarely induces microbial resistance. However, bringing AMPs into clinical field is hampered by some intrinsic limitations, encompassing low peptide bioavailability at the target site and high peptide susceptibility to proteolytic degradation. In this regard, nanotechnologies represent an innovative strategy to circumvent these issues. According to the literature, a large variety of nanoparticulate systems has been employed for drug-delivery, bioimaging, biosensors or as nanoantibiotics. The possibility of conjugating different types of molecules, including AMPs, to these systems, allows the production of nanoformulations able to enhance the biological profile of the compound, while reducing its cytotoxicity and prolonging its residence time. In this mini-review, inorganic gold nanoparticles (NPs) and biodegradable polymeric NPs made of poly(lactide-co-glycolide) are described with particular emphasis on examples of conjugation of AMPs to them, to highlight the great potential of such nanoformulations as alternative antimicrobials
Olefin metathesis reaction as a locking tool for macrocycle and mechanomolecule construction
No full textThe present review deals with an updated visit to the olefin metathesis reaction as a powerful tool for the construction of sophisticated macromolecular architectures. Today, the reaction has proved to be one of the most popular processes, not only for the synthesis of novel cage and huge calixarene-based macrocycles, or more complex structures containing these privileged moieties, but also for the construction of complicated topologically intriguing molecules, such as catenanes, rotaxanes and knots. Notably, their use ranges from chemistry and biology, as catalysts and drug delivery systems, respectively, to materials research, as molecular motors and switches. The reaction effectiveness arises from the intrinsic specificity for the highly stable reactive end-groups (e.g. alkene moieties) and the feasibility to perform the reaction in relatively non-polar solvents, maximizing the supramolecular interactions often involved in the templation strategies. By moving from calixarene-based macrocycles to mechanically interlocked molecules, the review takes into account several synthetic strategies involving the olefin metathesis reaction highlighting its increasing utility and future potential in the synthesis of molecular machines
Molecular recognition of natural products by resorc[4]arene receptors
No full textThis review is aimed at providing an overview of the up-to-now published literature on resorc[4]arene macrocycles exploited as artificial receptors for the molecular recognition of some classes of natural products. A concise illustration of the main synthetic strategies developed to afford the resorc[4]arene scaffold is followed by a report on the principles of the gas-phase investigation of recognition phenomena by mass spectrometry (MS). Emphasis is placed on gas-phase studies of diastereoisomeric complexes generated inside a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer by resorc[4]arene receptors towards a series of natural products, namely amino acids, amphetamine, ethanolamine neurotransmitters, dipeptides, vinca alkaloids and nucleosides. The literature outcomes discussed here, taken largely from our own revisited work, have been completed by references to other studies, in order to draw a broader picture of this rapidly evolving field of research
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Resorc[4]arene-modified gold-decorated magnetic nanoparticles for immunosensor development
No full textIn recent years, several efforts have been made to develop selective, sensitive, fast response, and miniaturized immunosensors with improved performance for the monitoring and screening of analytes in several matrices, significantly expanding the use of this technology in a broad range of applications. However, one of the main technical challenges in developing immunosensors is overcoming the complexity of binding antibodies (Abs) to the sensor surface. Most immobilizing approaches lead to a random orientation of Abs, resulting in lower binding site density and immunoaffinity. In this context, supra-molecular chemistry has emerged as a suitable surface modification tool to achieve the preorganization of artificial receptors and to improve the functional properties of self-assembled monolayers. Herein, a supramolecular chemistry/nanotechnology-based platform was conceived to develop sensitive label-free electrochemical immunosensors, by using a resorcarene macrocycle as an artificial linker for the oriented antibody immobilization. To this aim, a water-soluble bifunctional resorc[4]arene architecture (RW) was rationally designed and synthesized to anchor gold-coated magnetic nanoparticles (Au@MNPs) and to maximize the amount of the active immobilized antibody (Ab) in the proper "end-on" orientation. The resulting supramolecular chemistry-modified nanoparticles, RW@Au@MNPs, were deposited onto graphite screen printed electrodes which were then employed to immobilize three different Abs. Furthermore, an immunosensor for atrazine (ATZ) analysis was realized and characterized by the differential pulse voltammetry technique to demonstrate the validity of the developed biosensing platform as a proof of concept for electrochemical immunosensors. The RW-based immunosensor improved AbATZ loading on Au@MNPs and sensitivity toward ATZ by almost 1.5 times compared to the random platform. Particularly, the electrochemical characterization of the developed immunosensor displays a linearity range toward ATZ within 0.05-1.5 ng/mL, a limit of detection of 0.011 ng/ml, and good reproducibility and stability. The immunosensor was tested by analyzing spiked fortified water samples with a mean recovery ranging from 95.7 to 108.4%. The overall good analytical performances of this immunodevice suggest its application for the screening and monitoring of ATZ in real matrices. Therefore, the results highlighted the successful application of the resorc[4]arene-based sensor design strategy for developing sensitive electrochemical immunosensors with improved analytical performance and simplifying the Ab immobilization procedure
The pictet-spengler reaction still on stage
No full textToday, in spite of being older than a century (born in 1911), the Pictet-Spengler two component reaction (PS-2CR) is still one of the most popular reactions, not only for the synthesis of tetrahydroisoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), or more complex structures containing these two privileged moieties, but also for the construction of novel scaffolds, available for structure-activity relationship (SAR) studies and/or for combinatorial libraries targeted at drug discovery. The prominence of the P-S cyclization is brought about by the inheritance from analogous enzyme-catalyzed reactions of the biogenetic pathways of natural products, mainly indole alkaloids, with a broad range of biological activities. This knowledge has been the starting point for the biomimetic synthesis or the bio-engineering production of pharmacologically important drugs. The long-lasting life of the P-S reaction depends on the discovery of its multiple facets, the modifications of its parameters and components, as well as the continuous renovation of solutions for the challenging stereochemical outcome of the transformation. This paper deals with an updated visit to the P-S reaction aiming to find the threads of the story without forgetting the numerous facets of the prism. It is organized as a theater piece, with a prologue and the main scene (namely, Act 1) where the readers can follow the parade of the two above-mentioned very recurring motifs (namely, THIQ and THBC) by moving from one step to another (a cyclization, an intramolecular attack, a stereoselective passage) to find the way out of the labyrinth of the P-S reaction
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