Hasil untuk "Organic chemistry"

I. Obot, D. Macdonald, D. Macdonald et al.

A. Laskin, J. Laskin, S. Nizkorodov

A. Fürstner

The current status of homogeneous iron catalysis in organic chemistry is contemplated, as are the reasons why this particular research area only recently starts challenging the enduring dominance of the late and mostly noble metals over the field. Centered in the middle of the d-block and able to support formal oxidation states ranging from −II to +VI, iron catalysts hold the promise of being able to encompass organic synthesis at large. They are expected to serve reductive as well as oxidative regimes, can emulate “noble tasks”, but are also able to adopt “early” transition metal character. Since a comprehensive coverage of this multidimensional agenda is beyond the scope of an Outlook anyway, emphasis is laid in this article on the analysis of the factors that perhaps allow one to control the multifarious chemical nature of this earth-abundant metal. The challenges are significant, not least at the analytical frontier; their mastery mandates a mindset that differs from the routines that most organic chemists interested in (noble metal) catalysis tend to cultivate. This aspect notwithstanding, it is safe to predict that homogeneous iron catalysis bears the chance to enable a responsible paradigm for chemical synthesis and a sustained catalyst economy, while potentially providing substantial economic advantages. This promise will spur the systematic and in-depth investigations that it takes to upgrade this research area to strategy-level status in organic chemistry and beyond.

Zhi‐Yuan Gu, Cheng‐Xiong Yang, Na Chang et al.

R. Chambers

M. Hudlický

F. Carey, R. Sundberg

T. Mason

Patrick A. Julien, C. Mottillo, T. Friščić

Muhammad Suhail bin Uzair, Yoshimichi Shimomura, Takuya Tanaka et al.

Fluorescent liquid crystals (LCs) have attracted considerable interest owing to their unique combination of fluidity, anisotropy, and intrinsic emission. However, most reported fluorescent LCs exhibit high phase transition temperatures and/or smectic phases, limiting their practical applications. To address this, we designed and synthesized a series of 2,1,3-benzothiadiazole (BTD)-based fluorescent nematic liquid crystals incorporating donor (D) or acceptor (A) groups to form D–A–D or D–A–A structures. Most of the synthesized derivatives exhibited supercooled nematic phases at room temperature. They composed various functional groups, such as secondary alkylamine, branched alkyl chain, and trifluoroacetyl groups, which are rarely used in calamitic nematic LCs. Notably, dimethylamine- and carbonyl-substituted derivatives exhibited relatively high fluorescence quantum yields (Φ_fl) in both solid and mesophase states, demonstrating their potential as efficient fluorescent materials. Our findings underscore the versatility of BTD-based mesogenic skeletons for designing room-temperature fluorescent nematic LCs with various functional groups. These materials offer promising opportunities for next-generation display technologies, optical sensors, and photonic applications.

Emmy D.G. Fleuren

Oncogenic FGFR4 signalling represents an attractive therapeutic target across multiple cancers, yet treatment resistance almost uniformly occurs. A critical mechanism steering resistance is a rapid and complex reprogramming of kinase signalling networks, called the adaptive bypass response. Capturing this dynamic rewiring to pinpoint, on a molecular level, the right combinatorial drug for the right FGFR4-driven cancer patient at the right time, will be key to achieving sustained tumour responses. But how can one accurately capture this process across different cancer types exhibiting contrasting levels of FGFR4 signalling pathway components and network behaviours? A recent study by Shin et al. delivers a technically elegant and biologically grounded exploration of the adaptive signalling landscape to tackle this, revealing cell context-dependent combinatorial strategies.

G. Palmisano, V. Augugliaro, M. Pagliaro et al.

C. Kappe

Archimede Rotondo, Giovanni Bartolomeo, Irene Maria Spanò et al.

Nuclear magnetic resonance (NMR) metabolomic analysis was applied to investigate the differences within nineteen Sicilian <i>Nocellara del Belice</i> monovarietal extra virgin olive oils (EVOOs), grown in two zones that are different in altitude and soil composition. Several classes of endogenous olive oil metabolites were quantified through a nuclear magnetic resonance (NMR) three-experiment protocol coupled with a yet-developed data-processing called MARA-NMR (Multiple Assignment Recovered Analysis by Nuclear Magnetic Resonance). This method, taking around one-hour of experimental time per sample, faces the possible quantification of different class of compounds at different concentration ranges, which would require at least three alternative traditional methods. NMR results were compared with the data of traditional analytical methods to quantify free fatty acidity (FFA), fatty acid methyl esters (FAMEs), and total phenol content. The presented NMR methodology is compared with traditional analytical practices, and its consistency is also tested through slightly different data treatment. Despite the rich literature about the NMR of EVOOs, the paper points out that there are still several advances potentially improving this general analysis and overcoming the other cumbersome and multi-device analytical strategies. Monovarietal EVOO’s composition is mainly affected by pedoclimatic conditions, in turn relying upon the nutritional properties, quality, and authenticity. Data collection, analysis, and statistical processing are discussed, touching on the important issues related to the climate changes in Sicily and to the specific influence of pedoclimatic conditions.

Letizia Crocetti, Andrei I. Khlebnikov, Gabriella Guerrini et al.

Chronic inflammation contributes to a number of diseases. Therefore, control of the inflammatory response is an important therapeutic goal. To identify novel anti-inflammatory compounds, we synthesized and screened a library of 80 pyrazolo[1,5-<i>a</i>]quinazoline compounds and related derivatives. Screening of these compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP-1Blue monocytic cells identified 13 compounds with anti-inflammatory activity (IC₅₀ < 50 µM) in a cell-based test system, with two of the most potent being compounds <b>13i</b> (5-[(4-sulfamoylbenzyl)oxy]pyrazolo[1,5-<i>a</i>]quinazoline-3-carboxamide) and <b>16</b> (5-[(4-(methylsulfinyl)benzyloxy]pyrazolo[1,5-<i>a</i>]quinazoline-3-carboxamide). Pharmacophore mapping of potential targets predicted that <b>13i</b> and <b>16</b> may be ligands for three mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 2 (ERK2), p38α, and <i>c</i>-Jun <i>N</i>-terminal kinase 3 (JNK3). Indeed, molecular modeling supported that these compounds could effectively bind to ERK2, p38α, and JNK3, with the highest complementarity to JNK3. The key residues of JNK3 important for this binding were identified. Moreover, compounds <b>13i</b> and <b>16</b> exhibited micromolar binding affinities for JNK1, JNK2, and JNK3. Thus, our results demonstrate the potential for developing lead anti-inflammatory drugs based on the pyrazolo[1,5-<i>a</i>]quinazoline and related scaffolds that are targeted toward MAPKs.

Chawapun Suttinont, Moe Tsutsumi, Tomohiro Numata et al.

Background/Aims: Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aβ-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs enwrapping c-fibers and myelinating SCs ensheathing Aβ and Aδ fibers. Recent research has unveiled new functions for cutaneous sensory SCs, highlighting the involvement of nociceptive SCs in pain perception and Meissner corpuscle SCs in tactile sensation. Furthermore, Piezo2, previously associated with Merkel cell tactile sensitivity, has been identified in SCs. The goal of this study was to investigate the channels implicated in SC mechanosensitivity and the release process of neurotrophic factor secretion. Methods: Immortalized IFRS1 SCs and human primary SCs generated two distinct subtypes of SCs: undifferentiated and differentiated SCs. Quantitative PCR was employed to evaluate the expression of differentiation markers and mechanosensitive channels, including TRP channels (TRPV4, TRPM7 and TRPA1) and Piezo channels (Piezo1 and Piezo2). To validate the functionality of specific mechanosensitive channels, Ca2+ imaging and electronic cell sizing experiments were conducted under hypotonic conditions, and inhibitors and siRNAs were used. Protein expression was assessed by Western blotting and immunostaining. Additionally, secretome analysis was performed to evaluate the release of neurotrophic factors in response to hypotonic stimulation, with BDNF, a representative trophic factor, quantified using ELISA. Results: Induction of differentiation increased Piezo2 mRNA expression levels both in IFRS1 and in human primary SCs. Both cell types were responsive to hypotonic solutions, with differentiated SCs displaying a more pronounced response. Gd3+ and FM1-43 effectively inhibited hypotonicity-induced Ca2+ transients in differentiated SCs, implicating Piezo2 channels. Conversely, inhibitors of Piezo1 and TRPM7 (Dooku1 and NS8593, respectively) had no discernible impact. Moreover, Piezo2 in differentiated SCs appeared to participate in regulatory volume decreases (RVD) after cell swelling induced by hypotonic stimulation. A Piezo2 deficiency correlated with reduced RVD and prolonged cell swelling, leading to heightened release of the neurotrophic factor BDNF by upregulating the function of endogenously expressed Ca2+-permeable TRPV4. Conclusion: Our study unveils the mechanosensitivity of SCs and implicates Piezo2 channels in the release of neurotrophic factors from SCs. These results suggest that Piezo2 may contribute to RVD, thereby maintaining cellular homeostasis, and may also serve as a negative regulator of neurotrophic factor release. These findings underscore the need for further investigation into the role of Piezo2 in SC function and neurotrophic regulation.

M. Larhed, C. Moberg, A. Hallberg

Maxim R. Ryzhikov, Yakov M. Gayfulin, Anton A. Ulantikov et al.

Understanding the processes that occur during the redox transformations of complexes coordinated by redox-active apical ligands is important for the design of electrochemically active compounds with functional properties. In this work, a detailed analysis of the interaction energy and electronic structure was performed for cluster complexes <i>trans</i>-[Re₆S₈bipy₄Cl₂]ⁿ (n = 2–, 4–, 6–, 8–), which can be obtained by stepwise electrochemical reduction of a neutral cluster <i>trans</i>-[Re₆S₈bipy₄Cl₂] in DMSO solution. It was shown that the formation of open-shell paramagnetic ions with S = 1, 2 and 1 is the most energetically favorable for n = 2–, 4– and 6–, respectively.

Dan Yin, Xiao Li, Xin Wang et al.

Bacterial infections seriously threaten human safety. Therefore, it is very important to develop a method for bacterial detection and treatment with rapid response, high sensitivity, and simple operation. A peptide CF₄KY^P (C, cysteine; F₄, phenylalanine tetrapeptide; K, lysine; Y^P, phosphorylated tyrosine) functionalized gold nanoparticle (AuNPs-CF₄KY^P) was synthesized for simultaneous detection and treatment of bacteria based on bacterial alkaline phosphatase (ALP). In solution, ALP can induce AuNPs-CF₄KY^P aggregation and produce significant color changes. After encountering bacteria, monodisperse AuNPs-CF₄KY^P can aggregate/assemble in situ on the surface of the bacterial membrane, change the color of the solution from wine red to grey, destroy the bacterial membrane structure, and induce the production of a large number of reactive oxygen species within the bacteria. The absorption change of AuNPs-CF₄KY^P solution has a good linear relationship with the number of bacteria. Furthermore, the aggregation of AuNPs-CF₄KY^P kills approximately 80% of <i>Salmonella typhimurium</i>. By combining enzyme-instructed peptide self-assembly technology and colorimetric analysis technology, we achieve rapid and sensitive colorimetric detection and killing of bacteria.

Ling Ji, Tianle Li, Huimin Chen et al.

Abstract Type I interferon (IFN-I) plays crucial roles in the regulation of inflammation and it is associated with various inflammatory diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and periodontitis, impacting people's health and quality of life. It is well-established that IFN-Is affect immune responses and inflammatory factors by regulating some signaling. However, currently, there is no comprehensive overview of the crucial regulatory role of IFN-I in distinctive pathways as well as associated inflammatory diseases. This review aims to provide a narrative of the involvement of IFN-I in different signaling pathways, mainly mediating the related key factors with specific targets in the pathways and signaling cascades to influence the progression of inflammatory diseases. As such, we suggested that IFN-Is induce inflammatory regulation through the stimulation of certain factors in signaling pathways, which displays possible efficient treatment methods and provides a reference for the precise control of inflammatory diseases.