Chemistry Values Research Articles

Mechanism Insight into Direct Amidation Catalyzed by Zr Salts: Evidence of Zr Oxo Clusters as Active Species.

The capricious reactivity and speciation of earth-abundant metals (EAM) hinder the mechanistic understanding essential to boost their efficiency and versatility in catalysis. Moreover, metal's solution chemistry and reactivity are conventionally controlled using organic ligands, while their fundamental chemistry in operando conditions is often overlooked. However, in this study, we showcase how a better understanding of in operando conditions may result in improved catalytic reactions. By assessing the composition and structure of active species for Zr-catalyzed direct amide bond formations under operating conditions, we discovered zirconium oxo clusters form quickly and are likely active species in the reactions. Formation of these clusters dismisses the use of additional organic ligands, inert atmosphere, anhydrous solvents, or even water scavenging to provide amides in good to excellent yields. More specifically, dodeca- and hexazirconium oxo clusters (Zr12 and Zr6, respectively) rapidly form from commercial, readily available Zr salts under reaction conditions known to afford amides directly from nonactivated carboxylic acid and amine substrates. Extended X-ray absorption fine structure (EXAFS) experiments confirm the presence of oxo clusters in solution throughout the reaction, while their key role in the mechanism is supported by an in-depth computational study employing density functional theory (DFT) and molecular dynamics (MD) methods. These results underline the value of (earth-abundant) metals' intrinsic solution chemistry to transformative mechanistic understanding and to enhance the sustainability of organic transformations.

Evaluate the safety of a novel photohydrolysis technology used to clean and disinfect indoor air: A murine study.

There is a pressing need to develop new technologies that continuously eliminates harmful pollutants and pathogens in occupied indoor spaces without compromising safety. This study was undertaken to test the safety of a novel air cleaning and disinfection technology called Advanced Photohydrolysis. Advanced Photohydrolysis generates a complex mixture of ions and molecules that are released into the air and has been shown to reduce airborne and surface pathogens. Mice (6-8-week-old) were exposed to therapeutic levels of Advanced Photohydrolysis for 90-days. During the study, the Advanced-Photohydrolysis-exposed and control mice were monitored for food consumption, body weight gain, and any overt adverse effects. In addition, at the conclusion of the study, the blood chemistry and hematology values of both groups were determined. Finally, the tissues of the conduction and respiratory portions of the airways of mice from both groups were examined for any pathological changes. The mice of both groups were found to be normal and healthy throughout the 90-day study; there were no differences in the behavior, food consumption and weight gain. Analysis of clinical chemistry values found no differences in hepatocellular function or other markers of cellular and organ function, and clinical hematology values were also unremarkable. Finally, and importantly, histopathology of the upper and lower airway tissues showed no deleterious effects. These results are the first to demonstrate directly the safety of Advanced Photohydrolysis on live mammals and encourage additional studies.

Anti-metastatic Effects of Bee Venom and Melittin in Breast Cancer Cells by Upregulation of BRMS1 and DRG1 Genes.

Apitherapy has started to gain tremendous recognition because of extraordinary pharmacological importance of honeybee-related ingredients and their derivatives. There has been a renewed interest in the bee venom-based therapies. Interdisciplinary researchers are studying the chemistry and translational value of venom for effective cancer treatment. Bee venom and its major component, melittin, are cytotoxic in cancer cells. In this study, MTT and scratch assays were performed for analysis of melittin-mediated antimetastatic effects. QPCR was used for expression profiling of metastasis-related genes. Three anti-metastatic genes (BRMS1, DRG1, and KAI1/CD82) were studied for the first time after bee venom and melittin treatment in MDA-MB-231 breast cancer cells compared with normal breast cells, and two prometastatic genes (EGFR and WNT7B) were also examined. KAI1/CD82 and BRMS1 are the negative regulators of EGFR. WNT7B is a negative regulator of KAI1/CD82. Selective cytotoxicity of bee venom and melittin was found to be higher as compared to cisplatin. Melittin induced an increase in the expression of BRMS1 and DRG1, whereas bee venom upregulated DRG1 and KAI1/CD82 expression in breast cancer. WNT7B was downregulated in bee venom-treated breast cancer cells. Results suggested that bee venom/melittin exerted antimetastatic effects primarily through upregulation of BRMS1, DRG1, and KAI1/CD82, and downregulation of WNT7B.

IUPAC Announces the 2024 Top Ten Emerging Technologies in Chemistry

Abstract IUPAC has released the 2024 Top Ten Emerging Technologies in Chemistry. The goal of this initiative is to showcase the transformative value of chemistry and to inform the general public about the potential of chemical sciences to foster the well-being of Society and the sustainability of our planet. The Jury The following comprised the panel of judges for the 2024 Top Ten Emerging Technologies in Chemistry: Chair, Michael Droescher, (German Association for the Advancement of Science and Medicine), Jorge Alegre-Cebollada (Centro Nacional de Investigaciones Cardiovasculares, Spain), Mamia El-Rhazi, (Université Hassan II de Casablanca, Mohammedia, Morocco), Ehud Keinan (Technion, Israel), Javier García Martínez (Universidad de Alicante, Spain), Rai Kookana (CSIRO Land & Water, Australia), Juliane Sempionatto (Caltech, USA), Molly Shoichet (University of Toronto, Canada), Zhigang Shuai (Tsinghua University, China), Natalia P. Tarasova (D. I. Mendeleev University of Chemical Technology, Russia), Kira Welter (Wiley-VCH, Germany), and Bernard West (Life Sciences Ontario, Canada) —an international panel of scientists with a varied and broad range of expertise- reviewed and discussed the diverse pool of nominations of emerging technologies submitted by researchers from around the globe and selected the final top ten, covering a range of fields from synthesis and polymer chemistry to health and machine learning. These technologies are defined as transformative innovations in between a discovery and a fully-commercialized technology, having outstanding potential to open new opportunities in chemistry, sustainability, and beyond.

Stereo- and Regioselective Installation of Vinyl Sulfonyl Fluoride onto Indoles without Transition-Metal Catalyst.

Herein, we developed a practical method for synthesizing a class of novel and highly valuable indolyl vinyl sulfonyl fluorides. This protocol has carved out a path for constructing a broad range of vinyl sulfonyl fluorinated indoles with exclusive stereo- and regioselectivity through the Friedel-Crafts/elimination reaction without any transition-metal catalyst. This transformation features mild conditions, high efficiency, excellent selectivity, and rich substrate compatibility, highlighting its significant value in medicinal chemistry and many related disciplines.

A portal to highly valuable indole-functionalized vinyl sulfonyl fluorides and allylic sulfonyl fluorides.

A practical and efficient method for the C-3 site selective alkenylation of indoles was developed for constructing novel indole-functionalized vinyl sulfonyl fluorides and indolyl allylic sulfonyl fluorides. The reaction is accomplished with exclusive regio- and stereoselectivity without using transition metal catalysts, providing novel products of great potential value in medicinal chemistry, chemical biology, and drug discovery.

Synthesis of non-canonical amino acids through dehydrogenative tailoring.

Amino acids are essential building blocks in biology and chemistry. Whereas nature relies on a small number of amino acid structures, chemists desire access to a vast range of structurally diverse analogues1-3. The selective modification of amino acid side-chain residues represents an efficient strategy to access non-canonical derivatives of value in chemistry and biology. While semisynthetic methods leveraging the functional groups found in polar and aromatic amino acids have been extensively explored, highly selective and general approaches to transform unactivated C-H bonds in aliphatic amino acids remain less developed4,5. Here we disclose a stepwise dehydrogenative method to convert aliphatic amino acids into structurally diverse analogues. The key to the success of this approach lies in the development of a selective catalytic acceptorless dehydrogenation method driven by photochemical irradiation, which provides access to terminal alkene intermediates for downstream functionalization. Overall, this strategy enables the rapid synthesis of new amino acid building blocks and suggests possibilities for the late-stage modification of more complex oligopeptides.

Clinical and diagnostic evaluation of a wild ocelot (Leopardus pardalis) specimen.

Monitoring the health of wild animals under the principles of one health contributes to the prevention of diseases and the preservation of human and animal health, thus contributing to the conservation of species. The current study describes the clinical and paraclinical status of an ocelot (Leopardus pardalis) captured in Buriticá, Antioquia, Colombia, for research purposes with the aim of contributing to the construction of animal health reference values in the wild, considering the scarcity of published data for the country on capture, management, and paraclinical parameters related to this species. For this, hematological parameters, blood chemistry, urine cytochemical analyses, and coprological examinations were carried out. The hematological values of the captured individual do not show relevant differences concerning those reported in the literature in both captive and free specimens. However, differences were identified between the reference blood chemistry and urine cytochemical values between reports of animals in captivity and the wild, revealing the need to develop reference standards for animals in the wild that guarantee adequate management of these species and favor their conservation. A possible picture of renal failure and multiple parasitic infections of epidemiological importance was found. This study reports for the first time a urine infection by Capillaria sp. and an infection by Dicrocoelium spp. in fecal matter for the species.

Revisiting Elevated δ13C Values of Sediment on Modern Carbonate Platforms

AbstractThe measured carbon isotopic compositions of carbonate sediments (δ13Ccarb) on modern platforms are commonly 13C‐enriched compared to predicted values for minerals forming in isotopic equilibrium with the dissolved inorganic carbon (DIC) of modern seawater. This offset undermines the assumption that δ13Ccarb values of analogous facies in the rock record are an accurate archive of information about Earth's global carbon cycle. We present a new data set of the diurnal variation in carbonate chemistry and seawater δ13CDIC values on a modern carbonate platform. These data demonstrate that δ13Ccarb values on modern platforms are broadly representative of seawater, but only after accounting for the recent decrease in the δ13C value of atmospheric CO2 and shallow seawater DIC due to anthropogenic carbon release, a phenomenon commonly referred to as the 13C Suess effect. These findings highlight an important, yet overlooked, aspect of some modern carbonate systems, which must inform their use as ancient analogs.

Stereodivergent Synthesis of Pyridyl Cyclopropanes via Enzymatic Activation of Pyridotriazoles.

Hemoproteins have recently emerged as powerful biocatalysts for new-to-nature carbene transfer reactions. Despite this progress, these strategies have remained largely limited to diazo-based carbene precursor reagents. Here, we report the development of a biocatalytic strategy for the stereoselective construction of pyridine-functionalized cyclopropanes via the hemoprotein-mediated activation of pyridotriazoles (PyTz) as stable and readily accessible carbene sources. This method enables the asymmetric cyclopropanation of a variety of olefins, including electron-rich and electrodeficient ones, with high activity, high stereoselectivity, and enantiodivergent selectivity, providing access to mono- and diarylcyclopropanes that incorporate a pyridine moiety and thus two structural motifs of high value in medicinal chemistry. Mechanistic studies reveal a multifaceted role of 7-halogen substitution in the pyridotriazole reagent toward favoring multiple catalytic steps in the transformation. This work provides the first example of asymmetric olefin cyclopropanation with pyridotriazoles, paving the way to the exploitation of these attractive and versatile reagents for enzyme-catalyzed carbene-mediated reactions.

Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)-Catalyzed Enantioselective C(sp3)-H Functionalization.

Palladium-catalyzed enantioselective C(sp3)-H functionalization reactions has attracted considerable attention due to its ability for the synthesis of enantiomerically enriched molecules and stimulation of novel retrosynthetic disconnections. Understanding the reaction mechanism, especially the stereochemical process of the reaction, is crucial for the rational design of more efficient catalytic systems. Previously, we developed a Pd(II)/sulfoxide-2-hydroxypridine (SOHP) catalytic system for asymmetric C(sp3)-H functionalization reactions. In this study, we focused on unraveling the chemistry of chiral palladacycles involved in the Pd(II)-catalyzed enantioselective C(sp3)-H functionalization. We have isolated key palladacycle intermediates involved in the enantioselective β-C(sp3)-H arylation of carboxylic acids catalyzed by the Pd(II)/SOHP system. These palladacycles, exhibiting ligand-induced chirality, provided a significant opportunity to investigate the stereochemical process and the ligand effect in this asymmetric C-H functionalization. Our investigation provided direct evidence for the C-H palladation step as the enantioselectivity-determining step, which forms diastereomeric palladacycles that exhibited preservation of chirality in the functionalization step. DFT calculations provided insights into the chiral induction in palladacycle formation. This work highlights the value of chiral palladacycle chemistry in offering mechanistic insights into the Pd(II)-catalyzed asymmetric C(sp3)-H functionalization reactions.

Synthesis of Sterically Hindered Dialkyl Ethers via Palladium-Catalyzed Fluoro-alkoxylation of gem-Difluoroalkenes.

Organofluorine compounds are of high value in medicinal and agricultural chemistry. Herein, we report a palladium-catalyzed fluoro-alkoxylation of gem-difluoroalkenes for the synthesis of much more challenging sterically hindered ethers. This reaction represents a direct synthesis method for α-trifluoromethyl ethers with a broad functional group tolerance and excellent regioselectivity. This system employs N-fluorobenzenesulfonimide (NFSI) as an electrophilic fluorine source and alcohols as nucleophilic donors, including but not limited to sterically hindered tert-substituted alcohols.

Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)‐Catalyzed Enantioselective C(sp3)−H Functionalization

AbstractPalladium‐catalyzed enantioselective C(sp3)−H functionalization reactions has attracted considerable attention due to its ability for the synthesis of enantiomerically enriched molecules and stimulation of novel retrosynthetic disconnections. Understanding the reaction mechanism, especially the stereochemical process of the reaction, is crucial for the rational design of more efficient catalytic systems. Previously, we developed a Pd(II)/sulfoxide‐2‐hydroxypridine (SOHP) catalytic system for asymmetric C(sp3)−H functionalization reactions. In this study, we focused on unraveling the chemistry of chiral palladacycles involved in the Pd(II)‐catalyzed enantioselective C(sp3)−H functionalization. We have isolated key palladacycle intermediates involved in the enantioselective β‐C(sp3)−H arylation of carboxylic acids catalyzed by the Pd(II)/SOHP system. These palladacycles, exhibiting ligand‐induced chirality, provided a significant opportunity to investigate the stereochemical process and the ligand effect in this asymmetric C−H functionalization. Our investigation provided direct evidence for the C−H palladation step as the enantioselectivity‐determining step, which forms diastereomeric palladacycles that exhibited preservation of chirality in the functionalization step. DFT calculations provided insights into the chiral induction in palladacycle formation. This work highlights the value of chiral palladacycle chemistry in offering mechanistic insights into the Pd(II)‐catalyzed asymmetric C(sp3)−H functionalization reactions.

Boron sources of tourmaline-rich Nb-Y-F-pegmatites in south Norway: Implications for pegmatite melt origin

Tourmaline is common in rare element pegmatites of the Nb-Y-F (NYF) type in the south-central part of the Proterozoic Sveconorwegian orogen in southern Norway. In the global context, however, tourmaline appears rare in this type of pegmatite. This study aims to explain the unusual tourmaline abundance in these pegmatites and the origin of boron (B) in the respective melts, and to raise awareness of tourmaline in NYF pegmatites generally. Tourmalines from six pegmatites in three Sveconorwegian lithotectonic units: Bamble, Kongsberg and Idefjorden, were investigated in terms of their mineral chemistry and δ11B values, in addition to bulk rock analyses of pegmatites and host rocks. Tourmalines in pegmatites from Bamble and Kongsberg record B isotopic compositions (δ11B = -1.0 to + 9.9 ‰) that are heavy relative to continental crust and mantle sources. In contrast, tourmaline in pegmatites and host rocks from Idefjorden have light B isotopic ratios (δ11B = -14.8 to −12.5 ‰) that are typical crustal values. We suggest that the latter melts were sourced from orthogneisses at depth. We relate the heavy B isotopic composition of Bamble and Kongsberg pegmatites to regional Na-metasomatism by fluids sourced from Mesoproterozoic shallow marine sediments. This is supported by previously published δ11B ratios from metasomatized Bamble host rocks. The spatial association of pegmatites with Na-metasomatism in the basement rocks suggests that metasomatism enhanced the fertility and B-concentration in the affected lithologies, favouring partial melting and the formation of tourmaline-bearing pegmatites.These findings contribute to understanding the petrogenesis of Sveconorwegian pegmatites but they also imply that B can play a greater role in the formation of NYF pegmatites than previously thought and that tourmaline has value as a petrogenetic tool in this type of pegmatites as well as in the Li-Cs-Ta (LCT) type to which is it is more commonly applied.

Feeding dogs a high-fat diet induces metabolic changes similar to natural aging, including dyslipidemia, hyperinsulinemia, and peripheral insulin resistance.

The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers also associated with the metabolic dysfunction that occurs with natural aging. 24 male Beagle dogs, 3 to 7 years of age, of mixed castration status. Dogs were randomly assigned to continue twice daily feeding of the commercial adult maintenance diet (n = 12, including 2 intact) that they were previously fed or to a high-fat diet (12, including 2 intact) for 17 weeks between December 1, 2021, and April 28, 2022. Assessments included body composition (weight, body condition score, and adipose mass determined by deuterium enrichment), clinical chemistries, plasma fatty acid quantification, oral glucose tolerance test, and histology of subcutaneous and visceral adipose biopsy samples. The high-fat diet led to increased body weight, body condition score, fat mass and adipocyte size, hyperinsulinemia and peripheral insulin resistance, and elevations in serum lipids, including cholesterol, triglycerides, and several species of free fatty acids. Leptin levels increased in dogs fed a high-fat diet but not in control dogs. There were no significant changes in routine clinical chemistry values in either group. Feeding a high-fat diet for 17 weeks led to potentially deleterious changes in metabolism similar to those seen in natural aging in dogs, including hyperinsulinemia, insulin resistance, and dyslipidemia. A high-fat diet model may provide insights into the similar metabolic dysfunction that occurs during natural aging.

Structures and Acetylcholinesterase Inhibition Abilities of some Derivatives Bearing (Pyridin-2-yl)tetrazole Scaffold

Tetrazole derivatives are a prominent class of heterocycles that hold significant value in medicinal chemistry and drug design. Their importance stems from their bioisosteric resemblance to carboxylic acid and amide moieties and their favorable metabolic stability and other beneficial physicochemical properties. In light of this, novel derivatives bearing the (pyridine-2-yl)tetrazol scaffold were synthesized with the presence of acid, ester and amide moieties and evaluated for their inhibitory effects on the enzyme acetylcholinesterase (AChE). Through a three-step synthesis reaction initiated with 2-pyridine carbonitrile, compound IV was successfully obtained with II and III as the intermediates. All substances II - III - IV demonstrated inhibitory activity against the enzyme acetylcholinesterase. Notably, substance IV exhibited the highest percentage of inhibition, achieving 23,7 % at a concentration of 75 µM. Based on molecular docking simulations, compounds containing stronger nucleophilic substituents exhibit more robust AChE enzyme inhibitory activity due to a greater abundance of hydrogen bonds. This drug-likeness simulation and ADME prediction highlight the potential of tetrazole derivatives as a promising treatment for Alzheimer's disease.

Adolescents’ Intentions to Study Science: the Role of Classroom-based Social Support, Task Values, and Self-efficacy

AbstractDeclining enrolments in senior secondary science have heightened concerns for meeting the demands for more STEM-qualified workers and a scientifically literate society. Students' attitudes to science are formed during schooling, particularly in adolescence when they are exposed to a variety of science topics. Students’ perceptions of their ability in science and their subjective task values are well established as predictors of their likelihood of engaging with and continuing their study of science. However, the role of classroom-based social support in supporting ability perceptions and task values is less well understood. In this study, we examined relationships between adolescents’ perceived classroom-based social support, task values, and self-efficacy, and how these perceptions and attitudes predicted adolescents’ intentions to study the three major science subjects (biology, chemistry, and physics) in senior high school. Participants were 475 adolescents in Grades 8 to 10 recruited from six schools in Sydney, Australia. Structural equation modelling was employed to test the hypothesised model in which social support from science teachers and peers predicted intended science subject selections through science self-efficacy, intrinsic valuing of science, and utility value of science. Results indicate that science teacher and peer support were not directly related to adolescents’ intentions to study senior science subjects. Instead, they were indirectly related via their positive relationship with science self-efficacy and task values. Utility value was the strongest predictor of adolescents’ intentions to study biology, chemistry, and physics, while self-efficacy and intrinsic value also predicted adolescents’ intentions to study chemistry. These results suggest that classroom-based social supports are important for supporting adolescents’ attitudes towards science, and that science utility value interventions may be useful in efforts to improve enrolments in senior science subjects.

Boosting Critical Thinking Skills: Applying the Dilemma Stories Approach with the 5E Learning Cycle in Buffer Subject Education

This study explores the impact of the Dilemmas approach, rooted in transformative learning, on enhancing critical thinking skills in buffer chemistry subjects among high school students. Employing a mixed-methods design and purposive sampling, the research involved 34 eleventh-grade students from SMAN 1 Surakarta. The implementation of dilemma stories integrated with a 5E learning cycle was scrutinized using various data collection methods, including observations, student reflective journals, pretest-posttest assessments, the Constructivist Chemistry Values Learning Environment Survey (CCVLES), and interviews. Observations assessed the application of the dilemma stories and the 5E learning cycle. Pretest-posttest evaluations measured changes in students' critical thinking abilities, while reflective journals and CCVLES questionnaires captured students' perceptions of their critical thinking skills and their learning experiences. Interviews were conducted to validate the findings from the tests, journals, and questionnaires. Data analysis involved reduction, display, and conclusion-drawing techniques. The findings suggest that the Dilemmas approach significantly fosters students' ability to think critically and apply chemical concepts practically. This was evidenced by students' analyses of dilemma stories and responses in interviews, CCVLES questionnaires, and reflective journals, indicating a deeper engagement with and understanding of the subject matter through this innovative learning strategy.

Electrochemical oxidative radical cascade cyclization of dienes and diselenides towards the synthesis of seleno-benzazepines.

Selenium-containing compounds are important scaffolds owing to their value in medicinal chemistry, biochemistry and material chemistry. Herein, we report an electrochemical approach to access seleno-benzazepines through an oxidative radical cascade cyclization of dienes with diselenides under metal-free, external oxidant-free and base-free conditions. In a simple undivided cell, various dienes and diselenides were suitable for this transformation, generating the desired products in up to 84% yields. This method provides a green and convenient route for the synthesis of valuable selenium-containing seven-membered N-heterocycles from simple starting materials.

Phosphoric Acid Catalyzed N-Addition/ C-Addition Reaction of 3-Vinyl Indoles with Pyrazole/Pyrazolone to Construct Pyrazole-Substituted 3-(1-Heteroarylethyl)-indole Scaffolds.

Developing a highly efficient atom-economic method for the preparation of 3-(1-heteroarylethyl)-indole scaffolds is of significant value in pharmaceutical and agricultural chemistry. Herein, a phosphoric acid-catalyzed N-addition reaction of 3-vinyl indoles with pyrazoles and C-addition reaction of 3-vinyl indoles with pyrazolones were developed. A series of pyrazole-substituted 3-(1-heteroarylethyl)-indole scaffolds were synthesized in excellent yields (up to 99% yield) under mild reaction conditions. A reasonable reaction mechanism was proposed to explain the experimental results.