Chemistry - A European Journal最新文献

{"title":"One-Step and Universal Strategy for the Synthesis of Hypermodified Uracil Phosphoramidites acp³U and cmnm⁵U.","authors":"Ewa Mejdr, Lena Heinickel, Thomas Carell, Ivana Mejdr","doi":"10.1002/chem.202502848","DOIUrl":"10.1002/chem.202502848","url":null,"abstract":"<p><p>Hypermodified nucleosides have recently been at the center of scientific attention. They represent a unique group of nucleosides with an alternated structure, such as the addition of functional groups or amino acids. Their distinctive structures and positions in RNAs are crucial for the processes of translation and stability. High demand for oligonucleotides bearing those hypermodified nucleobases led us to the development of a single-step synthesis of acp³U phosphoramidite, as acp³U has been recognized as an important molecule for the structural integrity of tRNA and native immunity. We also present a novel synthesis of cmnm⁵U phosphoramidite and its incorporation into an oligonucleotide from a highly versatile starting material, allowing a transformation into at least two other hypermodified nucleosides.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e02848"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chain Versus Ring: Characterization of a Meta-Phenylene Ladder Polymer and Its Octameric Macrocycle.","authors":"Paulo D Nunes Barradas, Hauke J Jötten, Ngoc B B Nguyen, Ullrich Scherf, J Sérgio de Seixas de Melo","doi":"10.1002/chem.70744","DOIUrl":"10.1002/chem.70744","url":null,"abstract":"<p><p>A methyl-substituted ladder meta-phenylene macrocycle (MeLMMP) and its corresponding ladder polymer (MeLPMP), a meta-analogue of the well-known ladder-type poly(para-phenylene), LPPP, were synthesized and comprehensively investigated. Both compounds exhibit limited conjugation due to the meta-linked phenylene units, resulting in absorption and emission features shaped by cross-conjugation. Despite having a longer chain, MeLPMP and MeLMMP exhibit nearly identical electronic and photophysical behavior, suggesting that the number of repeat units has minimal influence. MeLPMP exhibits enhanced vibronic resolution compared to MeLMMP due to a broadening of the optical bands of the macrocycle caused by the presence of a mixture of stereoisomers formed during the non-stereoselective ladderization step. A small amount of fluorenone-type keto defects produces a weak emission near 500 nm, more evident in the macrocycle, and introduces radiationless decay pathways that compete with fluorescence. This decay pathway, together with the weak π,π* conjugation in these angular compounds, lowers the fluorescence quantum yield when compared with the linear MeLPPP, while promoting singlet-triplet conversion and phosphorescence. The data indicate the presence of three chromophoric populations: pristine oligo(meta-phenylene) units; units quenched by nearby keto defects; and intramolecular charge-transfer complexes (ICTCs) formed between oligo(meta-phenylene) units and keto defects. These findings clarify the photophysics of meta-phenylene ladder systems, showing that the MeLMMP macrocycle can act as a structural and electronic model for related ladder polymers.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e70744"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-Step Synthesis of a Chiral Fluorinated Alcohol With Silica-Supported Enzyme RrADH in Batch and Continuous Flow Mode.","authors":"Egzon Cermjani, Greta Nölke, Stefano Di Fiore, Christoph Deckers, Doris Hanselmann, Bettina Herbig, Susanne Wintzheimer, Thomas H Rehm","doi":"10.1002/chem.202503304","DOIUrl":"10.1002/chem.202503304","url":null,"abstract":"<p><p>The growing demand for sustainable and efficient methods for synthesizing fine chemicals has increased interest in innovative approaches for accessing high-quality chiral building blocks, particularly fluoroalcohols, which are relevant for the production of active pharmaceutical ingredients (APIs). This study presents the complete integration of a two-step process in a continuous flow reactor system for the synthesis of (R)-2-fluoro-1-phenylethanol as a reference molecule. To this end, the individual reaction steps and technologies for the decarboxylative fluorination of 3-oxo-3-phenylpropanoic acid in aqueous media, followed by an enantioselective biocatalytic reduction of the prochiral intermediate phenacyl fluoride, were adapted and implemented in a compact laboratory system for performance demonstration. Alcohol dehydrogenase (ADH) from Rhodococcus ruber (RrADH) produced in a plant-derived BY2 cell-free expression system was used as the biocatalyst, which was immobilized via an imine bond on glutaraldehyde-modified silica supraparticles. The immobilized enzymes were used in batch mode for comprehensive kinetic studies of the enantioselective reduction, including evaluations of their operational and storage stability. Excellent enantiomeric excess (> 99.9%) and overall yields of up to 91% were achieved for both synthesis steps. These results are a prerequisite for the targeted and stable use of the enzyme in a continuously operated two-step process, which was achieved by using a serial micro batch reactor (SMBR) setup with a capillary reactor for precise temperature control. This study demonstrates the advantages of combining immobilized biocatalysts with continuous-flow operation for achieving high efficiency and selectivity in the synthesis of chiral fluoroalcohols. The integrated process provides a sustainable and versatile basis for future developments in the green synthesis of fluorinated building blocks relevant to pharmaceutical applications.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e03304"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anion-π Interactions in Direct Amination of Core-Unsubstituted Perylene Monoimides.","authors":"Demet Demirci Gültekin, Murat Acar, Nezire Hanım Emanet, Seyda Aydogdu, Arzu Hatipoglu, Zhannur Myltykbayeva, Atıf Koca, Cavit Kazaz, Melek Fidan, Özgür Altan Bozdemir","doi":"10.1002/chem.70780","DOIUrl":"10.1002/chem.70780","url":null,"abstract":"<p><p>The incorporation of amino substituents at the peri-positions of perylene monoimides (PMIs) produces elusive push-pull systems with absorption and emission properties in the UV-vis and Near-IR regions. We describe a survey of different direct amination methods for the one-step synthesis of a series of 9-alkylamino and 9-arylamino PMIs. The first method tested is direct amination in neat amines and succesfull only for pyrrolidine. The second method uses the PCC/AgNO₃ oxidant system, and high yields are obtained with pyrrolidine. The third method employs KMnO₄/AgNO₃ as a stronger oxidant system. Pyrrolidine and piperidine are favorable amines for this method, and even diamino PMIs can be obtained. The fourth method uses a Cu(II) salt as a catalyst, and cyclic amines afford products in high yields. The final method is the anion-mediated direct amination and provides the most suitable method for a variety of cyclic, alkyl, and aryl amines to give 9-alkylamino and 9-arylamino PMIs in high yields. In this method, TBAF or TBAOH is used as the anion source, and our detailed spectroscopic and synthetic studies reveal that, as a result of single-electron transfer from the anion, PMIs can generate radical anions and participate in a radical mechanism in amination.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e70780"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of CuO/Co₃O₄ Heterojunction Catalyst for High-Efficiency Ammonia Synthesis via Nitrate Reduction.","authors":"Sha Song, Zhiwei Wang, Xinxiang Pei, Mingying Chen, Zhonghua Xu, Asmaa Farouk, Mohamed S Hamdy, Youcai Meng, Xiujuan Wu, Xuping Sun, Xijun Liu","doi":"10.1002/chem.202503623","DOIUrl":"10.1002/chem.202503623","url":null,"abstract":"<p><p>Electrochemical nitrate reduction reaction (NO₃RR) offers a sustainable approach to convert nitrate pollutants into ammonia (NH₃). However, challenges such as low NH₃ yield, competition from the hydrogen evolution reaction (HER), and limited nitrate adsorption restrict its efficiency. Here, we developed CuO/Co₃O₄ heterojunction catalysts with strong interfacial coupling that synergistically modulate the electronic structure to promote efficient electron transfer. This enhances nitrate adsorption and activation while suppressing HER by accelerating active hydrogen species formation. The catalyst demonstrated a high Faradaic efficiency (FE) of 94.58%, accompanied by an NH₃ production rate of 2306.44 µmol h^-1 mg^-1. Notably, it exhibited exceptional durability.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e03623"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pd-Catalyzed C─C Bond Borylation of Biphenylenes Leading to Tri-Ortho-Substituted Biaryls.","authors":"Robyn V Presland, Konstantin V Luzyanin, Luke A Wilkinson, Oliver L Jacobs, Nathan R Halcovitch, Alexey G Sergeev","doi":"10.1002/chem.202503515","DOIUrl":"10.1002/chem.202503515","url":null,"abstract":"<p><p>Ring-opening diborylation of carbon─carbon (C─C) single bonds is a powerful strategy for installing two versatile functional groups at nonadjacent carbon atoms, enabling skeletal editing of strained ring systems. However, such transformations remain rare for rings larger than cyclopropanes due to kinetic and thermodynamic challenges. Herein, we describe a palladium-catalyzed diborylation of 1-substituted biphenylenes enabled by a highly electron-rich and sterically demanding N-heterocyclic carbene (NHC) ligand. The reaction proceeds via selective cleavage of the least sterically hindered C─C bond and affords ortho-diborylated biphenyls in 39%-89% isolated yields across a broad range of 1-substituted biphenylenes with diverse steric and electronic properties. High regioselectivities (up to >20:1) are observed for cleavage of the least sterically hindered C─C bond. Regioselectivity is modulated by both electronic and steric effects: electron-donating aryl substituents enhance selectivity, as indicated by a Hammett correlation, whereas spherical substituents favour higher selectivity than planar aryl groups. Supporting stoichiometric experiments indicate a pathway involving initial C─C bond activation. The resulting sterically hindered tri-ortho-substituted biaryls may serve as valuable synthetic intermediates, as demonstrated by selective sequential orthogonal postfunctionalization of a representative example.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e03515"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strong Implications From Small Deviations in Labeling Patterns: The Mechanism of Burkholderia gladioli Pacifigorgiadiene Synthase.","authors":"Zhiyong Yin, Zhehui Hu, Xiyuan He, Juan Xu, Bernd Goldfuss, Jeroen S Dickschat, Guangkai Bian","doi":"10.1002/chem.202600029","DOIUrl":"10.1002/chem.202600029","url":null,"abstract":"<p><p>The sesquiterpene synthase BgPgS from Burkholderia gladioli produces the main product (-)-1-epi-pacifigorgia-6,10-diene, besides a few structurally related compounds. The enzyme mechanism of BgPgS was addressed through isotopic labeling experiments, revealing several intricate mechanistic problems. Unexpectedly, the isotopic labelings for the Me groups C12 and C13 occurred in different positions for the main and the side products. Moreover, as demonstrated in this study, two hydrogen atoms must change from the bottom to the top hemisphere, which is not possible through standard terpene biosynthesis routines with suprafacial hydrogen migrations. Our rational solution involves two mechanistic explanations: First, a key rearrangement may be associated with a conformational change that rotates one hydrogen from bottom to top. Second, a \"break-flip-cyclize\" sequence explains the change of side by the other hydrogen. DFT calculations show that the proposed terpene cyclization cascades are energetically feasible; only one problematic activation barrier (>25 kcal/mol) remains. However, several mechanistic alternatives either failed to explain the experimental results of the isotopic labeling experiments or were associated with even higher activation barriers. Our biosynthetic proposal for pacifigorgiadiene biosynthesis can be understood as a contribution that awaits further investigation and scientific debate for its ultimate resolution.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e00029"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinspired Manganese Catalyzed Direct Deamination of Primary Amines With Water Forming Carboxylic Acids and Ketones.","authors":"Sachin Jalwal, Akash Gutal, Rohit Kumar Saini, Aman Anand, Soumojyati Prodhan, Debangsu Sil, Manikandan Paranjothy, Subrata Chakraborty","doi":"10.1002/chem.70774","DOIUrl":"10.1002/chem.70774","url":null,"abstract":"<p><p>Herein, we are demonstrating an earth-abundant manganese-catalyzed oxidative deamination of linear and branched primary amines to selectively form carboxylic acids and ketones using water as the oxygen atom source. A series of pincer and non-pincer Mn complexes were assessed for these deaminative transformations. A bio-inspired DAFO (4,5-diazafluoren-9-one) ligand-based [(DAFO)Mn(CO)₃Br] complex (Mn-1) was found to be effective for the reaction proceeding under mildly basic aqueous medium, generating NH₃ and H₂ as sole by-products without the requirement of any oxidant. An optimized condition of 5 mol% Mn-1, Na₂CO₃ (1 equiv) at 150°C for 48 h in water/1,4-dioxane mixture furnished 92% of the corresponding benzoic acid from benzylamine. A wide variety of electron-donating and withdrawing para-, meta-, and ortho-substituted benzylamines, including promising hetero and aliphatic linear primary amines, afforded moderate to excellent yield of the desired carboxylate product. We have also examined a few branched primary amines using 5 mol% Mn-1 and catalytic sodium carbonate at 150°C for 48 h, affording good yield of ketones. The reaction was found to be chemo-selective for primary amine moieties over alcohol functionalities. Further, stoichiometric mechanistic investigation and preliminary computational data provide insights into the possible mechanistic steps.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e70774"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Turning Color Confusion to Clarity: A Layered Ce-Based Nanozyme Drives Rapid Wavelength Transition for Discriminative Detection of Nerve Agent during Decontamination.","authors":"Huidrom Mangalsana, Sruthy K, Amit A Vernekar","doi":"10.1002/chem.202503606","DOIUrl":"10.1002/chem.202503606","url":null,"abstract":"<p><p>Organophosphate (OP)-based nerve agents (NAs) pose serious risks to human life, demanding materials that facilitate rapid decontamination and reliable detection with selectivity. Ce-based metal organic frameworks (MOFs) are considered as promising candidates due to their high reactivity. However, their intrinsic yellow color misleads detection of NAs such as paraoxon, which releases yellow p-nitrophenol. Here, we report a bioinspired 2D metal-organic layer (MOL) construct, Ce-BTB-MOL, a phosphotriesterase nanozyme with abundant binding sites that not only facilitate rapid degradation of paraoxon (t_1/2 = 6 min), but quick detection by a smart mechanism. This nanozyme seamlessly arrests product with its binding to Ce clusters and triggering wavelength transition that overcomes color confusion, enabling quick and confident detection within 13 s on paper strips. Mechanistic studies reveal that p-nitrophenol binding to Ce clusters induces ligand-to-metal charge transfer (LMCT), producing an intense orange-brown signal. Based on the wavelength transition response, this nanozyme also showcases selective discrimination of structurally similar OPs, a challenge for conventional systems. Ce-BTB-MOL achieves real-time, affordable, portable, easy, and rapid sensing without the requirement of sophisticated equipment, with a detection limit as low as 1.24 µg, quantifiable by smartphone RGB analysis. Importantly, the nanozyme demonstrates high selectivity against several interferents, allowing precise surface contamination analysis.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e03606"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating the Discovery of Targeted Protein Degraders: Advances in Synthetic Methodologies and Screening Tactics.","authors":"Baoli Ding, Xiaotong Chen, Yulu Chen, Ji Cao, Bo Yang, Li Jiang, Cheng-Liang Zhu","doi":"10.1002/chem.202503641","DOIUrl":"10.1002/chem.202503641","url":null,"abstract":"<p><p>Targeted protein degradation (TPD) is significantly expanding the druggable landscape to include proteins that are intractable to conventional occupancy-based inhibition. However, the discovery of targeted protein degraders is often less efficient due to their structural complexity and the labor-intensive nature of traditional medicinal chemistry campaigns. To capture the recent advances developed to streamline and accelerate degrader discovery, this review summarizes enabling synthetic methodologies and state-of-the-art screening strategies specialized for this field. From the well-established click chemistry to emerging late-stage functionalization, we highlight a wide array of robust and versatile chemistries that facilitate the rapid construction of diverse degrader libraries. Moreover, we elucidate how these synthetic toolkits synergize with screening tactics to expand the biological space and maximize the efficiency of identifying promising degrader candidates. Furthermore, we underscore that evolving automation and robotic workflows are integrating with these synthetic and screening strategies to propel a new era of degrader discovery. By providing a comprehensive overview and critical perspectives on these advancements, this review aims to offer a practical roadmap for researchers to streamline degrader synthesis and strategically screen their libraries, with the hope of inspiring continued innovation to expedite the discovery of novel degraders with both biological and therapeutic importance.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e03641"},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}