Pub Date : 2026-02-09Epub Date: 2026-01-27DOI: 10.1021/acs.biomac.5c02213
Robert Dec, Wojciech Dzwolak, Roland Winter
Liquid-liquid phase separation (LLPS) is involved in both the self-assembly of vital cellular organelles and the disease-associated protein misfolding, where LLPS precedes a liquid-solid phase transition (LSPT) leading to amyloid aggregates. Chimeric ACC1-13Kn peptides are insightful models to study coupled LLPS/LSPT processes triggered by ATP-binding. Here, we investigated the impact of macromolecular crowding on the selection of the aggregation pathway in the ACC1-13K8-ATP system. While it has been previously shown that peptides with relatively short oligolysine segments (K16 and shorter) skip the LLPS stage on their pathway to amyloid fibrils, we show here that concentrated polyethylene glycol (PEG), mimicking intracellular crowding conditions, induces prior formation of liquid droplets that subsequently facilitate fibril formation. The influence of PEG contrasts with the behavior of other types of macromolecular crowding agents, Dextran and Ficoll, which accelerate aggregation without a detectable LLPS phase, and that of serum albumin, which prolongs the nucleation phase. In the presence of PEG-induced macromolecular crowding, the fibrillization in the ACC1-13K8-ATP system appears to reach a maximal rate limited by diffusion coupled to the conformational dynamics of the polypeptide chains within the droplets. Importantly, the ACC1-13K8-ATP fibrils formed in the presence of PEG are distinct from those of the ACC1-13K8-ATP amyloid formed in the absence of crowding in terms of their infrared characteristics, morphological features, and overall stability. Our findings suggest that macromolecular crowding can switch between kinetically and thermodynamically favored amyloid polymorphs and that the chemical properties of the crowding agents are key factors in their impact on protein aggregation processes. The results are discussed in the context of the mechanisms of LLPS-dependent protein misfolding and amyloid formation.
{"title":"Crowding-Induced Liquid-Liquid Phase Separation in the ATP-Binding ACC<sub>1-13</sub>K<sub>8</sub> Peptide Leads to a Distinct Amyloid Variant.","authors":"Robert Dec, Wojciech Dzwolak, Roland Winter","doi":"10.1021/acs.biomac.5c02213","DOIUrl":"10.1021/acs.biomac.5c02213","url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS) is involved in both the self-assembly of vital cellular organelles and the disease-associated protein misfolding, where LLPS precedes a liquid-solid phase transition (LSPT) leading to amyloid aggregates. Chimeric ACC<sub>1-13</sub>K<sub><i>n</i></sub> peptides are insightful models to study coupled LLPS/LSPT processes triggered by ATP-binding. Here, we investigated the impact of macromolecular crowding on the selection of the aggregation pathway in the ACC<sub>1-13</sub>K<sub>8</sub>-ATP system. While it has been previously shown that peptides with relatively short oligolysine segments (K<sub>16</sub> and shorter) skip the LLPS stage on their pathway to amyloid fibrils, we show here that concentrated polyethylene glycol (PEG), mimicking intracellular crowding conditions, induces prior formation of liquid droplets that subsequently facilitate fibril formation. The influence of PEG contrasts with the behavior of other types of macromolecular crowding agents, Dextran and Ficoll, which accelerate aggregation without a detectable LLPS phase, and that of serum albumin, which prolongs the nucleation phase. In the presence of PEG-induced macromolecular crowding, the fibrillization in the ACC<sub>1-13</sub>K<sub>8</sub>-ATP system appears to reach a maximal rate limited by diffusion coupled to the conformational dynamics of the polypeptide chains within the droplets. Importantly, the ACC<sub>1-13</sub>K<sub>8</sub>-ATP fibrils formed in the presence of PEG are distinct from those of the ACC<sub>1-13</sub>K<sub>8</sub>-ATP amyloid formed in the absence of crowding in terms of their infrared characteristics, morphological features, and overall stability. Our findings suggest that macromolecular crowding can switch between kinetically and thermodynamically favored amyloid polymorphs and that the chemical properties of the crowding agents are key factors in their impact on protein aggregation processes. The results are discussed in the context of the mechanisms of LLPS-dependent protein misfolding and amyloid formation.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"1603-1611"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058276","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}
Pub Date : 2026-02-09Epub Date: 2026-01-27DOI: 10.1021/acs.jcim.5c02503
Austė Kanapeckaitė, Sarper Okuyan, David James Wagg, Jan Koster, Ligita Jančorienė, Indrė Sakalauskaitė, Birutė Brasiu̅nienė, Andrea Townsend-Nicholson
Therapeutic interventions for complex diseases depend on the targeted modulation of key pathological pathways. While growing clinical needs continue to drive advancements in the drug discovery space, current strategies primarily rely on searching large volumes of chemical data without addressing the specific contributions of molecular features. Moreover, both clinicians and researchers recognize the need for improved drug discovery methods and characterization that could aid in clinical strategy selection. To address these challenges, we propose a new perspective on targeted therapy development as well as interactome mapping, utilizing molecular fragments. The present study focuses on therapeutic areas that represent emerging targets, namely JAK2 and GLP-1R, both of which have broad clinical potential. We developed a new self-adjusting neural network that enabled us to discover novel therapeutic candidates with improved in silico binding profiles, gain additional insights into drug-target binding that were not previously reported, and identify new metabolic trajectories. Importantly, our work revealed that even a small compound library can effectively generate lead candidates, expediting the search and exploration process. In addition, the fragment-guided bridging of chemical and biological spaces has revealed new opportunities for drug repurposing efforts and a means of improving the prediction of side effects. We concluded our study with insights into the recent high-profile clinical trial failure of danuglipron and how this could have been prevented with our methodology. Thus, building a robust in silico pipeline with integrated screening data can significantly reduce costs and guide therapy adoption. Furthermore, our proposed strategy highlights promising avenues for the discovery of new therapeutics and the development of clinical interventions.
{"title":"Fragment-Guided New Therapeutic Molecule Discovery and Mapping of Clinically Relevant Interactomes.","authors":"Austė Kanapeckaitė, Sarper Okuyan, David James Wagg, Jan Koster, Ligita Jančorienė, Indrė Sakalauskaitė, Birutė Brasiu̅nienė, Andrea Townsend-Nicholson","doi":"10.1021/acs.jcim.5c02503","DOIUrl":"10.1021/acs.jcim.5c02503","url":null,"abstract":"<p><p>Therapeutic interventions for complex diseases depend on the targeted modulation of key pathological pathways. While growing clinical needs continue to drive advancements in the drug discovery space, current strategies primarily rely on searching large volumes of chemical data without addressing the specific contributions of molecular features. Moreover, both clinicians and researchers recognize the need for improved drug discovery methods and characterization that could aid in clinical strategy selection. To address these challenges, we propose a new perspective on targeted therapy development as well as interactome mapping, utilizing molecular fragments. The present study focuses on therapeutic areas that represent emerging targets, namely JAK2 and GLP-1R, both of which have broad clinical potential. We developed a new self-adjusting neural network that enabled us to discover novel therapeutic candidates with improved in silico binding profiles, gain additional insights into drug-target binding that were not previously reported, and identify new metabolic trajectories. Importantly, our work revealed that even a small compound library can effectively generate lead candidates, expediting the search and exploration process. In addition, the fragment-guided bridging of chemical and biological spaces has revealed new opportunities for drug repurposing efforts and a means of improving the prediction of side effects. We concluded our study with insights into the recent high-profile clinical trial failure of danuglipron and how this could have been prevented with our methodology. Thus, building a robust in silico pipeline with integrated screening data can significantly reduce costs and guide therapy adoption. Furthermore, our proposed strategy highlights promising avenues for the discovery of new therapeutics and the development of clinical interventions.</p>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":" ","pages":"1482-1497"},"PeriodicalIF":5.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058410","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}
Cysteine fluorescent probes are specialized molecular tools that facilitate highly sensitive detection of cysteine via alterations in fluorescent signals. Currently, these probes have been widely employed in fields including disease biomarker monitoring, redox balance research, and drug toxicity assessment, thereby exhibiting substantial application potential in biochemical and biomedical studies. In this study, a novel fluorescent probe was designed for detecting cysteine based on the thiopyrone structure. Through characterization of its properties, it was found that this fluorescent probe exhibits a large Stokes shift (217 nm), excellent sensitivity (13.60 nM), rapid response time (3.0 min), high stability and selectivity. Furthermore, this cysteine fluorescent probe demonstrates excellent applications in RAW 264.7 cells, zebrafish, and actual samples. This study also proposes a more convenient method for testing cysteine levels using mobile phone software, and the findings indicate that the fluorescent probe under investigation has considerable potential for use in cysteine detection.
{"title":"A coumarin functionalized NIR fluorescent probe based on the thiopyrone skeleton for the detection of Cys and its applications.","authors":"Huan Zhang, Baoze Guo, Junqing Zhou, Cong Sun, Jinwei Zhang, Shuai Guo, Songhua Zhu, Youlai Zhang","doi":"10.1039/d5ay02068a","DOIUrl":"https://doi.org/10.1039/d5ay02068a","url":null,"abstract":"<p><p>Cysteine fluorescent probes are specialized molecular tools that facilitate highly sensitive detection of cysteine <i>via</i> alterations in fluorescent signals. Currently, these probes have been widely employed in fields including disease biomarker monitoring, redox balance research, and drug toxicity assessment, thereby exhibiting substantial application potential in biochemical and biomedical studies. In this study, a novel fluorescent probe was designed for detecting cysteine based on the thiopyrone structure. Through characterization of its properties, it was found that this fluorescent probe exhibits a large Stokes shift (217 nm), excellent sensitivity (13.60 nM), rapid response time (3.0 min), high stability and selectivity. Furthermore, this cysteine fluorescent probe demonstrates excellent applications in RAW 264.7 cells, zebrafish, and actual samples. This study also proposes a more convenient method for testing cysteine levels using mobile phone software, and the findings indicate that the fluorescent probe under investigation has considerable potential for use in cysteine detection.</p>","PeriodicalId":64,"journal":{"name":"Analytical Methods","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The accurate diagnosis of anxiety disorders remains challenging, as current detection methods primarily rely on subjective questionnaires. In this study, a novel electrochemical biosensor for the detection of fibroblast growth factor-2 (FGF-2), a biomarker associated with anxiety disorders, was developed for the first time. The sensing principle was based on monitoring the impedimetric signal changes generated by the interaction between anti-FGF-2 and the FGF-2 antigen, using a carbon screen-printed electrode as the transducer. To enhance the sensitivity and overall performance of the biosensor, a multi-walled carbon nanotube-gold-platinum (MWCNT-Au-Pt) hybrid nanocomposite was incorporated into the immunosensor structure. Critical parameters-including the amount of MWCNT-Au-Pt, the concentration, incubation time, and temperature of anti-FGF-2, as well as the incubation time and temperature for the anti-FGF-2/FGF-2 interaction-were systematically optimized. Under optimized conditions, the developed impedimetric FGF-2 immunosensor exhibited a linear response in the range of 10-100 ng/mL, with a limit of detection of 1.01 ng/mL and a limit of quantification of 3.10 ng/mL. The specificity of the sensor was confirmed in the presence of potential interfering substances. For real sample analysis, human saliva samples (n = 30) were diluted appropriately and spiked with FGF-2 at concentrations of 20, 50, and 75 ng/mL. The obtained recovery values demonstrated that the developed impedimetric FGF-2 immunosensor is highly suitable for real-sample applications and holds significant potential as a reliable tool for the detection of anxiety disorders.
{"title":"MWCNT-Au-Pt hybrid nanocomposite-based electrochemical immunosensor for FGF-2 detection: a novel strategy for anxiety disorder diagnosis.","authors":"Nil Su Çaylayik, Vasfiye Hazal Özyurt, Burak Ekrem Çitil, Ülkü Anik","doi":"10.1007/s00216-026-06346-z","DOIUrl":"https://doi.org/10.1007/s00216-026-06346-z","url":null,"abstract":"<p><p>The accurate diagnosis of anxiety disorders remains challenging, as current detection methods primarily rely on subjective questionnaires. In this study, a novel electrochemical biosensor for the detection of fibroblast growth factor-2 (FGF-2), a biomarker associated with anxiety disorders, was developed for the first time. The sensing principle was based on monitoring the impedimetric signal changes generated by the interaction between anti-FGF-2 and the FGF-2 antigen, using a carbon screen-printed electrode as the transducer. To enhance the sensitivity and overall performance of the biosensor, a multi-walled carbon nanotube-gold-platinum (MWCNT-Au-Pt) hybrid nanocomposite was incorporated into the immunosensor structure. Critical parameters-including the amount of MWCNT-Au-Pt, the concentration, incubation time, and temperature of anti-FGF-2, as well as the incubation time and temperature for the anti-FGF-2/FGF-2 interaction-were systematically optimized. Under optimized conditions, the developed impedimetric FGF-2 immunosensor exhibited a linear response in the range of 10-100 ng/mL, with a limit of detection of 1.01 ng/mL and a limit of quantification of 3.10 ng/mL. The specificity of the sensor was confirmed in the presence of potential interfering substances. For real sample analysis, human saliva samples (n = 30) were diluted appropriately and spiked with FGF-2 at concentrations of 20, 50, and 75 ng/mL. The obtained recovery values demonstrated that the developed impedimetric FGF-2 immunosensor is highly suitable for real-sample applications and holds significant potential as a reliable tool for the detection of anxiety disorders.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140741","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}
Pub Date : 2026-02-09DOI: 10.1016/j.ccr.2026.217667
S.G. Siddanth, Tiju Thomas
High-entropy (HE) design has materialized as a transformative paradigm in Na-based electrochemical energy storage, redefining the conventional boundaries of compositional and structural optimization. This review elucidates the fundamental principles governing configurational entropy, lattice disorder, and their impact on phase stability and ion-transport pathways in HE electrodes and solid-state electrolytes. Comparative analysis with traditional analogues reveals that compositional complexity stabilizes metastable frameworks, mitigates Jahn-Teller distortions, and broadens Na+ diffusion networks via entropy-mediated flattening of the free-energy surface, effectively lowering the energy above the convex hull. A critical examination of synthesis and processing methodologies, from solid-state and wet-chemical routes to high-pressure-field-assisted sintering, underlines the complex interplay of precursor chemistry, configurational homogeneity, and resulting electrochemical behavior. HE strategies across electrodes and interfaces are discussed with emphasis on the synergy of structural resilience, redox reversibility, and interfacial stability. Intrinsic stability aspects, including mechanical, air, and thermal stability, are correlated with compositional tuning. The review further identifies persisting challenges in entropy quantification, synthetic reproducibility, and predictive modeling of ion transport in disordered lattices. Finally, it presents perspectives integrating machine learning, density functional theory, and molecular dynamics within high-throughput frameworks to accelerate discovery and establish design-property correlations in complex chemical spaces.
{"title":"High-entropy design principles for sodium-based electrochemical energy storage systems","authors":"S.G. Siddanth, Tiju Thomas","doi":"10.1016/j.ccr.2026.217667","DOIUrl":"https://doi.org/10.1016/j.ccr.2026.217667","url":null,"abstract":"High-entropy (HE) design has materialized as a transformative paradigm in Na-based electrochemical energy storage, redefining the conventional boundaries of compositional and structural optimization. This review elucidates the fundamental principles governing configurational entropy, lattice disorder, and their impact on phase stability and ion-transport pathways in HE electrodes and solid-state electrolytes. Comparative analysis with traditional analogues reveals that compositional complexity stabilizes metastable frameworks, mitigates Jahn-Teller distortions, and broadens Na<sup>+</sup> diffusion networks via entropy-mediated flattening of the free-energy surface, effectively lowering the energy above the convex hull. A critical examination of synthesis and processing methodologies, from solid-state and wet-chemical routes to high-pressure-field-assisted sintering, underlines the complex interplay of precursor chemistry, configurational homogeneity, and resulting electrochemical behavior. HE strategies across electrodes and interfaces are discussed with emphasis on the synergy of structural resilience, redox reversibility, and interfacial stability. Intrinsic stability aspects, including mechanical, air, and thermal stability, are correlated with compositional tuning. The review further identifies persisting challenges in entropy quantification, synthetic reproducibility, and predictive modeling of ion transport in disordered lattices. Finally, it presents perspectives integrating machine learning, density functional theory, and molecular dynamics within high-throughput frameworks to accelerate discovery and establish design-property correlations in complex chemical spaces.","PeriodicalId":289,"journal":{"name":"Coordination Chemistry Reviews","volume":"22 1","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spin polarization governs the kinetics of multielectron water oxidation, yet benchmark catalysts like IrO2 lack intrinsic ferromagnetism at ambient temperature, precluding spin control. Here, we exploit the interfacial Dzyaloshinskii–Moriya interaction (DMI) in Co/IrO2 bilayers to induce spin-polarized states in the surface IrO2. This DMI-driven spin polarization boosts intrinsic oxygen evolution reaction activity by 1 order of magnitude, achieving a turnover frequency of 4.17 s–1 at 300 mV overpotential. Ferromagnetic resonance spectroscopy quantifies strong interfacial spin polarization via a 100% increase in the Gilbert damping. Spin-polarized DFT shows that DMI stabilizes a ferromagnetic ground state in IrO2 and reveals that spin ordering alters the adsorption configurations and lowers reaction barriers for *OH dehydrogenation and O–O coupling. Inserting a Cu spacer eliminates DMI, quenching both magnetism and catalytic enhancement. Our results establish interfacial DMI as a general strategy to activate hidden spin states in nonmagnetic oxides, offering a new route to surpass the activity limits in water-oxidation catalysis.
{"title":"Water Oxidation Promoted by Proximity-Induced Magnetism under Dzyaloshinskii–Moriya Interaction","authors":"Xiao Ren,Lei Tao,Tianze Wu,Rui Sun,Xiaotian Zhao,Xingjie Peng,Wu Zhou,Ding Ma,Shixuan Du,Zhichuan J. Xu","doi":"10.1021/jacs.5c17778","DOIUrl":"https://doi.org/10.1021/jacs.5c17778","url":null,"abstract":"Spin polarization governs the kinetics of multielectron water oxidation, yet benchmark catalysts like IrO2 lack intrinsic ferromagnetism at ambient temperature, precluding spin control. Here, we exploit the interfacial Dzyaloshinskii–Moriya interaction (DMI) in Co/IrO2 bilayers to induce spin-polarized states in the surface IrO2. This DMI-driven spin polarization boosts intrinsic oxygen evolution reaction activity by 1 order of magnitude, achieving a turnover frequency of 4.17 s–1 at 300 mV overpotential. Ferromagnetic resonance spectroscopy quantifies strong interfacial spin polarization via a 100% increase in the Gilbert damping. Spin-polarized DFT shows that DMI stabilizes a ferromagnetic ground state in IrO2 and reveals that spin ordering alters the adsorption configurations and lowers reaction barriers for *OH dehydrogenation and O–O coupling. Inserting a Cu spacer eliminates DMI, quenching both magnetism and catalytic enhancement. Our results establish interfacial DMI as a general strategy to activate hidden spin states in nonmagnetic oxides, offering a new route to surpass the activity limits in water-oxidation catalysis.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"39 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bereket L. Zekarias,Luis Pablo Arriaga Gonzalez,Olivia A. De Luca,Andrew Kelly,Kevin Qian,Eric A. Riesel,Connor Orrison,Dong Hee Son,Evripidis Michail,Matthew Y. Sfeir,Rachel N. Austin,Jonathan S. Owen,Makeda A. Tekle-Smith
Mn2+-doped CdS/ZnS quantum dots, in which surface stearate ligands are replaced with ligands that form ion pairs, are stable photocatalysts capable of reducing a variety of aryl chloride substrates, defluorinating fluorinated aromatic compounds, and facilitating the formation of new C–C bonds. Enhanced activity of the electrostatically stabilized quantum dot dispersions in polar solutions is observed at very low catalyst loadings (0.0005 mol %). The full scope of the reactions studied points to the importance of engineering quantum dot surface chemistry to control the reactivity afforded by hot electrons generated by multiphoton absorption and Auger upconversion.
{"title":"Engineering Mn2+-Doped CdS/ZnS Quantum Dot Surfaces to Control Auger Upconversion Photocatalysis","authors":"Bereket L. Zekarias,Luis Pablo Arriaga Gonzalez,Olivia A. De Luca,Andrew Kelly,Kevin Qian,Eric A. Riesel,Connor Orrison,Dong Hee Son,Evripidis Michail,Matthew Y. Sfeir,Rachel N. Austin,Jonathan S. Owen,Makeda A. Tekle-Smith","doi":"10.1021/jacs.5c21777","DOIUrl":"https://doi.org/10.1021/jacs.5c21777","url":null,"abstract":"Mn2+-doped CdS/ZnS quantum dots, in which surface stearate ligands are replaced with ligands that form ion pairs, are stable photocatalysts capable of reducing a variety of aryl chloride substrates, defluorinating fluorinated aromatic compounds, and facilitating the formation of new C–C bonds. Enhanced activity of the electrostatically stabilized quantum dot dispersions in polar solutions is observed at very low catalyst loadings (0.0005 mol %). The full scope of the reactions studied points to the importance of engineering quantum dot surface chemistry to control the reactivity afforded by hot electrons generated by multiphoton absorption and Auger upconversion.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"45 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henrik R. Wilke,Marlene Fadel,Kacper J. Patej,Jan P. Prohaska,Jonathan Kastner,Veronika Avramenko,Oscar Garcia Gonzalez,Rüveyda Bal,Matteo C. Amberg,Jameel Ahmad,Nima Nasiri,Tobias K. Jenny,Erick M. Carreira
We report the first total synthesis of (±)-dhilirolide U, a highly oxidized meroterpenoid featuring a densely functionalized 6/6/6/5/5-pentacyclic skeleton. Central to the strategy are a MnIII-mediated cyclization sequence and a Payne-type rearrangement cascade, which together forge a bicyclo[3.2.1]octane fused to a γ-lactone─the defining motif of the dhilirolide natural product family. Both transformations proceed in high yields and with excellent diastereocontrol. Intramolecular Ni-catalyzed conjugate addition was leveraged to install the vicinal quaternary carbon centers. This transformation set the stage for construction of the tetrahydroisochromenone subunit and completion of (±)-dhilirolide U. The reported route to the highly decorated bicyclo[3.2.1]octane provides a blueprint to access the diverse family that are the complex dhilirolide meroterpenoids.
{"title":"Total Synthesis of (±)-Dhilirolide U","authors":"Henrik R. Wilke,Marlene Fadel,Kacper J. Patej,Jan P. Prohaska,Jonathan Kastner,Veronika Avramenko,Oscar Garcia Gonzalez,Rüveyda Bal,Matteo C. Amberg,Jameel Ahmad,Nima Nasiri,Tobias K. Jenny,Erick M. Carreira","doi":"10.1021/jacs.5c22734","DOIUrl":"https://doi.org/10.1021/jacs.5c22734","url":null,"abstract":"We report the first total synthesis of (±)-dhilirolide U, a highly oxidized meroterpenoid featuring a densely functionalized 6/6/6/5/5-pentacyclic skeleton. Central to the strategy are a MnIII-mediated cyclization sequence and a Payne-type rearrangement cascade, which together forge a bicyclo[3.2.1]octane fused to a γ-lactone─the defining motif of the dhilirolide natural product family. Both transformations proceed in high yields and with excellent diastereocontrol. Intramolecular Ni-catalyzed conjugate addition was leveraged to install the vicinal quaternary carbon centers. This transformation set the stage for construction of the tetrahydroisochromenone subunit and completion of (±)-dhilirolide U. The reported route to the highly decorated bicyclo[3.2.1]octane provides a blueprint to access the diverse family that are the complex dhilirolide meroterpenoids.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"5 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1016/j.ccr.2026.217624
Anton Vidal-Ferran
Since its emergence in the late 1970s, supramolecular chemistry has become a cornerstone of modern chemical science. Defined by the controlled assembly of molecular components through reversible interactions, it encompasses a wide spectrum of forces, among which halogen bonding (XB) has gained prominence as a versatile and directional interaction with unique applications in molecular design and catalysis. This review highlights catalytic systems in which halogen bonding functions either (i) as an activating interaction toward functional groups; (ii) as a promoter of halogen abstraction in organic substrates and metal complexes; or (iii) as a structural element directing the assembly of the catalyst framework. To maintain a focused and critical perspective, only catalytic systems employing 10 mol% of catalyst or less and demonstrating applicability to the synthesis of structurally diverse product arrays are discussed. The review is organized according to the role of the catalyst, providing a coherent framework for understanding how halogen bonding governs activation, selectivity, and molecular organization. Collectively, the studies discussed herein illustrate how halogen bonding has evolved from a supramolecular curiosity into a tool in catalysis, expanding both the conceptual and practical boundaries of modern supramolecular catalysis.
{"title":"The rise of halogen bonding in (stereo)selective supramolecular catalysis","authors":"Anton Vidal-Ferran","doi":"10.1016/j.ccr.2026.217624","DOIUrl":"https://doi.org/10.1016/j.ccr.2026.217624","url":null,"abstract":"Since its emergence in the late 1970s, supramolecular chemistry has become a cornerstone of modern chemical science. Defined by the controlled assembly of molecular components through reversible interactions, it encompasses a wide spectrum of forces, among which halogen bonding (XB) has gained prominence as a versatile and directional interaction with unique applications in molecular design and catalysis. This review highlights catalytic systems in which halogen bonding functions either (i) as an activating interaction toward functional groups; (ii) as a promoter of halogen abstraction in organic substrates and metal complexes; or (iii) as a structural element directing the assembly of the catalyst framework. To maintain a focused and critical perspective, only catalytic systems employing 10 mol% of catalyst or less and demonstrating applicability to the synthesis of structurally diverse product arrays are discussed. The review is organized according to the role of the catalyst, providing a coherent framework for understanding how halogen bonding governs activation, selectivity, and molecular organization. Collectively, the studies discussed herein illustrate how halogen bonding has evolved from a supramolecular curiosity into a tool in catalysis, expanding both the conceptual and practical boundaries of modern supramolecular catalysis.","PeriodicalId":289,"journal":{"name":"Coordination Chemistry Reviews","volume":"59 17 1","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The three-dimensional (3D) cyano-based organic–inorganic hybrid double perovskites (CHOIPs) have shown great application potential in the field of multifunctional materials due to their unique ferroelasticity, ferroelectricity, and dielectric-switching properties. However, the inherent spatial limitations of the 3D rigid framework greatly restrict the types and sizes of organic cations that can be introduced, and they limit the further regulation and optimization of material properties. A zero-dimensional (0D) CHOIPs ferroelastic material, (MA)3[Fe(CN)6] (MA = CH3NH3+), was reported to break through this limitation, providing an idea for the development of 0D CHOIPs phase-transition materials, but reports on 0D CHOIPs ferroelastic phase-transition materials are still scarce. In this study, we adopted the H/F substitution strategy and synthesized two 0D organic–inorganic hybrid metal cyanide materials, (EA)3[Fe(CN)6] (EA = CH3CH2NH3+, ethylamine) and (DFEA)3[Fe(CN)6] (DFEA = F2CHCH2NH3+). The results show that the phase transition of (DFEA)3[Fe(CN)6] originates from the coupling mechanism of the ordered–disordered transformation of organic cations and the coordinated rotation of inorganic [Fe(CN)6]3– octahedrons. By introducing fluorine atoms, the phase-transition temperature is significantly higher than that of EA+. This work provides ideas for the structural design and material-property optimization of 0D organic–inorganic hybrid metal cyanides.
{"title":"H/F Substitution Strategy in 0D Organic–Inorganic Hybrid Metal Cyanides Designing Ferroelastic Phase-Transition Materials","authors":"Luan-Ying Ji,Shu-Yi Liu,Jun-Si Zhou,Zhi-Lin Liao,Si-Qi Yu,Di Gao,Huang-Dong Wang,Jian-Chun Liu,Kai-Wen Jiang,Xiao-Gang Chen","doi":"10.1021/acs.inorgchem.6c00011","DOIUrl":"https://doi.org/10.1021/acs.inorgchem.6c00011","url":null,"abstract":"The three-dimensional (3D) cyano-based organic–inorganic hybrid double perovskites (CHOIPs) have shown great application potential in the field of multifunctional materials due to their unique ferroelasticity, ferroelectricity, and dielectric-switching properties. However, the inherent spatial limitations of the 3D rigid framework greatly restrict the types and sizes of organic cations that can be introduced, and they limit the further regulation and optimization of material properties. A zero-dimensional (0D) CHOIPs ferroelastic material, (MA)3[Fe(CN)6] (MA = CH3NH3+), was reported to break through this limitation, providing an idea for the development of 0D CHOIPs phase-transition materials, but reports on 0D CHOIPs ferroelastic phase-transition materials are still scarce. In this study, we adopted the H/F substitution strategy and synthesized two 0D organic–inorganic hybrid metal cyanide materials, (EA)3[Fe(CN)6] (EA = CH3CH2NH3+, ethylamine) and (DFEA)3[Fe(CN)6] (DFEA = F2CHCH2NH3+). The results show that the phase transition of (DFEA)3[Fe(CN)6] originates from the coupling mechanism of the ordered–disordered transformation of organic cations and the coordinated rotation of inorganic [Fe(CN)6]3– octahedrons. By introducing fluorine atoms, the phase-transition temperature is significantly higher than that of EA+. This work provides ideas for the structural design and material-property optimization of 0D organic–inorganic hybrid metal cyanides.","PeriodicalId":40,"journal":{"name":"Inorganic Chemistry","volume":"3 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138935","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}