Yinpeng Wang, Yi Li, Haorui Wang, Lujie Ji, Yu Fu, Xingzhong Gao, Qi-Lin Zhou, Weiwei Xu, Mengchun Ye
Transition metal-catalyzed enantioselective intermolecular cycloaddition of cyclopropyl ketones and π-unsaturated compounds represents a long-standing challenge in the asymmetric C–C bond activation of cyclopropanes. Developed strategies rely on substrate modifications to mitigate racemization or to stabilize radical intermediates. In contrast, an efficient approach governed by transition-metal catalysts for general cyclopropyl ketones remains an elusive challenge. Herein, we report a highly active chiral diamine–phosphine oxide-ligated Ni–Al bimetallic catalyst that promotes enantioselective C–C cycloaddition under mild conditions. This system effectively suppresses product racemization and affords a diverse range of cyclopentyl ketones bearing a chiral α-tertiary carbon center in up to 99% yield and 99% ee.
{"title":"Enantioselective Ni–Al Bimetal-Catalyzed Cycloaddition of Cyclopropyl Ketones with Alkynes under Mild Conditions","authors":"Yinpeng Wang, Yi Li, Haorui Wang, Lujie Ji, Yu Fu, Xingzhong Gao, Qi-Lin Zhou, Weiwei Xu, Mengchun Ye","doi":"10.1021/jacs.5c18087","DOIUrl":"https://doi.org/10.1021/jacs.5c18087","url":null,"abstract":"Transition metal-catalyzed enantioselective intermolecular cycloaddition of cyclopropyl ketones and π-unsaturated compounds represents a long-standing challenge in the asymmetric C–C bond activation of cyclopropanes. Developed strategies rely on substrate modifications to mitigate racemization or to stabilize radical intermediates. In contrast, an efficient approach governed by transition-metal catalysts for general cyclopropyl ketones remains an elusive challenge. Herein, we report a highly active chiral diamine–phosphine oxide-ligated Ni–Al bimetallic catalyst that promotes enantioselective C–C cycloaddition under mild conditions. This system effectively suppresses product racemization and affords a diverse range of cyclopentyl ketones bearing a chiral α-tertiary carbon center in up to 99% yield and 99% ee.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"40 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718437","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}
We designed and developed a phosphine–heteroarenesulfonamide ligand and found that it functions as a chiral dinuclear silver catalyst capable of cooperatively activating both nucleophiles and electrophiles. As a result, a highly enantioselective Mannich-type reaction between glycinate Schiff bases and acyclic ketiminoesters, unattainable by mononuclear catalytic systems, was achieved, affording α,β-diamino acid derivatives bearing tetrasubstituted chiral carbon centers in excellent yields and enantioselectivities. The resulting α,β-diamino acid derivatives were readily transformed into optically active 2-imidazolidinone and a dipeptide. Comprehensive mechanistic studies combining global reaction route mapping (GRRM), artificial force-induced reaction (AFIR), and density functional theory calculations revealed a cooperative bimetallic transition-state architecture responsible for the observed stereocontrol. These findings establish a new design principle for asymmetric catalysis based on homodinuclear activation and highlight the potential of dinuclear silver catalysis for the construction of complex chiral molecules.
{"title":"Design of Phosphine-Heteroarenesulfonamide Ligands as Dinuclear Silver Catalysts for Enantioselective Construction of α,β-Diamino Acids","authors":"Yuka Iizuka, Sayuri Okajima, Yamato Ueno, Tsunayoshi Takehara, Takeyuki Suzuki, Satoshi Maeda, Shuichi Nakamura","doi":"10.1021/jacs.5c18426","DOIUrl":"https://doi.org/10.1021/jacs.5c18426","url":null,"abstract":"We designed and developed a phosphine–heteroarenesulfonamide ligand and found that it functions as a chiral dinuclear silver catalyst capable of cooperatively activating both nucleophiles and electrophiles. As a result, a highly enantioselective Mannich-type reaction between glycinate Schiff bases and acyclic ketiminoesters, unattainable by mononuclear catalytic systems, was achieved, affording α,β-diamino acid derivatives bearing tetrasubstituted chiral carbon centers in excellent yields and enantioselectivities. The resulting α,β-diamino acid derivatives were readily transformed into optically active 2-imidazolidinone and a dipeptide. Comprehensive mechanistic studies combining global reaction route mapping (GRRM), artificial force-induced reaction (AFIR), and density functional theory calculations revealed a cooperative bimetallic transition-state architecture responsible for the observed stereocontrol. These findings establish a new design principle for asymmetric catalysis based on homodinuclear activation and highlight the potential of dinuclear silver catalysis for the construction of complex chiral molecules.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"365 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718438","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}
Samantha O. Shepherd, Austin W. Green, Evan P. Wylie, Kenneth R. Newton, Ruwan T. Kurulugama, James S. Prell
In native ion mobility-mass spectrometry (nIM-MS) experiments, biomolecular ions are typically introduced into the gas phase from buffered solution while preserving their native structures, which can then be characterized using gas-phase methods. One of the most important gas-phase characterization techniques available with contemporary commercial mass spectrometers is collision-induced dissociation (CID), in which ions are heated by collisions with neutral buffer gas to cause dissociation, revealing subunit masses and often providing information about quaternary structure. The extent of CID observed is sensitive to instrument design, electric fields, and buffer gas identity and pressure, greatly complicating the comparison of results across instruments and conditions. In contrast, the ion’s underlying potential energy surface is invariant to these conditions and can in principle be probed by accurately modeling ion temperature and dissociation kinetics. Here, the recently developed improved impulsive collision theory, implemented in the “IonSPA” software, is benchmarked against noncovalent dissociation of two prototypical protein complexes, holomyoglobin and Shiga toxin 1 subunit B pentamer, for which thermochemical dissociation barriers were previously reported. Their thermochemical gas-phase unfolding barriers are also determined with IonSPA to provide additional insight into the dissociation process. IonSPA is then used to investigate covalent CID of the well-studied ions ubiquitin and bradykinin, for which significant effects of temperature and initial ion structure are observed compared to previously reported experiments. Despite several simplifying approximations used in IonSPA, these studies illustrate the utility and robustness of IonSPA and pave the way for more quantitative characterization of higher-order native biomolecular structures with gas-phase CID and collision-induced unfolding (CIU).
{"title":"Determination of Thermochemical Barriers in Multiple-Collision-Induced Dissociation Experiments on Gas-Phase Protein Complexes","authors":"Samantha O. Shepherd, Austin W. Green, Evan P. Wylie, Kenneth R. Newton, Ruwan T. Kurulugama, James S. Prell","doi":"10.1021/jacs.5c07327","DOIUrl":"https://doi.org/10.1021/jacs.5c07327","url":null,"abstract":"In native ion mobility-mass spectrometry (nIM-MS) experiments, biomolecular ions are typically introduced into the gas phase from buffered solution while preserving their native structures, which can then be characterized using gas-phase methods. One of the most important gas-phase characterization techniques available with contemporary commercial mass spectrometers is collision-induced dissociation (CID), in which ions are heated by collisions with neutral buffer gas to cause dissociation, revealing subunit masses and often providing information about quaternary structure. The extent of CID observed is sensitive to instrument design, electric fields, and buffer gas identity and pressure, greatly complicating the comparison of results across instruments and conditions. In contrast, the ion’s underlying potential energy surface is invariant to these conditions and can in principle be probed by accurately modeling ion temperature and dissociation kinetics. Here, the recently developed improved impulsive collision theory, implemented in the “IonSPA” software, is benchmarked against noncovalent dissociation of two prototypical protein complexes, holomyoglobin and Shiga toxin 1 subunit B pentamer, for which thermochemical dissociation barriers were previously reported. Their thermochemical gas-phase unfolding barriers are also determined with IonSPA to provide additional insight into the dissociation process. IonSPA is then used to investigate covalent CID of the well-studied ions ubiquitin and bradykinin, for which significant effects of temperature and initial ion structure are observed compared to previously reported experiments. Despite several simplifying approximations used in IonSPA, these studies illustrate the utility and robustness of IonSPA and pave the way for more quantitative characterization of higher-order native biomolecular structures with gas-phase CID and collision-induced unfolding (CIU).","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"29 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729254","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}
Ram R. Kaswan, Lydia Ferrer-López, Desire Molina Alcaide, Ángela Sastre-Santos, Francis D’Souza
Photoinduced symmetry-breaking charge separation (SB-CS) in a symmetrical pair of dimers is known to maximize energy conversion during the light-to-chemical energy conversion process. Although this has been shown in a few covalently linked dimers, the demonstration of such an event in self-assembled chromophore dimers has been very rare, especially in dimers formed by hydrogen bonding interactions. Here, we present a classic example of hydrogen bonding paired self-assembled zinc phthalocyanine dimers ((ZnPc-COOH)2 and (ZnPc-Ph-COOH)2) of different chromophore distances and demonstrate SB-CS resulting in ZnPc•+-ZnPc•– electron transfer products upon far-red light illumination. The occurrence of SB-CS in the ZnPc-dimers was confirmed by multiple studies, including fluorescence emission, which showed significant quenching in the dimer. Estimation of energy stored in the charge-separated states from electrochemical studies (redox gap of ∼1.55 eV) revealed the energy to be close to the pumping energy (E0,0 ∼ 1.80 eV), thus minimizing the energy loss during light-to-energy conversion. While DFT studies were able to assess geometry and carboxylic acid pairing strength, the TD-DFT studies were able to point out the excited states responsible for promoting excited-state electron transfer within the ZnPc-dimers. Finally, femtosecond pump–probe studies provided definitive evidence of SB-CS, with electron transfer rate constants of 5 × 1011 and 0.7 × 1011 s–1, respectively, for (ZnPc-COOH)2 and (ZnPc-Ph-COOH)2, revealing the significance of H-bond-pairing in promoting efficient charge separation in the far-red capturing ZnPc dimers.
{"title":"Symmetry Breaking Charge Separation in Zinc Phthalocyanine Dimers Self-Assembled via Hydrogen Bonding","authors":"Ram R. Kaswan, Lydia Ferrer-López, Desire Molina Alcaide, Ángela Sastre-Santos, Francis D’Souza","doi":"10.1021/jacs.5c15716","DOIUrl":"https://doi.org/10.1021/jacs.5c15716","url":null,"abstract":"Photoinduced symmetry-breaking charge separation (SB-CS) in a symmetrical pair of dimers is known to maximize energy conversion during the light-to-chemical energy conversion process. Although this has been shown in a few covalently linked dimers, the demonstration of such an event in self-assembled chromophore dimers has been very rare, especially in dimers formed by hydrogen bonding interactions. Here, we present a classic example of hydrogen bonding paired self-assembled zinc phthalocyanine dimers ((ZnPc-COOH)<sub>2</sub> and (ZnPc-Ph-COOH)<sub>2</sub>) of different chromophore distances and demonstrate SB-CS resulting in ZnPc<sup><b>•+</b></sup>-ZnPc<sup><b>•–</b></sup> electron transfer products upon far-red light illumination. The occurrence of SB-CS in the ZnPc-dimers was confirmed by multiple studies, including fluorescence emission, which showed significant quenching in the dimer. Estimation of energy stored in the charge-separated states from electrochemical studies (redox gap of ∼1.55 eV) revealed the energy to be close to the pumping energy (<i>E</i><sub>0,0</sub> ∼ 1.80 eV), thus minimizing the energy loss during light-to-energy conversion. While DFT studies were able to assess geometry and carboxylic acid pairing strength, the TD-DFT studies were able to point out the excited states responsible for promoting excited-state electron transfer within the ZnPc-dimers. Finally, femtosecond pump–probe studies provided definitive evidence of SB-CS, with electron transfer rate constants of 5 × 10<sup>11</sup> and 0.7 × 10<sup>11</sup> s<sup>–1</sup>, respectively, for (ZnPc-COOH)<sub>2</sub> and (ZnPc-Ph-COOH)<sub>2,</sub> revealing the significance of H-bond-pairing in promoting efficient charge separation in the far-red capturing ZnPc dimers.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"226 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729261","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}
Zhong Li, Xiaojin Wen, Seseg B. Bolotova, Florian P. Seebeck
Enzyme-mediated transfer of methyl groups to specific nucleophilic functions on small metabolites, proteins, and nucleic acids is an essential activity in all known life forms. Most of these transferred methyl groups originate from the one-carbon metabolism through methyl-tetrahydrofolate-dependent methylation of homocysteine, followed by adenosylation of methionine to form the primary methyltransferase cofactor, S-adenosylmethionine (SAM). In this report, we describe a strain of Escherichia coli with a Short-Circuited SAM-Cycle (SCSC) that maintains its SAM pool exclusively by methylating S-adenosylhomocysteine (SAH) using a synthetic methyl donor. Construction of this strain was made possible by the identification of an aryl sulfonate methyl ester as a biocompatible methyl donor and methyltransferases that accept this compound as substrate for in vivo methylation of SAH. We exploited this organism for the optimization of SAH-methylating enzymes by in vivo selection and to produce isotope-labeled natural products. Looking ahead, we anticipate that strains with SCSCs will open new possibilities for methyltransferase biocatalysis, natural product discovery, and bacterial metabolomics.
{"title":"Short-Circuiting the SAM-Cycle in Escherichia coli","authors":"Zhong Li, Xiaojin Wen, Seseg B. Bolotova, Florian P. Seebeck","doi":"10.1021/jacs.5c17370","DOIUrl":"https://doi.org/10.1021/jacs.5c17370","url":null,"abstract":"Enzyme-mediated transfer of methyl groups to specific nucleophilic functions on small metabolites, proteins, and nucleic acids is an essential activity in all known life forms. Most of these transferred methyl groups originate from the one-carbon metabolism through methyl-tetrahydrofolate-dependent methylation of homocysteine, followed by adenosylation of methionine to form the primary methyltransferase cofactor, <i>S</i>-adenosylmethionine (SAM). In this report, we describe a strain of <i>Escherichia coli</i> with a Short-Circuited SAM-Cycle (SCSC) that maintains its SAM pool exclusively by methylating <i>S</i>-adenosylhomocysteine (SAH) using a synthetic methyl donor. Construction of this strain was made possible by the identification of an aryl sulfonate methyl ester as a biocompatible methyl donor and methyltransferases that accept this compound as substrate for <i>in vivo</i> methylation of SAH. We exploited this organism for the optimization of SAH-methylating enzymes by <i>in vivo</i> selection and to produce isotope-labeled natural products. Looking ahead, we anticipate that strains with SCSCs will open new possibilities for methyltransferase biocatalysis, natural product discovery, and bacterial metabolomics.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"11 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729266","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}
Yiyi Chen, Yi Xu, Shuangquan Zhang, Xiaohui Chen, Fangqun Gan, Xianliang Tan, Kun Feng, Xiao Xiao, Zhong Yan Cao, Ming Chen, Xianqiang Kong
Direct dehydroxymethylative functionalization of alcohols offers a streamlined platform for molecular diversification but remains underdeveloped. An electrochemical platform operating under mild, metal-free conditions leverages a hydrogen atom transfer (HAT)/O2–Criegee relay to convert various alcohols (such as aliphatic, benzylic, and allylic alcohols) into one-carbon-shortened radicals, enabling dehydroxymethylative nitration, fluorosulfonylation, azidation, and phosphinoylation with broad functional-group tolerance and gram-scale practicality. Pairing the anodic radical generation with a cathodic Ni cycle further delivers C(sp2)–C(sp3) coupling, including the one-step methylation of aryl halides using ethanol as a feedstock methyl source. Mechanistic experiments (control studies and electron paramagnetic resonance/high-resolution mass spectrometry/cyclic voltammetry) support a sequence of HAT, O2 trapping, Criegee assembly, Baeyer–Villiger oxygenation, anodic decarboxylation, and radical interception and indicate mediator-first anodic gating. The platform expands access to C–N, C–SO2F, C–P, and C–C bonds directly from simple alcohols, providing a general strategy for selective editing of inert C–C bonds and late-stage diversification of biorelevant molecules.
{"title":"Electrochemical Dehydroxymethylative Functionalization of Unactivated Alcohols via Criegee–Kolbe Radical Relay","authors":"Yiyi Chen, Yi Xu, Shuangquan Zhang, Xiaohui Chen, Fangqun Gan, Xianliang Tan, Kun Feng, Xiao Xiao, Zhong Yan Cao, Ming Chen, Xianqiang Kong","doi":"10.1021/jacs.5c18031","DOIUrl":"https://doi.org/10.1021/jacs.5c18031","url":null,"abstract":"Direct dehydroxymethylative functionalization of alcohols offers a streamlined platform for molecular diversification but remains underdeveloped. An electrochemical platform operating under mild, metal-free conditions leverages a hydrogen atom transfer (HAT)/O<sub>2</sub>–Criegee relay to convert various alcohols (such as aliphatic, benzylic, and allylic alcohols) into one-carbon-shortened radicals, enabling dehydroxymethylative nitration, fluorosulfonylation, azidation, and phosphinoylation with broad functional-group tolerance and gram-scale practicality. Pairing the anodic radical generation with a cathodic Ni cycle further delivers C(sp<sup>2</sup>)–C(sp<sup>3</sup>) coupling, including the one-step methylation of aryl halides using ethanol as a feedstock methyl source. Mechanistic experiments (control studies and electron paramagnetic resonance/high-resolution mass spectrometry/cyclic voltammetry) support a sequence of HAT, O<sub>2</sub> trapping, Criegee assembly, Baeyer–Villiger oxygenation, anodic decarboxylation, and radical interception and indicate mediator-first anodic gating. The platform expands access to C–N, C–SO<sub>2</sub>F, C–P, and C–C bonds directly from simple alcohols, providing a general strategy for selective editing of inert C–C bonds and late-stage diversification of biorelevant molecules.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"15 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729268","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}
Donatella Loru, Elena R. Alonso, Aran Insausti, Cristóbal Pérez, Luca Evangelisti, Juan L. Asensio, Francisco Corzana, Brooks H. Pate, Emilio J. Cocinero, M. Eugenia Sanz
Understanding the interactions of chiral molecules with water is crucial, given the central role that water plays in chemical and biological processes. We report the investigation of the amino alcohol prolinol, a widely used chiral catalyst and auxiliary in asymmetric synthesis, and its interactions with one to three water molecules by applying broadband rotational spectroscopy. Bare prolinol adopts two low-energy conformations stabilized by an intramolecular O–H···N hydrogen bond. Upon complexation with a single water molecule, four prolinol–H2O isomers are identified, showing addition and insertion structures, where the original prolinol conformations are conserved. Notably, complexation with two and three water molecules induces prolinol to adopt its highest energy conformations, which lie more than 9.5 kJ mol–1 above the global minimum and feature an intramolecular N–H···O hydrogen bond. In prolinol–(H2O)2,3, water acts as a conformational switch for prolinol, binding to both the amino and hydroxyl groups. Combined NMR studies and molecular dynamics simulations reveal that, in bulk water, prolinol exists as a highly flexible conformational ensemble, with no evidence of a stable intramolecular hydrogen bond, and mainly samples the same conformational space as that displayed in prolinol–(H2O)2,3. Our results illustrate how stepwise hydration proceeds and reveal the profound changes that water can induce in flexible chiral molecules. These findings provide a solid foundation for future experiments and modeling of solvation-induced processes.
{"title":"Stepwise Hydration Reveals Conformational Switching in Chiral Prolinol","authors":"Donatella Loru, Elena R. Alonso, Aran Insausti, Cristóbal Pérez, Luca Evangelisti, Juan L. Asensio, Francisco Corzana, Brooks H. Pate, Emilio J. Cocinero, M. Eugenia Sanz","doi":"10.1021/jacs.5c13582","DOIUrl":"https://doi.org/10.1021/jacs.5c13582","url":null,"abstract":"Understanding the interactions of chiral molecules with water is crucial, given the central role that water plays in chemical and biological processes. We report the investigation of the amino alcohol prolinol, a widely used chiral catalyst and auxiliary in asymmetric synthesis, and its interactions with one to three water molecules by applying broadband rotational spectroscopy. Bare prolinol adopts two low-energy conformations stabilized by an intramolecular O–H···N hydrogen bond. Upon complexation with a single water molecule, four prolinol–H<sub>2</sub>O isomers are identified, showing addition and insertion structures, where the original prolinol conformations are conserved. Notably, complexation with two and three water molecules induces prolinol to adopt its highest energy conformations, which lie more than 9.5 kJ mol<sup>–1</sup> above the global minimum and feature an intramolecular N–H···O hydrogen bond. In prolinol–(H<sub>2</sub>O)<sub>2,3</sub>, water acts as a conformational switch for prolinol, binding to both the amino and hydroxyl groups. Combined NMR studies and molecular dynamics simulations reveal that, in bulk water, prolinol exists as a highly flexible conformational ensemble, with no evidence of a stable intramolecular hydrogen bond, and mainly samples the same conformational space as that displayed in prolinol–(H<sub>2</sub>O)<sub>2,3</sub>. Our results illustrate how stepwise hydration proceeds and reveal the profound changes that water can induce in flexible chiral molecules. These findings provide a solid foundation for future experiments and modeling of solvation-induced processes.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"10 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729259","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}
Sprayed water microdroplets act as open-air microreactors, unlocking reaction pathways that are often inaccessible in bulk solution. Here, we present that aerosolizing aqueous solutions of reducing sugars (d-glucose and l-fructose) spontaneously yield 5-hydroxymethylfurfural (HMF), a versatile platform chemical for biofuels, bioplastics, and pharmaceuticals. Mechanistic studies reveal that the super acidic and “water-starved microenvironment” at the microdroplet interface intrinsically activates sugars, driving the sequential loss of three water molecules via cyclic or acyclic pathways to form HMF. The reaction proceeds without the need for external reagents, catalysts, heat, or harsh conditions, unlike bulk-phase processes required for HMF production. The facile formation of HMF from glucose in water microdroplets under ambient conditions not only offers a sustainable route to a renewable chemical building block but also provides prebiotic insight, highlighting how such interfacial chemistry could have contributed to the molecular diversity essential for the origin of life.
{"title":"Water Microdroplets Transform Reducing Sugars into a Platform Chemical 5-Hydroxymethylfurfural","authors":"Abhijit Nandy, Shibdas Banerjee","doi":"10.1021/jacs.5c18607","DOIUrl":"https://doi.org/10.1021/jacs.5c18607","url":null,"abstract":"Sprayed water microdroplets act as open-air microreactors, unlocking reaction pathways that are often inaccessible in bulk solution. Here, we present that aerosolizing aqueous solutions of reducing sugars (<span>d</span>-glucose and <span>l</span>-fructose) spontaneously yield 5-hydroxymethylfurfural (HMF), a versatile platform chemical for biofuels, bioplastics, and pharmaceuticals. Mechanistic studies reveal that the super acidic and “water-starved microenvironment” at the microdroplet interface intrinsically activates sugars, driving the sequential loss of three water molecules via cyclic or acyclic pathways to form HMF. The reaction proceeds without the need for external reagents, catalysts, heat, or harsh conditions, unlike bulk-phase processes required for HMF production. The facile formation of HMF from glucose in water microdroplets under ambient conditions not only offers a sustainable route to a renewable chemical building block but also provides prebiotic insight, highlighting how such interfacial chemistry could have contributed to the molecular diversity essential for the origin of life.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"38 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718439","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}
Jie Xue, Jun Luo, Kin Ting Chang, Zihang Sun, Zonglong Zhu, Lingling Mao, Haipeng Lu
Entropy engineering has emerged as a versatile strategy for designing metastable materials with synergistic properties and functionalities. Here, we present a facile solution method that yields a new series of high-entropy metal-halide double perovskites (HE-DPs). Single crystals of HE-DPs with a general formula of Cs2MIMIIICl6 (MI = Ag+, Na+; MIII = In3+, Sb3+, Ho3+, Er3+, Bi3+, Yb3+, Dy3+, or Tb3+) are obtained under mild conditions. Structural and elemental analyses demonstrate the formation of high-entropy single-phase single crystals with five elements occupying the trivalent MIII site. The incorporation of multiple trivalent metal ions in a high-entropy manner appears to drastically improve the ambient stability of double perovskites up to more than three months. The optical bandgap is found to decrease upon alloying at the MIII site. Additionally, the random distribution of lanthanide ions within the crystal structure results in synergic electronic interactions between the lanthanide host and lanthanide-lanthanide ions. The interaction between lanthanides and host induces both broadband emissions and sharp Ln3+f–f transitions, while the lanthanide-lanthanide proximity leads to efficient NIR-to-visible photon upconversion. Our work underscores the high-entropy strategy for developing robust lanthanide perovskites featuring tailored, multichannel optical properties for advanced lighting, display, and sensing applications.
{"title":"High-Entropy Double Perovskites with Tailored Multichannel Luminescence","authors":"Jie Xue, Jun Luo, Kin Ting Chang, Zihang Sun, Zonglong Zhu, Lingling Mao, Haipeng Lu","doi":"10.1021/jacs.5c18097","DOIUrl":"https://doi.org/10.1021/jacs.5c18097","url":null,"abstract":"Entropy engineering has emerged as a versatile strategy for designing metastable materials with synergistic properties and functionalities. Here, we present a facile solution method that yields a new series of high-entropy metal-halide double perovskites (HE-DPs). Single crystals of HE-DPs with a general formula of Cs<sub>2</sub>M<sup>I</sup>M<sup>III</sup>Cl<sub>6</sub> (M<sup>I</sup> = Ag<sup>+</sup>, Na<sup>+</sup>; M<sup>III</sup> = In<sup>3+</sup>, Sb<sup>3+</sup>, Ho<sup>3+</sup>, Er<sup>3</sup><sup>+</sup>, Bi<sup>3+</sup>, Yb<sup>3</sup><sup>+</sup>, Dy<sup>3</sup><sup>+</sup>, or Tb<sup>3</sup><sup>+</sup>) are obtained under mild conditions. Structural and elemental analyses demonstrate the formation of high-entropy single-phase single crystals with five elements occupying the trivalent M<sup>III</sup> site. The incorporation of multiple trivalent metal ions in a high-entropy manner appears to drastically improve the ambient stability of double perovskites up to more than three months. The optical bandgap is found to decrease upon alloying at the M<sup>III</sup> site. Additionally, the random distribution of lanthanide ions within the crystal structure results in synergic electronic interactions between the lanthanide host and lanthanide-lanthanide ions. The interaction between lanthanides and host induces both broadband emissions and sharp Ln<sup>3+</sup> <i>f</i>–<i>f</i> transitions, while the lanthanide-lanthanide proximity leads to efficient NIR-to-visible photon upconversion. Our work underscores the high-entropy strategy for developing robust lanthanide perovskites featuring tailored, multichannel optical properties for advanced lighting, display, and sensing applications.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"372 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732556","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}
Hao Fang, Aimara García-Camacho, Ho Seong Hwang, Atthawut Sudsamart, Constantin G. Daniliuc, Oleksandr O. Grygorenko, Ignacio Funes-Ardoiz, John J. Molloy
The efficient design of (C)sp3-rich molecular scaffolds with defined exit vectors is central to expanding drug-like chemical space. Here, we report a boron-enabled strategy for the synthesis of polysubstituted housanes from nonsymmetrical dienes. A geminal diboron system ensures site-, regio-, and diastereoselectivity in an energy transfer-catalyzed [2 + 2] cycloaddition of nonsymmetrical dienes while also facilitating the mild generation of a cyclobutyl anion that triggers a stereospecific intramolecular annulation via conjugate addition, delivering complex housanes, with three defined exit vectors, in just two steps. Systematic derivatization across all substituents demonstrates the breadth of chemical diversification, while mechanistic and density functional theory (DFT) computational studies reveal the stereoelectronic origins of diastereoselectivity and the counterintuitive electrophile-driven reactivity of the housane framework. This work establishes housanes as stable, derivatizable, and structurally rigid fragments that provide multidirectional exit vectors, offering a powerful platform for the exploration of three-dimensional (3D) chemical space in medicinal chemistry.
{"title":"Boron-Enabled Stereoselective Synthesis of Polysubstituted Housanes","authors":"Hao Fang, Aimara García-Camacho, Ho Seong Hwang, Atthawut Sudsamart, Constantin G. Daniliuc, Oleksandr O. Grygorenko, Ignacio Funes-Ardoiz, John J. Molloy","doi":"10.1021/jacs.5c17624","DOIUrl":"https://doi.org/10.1021/jacs.5c17624","url":null,"abstract":"The efficient design of (C)sp<sup>3</sup>-rich molecular scaffolds with defined exit vectors is central to expanding drug-like chemical space. Here, we report a boron-enabled strategy for the synthesis of polysubstituted housanes from nonsymmetrical dienes. A <i>geminal</i> diboron system ensures site-, regio-, and diastereoselectivity in an energy transfer-catalyzed [2 + 2] cycloaddition of nonsymmetrical dienes while also facilitating the mild generation of a cyclobutyl anion that triggers a stereospecific intramolecular annulation via conjugate addition, delivering complex housanes, with three defined exit vectors, in just two steps. Systematic derivatization across all substituents demonstrates the breadth of chemical diversification, while mechanistic and density functional theory (DFT) computational studies reveal the stereoelectronic origins of diastereoselectivity and the counterintuitive electrophile-driven reactivity of the housane framework. This work establishes housanes as stable, derivatizable, and structurally rigid fragments that provide multidirectional exit vectors, offering a powerful platform for the exploration of three-dimensional (3D) chemical space in medicinal chemistry.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"20 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729267","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}
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