Journal of the American Chemical Society最新文献

{"title":"3-Center-3-Electron σ-Adduct Enables Silyl Radical Transfer below the Minimum Barrier for Silyl Radical Formation","authors":"Zihang Qiu, Paolo Cleto Bruzzese, Zikuan Wang, Hao Deng, Markus Leutzsch, Christophe Farès, Sonia Chabbra, Frank Neese, Alexander Schnegg, Constanze N. Neumann","doi":"10.1021/jacs.4c18445","DOIUrl":"https://doi.org/10.1021/jacs.4c18445","url":null,"abstract":"Transition-metal-catalyzed cleavage of the Si–H bond in silanes to yield silyl radicals requires substantial amounts of energy, which are commonly supplied by photons. For Rh(II) porphyrins, efficient hydrosilylation catalysis becomes accessible only upon site isolation in a metal–organic framework (MOF), and the formation of free silyl radicals likewise requires irradiation. Within the MOF, however, an uncommonly facile direct silyl radical transfer to olefin substrates is also possible, which makes thermal olefin hydrosilylation accessible at room temperature. The ability of MOF-supported Rh(II) metalloradicals to furnish an unprecedented 3-center-3-electron (3c-3e) Rh(II)-silane σ-adduct enables the assembly of a tricomponent transition state that is comprised of Rh(II), silane, and ethylene. The tricomponent transition state bypasses the high-energy silyl radical species and enables silyl radical transfer with an activation free energy ∼15 kcal·mol^–1 below the minimum energy barrier for silyl radical formation. We report direct observation of the 3c-3e silane σ-adduct, which is a stable species in the absence of light and olefins. Furthermore, a combination of experiments and quantum chemical calculations shows that direct silyl radical transfer to ethylene is promoted by the temporary oxidation of the transition structure by a proximal Rh(II) center. Thus, the crucial role of the MOF matrix is to fix the inter-Rh separation in our catalyst at a value large enough for 3c-3e silane adduct formation but short enough for facile electron transfer.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"33 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723856","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}

{"title":"Bilayer Kagome Ferrimagnet Exhibiting Exceptional Spontaneous Exchange Bias in TbMn6(Ge,Ga)6","authors":"Hankun Xu, Wenjie Li, Junjie Chen, Sergii Khmelevskyi, Dmitry Khalyavin, Pascal Manuel, Chuanying Xi, Shogo Kawaguchi, Jing Chen, Wanda Yang, Qinghua Zhang, Yili Cao, Chengyi Yu, Yang Ren, Kun Lin, Xianran Xing","doi":"10.1021/jacs.4c17505","DOIUrl":"https://doi.org/10.1021/jacs.4c17505","url":null,"abstract":"Manipulating interlayer interactions in two-dimensional (2D) materials has led to intriguing behaviors. Borrowing these 2D signatures to bulk materials is likely to unlock exceptional properties. Here, we report an emergent 2D-like bilayer Kagome ferrimagnet through reducing the interbilayer magnetic interaction to nearly zero. This concept is realized within bulk TbMn₆(Ge,Ga)₆ compounds, characterized by an isolated and pure Mn Kagome lattice, simply by the chemical substitution of Ge with Ga. Specifically, the targeted compound TbMn₆Ge₅Ga₁ exhibits a giant spontaneous exchange bias (SEB) of approximately 1.6 T, which is more than twice that observed in known materials. Field-dependent neutron diffraction reveals the robust nature of the compensated ferrimagnetic (FiM), characterized by almost two-thirds of the moments being pinned and irreversible under fields up to 9 T. Through magnetic and structural analysis, alongside theoretical calculations, we demonstrate that the substantial SEB is related to the intense competition between local robust and weak FiM states within the bilayer Kagome configuration, which are stabilized by an incommensurate spin arrangement. The concept of a bilayer Kagome magnet offers new opportunities for discovering attractive properties in 2D-like materials.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"16 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713722","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}

{"title":"Ligand-Controlled Regioselective Dearomative Vicinal and Conjugate Hydroboration of Quinolines","authors":"Chao Hu, Chen-Yan Cai, Elizabeth S. Barta, Rohan R. Merchant, Bryan S. Matsuura, Si-Jie Chen, Shuming Chen, Tian Qin","doi":"10.1021/jacs.4c17247","DOIUrl":"https://doi.org/10.1021/jacs.4c17247","url":null,"abstract":"A dearomative strategy to regioselectively modify arenes using a “diene” synthon within aromatic rings provides access to highly functionalized heterocycles from abundant aromatic feedstocks and represents an alternative synthetic approach besides traditional cross-coupling and C–H functionalization methodologies. In this study, we present an efficient method for selectively introducing boron onto quinolines through dearomative hydroboration using easily accessible and stable phosphine-ligated borane complexes. The vicinal 5,6- and conjugate 5,8-hydroborated products could be obtained regioselectively by modifying the phosphine ligand. Drawing inspiration from diverse organoboron transformations, these borane building blocks were diversified by a range of downstream functionalizations, providing modular pathways for the skeletal modifications of quinolines to access a variety of challenging functionalized heterocycles.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"64 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723853","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}

{"title":"Structural Context Modulates the Conformational Ensemble of the Intrinsically Disordered Amino Terminus of α-Synuclein","authors":"Rania Dumarieh, Dominique Lagasca, Sakshi Krishna, Jaka Kragelj, Yiling Xiao, Shoyab Ansari, Kendra K. Frederick","doi":"10.1021/jacs.4c15653","DOIUrl":"https://doi.org/10.1021/jacs.4c15653","url":null,"abstract":"Regions of intrinsic disorder play crucial roles in biological systems, yet they often elude characterization by conventional biophysical techniques. To capture conformational distributions across different time scales, we employed a freezing approach coupled with solid-state NMR analysis. Using segmentally isotopically labeled α-synuclein (α-syn), we investigated the conformational ensembles of the six alanines, three glycines, and a single site (L8) in the disordered amino terminus under three distinct conditions: in 8 M urea, as a frozen monomer in buffer, and within the disordered regions flanking the amyloid core. The experimental spectra varied significantly among these conditions and deviated from those of a statistical coil. In 8 M urea, monomeric α-syn exhibited the most restricted conformational sampling, rarely accessing chemical shifts characteristic of α-helices or β-strands. In buffer, monomeric α-syn showed a broader conformational sampling, favoring α-helical conformations and, to a lesser extent, random coil states. Notably, amino acids in the disordered regions flanking the amyloid core demonstrated the most extensive conformational sampling, with broad peaks encompassing the entire range of possible chemical shifts and a marked increase in highly extended β-strand conformations. Collectively, this work demonstrates that intrinsically disordered regions exhibit distinct conformational ensembles, which are influenced not only by the chemical environment but also by the conformations of adjacent protein sequences. The differences in the conformational ensembles of the disordered amino terminus may explain why the monomer and the amyloid form of α-syn interact with different biomolecules inside cells.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"34 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723870","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}

{"title":"Chemoselective Hydrogenation of Halonitrobenzenes by Platinum Nanoparticles with Auxiliary Co–N4 Single Sites in Sandwiched Catalysts","authors":"Tian Lin, Zhouwen Cao, Junqi Pei, Bohua Wang, Hanlin Liu, Bin Tu, Caoyu Yang, Fengbin Zheng, Wenxing Chen, Qiaojun Fang, Wei Liu, Zhiyong Tang, Guodong Li","doi":"10.1021/jacs.4c18288","DOIUrl":"https://doi.org/10.1021/jacs.4c18288","url":null,"abstract":"The chemoselective hydrogenation of halonitrobenzenes to haloanilines is of great importance but remains challenging to simultaneously achieve high catalytic activity, excellent selectivity, and good reusability, especially for <i>ortho</i>-substituted substrates. This is due to the occurrence of hydrogenolysis of halogen groups, as well as the easy migration and aggregation of active species on the catalyst surface during the hydrogenation of nitro groups. In this study, we integrate Pt nanoparticles (NPs) with auxiliary Co–N₄ single sites from a porphyrinic metal–organic framework [known as PCN-221(Co)] in a sandwiched nanostructure as a catalyst for the chemoselective hydrogenation of <i>ortho</i>-halonitrobenzenes at 80 °C and 1 MPa H₂ in a 50 mL batch microreactor. This sandwiched catalyst achieves 97.3% selectivity for <i>ortho</i>-chloroaniline at nearly complete conversion of <i>ortho</i>-chloronitrobenzene, with an exceptionally high turnover frequency (TOF) of 11,625 h^–1 and good reusability over ten cycles, outperforming state-of-the-art heterogeneous supported metal catalysts. Theoretical and experimental investigations reveal that the nitro group in <i>ortho</i>-chloronitrobenzene is preferentially hydrogenated by Pt NPs, while the <i>ortho</i>-chloro group is selectively adsorbed by Co–N₄ single sites in PCN-221(Co), preventing its hydrogenolysis and enhancing selectivity for <i>ortho</i>-chloroaniline. Furthermore, the PCN-221(Co) shell in the sandwiched catalyst plays a key role in enriching <i>ortho</i>-chloronitrobenzene and stabilizing the supported Pt NPs, thus leading to high catalytic activity and good reusability. Additionally, at nearly complete conversion of <i>ortho</i>-fluoronitrobenzene and <i>ortho</i>-bromonitrobenzene, this sandwiched Pt catalyst displays 100% selectivity for <i>ortho</i>-fluoroaniline with a TOF of 8680 h^–1 and 99.2% selectivity for <i>ortho</i>-bromoaniline with a TOF of 5859 h^–1, respectively. When <i>meta</i>- and <i>para</i>-halonitrobenzenes are used as substrates, high activity and excellent selectivity for the corresponding haloanilines are also achieved by the sandwiched Pt catalysts.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"72 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713584","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}

{"title":"Enantiospecific Synthesis of α-Tertiary Amines: Ruthenium-Catalyzed Allylic Amination with Aqueous Ammonia","authors":"Sven M. Papidocha, Henrik R. Wilke, Kacper J. Patej, Mayuko Isomura, Tim J. Stucky, Lukas Rothenbühler, Erick M. Carreira","doi":"10.1021/jacs.5c01928","DOIUrl":"https://doi.org/10.1021/jacs.5c01928","url":null,"abstract":"Ammonia stands out as the most available, cost-effective, and atom-economical source of nitrogen for organic synthesis. In the laboratory, it is safely and most conveniently handled in aqueous solution. Despite the advantages, the direct application of aqueous ammonia in the field of transition-metal catalysis remains a significant challenge. In this study, we report the first ruthenium-catalyzed allylic substitution using ammonia. The catalytic system, consisting of [Cp*Ru(MeCN)₃]PF₆ and a phenoxythiazoline ligand, enables the enantiospecific amination of tertiary allylic carbonates in aqueous media and affords enantioenriched primary amines as single regioisomers in high yields.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"3 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713723","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}

{"title":"Mechanistic Characterization of Diterpene Synthase Pairs for Tricyclic Diterpenes from Cyanobacteria","authors":"Jiayi Yu, Taro Shiraishi, Kizerbo A. Taizoumbe, Yusaku Karasuno, Ayako Yoshida, Makoto Nishiyama, Jeroen S. Dickschat, Tomohisa Kuzuyama","doi":"10.1021/jacs.4c16710","DOIUrl":"https://doi.org/10.1021/jacs.4c16710","url":null,"abstract":"In recent years, genome mining in cyanobacteria has revealed abundant gene clusters related to natural product biosynthesis. However, only a few terpene synthases (TSs) have been identified from this bacterial phylum. Pfam profiles, such as PF03936 and PF19086, which are frequently used for TS retrieval, are built from plant, bacterial, and fungal TSs. Herein, we constructed a new hidden Markov model (HMM) specific to bacterial TSs on the basis of 110 bacterial TSs experimentally validated in recent years. Using this model, we identified a pair of diterpene synthases, Cpt11 (class II TS) and Cts11 (class I TS), in the cyanobacterium <i>Scytonema tolypothrichoides</i>. <i>In vitro</i> experiments demonstrated that Cpt11 catalyzes the formation of <i>syn</i>-copalyl diphosphate from geranylgeranyl diphosphate and that Cts11 subsequently converts <i>syn</i>-copalyl diphosphate into a rare 6,6,7-tricyclic diterpene alcohol. Its biosynthesis was established through isotope labeling experiments, which revealed a unique sequence of a 1,6-proton shift and ring expansion to a seven-membered ring. We solved the crystal structure of Cts11 at a resolution of 1.76 Å. Additionally, via site-directed mutagenesis experiments, we identified two amino acid residues whose exchanges affected the formation of the original diterpene alcohol, leading to the formation of two new compounds: a 6,6,7-tricyclic diterpene hydrocarbon and another 6,6,6-tricyclic diterpene alcohol. A BLAST search revealed several sequences that shared over 70% identity with Cts11 from cyanobacteria that could produce diverse diterpenes. This study demonstrates the potential for cyanobacteria to produce unprecedented terpenoids and lays the foundation for studying the physiological activities of terpenoids in cyanobacteria.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"57 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713721","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}

{"title":"Spontaneous Generation of an Endogenous RORγt Agonist","authors":"Xiao Corey Ma, Jon Clardy","doi":"10.1021/jacs.5c02724","DOIUrl":"https://doi.org/10.1021/jacs.5c02724","url":null,"abstract":"The transcription factor RORγt regulates the development of Th17 cells and their inflammatory cytokine IL-17─a pathway that can both clear bacterial pathogens and drive autoimmune diseases. An endogenous RORγt agonist with a noncanonical structure, a lysophosphatidylethanolamine (1-18:1-LPE or <b>1</b>), was recently identified, and its identity both increases our understanding of immune regulation and creates options for therapeutic intervention. Compound <b>1</b> could be formed directly through enzymatic cleavage of a suitable phosphatidylethanolamine (PE) by a phospholipase A2 (PLA2) or by “triggering” of a suitable plasmalogen with accompanying 1,2-acyl migration from the <i>sn</i>-2 to <i>sn</i>-1 positions of glycerol. This study illustrates the plausibility of a plasmalogen-based pathway through synthesis of the plasmalogen precursor (<b>2</b>) and triggering the plasmalogen’s electron-rich vinyl ether with small electrophiles characteristic of inflammatory and tumor environments to create 1-18:1-LPE (<b>1</b>). The plasmalogen-based pathway is consistent with previous studies on the formation of <b>1</b>, and it also conforms to Lands rules for acyl chain distribution and provides a mechanism for immune signaling with both spatial and temporal control.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"49 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713726","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}

{"title":"O-Cyanobenzaldehydes Irreversibly Modify Both Buried and Exposed Lysine Residues in Live Cells","authors":"Huan Ling, Lin Li, Liping Duan, Weixue Huang, Jiangnan Zheng, Shijie Zhang, Xinling Li, Xiaorong Qiu, Yang Zhou, Nan Ma, Xiaomei Ren, Jinwei Zhang, Zhen Wang, Yujun Zhao, Ruijun Tian, Zhi-Min Zhang, Ke Ding","doi":"10.1021/jacs.4c18006","DOIUrl":"https://doi.org/10.1021/jacs.4c18006","url":null,"abstract":"Lysine residue represents an attractive site for covalent drug development due to its high abundance (5.6%) and critical functions. However, very few lysines have been characterized to be accessible to covalent ligands and perturb the protein functions, owing to their protonation state and adjacent steric hindrance. Herein, we report a new lysine bioconjugation chemistry, <i>O</i>-cyanobenzaldehyde (CNBA), that enables selective modification of the lysine ε-amine to form iso-indolinones under physiological conditions. Activity-based proteome profiling enabled the mapping of 3451 lysine residues and 85 endogenous kinases in live cells, highlighting its potential for modifying hyper-reactive lysines within the proteome or buried catalytic lysines within the kinome. Further protein crystallography and mass spectrometry confirmed that K271_ABL1 and K162_AURKA are covalently targetable sites in kinases. Leveraging a structure-based drug design, we incorporated CNBA into the core structure of Nutlin-3 to irreversibly inhibit the MDM2-p53 interaction by targeting an exposed lysine K94 on the surface of murine double minute 2. Importantly, we have demonstrated the potential application of CNBA as a lysine-recognized bioconjugation agent for developing new antibody-drug conjugates. The results collectively validate CNBA as a new selective and efficient modifying agent with broad applications for both buried and exposed lysine residues in live cells.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"36 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723854","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}

{"title":"How Temperature Change Affects the Lattice Parameters, Molecular Conformation, and Reaction Cavity in Enantiomeric and Racemic Crystals of Thalidomide","authors":"Ayaka Matsumoto, Kenta Nakagawa, Takuya Nakanishi, Akiko Sekine, Sosuke Kojo, Mizuki Kira, Sota Sato, Norio Shibata, Toru Asahi","doi":"10.1021/jacs.4c18394","DOIUrl":"https://doi.org/10.1021/jacs.4c18394","url":null,"abstract":"For the single crystals of thalidomide (C₁₃H₁₀N₂O₄, TD) grown by the solvent evaporation method, the temperature dependences of the crystal structures have been investigated over a wide temperature range between 100 and 423.15 K. Comparing the α-form of a racemic TD crystal, which consists of symmetric heterochiral dimers and belongs to <i>P</i>2₁/<i>n</i> space group, with the enantiomeric TD crystal, which belongs to <i>P</i>2₁ and consists of asymmetric (pseudosymmetric) homochiral dimers, there have been clear differences in the temperature-dependent changes of the lattice parameters, the isobaric linear thermal expansion coefficients (along the crystallographic and the principal Cartesian axes), the volumetric expansion coefficients of the unit cell, and the structures of hydrogen-bonded dimer in the crystal such as intra- and intermolecular dihedral angles, cavities (reaction cavities), and the hydrogen-bond length. In the asymmetric homochiral dimers, one monomer with a larger reaction cavity changes its intramolecular dihedral angle with temperature, while the other monomer with a smaller cavity does not. In contrast, in the symmetric heterochiral dimers, two monomers with the same cavity volume similarly change their intramolecular dihedral angles with the temperature. Such differences in the temperature-dependent conformational changes between asymmetric and symmetric dimers cause differences between enantiomeric and racemic crystals.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"100 5 Pt 1 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723855","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}