JACS Au最新文献

{"title":"Opposed Aromatic Surfaces Behave as Independent Binding Sites for Carbohydrate Stacking: Analysis of Sandwich-like CH/π/CH Complexes","authors":"Laura Díaz-Casado,&nbsp;Enrique Mann,&nbsp;Ester Jiménez-Moreno,&nbsp;Alejandro Villacampa,&nbsp;Laura Montalvillo-Jiménez,&nbsp;Claudia Sánchez-García,&nbsp;Francisco Corzana,&nbsp;Jesús Jiménez-Barbero,&nbsp;Ana María Gómez,&nbsp;Andrés G. Santana and Juan Luis Asensio*,&nbsp;","doi":"10.1021/jacsau.4c0079510.1021/jacsau.4c00795","DOIUrl":"https://doi.org/10.1021/jacsau.4c00795https://doi.org/10.1021/jacsau.4c00795","url":null,"abstract":"<p >CH/π bonds are versatile elements for the construction of complex molecular architectures, thus playing key roles in many biomolecular recognition processes. Although seldom acknowledged, aromatic units are inherently bivalent and can participate in CH/π bonds through either face simultaneously, leading to the formation of <i>ternary</i> stacking complexes. This sandwich-like arrangement is by far the most common in natural complexes and could potentially lead to negative cooperativity due to unfavorable polarization or electrostatic effects, especially when polarized CH fragments are involved. To evaluate the energetics of such interaction modes, we selected a biologically relevant model, <i>carbohydrate/aromatic stacking</i>, and conducted an experimental analysis comparing <i>binary</i> CH/π interactions to <i>ternary</i> CH/π/CH stacking. Our approach utilized a dynamic combinatorial strategy, which is well-suited to reveal minor stability differences among aromatic complexes. Our results showed that carbohydrate/aromatic stacking is relatively insensitive to molecular recognition events occurring on the opposite side of the aromatic platform, whether exposed to water or involved in additional CH/π contacts, with free energy fluctuations lower than 10%. Based on these data, for all practical purposes, the two opposing aromatic surfaces can be considered independent, noninteracting binding sites, making aromatic platforms optimal connecting elements for supramolecular cross-linking.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4466–4473 4466–4473"},"PeriodicalIF":8.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent Synthesis of Chiroptical Molecular Switches Based on 1,2-Diaxial Atropisomers","authors":"Tian-Jiao Han,&nbsp;Qiu-Le Yang,&nbsp;Jiaen Hu,&nbsp;Min-Can Wang and Guang-Jian Mei*,&nbsp;","doi":"10.1021/jacsau.4c0077710.1021/jacsau.4c00777","DOIUrl":"https://doi.org/10.1021/jacsau.4c00777https://doi.org/10.1021/jacsau.4c00777","url":null,"abstract":"<p >The development of chiroptical molecular switches for chiral sensing, data communication, optical displays, chiral logic gates, and asymmetric catalysis is currently a vibrant frontier of science and technology. Herein, we report a practical artificial dynamic system based on a 1,2-diaxial atropisomer. Organocatalytic parallel kinetic resolution allows the divergent synthesis of two sets of stereoisomers with vicinal C–C and N–N axes from the same racemic single-axis substrates. By simply varying the configuration of the single catalyst, all four stereoisomers are accessible. The successive conduction of covalent unlocking/locking and thermal-isomerization processes enables sequential switching between all four atropisomeric states with electronic circular dichroism signal reversal, providing an example of multistate chiroptical molecular switches.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4445–4454 4445–4454"},"PeriodicalIF":8.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective [3 + 2] C–H/C–H Alkyne Annulation via Dual (Distal) C(β, δ)–H Bond Activation Relay: A Novel Therapeutic Quinazolone-Tethered Benzofulvenes for Oral Cancer","authors":"Dinesh Parshuram Satpute,&nbsp;Garvita Narang,&nbsp;Harshal Rohit,&nbsp;Jagdish Manjhi,&nbsp;Divita Kumar,&nbsp;Sangita Dattatray Shinde,&nbsp;Shyam Kumar Lokhande,&nbsp;Priyanka Patel Vatsa,&nbsp;Vinal Upadhyay,&nbsp;Shivkanya Madhavrao Bhujbal,&nbsp;Amit Mandoli* and Dinesh Kumar*,&nbsp;","doi":"10.1021/jacsau.4c0080210.1021/jacsau.4c00802","DOIUrl":"https://doi.org/10.1021/jacsau.4c00802https://doi.org/10.1021/jacsau.4c00802","url":null,"abstract":"<p >In contrast to proximal C–H bond activations, distal C–H bond activation is fundamentally more challenging and requires distinctly specialized directing partners or techniques. In this context, we report an unprecedented dual (distal) β-C(benzylic)–H and δ-C(aryl)–H bond activation relay protocol for the chemo-, regio-, and stereoselective construction of heterocycle-tethered benzofulvenes via [3 + 2] CH/CH-alkyne annulation under palladium catalysis. The protocol overrides the more favorable [4 + 2] CH/NH annulation and does not follow the vinylic C–H bond activation pathway. Mechanistic studies provide insight into the favored cyclopalladation of key intermediates (resulting from β-C(benzylic)–H bond cleavage) through relay δ-C(aryl)–H cleavage (vs N–H cleavage) prior to reductive elimination, which is the key to desired annulation. The synthesized new chemical entities (NCEs) constitute a novel scaffold with favorable anticancer activity against oral squamous cell carcinoma (OSCC). Detailed biomolecular studies, including RNA-sequencing and analysis, indicate that these compounds (<b>4e</b> and <b>4w</b>) arrest the cell cycle at the S-phase and target multiple cancer hallmarks, such as the activation of apoptotic pathways and impairment of mitochondrial activity simultaneously, suggesting their chemotherapeutic potential for oral cancer by addressing the complexity and adaptability of cancer cells in chorus.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4474–4487 4474–4487"},"PeriodicalIF":8.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalytic Hydrodeoxygenation of Mixed Plastic Wastes into Sustainable Naphthenes","authors":"Jieyi Liu,&nbsp;Nan Wang,&nbsp;Sibao Liu* and Guozhu Liu*,&nbsp;","doi":"10.1021/jacsau.4c0070110.1021/jacsau.4c00701","DOIUrl":"https://doi.org/10.1021/jacsau.4c00701https://doi.org/10.1021/jacsau.4c00701","url":null,"abstract":"<p >The chemical upcycling of plastic wastes by converting them into valuable fuels and chemicals represents a sustainable approach as opposed to landfilling and incineration. However, it encounters challenges in dealing with mixed plastic wastes due to their complex composition and sorting/cleaning costs. Here, we present a one-pot hydrodeoxygenation (HDO) method for converting mixed plastic wastes containing poly(ethylene terephthalate) (PET), polycarbonate (PC), and poly(phenylene oxide) (PPO) into sustainable naphthenes under mild reaction conditions. To facilitate this process, we developed a cost-effective, contaminant-tolerant, and reusable Ni/HZSM-5 bifunctional catalyst through an ethylene glycol-assisted impregnation method. The metallic Ni site plays a pivotal role in catalyzing C–O and C–C cleavages as well as hydrogenation reactions, while the acidic site of HZSM-5 facilitates dehydration and isomerization reactions. The collaboration between metal and acid dual sites on Ni/HZSM-5 enabled efficient HDO of a wide range of substrates, including bottles, textile fibers, pellets, sheets, CDs/DVDs, and plastics without cleaning or pigments removal and even their various mixtures, into naphthenes with a high yield up to 99% at 250 °C and 4 MPa H₂ within 4–6 h. Furthermore, the metal-acid balance of the Ni/HZSM-5 catalyst is crucial for determining both HDO activity and product distribution. This proposed one-pot HDO process utilizing earth-abundant metal catalysts provides a promising avenue toward practical valorization of mixed plastic wastes.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4361–4373 4361–4373"},"PeriodicalIF":8.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-Free Aziridination of Unactivated Olefins via Transient N-Pyridinium Iminoiodinanes","authors":"Hao Tan,&nbsp;Phong Thai,&nbsp;Uddalak Sengupta,&nbsp;Isaac R. Deavenport,&nbsp;Cali M. Kucifer and David C. Powers*,&nbsp;","doi":"10.1021/jacsau.4c0055610.1021/jacsau.4c00556","DOIUrl":"https://doi.org/10.1021/jacsau.4c00556https://doi.org/10.1021/jacsau.4c00556","url":null,"abstract":"<p >We describe a metal-free aziridination of unactivated olefins to generate <i>N-</i>pyridinium aziridines. Subsequent cross-coupling affords <i>N</i>-aryl aziridines, and reductive depyridylation affords N–H aziridines. Kinetics experiments, based on a variable time normalization analysis (VTNA), indicate that aziridination proceeds via a highly electrophilic <i>N</i>-pyridinium iminoiodinane intermediate. These studies expand <i>build-and-couple</i> aziridine synthesis to unactivated olefins and introduce charge-enhanced electrophilicity into the chemistry of iminoiodinanes.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4187–4193 4187–4193"},"PeriodicalIF":8.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Thermal Stress on Morphology in High-Performance Organic Photovoltaic Blends","authors":"Haoyu Zhao,&nbsp;Nathaniel Prine,&nbsp;Soumya Kundu,&nbsp;Guorong Ma and Xiaodan Gu*,&nbsp;","doi":"10.1021/jacsau.4c0063110.1021/jacsau.4c00631","DOIUrl":"https://doi.org/10.1021/jacsau.4c00631https://doi.org/10.1021/jacsau.4c00631","url":null,"abstract":"<p >Thermal stress is a critical factor causing long-term instability in bulk heterojunction (BHJ) layers of organic photovoltaic (OPV) devices. This study provides direct insights into the thermal properties of Y6, PM6, and their binary blends by employing fast differential scanning calorimetry (flash DSC) to analyze their chain dynamics. The glass transition temperatures (<i>T</i>_g) of Y6 and PM6 were measured, with Y6 exhibiting a <i>T</i>_g of 175.2 °C and PM6 showing two <i>T</i>_gs at 39.7 and 107.6 °C. Our findings indicate that average OPVs’ operational temperatures are lower than the blend’s primary <i>T</i>_g of 138.2 °C. Thus, the mobility of PM6 and Y6 is not the critical factor that results in drastic drifts in the device morphology. Instead, we discovered that the crystallization of small molecules Y6 in the BHJ film at elevated operation temperatures <i>significantly contributes</i> to the morphological instability of the BHJ layer, based on a flash DSC isotherm crystallization study. The crystallization of the acceptor leads to severe phase separation between donors and acceptors and results in device failure. The acceptor Y6’s crystallization rate also increased when blended with donor PM6, compared to that of pure Y6 molecules. Furthermore, AFM–IR analysis of the morphology of the BHJ layer after high thermal stress of 200 °C revealed an apparent demixing of donor PM6 and acceptor Y6, revealing Y6 globules about 200 nm in diameter, with PM6 domains surrounding the Y6 regions. This crystallization-induced morphology change was later confirmed to correlate well with the device performance drop. This study offers valuable insights into the origin of BHJ layer instability in OPV devices containing nonfullerene small molecule acceptors and polymer donors. Additionally, it emphasizes the importance of addressing thermal stress to enhance the performance and durability of such devices and informs strategies for developing more stable organic solar cells.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4334–4344 4334–4344"},"PeriodicalIF":8.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Materials Design and Process Engineering for n-Type Polymer Thermoelectrics","authors":"Xin-Yu Deng,&nbsp;Zhi Zhang and Ting Lei*,&nbsp;","doi":"10.1021/jacsau.4c0063810.1021/jacsau.4c00638","DOIUrl":"https://doi.org/10.1021/jacsau.4c00638https://doi.org/10.1021/jacsau.4c00638","url":null,"abstract":"<p >Polymer thermoelectrics (TEs) have attracted increasing interest in recent years, owing to their great potential in intimate integration with wearable electronics for powering small electronics/sensors and personal temperature regulation. Over the past few decades, substantial progress has been made in enhancing polymer TE performance. However, the electrical conductivity and power factor of most n-doped polymers are about an order of magnitude lower than those of their p-type counterparts, impeding the development of highly efficient polymer TE devices. In addition, unlike well-studied inorganic materials, the complex charge transport mechanism and polymer–dopant interactions in polymer TE materials have hindered a comprehensive understanding of the structure–property relationships. This Perspective aims to survey recent achievements in understanding the charge transport mechanism and selectively provide some critical insights into molecular design and process engineering for n-type polymer TEs. We also highlight the great potential of polymer TEs in wearable electronics and offer an outlook for future development.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4066–4083 4066–4083"},"PeriodicalIF":8.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total Synthesis of (−)-Bipolarolide D","authors":"Gleb A. Chesnokov,&nbsp;Julia Friedli,&nbsp;Francis J. Carta and Karl Gademann*,&nbsp;","doi":"10.1021/jacsau.4c0068010.1021/jacsau.4c00680","DOIUrl":"https://doi.org/10.1021/jacsau.4c00680https://doi.org/10.1021/jacsau.4c00680","url":null,"abstract":"<p >(−)-Bipolarolide D is an ophiobolin-derived sesteterpenoid with a unique tetraquinane (5/5/5/5) tetracyclic skeleton decorated with a diverse set of functionalities. Herein we report a robust, scalable, and efficient total synthesis of this natural product in 1.8% overall yield. The developed approach features a diastereoselective Pauson–Khand reaction, a highly efficient Rautenstrauch cycloisomerization, and radical cyclization to forge the carbon backbone and the installation of the side chain via crotylation with 1-methyl-2-propenylmagnesium chloride followed by Suzuki cross-coupling.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4194–4198 4194–4198"},"PeriodicalIF":8.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatic Routes to Designer Hemicelluloses for Use in Biobased Materials","authors":"Thu V. Vuong,&nbsp;Mohammad Aghajohari,&nbsp;Xuebin Feng,&nbsp;Amanda K. Woodstock,&nbsp;Deepti M. Nambiar,&nbsp;Zeina C. Sleiman,&nbsp;Breeanna R. Urbanowicz* and Emma R. Master*,&nbsp;","doi":"10.1021/jacsau.4c0046910.1021/jacsau.4c00469","DOIUrl":"https://doi.org/10.1021/jacsau.4c00469https://doi.org/10.1021/jacsau.4c00469","url":null,"abstract":"<p >Various enzymes can be used to modify the structure of hemicelluloses directly in vivo or following extraction from biomass sources, such as wood and agricultural residues. Generally, these enzymes can contribute to designer hemicelluloses through four main strategies: (1) enzymatic hydrolysis such as selective removal of side groups by glycoside hydrolases (GH) and carbohydrate esterases (CE), (2) enzymatic cross-linking, for instance, the selective addition of side groups by glycosyltransferases (GT) with activated sugars, (3) enzymatic polymerization by glycosynthases (GS) with activated glycosyl donors or transglycosylation, and (4) enzymatic functionalization, particularly via oxidation by carbohydrate oxidoreductases and via amination by amine transaminases. Thus, this Perspective will first highlight enzymes that play a role in regulating the degree of polymerization and side group composition of hemicelluloses, and subsequently, it will explore enzymes that enhance cross-linking capabilities and incorporate novel chemical functionalities into saccharide structures. These enzymatic routes offer a precise way to tailor the properties of hemicelluloses for specific applications in biobased materials, contributing to the development of renewable alternatives to conventional materials derived from fossil fuels.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 11","pages":"4044–4065 4044–4065"},"PeriodicalIF":8.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrimidine Azepine Targets the <i>Plasmodium bc</i> ₁ Complex and Displays Multistage Antimalarial Activity.","authors":"Juliana Calit, Surendra K Prajapati, Ernest D Benavente, Jessica E Araújo, Bingbing Deng, Kazutoyo Miura, Yasmin Annunciato, Igor M R Moura, Miho Usui, Jansen F Medeiros, Carolina H Andrade, Sabrina Silva-Mendonça, Anton Simeonov, Richard T Eastman, Carole A Long, Maisa da Silva Araujo, Kim C Williamson, Anna Caroline C Aguiar, Daniel Y Bargieri","doi":"10.1021/jacsau.4c00674","DOIUrl":"10.1021/jacsau.4c00674","url":null,"abstract":"<p><p>Malaria control and elimination efforts would benefit from the identification and validation of new malaria chemotherapeutics. Recently, a transgenic <i>Plasmodium berghei</i> line was used to perform a series of high-throughput in vitro screens for new antimalarials acting against the parasite sexual stages. The screens identified pyrimidine azepine chemotypes with potent activity. Here, we validate the activity of <b>PyAz90</b>, the most potent pyrimidine azepine chemotype identified, against <i>P. falciparum</i> and <i>P. vivax</i> in the asexual and sexual stages. <b>PyAz90</b> blocked parasite transmission to the mosquito vector at nanomolar concentrations and inhibited in vitro asexual parasite multiplication with a fast-action profile. Through the generation of <i>P. falciparum</i> <b>PyAz90-</b>resistant parasites and in vitro assays of mitochondrial activity, we identified cytochrome <i>b</i> as a molecular target of <b>PyAz90</b>. This work characterizes a promising chemotype that can be explored for the future development of new antimalarials targeting the <i>Plasmodium</i> cytochrome <i>bc</i> ₁ complex.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 10","pages":"3942-3952"},"PeriodicalIF":8.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}