Chemical Science最新文献

{"title":"Ultrafast Solvent Migration in an Iron Complex Revealed by Nonadiabatic Dynamics Simulations","authors":"Severin Polonius, Leticia González, Sebastian Mai","doi":"10.1039/d5sc01174d","DOIUrl":"https://doi.org/10.1039/d5sc01174d","url":null,"abstract":"The response of a solvation shell to molecular solute photoexcitation is an ubiquitous phenomenon of great relevance in chemistry. This response can occur within just few tens of femtoseconds, making it very challenging to resolve experimentally. Thus, the details of the (an)isotropy of the solvent response around a solute, the presence of coherent solvent fluctuations, hydrogen bond reorganization mechanisms, and the intricate interplay between electronic, spin, nuclear, and solvent dynamics remain elusive. Here, we report large-scale nonadiabatic molecular dynamics simulations of [Fe(CN)4(bipy)]2− (bipy=2,2’-bipyridine) in water, where the electronic evolution from singlet metal-to-ligand charge transfer (MLCT) states to triplet MLCT and metal-centered (MC) states overlaps temporally with the molecule’s nuclear motion and a strong solvent shell response. We leverage vibronic coupling model potentials combined with electrostatic embedding, within our so-called vibronic coupling/molecular mechanics (VC/MM) method, to be able to compute several thousand nonadiabatic excited-state trajectories, including all relevant singlet and triplet states as well as several thousand explicit water molecules. This superior statistics affords an unprecedented view on the three-dimensional solvent distribution dynamics at few-fs and sub-Å resolution. The results reveal a direct solvent migration mechanism, where excitation to the MLCT states leads to the breaking of hydrogen bonds to the cyanide ligands within less than 100 fs, followed by the formation of hydrogen bonds with the negatively charged bipyridyl ligand by the same water molecules. Furthermore, the MLCT and MC states show very distinct solvent responses, which are overlapping in time, as governed by the electronic dynamics. More broadly, this work demonstrates how VC/MM nonadiabatic dynamics simulations can resolve anisotropic solvent dynamics around a photoexcited solute with unprecedented detail, offering a new perspective that could stimulate the development of time-resolved experimental techniques capable of probing such solvent behaviour.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"32 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946013","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":"Exploring the Chemical Design Space of Metal-Organic Frameworks for Photocatalysis","authors":"Beatriz Mouriño, Sauradeep Majumdar, Xin Jin, Fergus Mcilwaine, Joren Van Herck, Andres Ortega-Guerrero, Susana García, Berend Smit","doi":"10.1039/d5sc01100k","DOIUrl":"https://doi.org/10.1039/d5sc01100k","url":null,"abstract":"In this work, we introduce a combined DFT and machine learning approach to obtain insights into the chemical design of metal-organic framework (MOF) photocatalysts for hydrogen (HER) and oxygen (OER) evolution reactions. To train our machine learning models, we evaluated a dataset of 314 MOFs using a dedicated DFT workflow that computes a set of five descriptors for both closed and open shell MOFs. Our dataset is composed of a diverse selection of the QMOF database and experimentally reported MOF photocatalysts. In addition, to ensure a balanced dataset, we designed a set of MOFs (CDP–MOF) inspired by insights obtained regarding different types of photocatalytic materials. Our machine-learning approach allowed us to screen the entire QMOF and CDP–MOF databases for promising candidates. Our analysis of the chemical design space shows that we have many materials with a suitable spatial overlap of electron and hole, band gap, band-edge alignment to HER, and charge-carrier effective masses. However, we have identified in the QMOF database only a very small percentage of materials that also have the right band-edge alignment to OER. With the CDP–MOF database, we successfully targeted building blocks that potentially have the correct OER band alignment, and indeed obtained a larger percentage of materials that obey this criteria. Among those, a few motifs stood out, such as Au-pyrazolate, Ti clusters and rod-shaped metal nodes, and a particular MOF designed with the Mn4Ca cluster, which mimics the OER center in the photosystem II of photosynthesis.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"117 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946074","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":"Electrosynthesis of Molecular Memory Elements","authors":"Pradeep Sachan, Anwesha Mahapatra, Rajwinder Kaur, Lalith Adithya Sai Channapragada, Subham Sahay, Prakash Chandra Mondal","doi":"10.1039/d4sc08461f","DOIUrl":"https://doi.org/10.1039/d4sc08461f","url":null,"abstract":"The increasing pace of computing beyond Moore’s law scaling and the von Neumann bottleneck necessitates a universal memory solution that offers high speed, low-power consumption, scalability, and non-volatility, such as resistive switching memristors. However, inconsistencies in the homogeneity and uniformity of surface coverage for switching materials on various electrode substrates, especially those prepared via non-covalent methods, result in reduced interfacial stability, thus yielding poor device reproducibility. Electrosynthesis, a reliable and versatile technique for creating covalently bound molecular films on electrode surfaces, enables controlled deposition of large-area, high-quality molecular thin films with nanoscale thicknesses, making it an ideal platform for scalable nanoelectronics. This study explores the electrochemical grafting of two distinct ruthenium complexes: structurally symmetrical [Ru(tpy-ph-NH2<small></small><small></small>)2](2PF6<small></small>)] (1), and the asymmetrical [Ru(tpy-ph-NH2<small></small><small></small>)(naptpy)](2PF6<small></small>)] (2), for the fabrication of large-area, two-terminal molecular junctions intended for resistive switching memory applications. A comparative analysis reveals that 2 exhibits a relatively superior memory performance than 1, attributed to its donor–acceptor configuration playing a crucial role. Stable vertical molecular junctions with the configuration ITO/Ru complex24nm<small></small>/Al were fabricated, and electrical measurements were carried out to understand the enhanced switching characteristics. The redox-active molecular devices demonstrate non-volatile resistive switching behavior within ±3.0 V operation window, large ION/IOFF ratio (~103<small></small>), high ratios of power consumption (SET/RESET = 25.5 mJ/75000 mJ), and switching time (SET/RESET = 56/24 ms). Synapse-like potentiation and convolutional neural network simulation were made, highlighting the potential of these devices for in-memory data processing applications.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"76 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939749","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":"Diastereoselective Umpolung cyclisation of ketones promoted by hypervalent iodine","authors":"Giulia Iannelli, Philipp Spieß, Ricardo Meyrelles, Daniel Kaiser, Boris Maryasin, Leticia González, Nuno Maulide","doi":"10.1039/d5sc01085c","DOIUrl":"https://doi.org/10.1039/d5sc01085c","url":null,"abstract":"Umpolung reactivity facilitated by hypervalent iodine has emerged as an appealing method for the efficient α‑functionalisation of ketones. However, skeletal reorganisation or migration reactions remain comparatively underexplored, primarily due to the challenging taming of transient carbocationic intermediates. In this study, we introduce a method for the functionalisation of ketones, employing a <em>6-endo-trig</em> cyclisation initiated by Umpolung of silyl enol ethers, resulting in the diastereoselective formation of <em>syn</em>-substituted cyclohexanes. Additional investigations, both experimental and computational, give insight into the mechanistic intricacies of this process, and shed light on an unconventional I(III)‑reactivation mechanism.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"55 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939999","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":"Evolutionary insights into the selectivity of sterol oxidising cytochrome P450 enzymes based on ancestral sequence reconstruction.","authors":"Daniel Z Doherty, James Joseph De Voss, John B Bruning, Stephen G Bell","doi":"10.1039/d5sc01863c","DOIUrl":"https://doi.org/10.1039/d5sc01863c","url":null,"abstract":"The cytochrome P450 (CYP) enzyme CYP125A1 is a crucial enzyme for the long-term survival and pathogenicity of Mycobacterium tuberculosis. CYP125 genes are found not only in pathogenic mycobacteria but are also widely dispersed within the Actinobacteria phylum, with many species possessing multiple copies of CYP125 encoding genes. Their primary function is the catalytic hydroxylation of the terminal methyl group of cholesterol and phytosterols. We have previously shown that CYP125 enzymes from distinct mycobacteria have substrate selectivity preferences for animal versus plant steroid oxidation. An evolutionary understanding of this selectivity is not known. Here, we use Ancestral Sequence Reconstruction (ASR), to support the hypothesis that some CYP125 enzymes evolved in a manner reflective of their adaptation to a pathogenic niche. We constructed a maximum-likelihood, most-recent common ancestor of the CYP125 clade (CYP125MRCA). We were then able to produce and characterise this enzyme both functionally and structurally. We found that CYP125MRCA was able to catalyse the terminal hydroxylation of cholesterol, phytosterols, and vitamin D3 (cholecalciferol); the latter was hydroxylated at both C-25 and C-26. This is the first example to date of vitamin D3 oxidation by a CYP125 enzyme, thereby demonstrating an increased substrate range of CYP125MRCA relative to its characterised extant relatives. The X-ray crystal structures of CYP125MRCA bound with sitosterol and vitamin D3 were determined, providing important insight into the changes that enable the expanded substrate range.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"43 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946015","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":"Engineering of soluble bacteriorhodopsin","authors":"Andrey Nikolaev, Yaroslav Orlov, Fedor Tsybrov, Elizaveta Kuznetsova, Pavel Shishkin, Alexander Kuzmin, Anatolii E. Mikhailov, Yulia S. Nikolaeva, Arina Anuchina, Igor Chizhov, Oleg Semenov, Ivan Kapranov, Valentin Borshchevskiy, Alina Remeeva, Ivan Gushchin","doi":"10.1039/d5sc02453f","DOIUrl":"https://doi.org/10.1039/d5sc02453f","url":null,"abstract":"Studies and applications of membrane proteins remain challenging due to the requirement of maintaining them in a lipid membrane or a membrane mimic. Modern machine learning-based protein engineering methods offer a possibility of generating soluble analogs of membrane proteins that retain the active site structure and ligand-binding properties, however, clear examples are currently missing. Here, we report successful engineering of proteins dubbed NeuroBRs that mimic the active site (retinal-binding pocket) of bacteriorhodopsin, a light-driven proton pump and well-studied model membrane protein. NeuroBRs are soluble and stable, bind retinal and exhibit photocycle under illumination. Crystallographic structure of NeuroBR_A, determined at anisotropic resolution reaching 1.76 Å, reveals an excellently conserved chromophore binding pocket and tertiary structure. Thus, NeuroBRs are promising microbial rhodopsin mimics for studying retinal photochemistry and potential soluble effector modules for optogenetic tools. Overall, our results highlight the power of modern protein engineering approaches and pave the way towards wider development of molecular tools derived from membrane proteins.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"28 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946014","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":"Adapting Gas Fermenting Bacteria for Light-driven Domino Valorization of CO2","authors":"Lin Su, Santiago Rodríguez-Jiménez, Marion I. M. Short, Erwin Reisner","doi":"10.1039/d5sc00764j","DOIUrl":"https://doi.org/10.1039/d5sc00764j","url":null,"abstract":"The solar-driven valorization of CO<small>₂</small> to fuels and chemicals provides an exciting opportunity to develop a circular chemical industry, but the controlled production of multicarbon organics remains a major challenge. Here, we present an abiotic-biotic domino strategy that integrates a photocatalytic CO₂-to-syngas conversion system with evolved syngas-fermenting bacteria to enable the upcycling of CO₂ into valuable C₂ products, including acetate and ethanol. To optimize microbial syngas fermentation through an accessible and chemist-friendly platform, we employ adaptive laboratory evolution (ALE) of <em>Clostridium ljungdahlii</em> (<em>Cl</em>). The adapted strain, <em>Cl</em><small>_adapt</small>, exhibits a 2.5-fold increase in growth rate and a 120-fold enhancement in C₂ production compared to the wild-type (<em>Cl</em><small>_wt</small>). Isotopic labeling confirmed <em>Cl</em><small>_adapt</small>'s high conversion efficiency, yielding 6:1 and 9:1 ratios of ¹³C:¹²C in acetate and ethanol, respectively. Whole genome sequencing revealed eight unique mutations in <em>Cl</em><small>_adapt</small>, whereas RNA-seq identified significant alterations in gene expression, shedding light on its enhanced metabolism. A scaled-up semiconductor-molecule hybrid photocatalyst, TiO₂|phosphonated Co(terpyridine)₂, was employed to generate sufficient syngas (CO/H<small>₂</small>ratio: ~30:70 with 1.3 mmol of CO after 6 days) for <em>Cl</em><small>_adapt</small> to demonstrate photocatalytic CO<small>₂</small>®syngas®C<small>₂</small> conversion (yielding 0.46 ± 0.07 mM, or 3.2 µmol, of acetate). This study offers a streamlined approach to improving syngas fermentation in <em>Cl</em>, insights into microbial adaptability, and an ALE-guided pathway for solar-powered CO₂ upcycling using an inorganic-microbial domino strategy.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"2 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933362","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":"β-Lactamase-Activated Antimicrobial Dendron via the Amine Uncaging Strategy","authors":"Hao Luo, Zeyu Shao, Karen Hakobyan, Jiangtao Xu, Rhiannon P. Kuchel, Shyam Kumar Mishra, Mark D. P. Willcox, Edgar Wong","doi":"10.1039/d5sc02412a","DOIUrl":"https://doi.org/10.1039/d5sc02412a","url":null,"abstract":"The development of new antimicrobial agents to combat multidrug-resistant (MDR) bacteria, especially those that produce β-lactamase enzymes, is a critical step in preventing a post-antibiotic era. Herein, we develop a new membrane-active antimicrobial prodrug (<strong>BLM-Dendron</strong>) based on the amine uncaging strategy (AUS) whereby the amine groups of a cationic amphipathic dendron are caged/masked initially but can be uncaged specifically in the presence of β-lactamase enzymes (e.g., penicillinase) to enable precise antimicrobial activation. <strong>BLM-Dendron</strong> undergoes self-assembly in water to form spherical nanoparticles with average hydrodynamic diameter (<em>D</em><small>_H-avg</small>) of ca. 200 nm and is bacteriostatic against (MDR) <em>P. aeruginosa</em>, <em>E. coli</em> and <em>S. aureus</em> in the presence of penicillinase. In addition, the uncaged dendron also has bactericidal and antibiofilm activities against wild-type <em>P. aeruginosa</em>. For instance, once uncaged, the dendron has the capacity to eliminate ≥ 99.99999% of planktonic cells after 24 h of treatment. Mechanistic studies show that the activated dendron is indeed membrane-active and disrupts the inner and outer membranes of bacteria cells. Notably, the prodrug <strong>BLM-Dendron</strong> has excellent hemocompatibility (at least 3.6 times higher) and low cytotoxicity (at least twice better) compared to the original molecule with exposed cationic groups. This study importantly demonstrates the benefit of using AUS to bestow cationic amphipathic antimicrobial agents with higher biocompatibility and targeted activation capabilities, as these features are key for translation into clinical settings.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"118 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933416","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":"Arylation of gold nanoclusters and insights into structure-related CO2 reduction reaction performances","authors":"Chen Zhu, Bo Li, Chen Li, Luyao Lu, Hao Li, Xinhua Yuan, Xi Kang, De-en Jiang, Manzhou Zhu","doi":"10.1039/d5sc01200g","DOIUrl":"https://doi.org/10.1039/d5sc01200g","url":null,"abstract":"Research on arylgold complexes and ligand-protected gold nanoclusters has proceeded independently thus far due to the difficulty in controllably introducing aryl groups to synthesize arylgold nanoclusters. Herein we synthesized an arylgold Au<small>₁₅</small> nanocluster, Au<small>₁₅</small>(DPPOE)<small>₃</small>(S-Ph<small>^<em>p</em></small>Me)<small>₄</small>(Ph)<small>₂</small>, thereby bridging the two independent research fields. Tetraarylborates were exploited as arylating agents to transfer aryl groups onto the nanocluster kernel, triggering the arylation of the Au<small>₁₅</small> cluster while maintaining the molecular framework. Furthermore, two other arylgold Au<small>₁₅</small> nanoclusters with halogenated surfaces were controllably synthesized by substituting the arylating agent NaBPh<small>₄</small> with its benzene ring-halide derivatives. In addition, the change in the electronic structure from Au-SR to Au-aryl and the energetics of the arylation process from Au<small>₁₅</small>-SR to Au<small>₁₅</small>-Ph were elucidated computationally. Furthermore, the catalytic capability of the two Au<small>₁₅</small> nanoclusters with nuanced ligand differences was investigated in the electrochemical reduction of CO<small>₂</small>, and the comparable reactivity of the two cluster-based nanocatalysts was theoretically rationalized. Our findings have cross-fertilized the fields of arylgold complexes and gold nanoclusters, pointing toward a new avenue of exploration for novel arylgold nanoclusters.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"44 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933359","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":"Discovery and optimisation of a covalent ligand for TRIM25 and its application to targeted protein ubiquitination","authors":"Katherine A. McPhie, Diego Esposito, Jonathan Pettinger, Daniel Norman, Thilo Werner, Toby Mathieson, Jacob T. Bush, Katrin Rittinger","doi":"10.1039/d5sc01540e","DOIUrl":"https://doi.org/10.1039/d5sc01540e","url":null,"abstract":"The tripartite motif (TRIM) family of RING-type E3 ligases catalyses the formation of many different types of ubiquitin chains, and as such, plays important roles in diverse cellular functions, ranging from immune regulation to cancer signalling pathways. Few ligands have been discovered for TRIM E3 ligases, and these E3s are under-represented in the rapidly expanding field of induced proximity. Here we present the identification of a novel covalent ligand for the PRYSPRY substrate binding domain of TRIM25. We employ covalent fragment screening coupled with high-throughput chemistry direct-to-biology optimisation to efficiently elaborate covalent fragment hits. We demonstrate that our optimised ligand enhances the <em>in vitro</em> auto-ubiquitination activity of TRIM25 and engages TRIM25 in live cells. We also present the X-ray crystal structure of TRIM25 PRYSPRY in complex with this covalent ligand. Finally, we incorporate our optimised ligand into heterobifunctional proximity-inducing compounds and demonstrate the <em>in vitro</em> targeted ubiquitination of a neosubstrate by TRIM25.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"38 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933361","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}