ACS Chemical Neuroscience最新文献

{"title":"Pathological Mutations D169G and P112H Electrostatically Aggravate the Amyloidogenicity of the Functional Domain of TDP-43.","authors":"Meenakshi Pillai, Anjali D Patil, Atanu Das, Santosh Kumar Jha","doi":"10.1021/acschemneuro.4c00372","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00372","url":null,"abstract":"<p><p>Aggregation of TDP-43 is linked to the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, electrostatic point mutations such as D169G and P112H, located within the highly conserved functional tandem RNA recognition motif (RRM) domains of the TDP-43 protein (TDP-43^tRRM), have been identified in diseased patients as well. In this study, we address how the electrostatic mutations alter both the native state stability and aggregation propensity of TDP-43^tRRM. The mutants D169G and P112H show increased chemical stability compared to the TDP-43^tRRM at physiological pH. However, at low pH, both the mutants undergo a conformational change to form amyloid-like fibrils, though with variable rates─the P112H mutant being substantially faster than the other two sequences (TDP-43^tRRM and D169G mutant) showing comparable rates. Moreover, among the three sequences, only the P112H mutant undergoes a strong ionic strength-dependent aggregability trend. These observations signify the substantial contribution of the excess charge of the P112H mutant to its unique aggregation process. Complementary simulated observables with atomistic resolution assign the experimentally observed sequence-, pH-, and ionic strength-dependent aggregability pattern to the degree of thermal lability of the mutation site-containing RRM1 domain and its extent of dynamical anticorrelation with the RRM2 domain whose combination eventually dictate the extent of generation of aggregation-prone partially unfolded conformational ensembles. Our choice of a specific charge-modulated pathogenic mutation-based experiment-simulation-combination approach unravels the otherwise hidden residue-wise contribution to the individual steps of this extremely complicated multistep aggregation process.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Frontiers in Conformational Exploration of Disordered Proteins: Integrating Autoencoder and Molecular Simulations.","authors":"Jiyuan Zeng, Zhongyuan Yang, Yiming Tang, Guanghong Wei","doi":"10.1021/acschemneuro.4c00670","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00670","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs) are closely associated with a number of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Due to the highly dynamic nature of IDPs, their structural determination and conformational exploration pose significant challenges for both experimental and computational research. Recently, the integration of machine learning with molecular dynamics (MD) simulations has emerged as a promising methodology for efficiently exploring the conformation spaces of IDPs. In this viewpoint, we briefly review recently developed autoencoder-based models designed to enhance the conformational exploration of IDPs through embedding and latent sampling. We highlight the capability of autoencoders in expanding the conformations sampled by MD simulations and discuss their limitations due to the non-Gaussian latent space distribution and the limited conformational diversity of training conformations. Potential strategies to overcome these limitations are also discussed.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the Monomeric and Dimeric Conformational Landscapes of the Full-Length TDP-43 and the Impact of the C-Terminal Domain.","authors":"Vaishnavi Tammara, Abhilasha A Doke, Santosh Kumar Jha, Atanu Das","doi":"10.1021/acschemneuro.4c00557","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00557","url":null,"abstract":"<p><p>The aberrant aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in cells leads to the pathogenesis of multiple fatal neurodegenerative diseases. Decoding the proposed initial transition between its functional dimeric and aggregation-prone monomeric states can potentially design a viable therapeutic strategy, which is presently limited by the lack of structural detail of the full-length TDP-43. To achieve a complete understanding of such a delicate phase space, we employed a multiscale simulation approach that unearths numerous crucial features, broadly summarized in two categories: (1) state-independent features that involve inherent chain collapsibility, rugged polymorphic landscape dictated by the terminal domains, high β-sheet propensity, structural integrity preserved by backbone-based intrachain hydrogen bonds and electrostatic forces, the prominence of the C-terminal domain in the intrachain cross-domain interfaces, and equal participation of hydrophobic and hydrophilic (charged and polar) residues in cross-domain interfaces; and (2) dimerization-modulated characteristics that encompass slower collapsing dynamics, restricted polymorphic landscape, the dominance of side chains in interchain hydrogen bonds, the appearance of the N-terminal domain in the dimer interface, and the prominence of hydrophilic (specifically polar) residues in interchain homo- and cross-domain interfaces. In our work, the ill-known C-terminal domain appears as the most crucial structure-dictating domain, which preferably populates a compact conformation with a high β-sheet propensity in its isolated state stabilized by intrabackbone hydrogen bonds, and these signatures are comparatively faded in its integrated form. Validation of our simulated observables by a complementary spectroscopic approach on multiple counts ensures the robustness of the computationally predicted features of the TDP-43 aggregation landscape.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of the First-in-Class Dual TSPO/Carbonic Anhydrase Modulators with Promising Neurotrophic Activity.","authors":"Valeria Poggetti, Elisa Angeloni, Lorenzo Germelli, Benito Natale, Muhammad Waqas, Giuliana Sarno, Andrea Angeli, Simona Daniele, Silvia Salerno, Elisabetta Barresi, Sandro Cosconati, Sabrina Castellano, Eleonora Da Pozzo, Barbara Costa, Claudiu T Supuran, Federico Da Settimo, Sabrina Taliani","doi":"10.1021/acschemneuro.4c00477","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00477","url":null,"abstract":"<p><p>In searching for putative new therapeutic strategies to treat neurodegenerative diseases, the mitochondrial 18 kDa translocator protein (TSPO) and cerebral isoforms of carbonic anhydrase (CA) were exploited as potential targets. Based on the structures of a class of highly affine and selective TSPO ligands and a class of CA activators, both developed by us in recent years, a small library of 2-phenylindole-based dual TSPO/CA modulators was developed, able to bind TSPO and activate CA VII in the low micromolar/submicromolar range. The interaction with the two targets was corroborated by computational studies. Biological investigation on human microglia C20 cells identified derivative <b>3</b> as a promising lead compound worthy of future optimization due to its (i) lack of cytotoxicity, (ii) ability to stimulate TSPO steroidogenic function and activate CA VII, and (iii) ability to effectively upregulate gene expression of the brain-derived neurotrophic factor.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial bioadaptive scaffold promotes vascularized bone regeneration by synergistical action of intrinsic stimulation and immunomodulatory activity","authors":"Yuhan Qian, Chenglin Li, Qian Feng, Xiaojun Mao, Guang Yang, Shuo Chen, Tao Li, Xiaojun Zhou, Chuanglong He","doi":"10.1016/j.cej.2024.157682","DOIUrl":"https://doi.org/10.1016/j.cej.2024.157682","url":null,"abstract":"The coupling of angiogenesis and osteogenesis is the fundamental necessity in bone fracture healing, thus simulative action of tissue-engineered bone provides powerful and beneficial effects in the treatment of bone defect. Herein, an immunoregulatory biocomposite scaffold with intrinsic activities of coupling angiogenesis and osteogenesis was constructed based on polyelectrolytes-modified 3D-printed scaffold for enhanced bone regeneration. The doping of Sr-doped hydroxyapatite (SrHA) within 3D-printed polycaprolactone (PCL) scaffold and subsequent slit guidance ligand 3 (SLIT3) protein adsorption through surface coating of carboxymethyl chitosan (CCS)/hyperbranched polylysine (HBPL) achieved on-demand delivery of SLIT3 and Sr ions. The antibacterial property of polyelectrolytes-modified scaffold was characterized and was directly proportional to the layer number of polyelectrolytes coating. The dual-factor delivery scaffold had good biocompatibility to support cell proliferation and migration, and was capable of stimulating angiogenesis and osteogenesis by intrinsic stimulation from released SLIT3 protein and Sr ions. Importantly, the multifunctional scaffold had immunomodulatory effects of promoting M2-type polarization of macrophages and thereby increasing anti-inflammatory factors level, as well as indirectly promoting angiogenesis and osteogenesis. The <em>in vivo</em> experiments revealed that the anti-inflammatory effect was significantly reinforced for providing a better regenerative microenvironment and bone regeneration capacity was dramatically enhanced accompanied with type H vessels formation when implanted with multifunctional scaffold. Therefore, the bioadaptive scaffold possessed amplified bone regeneration performance through intrinsic stimulation and immunomodulatory effects, suggesting a promising therapeutic candidate for bone defect repair.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"13 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Potential of Oxymatrine: A Comprehensive Review of Its Neuroprotective Mechanisms and Therapeutic Prospects in Neurological Disorders.","authors":"Yogita Dhurandhar, Shubham Tomar, Ashmita Das, As Pee Singh, Jeevan Lal Prajapati, Surendra H Bodakhe, Kamta P Namdeo","doi":"10.1021/acschemneuro.4c00338","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00338","url":null,"abstract":"<p><p><i>Sophora flavescens</i>, the source of oxymatrine, is gaining popularity due to its potential in neuroprotection and treatment of various neurological conditions like epilepsy, depression, Parkinson's, Alzheimer's and multiple sclerosis. Its natural occurrence and promising preliminary research highlight its ability to reduce nerve cell damage and inflammation, attributed to its antiapoptotic, antioxidant and anti-inflammatory properties. However, challenges like solubility, potential adverse effects and limited bioavailability hinder its full therapeutic utilization. Current strategies, including formulation optimization and innovative drug delivery systems, aim to enhance its efficacy and safety. Despite its potential, further research is necessary to overcome these obstacles and maximize its clinical effectiveness. Conclusively, oxymatrine demonstrates distinct neuroprotective properties, offering unique advantages over other agents currently being studied or used in clinical practice for neurological disorders. nevertheless, additional study is necessary to surmount current obstacles and maximize its effectiveness for clinical settings. This study provides a comprehensive overview of oxymatrine's neuroprotective mechanisms and therapeutic potential while emphasizing the need for continued investigation and development for practical clinical application.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and optimization of novel vortex microreactors for ultrasound-assisted synthesis of high-performance Fe3O4 nanoparticles","authors":"Su Wang, Jiaxiang Zhang, Kaixuan Ma, Wanyao Zhang, Yan Gao, Pengjie Yu, Shuangfei Zhao, Yirong Feng, Jiming Yang, Ruiyan Sun, Yuguang Li, Ning Zhu, Wei He, Kai Guo","doi":"10.1016/j.cej.2024.157672","DOIUrl":"https://doi.org/10.1016/j.cej.2024.157672","url":null,"abstract":"Microreactors excel in nanomaterial preparation but are limited by microchannel clogging for sustained long-term use. This study reports an innovative design of an ultrasound-assisted vortex microreactor for the continuous synthesis of high-performance nano-Fe₃O₄ particles. Combining visual experiments with computational fluid dynamics (CFD) simulations, four vortex microreactors were designed, and their mixing and heat transfer processes were investigated. Through comprehensive analysis, microreactor-4 was identified as the optimal configuration, with an optimal flow rate of 1 mL/min and a temperature of 70 °C. By coupling the microreactor with ultrasound, a continuous preparation method for nano-Fe3O4 was realized. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD) analyses revealed that the synthesized nano-Fe3O4 particles exhibit a spherical crystal morphology with an average particle size of approximately 6.68 nm, which is 24.4 % and 20.5 % smaller than those prepared by the beaker method and by a stirred-field coupled microreactor reported in the literature, respectively. Vibrating sample magnetometry (VSM) measurements indicated a saturation magnetization of 45.75 emu/g for the nano-Fe3O4, representing a 32.3 % increase over the beaker method and demonstrating excellent superparamagnetic properties. This study provides a novel and effective pathway for the continuous preparation of nanoscale magnetic materials.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"108 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of Cu-doped α-Fe2O3/γ-Fe2O3 hetero-phase junction composite and its photocatalytic performance","authors":"Shunzhi Li, Hongqing He, Xianbin Li, Weiwei Zhu, Chong Yang, Bangjie Jiang, Yang Cao","doi":"10.1016/j.cej.2024.157678","DOIUrl":"https://doi.org/10.1016/j.cej.2024.157678","url":null,"abstract":"Chlortetracycline hydrochloride (CTC), a class of antibiotics, poses a significant environmental hazard, particularly in aquatic ecosystems. The advancement of highly efficient and readily recyclable materials for water treatment remains an important focus of research in environmental remediation. In this study, Cu-doped α-Fe₂O₃/γ-Fe₂O₃ hetero-phase junction materials were prepared by a solvothermal method and a controlled calcination process to enhance the photocatalytic degradation of CTC in water by Fe₂O₃. Experimental results indicate that the composite material has superior magnetic properties, with Cu2-α-Fe₂O₃/γ-Fe₂O₃, featuring a high specific surface area and small pores, showing the best CTC adsorption. The α-Fe₂O₃/γ-Fe₂O₃′s interlaced energy levels facilitate quick electron transfer, and copper ion addition optimizes electron paths, generating numerous oxygen vacancies. This, combined with the hetero-phase junction, boosts charge separation and migration. Among the samples tested, The Cu2-α-Fe₂O₃/γ-Fe₂O₃ composite demonstrated the most efficient photocatalytic performance, with a degradation rate of 90.19 % for CTC achieved under Visible Light Irradiation. The proposed second-order reaction rate constants were approximately 31.99, 10.07, and 4.48 times higher than those for α-Fe₂O₃, γ-Fe₂O₃, and α-Fe₂O₃/γ-Fe₂O₃, respectively. The material also demonstrates good degradation effects on other antibiotics (such as oxytetracycline, tetracycline hydrochloride, etc.). Moreover, the structural morphology of the sample remains stable after cycling. ^{<img alt=\"radical dot\" src=\"https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/55/entities/rad.gif\" style=\"vertical-align:middle\"/>}O₂^– and h⁺ are the main active species in the photocatalytic degradation process of CTC, while ^{<img alt=\"radical dot\" src=\"https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/55/entities/rad.gif\" style=\"vertical-align:middle\"/>}OH plays a secondary role. The possible degradation pathways were elucidated by calculating predicted free radical attack sites using density-functional theory (DFT) and by analyzing the products of the CTC degradation process. Additionally, the toxicity risk assessment indicates that the intermediate products have low toxicity and pose a minimal potential risk to the aquatic environment.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"4 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOGCN: Prediction of key properties of MR-TADF materials using graph convolutional neural networks","authors":"Yingfu Li, Bohua Zhang, Aimin Ren, Dongdong Wang, Jun Zhang, Changming Nie, Zhongmin Su, Luyi Zou","doi":"10.1016/j.cej.2024.157676","DOIUrl":"https://doi.org/10.1016/j.cej.2024.157676","url":null,"abstract":"The exploration of the structure and properties of the luminescent materials in OLED devices using Multiple Resonance Thermally Activated Delayed Fluorescence (MR-TADF) is constrained by challenges related to long cycles and high experimental costs, making it a key obstacle in the development of new materials. In response to this challenge, we propose an innovative approach by constructing a graph convolutional neural network model named SOGCN to quickly determine whether an unsynthesized material has the potential to become an MR material, and accurately predict its energy gap and half-peak width, thereby expediting the development process of MR-TADF materials. We constructed the MR220 dataset for training the model based on 220 MR-TADF molecules reported in experiments. To ensure the reliability of the SOGCN model in predicting new samples, we have established a rigorous set of theoretical calculation evaluation standards, providing crucial references for the model. In the prediction of the properties of 37 new samples of MR-TADF molecules, SOGCN successfully predicted the singlet–triplet energy gap (ΔE_ST) of some samples, demonstrating a good trend in FWHM prediction as well. Finally, we have synthesized our designed molecule, Design3 (<strong>DtCzB-Boz</strong>), the organic light-emitting diodes based on <strong>DtCzB-Boz</strong> exhibit an emission peak at 508 nm, with the FWHM is 27 nm. The result of photophysical characterization is highly consistent with the predicted value of SOGCN. Notably, the mean absolute errors (MAE) between our model predictions and experimental/computational values were as low as 0.037 eV and 12 nm, respectively. This indicates that SOGCN exhibits higher efficiency and accuracy in predicting the properties of MR-TADF materials.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"216 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switch on amine substrate reactivity towards hexaazaisowurtzitane cage: Insights from a tailored machine learning model","authors":"Kaile Dou, Weibo Zhao, Chenyue Wang, Yuanchen Fan, Chunlin He, Lei Zhang, Siping Pang","doi":"10.1016/j.cej.2024.157677","DOIUrl":"https://doi.org/10.1016/j.cej.2024.157677","url":null,"abstract":"The efficient synthesis of novel hexaazaisowurtzitane cage compounds has remained a formidable challenge for years due to the complicated reaction mechanism and the uncertainty of amine substrate selection. Here, we developed a tailored machine learning model to predict the reactivity of amine substrates towards hexaazaisowurtzitane cage based on high-throughput quantum mechanical calculations of 3428 property parameters of 118 amine substrates. The customized model was developed through an appropriately weighted fusion of advanced universal models, achieving comprehensive predictive capability with an accuracy of 91.4 %, an F1 score of 89.1 %, and a recall of 91.4 %. Further, the customized model exhibits a narrow interquartile range of accuracy, surpassing universal models by 30.6–54.4 % and demonstrating robustness across various data splits. The data-driven analysis identified that electronic and geometric features are the dominant regulating factors of amine’s reactivity. Further, physics-driven insights revealed that a low electron-density environment near the nitrogen in the amine group is a key for switching on the reactivity of the amine substrates, which can be characterized by a sufficiently high NMR signal around 225.7 ppm with a narrow fluctuation of 2.6 ppm. Based on the revealed guiding factors and regulating mechanism, we selected 27 commercially available amine substrates for reactivity assessment and recommended 5 candidates with a probability exceeding 90 % for synthesis trials. This work pioneers machine learning and high-throughput quantum mechanical computationally assisted prediction of substrate selection for the rational synthesis of hexaazaisowurtzitane cages.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"11 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}