[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-128532-en":3,"doc-seo-128532-105":30,"detail-sidebar-cat-0-en-105":92},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":20,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29},128532,687207020761,"Patrick","https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d",8,"Research & Report","Bringing Machine-Learning Enhanced Quantum Chemistry and Microwave Spectroscopy to Conformational Landscape Exploration - the Paradigmatic Case of 4-Fluoro-Threonine","A combined experimental and theoretical investigation examines 4-fluoro-threonine, the only naturally occurring fluorinated amino acid, highlighting how fluorination of the methyl group substantially increases conformational complexity relative to threonine. The study provides a detailed characterization of inter-conversion pathways and determines 13 stable low-energy minima. The resulting dense rotational spectrum is assigned using a strategy that integrates multiple quantum chemical calculation levels with machine learning, enabling experimental characterization of 12 conformers.","Chemistry—A EuropeanJournal  \nResearch Article  \n[doi.org/10.1002/chem.202203990](doi.org/10.1002/chem.202203990)  \n[www.chemeurj.org](www.chemeurj.org)  \nBringing Machine-Learning Enhanced Quantum Chemistry and Microwave Spectroscopy to Conformational Landscape Exploration: the Paradigmatic Case of 4-Fluoro-Threonine  \nV. Barone,*[a] M. Fusè,[a] R. Aguado,[b] S. Potenti,[a, c] I. León,[b] E. R. Alonso,[b] S. Mata,[b]  \nF. Lazzari,[a] G. Mancini,[a] L. Spada,[a] A. Gualandi,[c] P. G. Cozzi,[c] C. Puzzarini,*[c] and  \nJ. L. Alonso*[b]  \n\n| \u003Cbr>Abstract: A combined experimental and theoretical study has been carried out on 4-fluoro-threonine, the only naturally occurring fluorinated amino acid. Fluorination of the methyl group significantly increases the conformational complexity with respect to the parent amino acid threonine. The conformational landscape has been characterized in great detail, with special attention given to the inter-conversion pathways between different conformers. This led to the identification of 13 stable low-energy minima. The equili- | \u003Cbr>brium population of so many conformers produces a very complicated and congested rotational spectrum that could be assigned through a strategy that combines several levels of quantum chemical calculations with the principles of machine learning. Twelve conformers out of 13 could be experimentally characterized. The results obtained from the analysis of the intra-molecular interactions can be exploited to accurately model fluorine-substitution effects in biomole- |  |\n| --- | --- | --- |\n|  | cules. |  |\n\nIntroduction  \nFluorinated organic molecules play an important role in medicinal chemistry. [1,2] Before the Covid-19 pandemic, the most prescribed drug in the world was atorvastatin (Lipitor), which features a fluorinated phenyl substituent. Moreover, nearly half of the new small molecule drugs approved by the US Food and Drug Administration in 2018 contained a fluorine atom.[3] Replacement of a hydrogen by the similarly sized fluorine atom tends to have a negligible impact on steric properties and molecular shape, while the vastly different electronic properties of fluorine can have profound effects on binding energy, reactivity, and relative energy of corresponding  \n[a] Prof. Dr. V. Barone, Dr. M. Fusè, Dr. S. Potenti, F. Lazzari, Dr. G. Mancini, Dr. L. Spada  \nSMART Laboratory, Scuola Normale Superiore di Pisa, piazza dei Cavalieri 7, 56126 Pisa, Italy  \nE-mail: [vincenzo.barone@sns.it](vincenzo.barone@sns.it)  \n[b] R. Aguado, Dr. I. León, E. R. Alonso, S. Mata, Prof. Dr. J. L. Alonso  \nGrupo de Espectroscopia Molecular (GEM), Edificio Quifima, Laboratorios de Espectroscopia y Bioespectroscopia Parque Cientifico UVa, Universidad de Valladolid, 47005 Valladolid, Spain  \n[E-mail: jlalonso@qf.uva.es](E-mail: jlalonso@qf.uva.es)  \n[c] Dr. S. Potenti, Dr. A. Gualandi, Prof. Dr. P. G. Cozzi, Prof. Dr. C. Puzzarini Dipartimento di “Chimica Giacomo Ciamician”, University of Bologna, via F. Selmi 2, 40126, Bologna, Italy  \nE-mail: [cristina.puzzarini@unibo.it](cristina.puzzarini@unibo.it)  \n Supporting information for this article is available on the WWW under [https://doi.org/10.1002/chem.202203990](https://doi.org/10.1002/chem.202203990)  \n © 2023 The Authors. Chemistry-A European Journal published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.  \nconformers on the potential energy landscape. [1,4] For the structural and physical chemist, conformers of such fluorinated compounds tend to have geometries qualitatively similar to those of the parent compounds, although the introduction of the fluorine atom can lead to a breaking of equivalence of positions in the parent compound, which leads to a more complicated conformat","cbCaisxsVhYUUXNs","https://ap.wps.com/l/cbCaisxsVhYUUXNs","pdf",5016152,1,13,"English","en",105,"# Abstract\n# Introduction\n## Role of fluorinated organic molecules in medicinal chemistry\n## Focus on fluorinated α-amino acids and 4-fluoro-threonine\n## Study approach: gas-phase rotational spectroscopy with quantum chemistry and machine learning","[{\"question\":\"What compound is investigated and why is it significant?\",\"answer\":\"4-fluoro-threonine is studied because it is the only naturally occurring fluorinated amino acid and provides a clear case to explore how fluorination reshapes conformational behavior.\"},{\"question\":\"How is the conformational landscape characterized in the study?\",\"answer\":\"The work maps inter-conversion pathways and identifies 13 stable low-energy minima, then examines how these populations produce a congested rotational spectrum.\"},{\"question\":\"What methods are used to assign the complex rotational spectrum?\",\"answer\":\"A combined strategy uses several levels of quantum chemical calculations together with machine learning principles, allowing assignment of the rotational features and experimental characterization of 12 of the 13 conformers.\"}]","Bringing Machine-Learning Enhanced Quantum Chemistry and Microwave Spectroscopy to Conformational Landscape Exploration - the Paradigmatic Case of 4-Fluoro-Threonine | PDF",1786001585,33,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":13,"keywords":34,"description":14,"schema_data":35,"social_meta":87,"head_meta":89,"extra_data":91,"updated_unix":28},"bringing-machine-learning-enhanced-quantum-chemistry-and-microwave-spectroscopy-to-conformational-landscape-exploration-the-paradigmatic-case-of-4-fluoro-threonine","",{"@graph":36,"@context":86},[37,54,69],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,51],{"item":41,"name":42,"@type":43,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/document/","Document",2,{"item":49,"name":12,"@type":43,"position":50},"https://docshare.wps.com/document/research-report/",3,{"item":52,"name":13,"@type":43,"position":53},"https://docshare.wps.com/document/bringing-machine-learning-enhanced-quantum-chemistry-and-microwave-spectroscopy-to-conformational-landscape-exploration-the-paradigmatic-case-of-4-fluoro-threonine/128532/",4,{"url":52,"name":13,"@type":55,"author":56,"headline":13,"publisher":58,"fileFormat":61,"inLanguage":23,"description":14,"dateModified":62,"datePublished":63,"encodingFormat":61,"isAccessibleForFree":64,"interactionStatistic":65},"DigitalDocument",{"name":9,"@type":57},"Person",{"url":41,"name":59,"@type":60},"DocShare","Organization","application/pdf","2026-08-24","2026-08-06",true,{"@type":66,"interactionType":67,"userInteractionCount":20},"InteractionCounter",{"@type":68},"ViewAction",{"@type":70,"mainEntity":71},"FAQPage",[72,78,82],{"name":73,"@type":74,"acceptedAnswer":75},"What compound is investigated and why is it significant?","Question",{"text":76,"@type":77},"4-fluoro-threonine is studied because it is the only naturally occurring fluorinated amino acid and provides a clear case to explore how fluorination reshapes conformational behavior.","Answer",{"name":79,"@type":74,"acceptedAnswer":80},"How is the conformational landscape characterized in the study?",{"text":81,"@type":77},"The work maps inter-conversion pathways and identifies 13 stable low-energy minima, then examines how these populations produce a congested rotational spectrum.",{"name":83,"@type":74,"acceptedAnswer":84},"What methods are used to assign the complex rotational spectrum?",{"text":85,"@type":77},"A combined strategy uses several levels of quantum chemical calculations together with machine learning principles, allowing assignment of the rotational features and experimental characterization of 12 of the 13 conformers.","https://schema.org",{"og:url":52,"og:type":88,"og:title":13,"og:site_name":59,"og:description":14},"article",{"robots":90,"canonical":52},"index,follow",{"doc_id":7,"site_id":24},{"code":4,"msg":5,"data":93},[94,98,102,106,111,116,121,124,129,132,136],{"id":20,"doc_module":4,"doc_module_name":46,"category_name":95,"show_sort_weight":96,"slug":97},"Story & Novel",90,"story-novel",{"id":47,"doc_module":4,"doc_module_name":46,"category_name":99,"show_sort_weight":100,"slug":101},"Literature",80,"literature",{"id":53,"doc_module":4,"doc_module_name":46,"category_name":103,"show_sort_weight":104,"slug":105},"Exam",70,"exam",{"id":107,"doc_module":4,"doc_module_name":46,"category_name":108,"show_sort_weight":109,"slug":110},5,"Comic",60,"comic",{"id":112,"doc_module":4,"doc_module_name":46,"category_name":113,"show_sort_weight":114,"slug":115},6,"Technology",50,"technology",{"id":117,"doc_module":4,"doc_module_name":46,"category_name":118,"show_sort_weight":119,"slug":120},7,"Healthcare",40,"healthcare",{"id":11,"doc_module":4,"doc_module_name":46,"category_name":12,"show_sort_weight":122,"slug":123},30,"research-report",{"id":125,"doc_module":4,"doc_module_name":46,"category_name":126,"show_sort_weight":127,"slug":128},9,"Religion & Spirituality",20,"religion-spirituality",{"id":127,"doc_module":4,"doc_module_name":46,"category_name":130,"show_sort_weight":127,"slug":131},"World Cup","world-cup",{"id":133,"doc_module":4,"doc_module_name":46,"category_name":134,"show_sort_weight":133,"slug":135},10,"Lifestyle","lifestyle",{"id":137,"doc_module":4,"doc_module_name":46,"category_name":138,"show_sort_weight":107,"slug":139},19,"General","general"]