[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-123793-en":3,"doc-seo-123793-105":30,"detail-sidebar-cat-0-en-105":91},{"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":4,"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},123793,3848291630094,"Emma Wilson","https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45",8,"Research & Report","Completing and Balancing Database Excerpted Chemical Reactions with a Hybrid Mechanistic-Machine Learning Approach - ABSTRACT","Computer-aided synthesis planning (CASP) depends on complete reaction structures, yet most entries in existing databases omit reaction coparticipants. Although reaction prediction and atom-mapping tools can estimate major participants and track atom rearrangements, they cannot reliably infer the missing molecules because they learn from incomplete data records. A workflow is proposed: heuristics balance reactions from databases and candidate molecules complete imbalanced reactions, then a masked-language-model learns from completed SMILES to predict missing species. The hybrid approach covers over half of the reaction space.","This article is licensed under CC-BY 4.0   \n[http://pubs.acs.org/journal/acsodf](http://pubs.acs.org/journal/acsodf)  Article   \nCompleting and Balancing Database Excerpted Chemical Reactions with a Hybrid Mechanistic-Machine Learning Approach  \nChonghuan Zhang, Adarsh Arun, and Alexei A. Lapkin *  \n Cite This: ACS Omega 2024, 9, 18385−18399  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Computer-aided synthesis planning (CASP) development of reaction routes requires an understanding of complete reaction structures. However, most reactions in the current databases are missing reaction coparticipants. Although reaction prediction and atom mapping tools can predict major reaction participants and trace atom rearrangements in reactions, they fail to identify the missing molecules to complete reactions. This is because these approaches are data-driven models trained on the current reaction databases, which comprise incomplete reactions. In this work, a workflow was developed to tackle the reaction completion challenge. This includes a heuristic-based method to identify balanced reactions from reaction databases and complete some imbalanced reactions by adding candidate molecules. A machine learning masked language model (MLM) was trained to learn from simplified molecular input line entry system (SMILES) sentences of these completed reactions. The model predicted missing molecules for the incomplete reactions, a workflow analogous to predicting missing words in sentences. The model is promising for the prediction of small- and middle-sized missing molecules in incomplete reaction records. The workflow combining both the heuristic and machine learning methods completed more than half of the entire reaction space.  \n■ INTRODUCTION  \nTo enable the evaluation of reaction routes with respect to a set of target parameters, such as overall yield, impurities, economy, or greenness, knowledge of the complete reaction record is required. When all reaction participants (reactants, reagents, and products) are known, the reaction completion is simply a problem of mass conservation, i.e., using linear algebra to balance the reaction with stoichiometric coefficients. However, this is not always the case for data records that are currently accessible in Reaxys,1 USPTO,2 or any other nonmanually curated reaction databases. An example of a Reaxys reaction data record is shown in Figure 1. Three main aspects of the reaction data are often missing in records today:3 stoichiometric coefficients, reaction coparticipants, and integration of multiple reaction steps into a single reaction entry.  \nThere are historical and habitual reasons for the incompleteness of reaction data today. First, chemists report reactions in journal articles and patents based on the selfdefined scope of research, which does not typically have potential tasks of others in mind; side products are either not in the scope of studies or were not detected by the analytical techniques that were used. Second, although text-mining techniques could process chemical information from the literature, including properties and structures of molecules and reaction conditions, sometimes it is hard to identify reaction participants as they may appear in different sections of a publication. This aspect is being addressed by creating clear  \ntemplates for presenting and storing reaction data, such as the Open Reaction Database project.4 For data to be useful for machine learning tasks and for automated tasks of process development, it is necessary for existing data to be recalibrated to include the missing reaction participants and reduce the noise in the data sets.  \nIn the literature, several methods for reaction structure completion were published. Grzybowski et al. manually curated around 100,000 generalized reaction rules with complete understanding of reaction p","cbCaieFomr7ad96M","https://ap.wps.com/l/cbCaieFomr7ad96M","pdf",5514442,1,15,"English","en",105,"# ABSTRACT\n# INTRODUCTION\n## Reaction completeness and mass conservation\n## Reasons for missing reaction information in databases\n## Related work on reaction structure completion\n## Atom mapping and missing species inference","[{\"question\":\"Why is reaction completion necessary for computer-aided synthesis planning (CASP)?\",\"answer\":\"CASP evaluation of reaction routes requires complete reaction records including reactants, reagents, and products so mass conservation and downstream optimization can be performed reliably.\"},{\"question\":\"What problem do data-driven reaction prediction and atom-mapping tools face?\",\"answer\":\"They are trained on databases containing incomplete reactions, so they can predict major participants and atom rearrangements but fail to identify missing coparticipant molecules needed to complete the reaction.\"},{\"question\":\"How does the proposed workflow complete imbalanced and incomplete reactions?\",\"answer\":\"It uses heuristic methods to find balanced reactions and then adds candidate molecules to complete imbalanced records; a masked language model trained on SMILES from completed reactions predicts missing molecules for incomplete entries.\"}]","Completing and Balancing Database Excerpted Chemical Reactions with a Hybrid Mechanistic-Machine Learning Approach - ABSTRACT | PDF",1785818589,38,{"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":86,"head_meta":88,"extra_data":90,"updated_unix":28},"completing-and-balancing-database-excerpted-chemical-reactions-with-a-hybrid-mechanistic-machine-learning-approach-abstract","",{"@graph":36,"@context":85},[37,54,68],{"@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/completing-and-balancing-database-excerpted-chemical-reactions-with-a-hybrid-mechanistic-machine-learning-approach-abstract/123793/",4,{"url":52,"name":13,"@type":55,"author":56,"headline":13,"publisher":58,"fileFormat":61,"inLanguage":23,"description":14,"dateModified":62,"datePublished":62,"encodingFormat":61,"isAccessibleForFree":63,"interactionStatistic":64},"DigitalDocument",{"name":9,"@type":57},"Person",{"url":41,"name":59,"@type":60},"DocShare","Organization","application/pdf","2026-08-04",true,{"@type":65,"interactionType":66,"userInteractionCount":4},"InteractionCounter",{"@type":67},"ViewAction",{"@type":69,"mainEntity":70},"FAQPage",[71,77,81],{"name":72,"@type":73,"acceptedAnswer":74},"Why is reaction completion necessary for computer-aided synthesis planning (CASP)?","Question",{"text":75,"@type":76},"CASP evaluation of reaction routes requires complete reaction records including reactants, reagents, and products so mass conservation and downstream optimization can be performed reliably.","Answer",{"name":78,"@type":73,"acceptedAnswer":79},"What problem do data-driven reaction prediction and atom-mapping tools face?",{"text":80,"@type":76},"They are trained on databases containing incomplete reactions, so they can predict major participants and atom rearrangements but fail to identify missing coparticipant molecules needed to complete the reaction.",{"name":82,"@type":73,"acceptedAnswer":83},"How does the proposed workflow complete imbalanced and incomplete reactions?",{"text":84,"@type":76},"It uses heuristic methods to find balanced reactions and then adds candidate molecules to complete imbalanced records; 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