{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:02:18Z","timestamp":1790870538500,"version":"4.1.0"},"reference-count":19,"publisher":"American Chemical Society (ACS)","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fre\u0301chet ChemNet Distance (FCD) cannot distinguish E\/Z stereoisomers, because the ChemNet tokenizer maps the SMILES bond-direction symbols \/ and \\ to the same unknown token; inverting every double-bond configuration in MolT5-large\u2019s ChEBI-20 output (384 molecules altered) changes FCD by 0.001 resampling standard deviations while conditional per-bond accuracy falls from 98.97% to 1.03%, and MOSES and GuacaMol cannot expose the defect because their benchmark data contain no stereochemistry. A stereochemistry-aware correction is monotone under synthetic corruption yet prefers fully inverted real output, illustrating that a metric operating only on unpaired generated and reference embeddings cannot recover per-caption correctness. Across real generators FCD carries no dependable signal about a more-than-3-fold difference in E\/Z recall: on the double bonds where MolT5-large and BioT5-base both recover the molecular skeleton, recall is 0.26 versus 0.997, yet FCD does not separate the two models\u2500its ordering is statistically borderline, with a bootstrap interval that crosses zero. The failure is one of uninformativeness rather than of reversal. Where paired conditional references exist, stereochemistry should be reported directly, as coverage, precision, and recall, rather than inferred from a distributional score.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c02441","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:02:08Z","timestamp":1790787728000},"source":"Crossref","is-referenced-by-count":0,"title":["Fre\u0301chet\nChemNet Distance Is Blind to Double-Bond\nStereochemistry"],"prefix":"10.1021","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0589-941X","authenticated-orcid":true,"given":"Jinseong","family":"Yim","sequence":"first","affiliation":[{"name":"Kyung Hee University , , 1732 Deogyeong-daero, Giheung-gu , , ,","place":["Yongin-si, Gyeonggi-do, Republic of Korea, 17104"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"2026100111071640500_cit1","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1021\/acs.jcim.8b00234","article-title":"Fre\u0301chet ChemNet Distance: A Metric for Generative\nModels for Molecules in Drug Discovery","volume":"58","author":"Preuer","year":"2018","journal-title":"J. Chem.\nInf. Model."},{"key":"2026100111071640500_cit2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.565644","article-title":"Molecular Sets (MOSES): A Benchmarking Platform for\nMolecular Generation Models","volume":"11","author":"Polykovskiy","year":"2020","journal-title":"Front. Pharmacol."},{"key":"2026100111071640500_cit3","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1021\/acs.jcim.8b00839","article-title":"GuacaMol: Benchmarking\nModels for de Novo Molecular Design","volume":"59","author":"Brown","year":"2019","journal-title":"J. Chem.\nInf. Model."},{"key":"2026100111071640500_cit4","doi-asserted-by":"crossref","unstructured":"Edwards, C.; Lai, T.; Ros, K.; Honke, G.; Cho, K.; Ji, H. In  Translation between Molecules and Natural Language, Proceedings\nof the 2022 Conference on Empirical Methods in Natural Language Processing; Association for Computational Linguistics, 2022; pp 375\u2013413.","DOI":"10.18653\/v1\/2022.emnlp-main.26"},{"key":"2026100111071640500_cit5","doi-asserted-by":"crossref","unstructured":"Tao, W.; Tang, J.; Chan, A.; Hooi, B.; Bi, B.; Peng, N.; Liu, Y.; Wang, Y. In  How to\nMake Large\nLanguage Models Generate 100% Valid Molecules?, Proceedings\nof the 2025 Conference on Empirical Methods in Natural Language Processing.\nSuzhou, China; Association for Computational Linguistics, 2025; pp 26565\u201326580.","DOI":"10.18653\/v1\/2025.emnlp-main.1350"},{"key":"2026100111071640500_cit6","doi-asserted-by":"publisher","DOI":"10.1038\/212087a0","article-title":"Contrasting Endocrine\nActivities of cis and trans Isomers\nin a Series of Substituted Triphenylethylenes","volume":"212","author":"Harper","year":"1966","journal-title":"Nature"},{"key":"2026100111071640500_cit7","first-page":"112","article-title":"Bioactivities,\nEstrogen Receptor Interactions, and Plasminogen Activator-Inducing\nActivities of Tamoxifen and Hydroxy-Tamoxifen Isomers in MCF-7 Human\nBreast Cancer Cells","volume":"44","author":"Katzenellenbogen","year":"1984","journal-title":"Cancer Res."},{"key":"2026100111071640500_cit8","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.chempr.2016.12.005","article-title":"Structural\nBasis of cis- and trans-Combretastatin\nBinding to Tubulin","volume":"2","author":"Gaspari","year":"2017","journal-title":"Chem"},{"key":"2026100111071640500_cit9","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ddtec.2020.09.003","article-title":"On Failure\nModes in Molecule Generation and Optimization","volume":"32\u201333","author":"Renz","year":"2019","journal-title":"Drug Discovery Today: Technol."},{"key":"2026100111071640500_cit10","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgaf329","article-title":"Stereochemistry-Aware\nString-Based Molecular Generation","volume":"4","author":"Tom","year":"2025","journal-title":"PNAS Nexus"},{"key":"2026100111071640500_cit11","doi-asserted-by":"publisher","first-page":"D945","DOI":"10.1093\/nar\/gkw1074","article-title":"The ChEMBL\nDatabase in 2017","volume":"45","author":"Gaulton","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2026100111071640500_cit12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1073\/pnas.90.1.30","article-title":"Retinoic Acid\nReceptors and Retinoid X Receptors","volume":"90","author":"Allenby","year":"1993","journal-title":"Proc. Natl.\nAcad. Sci. U.S.A."},{"key":"2026100111071640500_cit13","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1210\/endo-112-2-442","article-title":"Estrogenic and Antiestrogenic Effects of Enclomiphene\nand Zuclomiphene on Gonadotropin Secretion by Ovine Pituitary Cells\nin Culture","volume":"112","author":"Huang","year":"1983","journal-title":"Endocrinology"},{"key":"2026100111071640500_cit14","doi-asserted-by":"crossref","unstructured":"Edwards, C.; Zhai, C.; Ji, H. In  Text2Mol:\nCross-Modal Molecule Retrieval\nwith Natural Language Queries, Proceedings of EMNLP; Association for Computational Linguistics, 2021; pp 595\u2013607.","DOI":"10.18653\/v1\/2021.emnlp-main.47"},{"key":"2026100111071640500_cit15","unstructured":"Sajjadi, M. S. M.; Bachem, O.; Lucic, M.; Bousquet, O.; Gelly, S. In  Assessing Generative Models via\nPrecision\nand Recall, Advances in Neural Information Processing Systems; NeurIPS, 2018."},{"key":"2026100111071640500_cit16","unstructured":"Kynka\u0308a\u0308nniemi, T.; Karras, T.; Laine, S.; Lehtinen, J.; Aila, T. In  Improved Precision and Recall Metric\nfor Assessing Generative Models, Advances in Neural Information\nProcessing Systems; NeurIPS, 2018."},{"key":"2026100111071640500_cit17","unstructured":"Jiralerspong, M.; Bose, J.; Gemp, I.; Qin, C.; Bachrach, Y.; Gidel, G. 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