{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:24:41Z","timestamp":1787005481334,"version":"build-2736575974"},"reference-count":53,"publisher":"AIP Publishing","issue":"8","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22333006"],"award-info":[{"award-number":["22333006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92270001"],"award-info":[{"award-number":["92270001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22303113"],"award-info":[{"award-number":["22303113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,28]]},"abstract":"<jats:p>As a leading candidate for prebiotic synthesis of carbohydrates, the formose reaction has been the subject of extensive investigation. However, formaldehyde\u2019s reactivity enables competing pathways that divert the formose condensation, generating dead-end products. Here, we employ our recently developed roto-translationally invariant potential-driven molecular dynamics to investigate the side pathways in the formose reaction network, identifying several new reaction mechanisms. Complementary density functional theory calculations with transition state optimization demonstrate the Cannizzaro disproportionation (yielding methanol and formate) as the dominant competing pathway, exhibiting a lower Gibbs free energy barrier (16.5\u00a0kcal mol\u22121) than both formaldehyde dimerization (26.9\u00a0kcal mol\u22121) and the formose autocatalytic cycle (18.0\u00a0kcal mol\u22121). In addition, carbon monoxide, carbon dioxide, and hydrogen gas may also form as by-products, with respective formation barriers of 24.2, 28.4, and 32.3\u00a0kcal mol\u22121. These results advance our understanding of reaction competition in prebiotic carbohydrate synthesis.<\/jats:p>","DOI":"10.1063\/5.0284892","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T10:26:03Z","timestamp":1755858363000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Mechanistic insights into formose side reactions: Cannizzaro disproportionation and competing pathways"],"prefix":"10.1063","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-5746","authenticated-orcid":false,"given":"Hei Wun","family":"Kan","sequence":"first","affiliation":[{"name":"Faculty of Synthetic Biology, Shenzhen University of Advanced Technology 1 , Shenzhen 518055,","place":["China"]},{"name":"State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences 2 , Shenzhen 518055,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2526-0722","authenticated-orcid":false,"given":"Xiao-Tian","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Synthetic Biology, Shenzhen University of Advanced Technology 1 , Shenzhen 518055,","place":["China"]},{"name":"State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences 2 , Shenzhen 518055,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4612-1863","authenticated-orcid":false,"given":"John Z. 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