Methylations with Methanol via Bioinspired Catalytic C–O bond Cleavage

Methylations with Methanol via Bioinspired Catalytic C–O bond Cleavage | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Methylations with Methanol via Bioinspired Catalytic C–O bond Cleavage Youwei Xie, Qing Huang, Yao Xiang, Yaqi Wu, Yuzhu Zheng, Rong-Zhen Liao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5122663/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Nature has a delicate system for catalysis due to optimization through evolution, which often displays unparalleled efficiency and selectivity. “learning from nature” is a popular and effective approach in designing new reactions and catalysts when traditional strategies fail. Here, we proved that it can be highly rewarding to consider nature’s repertoire of catalysis during the effort to facilitate the challenging heterolytic C–O bond cleavage of methanol (MeOH) by studying its metabolism by methyltransferase complex in certain methanogenic microorganisms that contains a Brønsted acid cluster flanked by a Zinc moiety, which led to the identification of the combination of an easily available Brønsted acid Cat.1 and Zn(OTf)2 as a highly efficient and practical binary catalyst for cooperative MeOH activation in various important methylation reactions, including some of those carried out in large scale in industry with significantly increased selectivity under relatively less demanding reaction conditions. This method activates MeOH via heterolytic C–O bond cleavage rather than C–H bond cleavage, therefore, inexpensive and less toxic CD3OD could be used directly as an effective d3-methylating agent. Mechanistic studies and density functional theory (DFT) calculations suggest a synergy between Cat.1 and Zn(OTf)2, suggestive of that found in methanol-activating MtaBC complex in Methanosarcina barkeri. Physical sciences/Chemistry/Catalysis/Homogeneous catalysis Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology Full Text Additional Declarations Yes there is potential Competing Interest. A patent application (CN119039096A, China) has been filed, dealing with the application of aliphatic alcohols for alkylation reactions by the catalysis described in this article. Supplementary Files Dataset1.pdf Dataset 1 SupplementaryInformation.pdf Supplementary Information Cite Share Download PDF Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5122663","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":414283033,"identity":"52983624-411e-475b-8635-44050cf89a3d","order_by":0,"name":"Youwei 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