Methylations with methanol via bioinspired catalytic C–O bond cleavage

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 alternative reactions and catalysts when traditional strategies fail. Here,...

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Main Authors: Qing Huang, Yao Xiang, Yaqi Wu, Yuzhu Zheng, Rong-Zhen Liao, Youwei Xie
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61200-7
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author Qing Huang
Yao Xiang
Yaqi Wu
Yuzhu Zheng
Rong-Zhen Liao
Youwei Xie
author_facet Qing Huang
Yao Xiang
Yaqi Wu
Yuzhu Zheng
Rong-Zhen Liao
Youwei Xie
author_sort Qing Huang
collection DOAJ
description 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 alternative reactions and catalysts when traditional strategies fail. Here, we demonstrate 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). Inspired by MeOH metabolism by methyltransferase complex in certain methanogenic microorganisms that contain a Brønsted acid cluster flanked by a Zinc moiety, we successfully identify the combination of an easily available Brønsted acid and Zn(OTf)2 as a highly efficient and practical binary catalyst for cooperative MeOH activation. This strategy enables the direct application of MeOH in various important methylation reactions, including some of those carried out in large scale in industry with significantly increased selectivity under relatively less demanding conditions. Mechanistic studies and density functional theory (DFT) calculations suggest a synergy between the Brønsted acid and Zn(OTf)2, suggestive of that found in methanol-activating MtaBC complex in Methanosarcina barkeri.
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institution Kabale University
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publishDate 2025-07-01
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series Nature Communications
spelling doaj-art-2d884ea516254b6f83f0b9ad7defcc9d2025-08-20T04:01:35ZengNature PortfolioNature Communications2041-17232025-07-0116111110.1038/s41467-025-61200-7Methylations with methanol via bioinspired catalytic C–O bond cleavageQing Huang0Yao Xiang1Yaqi Wu2Yuzhu Zheng3Rong-Zhen Liao4Youwei Xie5Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica; School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica; School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica; School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica; School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica; School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica; School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyAbstract 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 alternative reactions and catalysts when traditional strategies fail. Here, we demonstrate 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). Inspired by MeOH metabolism by methyltransferase complex in certain methanogenic microorganisms that contain a Brønsted acid cluster flanked by a Zinc moiety, we successfully identify the combination of an easily available Brønsted acid and Zn(OTf)2 as a highly efficient and practical binary catalyst for cooperative MeOH activation. This strategy enables the direct application of MeOH in various important methylation reactions, including some of those carried out in large scale in industry with significantly increased selectivity under relatively less demanding conditions. Mechanistic studies and density functional theory (DFT) calculations suggest a synergy between the Brønsted acid and Zn(OTf)2, suggestive of that found in methanol-activating MtaBC complex in Methanosarcina barkeri.https://doi.org/10.1038/s41467-025-61200-7
spellingShingle Qing Huang
Yao Xiang
Yaqi Wu
Yuzhu Zheng
Rong-Zhen Liao
Youwei Xie
Methylations with methanol via bioinspired catalytic C–O bond cleavage
Nature Communications
title Methylations with methanol via bioinspired catalytic C–O bond cleavage
title_full Methylations with methanol via bioinspired catalytic C–O bond cleavage
title_fullStr Methylations with methanol via bioinspired catalytic C–O bond cleavage
title_full_unstemmed Methylations with methanol via bioinspired catalytic C–O bond cleavage
title_short Methylations with methanol via bioinspired catalytic C–O bond cleavage
title_sort methylations with methanol via bioinspired catalytic c o bond cleavage
url https://doi.org/10.1038/s41467-025-61200-7
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AT yaoxiang methylationswithmethanolviabioinspiredcatalyticcobondcleavage
AT yaqiwu methylationswithmethanolviabioinspiredcatalyticcobondcleavage
AT yuzhuzheng methylationswithmethanolviabioinspiredcatalyticcobondcleavage
AT rongzhenliao methylationswithmethanolviabioinspiredcatalyticcobondcleavage
AT youweixie methylationswithmethanolviabioinspiredcatalyticcobondcleavage