Supramolecular docking structure determination of alkyl-bearing molecules

IF 50.5 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Nature Pub Date : 2025-04-09 DOI:10.1038/s41586-025-08833-2
Yitao Wu, Le Shi, Lei Xu, Jiale Ying, Xiaohe Miao, Bin Hua, Zhijie Chen, Jonathan L. Sessler, Feihe Huang
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引用次数: 0

Abstract

Numerous natural products and drugs contain flexible alkyl chains. The resulting conformational motion can create challenges in obtaining single crystals and thus determining their molecular structures by single-crystal X-ray diffraction (SCXRD)1–11. Here we demonstrate that by using pillar[5]arene-incorporated metal–organic frameworks (MOFs) and taking advantage of pillar[5]arene−alkyl chain host−guest recognition12–15, it is possible to reduce this motion and bring order to alkyl-chain-containing molecules as the result of docking within accessible pillar[5]arene units present in an overall MOF. This has allowed the single-crystal structures of 48 alkyl-chain-containing molecules, including 6 natural products, 2 approved drugs and 18 custom-made compounds collected from 16 research groups, to be determined using standard SCXRD instrumentation. The structures of alkyl-chain-containing molecules derived from crude reaction products can also be determined directly by SCXRD analyses without further purification. The simplicity, high efficiency and apparent generality of the present pillar[5]arene-incorporated MOF-based supramolecular docking approach suggest that it could emerge as a new tool for the analyses of natural products and drugs that might not be amenable to traditional SCXRD-based structure determination. A metal–organic framework (MOF)–pillar[5]arene hybrid can bind small molecules with long alkyl chains, such that single-crystal structures of the host–guest complexes can be obtained and therefore small molecular structures determined.

Abstract Image

Abstract Image

含烷基分子的超分子对接结构测定
许多天然产品和药物都含有柔性烷基链。由此产生的构象移动会给获得单晶并通过单晶 X 射线衍射(SCXRD)确定其分子结构带来挑战1,2,3,4,5,6,7,8,9,10,11。我们在此证明,通过使用柱[5]炔并入金属有机框架(MOFs),并利用柱[5]炔-烷基链的主客体识别12,13,14,15,可以减少这种运动,并使含烷基链的分子在整个 MOF 中可接触的柱[5]炔单元内对接而变得有序。这样就可以利用标准 SCXRD 仪器确定 48 种含烷基链分子的单晶结构,其中包括 6 种天然产品、2 种已获批准的药物和 18 种从 16 个研究小组收集的定制化合物。从粗反应产物中提取的含烷基链分子的结构也可直接通过 SCXRD 分析确定,无需进一步纯化。这种基于柱[5]炔并入 MOF 的超分子对接方法简便、高效、通用性强,表明它可以作为一种新工具,用于分析传统 SCXRD 结构测定法可能无法测定的天然产品和药物。
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来源期刊
Nature
Nature 综合性期刊-综合性期刊
CiteScore
90.00
自引率
1.20%
发文量
3652
审稿时长
3 months
期刊介绍: Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.
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