浙江大学黄飞鹤小组提出了含烷基分子的超分子对接结构测定。该研究于2025年4月9日发表于国际一流学术期刊《自然》杂志上。

在这里，课题组研究人员证明了通过主题柱[5]芳烃结合金属有机框架（mof）和利用柱[5]芳烃烷基链宿主宾客识别，有可能减少这种运动，并使含烷基链分子有序，因为在整个MOF中存在的可接近的柱[5]芳烃单元内对接。这使得48个含烷基链分子的单晶结构，包括6个天然产物，2个批准的药物和18个从16个研究组收集的烷基链合成化合物，可以被确定为标准SCXRD仪器。从粗反应产物中得到的含烷基链分子的结构也可以通过SCXRD分析直接确定，而无需进一步纯化。该方法具有简单、高效和通用性强的特点，可作为传统SCXRD结构分析方法无法实现的天然产物和药物分析的新工具。

据悉，许多天然产物和药物都含有柔性烷基链。由此产生的构象运动给单晶的获得和单晶x射线衍射（SCXRD）测定其分子结构带来了挑战。

附：英文原文

Title: Supramolecular docking structure determination of alkyl-bearing molecules

Author: Wu, Yitao, Shi, Le, Xu, Lei, Ying, Jiale, Miao, Xiaohe, Hua, Bin, Chen, Zhijie, Sessler, Jonathan L., Huang, Feihe

Issue&Volume: 2025-04-09

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)1,2,3,4,5,6,7,8,9,10,11. Here we demonstrate that by using pillar[5]arene-incorporated metal–organic frameworks (MOFs) and taking advantage of pillar[5]arenealkyl chain hostguest recognition12,13,14,15, 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.

DOI: 10.1038/s41586-025-08833-2

Source: https://www.nature.com/articles/s41586-025-08833-2