Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules
Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules
复制标题
DOI：
10.1016/j.chempr.2020.04.009
复制
发表时间：
2020-07
期刊：
影响因子：
23.5
通讯作者：
A. Tyler;Ronnie Ragbirsingh;C. McMonagle;P. Waddell;S. Heaps;J. Steed;P. Thaw;Michael J. Hall;M. Probert
中科院分区：
文献类型：
--
作者：
A. Tyler;Ronnie Ragbirsingh;C. McMonagle;P. Waddell;S. Heaps;J. Steed;P. Thaw;Michael J. Hall;M. Probert
单晶X射线衍射分析（SCXRD）是一种用于阐明分子结构和研究晶型的通用方法。然而，可行的结晶条件的发现在时间和分析物的量方面仍然具有实验挑战性和资源密集性。我们报告了一个机器人辅助的，高通量的有机可溶性小分子的结晶方法，在该方法中，我们每次实验只使用微克的分析物。这允许以最小的总体样品要求并行筛选数百种结晶条件。适用于SCXRD的晶体由分析物在有机溶剂中的溶液的纳升液滴生长，每个液滴被封装在惰性油中以控制溶剂损失的速率。这种包封的纳米液滴结晶方法也可用于寻找新的晶体形式，如通过我们发现奥氮平前体ROY的新的（第13）多晶型物和“不可结晶的”农用化学品二氰蒽醌的SCXRD分析所例证的。
Single-crystal X-ray diffraction analysis (SCXRD) constitutes a universal approach for the elucidation of molecular structure and the study of crystalline forms. However, the discovery of viable crystallization conditions remains both experimentally challenging and resource intensive in both time and the quantity of analyte(s). We report a robot-assisted, high-throughput method for the crystallization of organic-soluble small molecules in which we employ only micrograms of analyte per experiment. This allows hundreds of crystallization conditions to be screened in parallel with minimal overall sample requirements. Crystals suitable for SCXRD are grown from nanoliter droplets of a solution of analyte in organic solvent(s), each of which is encapsulated within an inert oil to control the rate of solvent loss. This encapsulated nanodroplet crystallization methodology can also be used to search for new crystal forms, as exemplified through both our discovery of a new (13th) polymorph of the olanzapine precursor ROY and SCXRD analysis of the "uncrystallizable" agrochemical dithianon.