New in situ solid-state NMR techniques for probing the evolution of crystallization processes: pre-nucleation, nucleation and growth

Author:

Hughes Colan E.1234,Williams P. Andrew1234,Keast Victoria L.1234,Charalampopoulos Vasileios G.1234,Edwards-Gau Gregory R.1234,Harris Kenneth D. M.1234

Affiliation:

1. School of Chemistry

2. Cardiff University

3. Cardiff CF10 3AT

4. UK

Abstract

The application of in situ techniques for investigating crystallization processes promises to yield significant new insights into fundamental aspects of crystallization science. With this motivation, we recently developed a new in situ solid-state NMR technique that exploits the ability of NMR to selectively detect the solid phase in heterogeneous solid–liquid systems (of the type that exist during crystallization from solution), with the liquid phase “invisible” to the measurement. As a consequence, the technique allows the first solid particles produced during crystallization to be observed and identified, and allows the evolution of different solid phases (e.g., polymorphs) present during the crystallization process to be monitored as a function of time. This in situ solid-state NMR strategy has been demonstrated to be a powerful approach for establishing the sequence of solid phases produced during crystallization and for the discovery of new polymorphs. The most recent advance of the in situ NMR methodology has been the development of a strategy (named “CLASSIC NMR”) that allows both solid-state NMR and liquid-state NMR spectra to be measured (essentially simultaneously) during the crystallization process, yielding information on the complementary changes that occur in both the solid and liquid phases as a function of time. In this article, we present new results that highlight the application of our in situ NMR techniques to successfully unravel different aspects of crystallization processes, focusing on: (i) the application of a CLASSIC NMR approach to monitor competitive inclusion processes in solid urea inclusion compounds, (ii) exploiting liquid-state NMR to gain insights into co-crystal formation between benzoic acid and pentafluorobenzoic acid, and (iii) applications of in situ solid-state NMR for the discovery of new solid forms of trimethylphosphine oxide and l-phenylalanine. Finally, the article discusses a number of important fundamental issues relating to practical aspects, the interpretation of results and the future scope of these techniques, including: (i) an assessment of the smallest size of solid particle that can be detected in in situ solid-state NMR studies of crystallization, (ii) an appraisal of whether the rapid sample spinning required by the NMR measurement technique may actually influence or perturb the crystallization behaviour, and (iii) a discussion of factors that influence the sensitivity and time-resolution of in situ solid-state NMR experiments.

Publisher

Royal Society of Chemistry (RSC)

Subject

Physical and Theoretical Chemistry

Reference74 articles.

1. Optically Anomalous Crystals

2. Crystal Growth and Nucleation, Faraday Discuss., 2006, 136

3. Phase transitions in molecular crystals from a chemical viewpoint

4. J. Bernstein , IUCr Monographs on Crystallography, Polymorphism in Molecular Crystals, Oxford University Press, Oxford, 2002

5. Pizzas, polymorphs and pills

Cited by 29 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

全球学者库

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"全球学者库"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前全球学者库共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2023 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3