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"What is This?" A Structure Analysis Tool for Rapid and Automated Solution of Small Molecule Structures

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Abstract

The structure of organic compounds, including their absolute configuration, is extremely critical to the activity of medicines, aroma chemicals, and agrochemicals. Nearly all of these structures have been determined by single-crystal X-ray diffraction (SC-XRD) analysis. However, it is widely believed that SC-XRD analysis is not versatile since it requires considerable crystal growth and expertise. Recently, crystal growth is becoming less critical by utilizing the microcrystal electron diffraction method (MicroED). However, there is still a gap between the two methods because MicroED has limitations with respect to crystal size and quality of the results. Moreover, modern instruments for SC-XRD analysis have evolved to analyze smaller crystals and are able to deliver a structure easier. Here, we propose a new approach to fill the above gap with the tool named "What is this? (WIT)". WIT is a fully automated process from evaluating the crystal to providing the 'structure'. This method assumes the situation where a researcher happens to obtain a shiny grain during a course of chemical synthesis and wants to know the structure of the molecule making up the grain. Therefore, WIT assumes no chemical information and collects a mere 60% of the full dataset to enable faster characterization of the molecule with enough quality to fulfill the requirement. To assess the utility of WIT, we compared the results obtained by MicroED on a crystal of the same compound and similar in size. In summarizing the results, we propose a possible functional classification of the analyzed structures.

Graphic Abstract

We have developed a new tool, “What is this?” (WIT) for the fully automated structure determination of small molecules concurrent with single crystal data collection and processing. WIT assumes the case where a researcher happens to obtain a shiny grain of unknown composition during a chemical synthesis and opts to try to determine the three-dimensional structure of the molecule making up the grain.

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Data Availability

CCDC 1986323, 1986318, 1986321, 1986322, and 1986319 contain the details of the crystallographic data in CIF format. These CIF files can be obtained free of charge from The Cambridge Crystallographic Data Centre.

Code Availability (software application or custom code)

The software for this study are available from Rigaku Oxford Diffraction Forum (https://www.rigakuxrayforum.com/index.php), but it is not generally available as it requires an AutoChem license.

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Authors and Affiliations

  1. Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima, Tokyo, 196-8666, Japan

    Takashi Matsumoto, Akihito Yamano & Takashi Sato

  2. Rigaku Americas Corporation, Inc., 9009 New Trails Drive, The Woodlands, TX, 77381-5209, USA

    Joseph D. Ferrara

  3. Rigaku Europe SE, Hugenottenallee 167, 63263, Neu Isenburg, Germany

    Fraser J. White

  4. Rigaku Polska Sp. Z O.O., ul. Szarskiego 3, 54-609, Wrocław, Poland

    Mathias Meyer

Authors
  1. Takashi Matsumoto
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  2. Akihito Yamano
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Correspondence to Takashi Matsumoto.

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Matsumoto, T., Yamano, A., Sato, T. et al. "What is This?" A Structure Analysis Tool for Rapid and Automated Solution of Small Molecule Structures. J Chem Crystallogr 51, 438–450 (2021). https://doi.org/10.1007/s10870-020-00867-w

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  • DOI: https://doi.org/10.1007/s10870-020-00867-w

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