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

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. 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.