High-Throughput Crystallization Screening Technique with Transmission PXRD Analysis

Abstract

The ability to quickly generate and identify crystalline solids for organic compounds in a parallel fashion requires a rapid, adaptable crystallization screening strategy that delivers reliable, valuable, and consistent results. The key to the system is a standard platform small-scale (0.5–2 mg) crystallizer screening array that reproducibly crystallizes compounds and facilitates the presentation of crystallization samples to both an automated polarized light microscope and an instrument capable of PXRD analysis. Data science technologies were leveraged to streamline the workflow of data visualization and processing. The fully developed workflow successfully used both single-crystal and PXRD analyses to identify multiple polymorphs of a test compound in a single screening experiment on 200 mg of input material with commercially available crystallizers and instruments to perform a highly detailed crystallization screening study. The methods and techniques described herein are fully transferrable to those working in the synthetic organic chemistry field.