Data-Driven Discovery of Polar Organic Cocrystals: Integration of Machine Learning and Automated Screening

Polar organic cocrystals hold significant promise for various advanced technological applications. However, their relatively low occurrence emphasizes the difficulties in achieving the desired polar packing arrangements, making their discovery complex and challenging. Here, we introduce a data-driven method that combines machine learning (ML) with high-throughput (HT) automation to speed up the discovery of polar organic cocrystals. Using ML techniques, we identified key factors that influence polar cocrystal formation, allowing for targeted selection of molecular candidates. We examined 13 cocrystal combinations with chloranilic acid (CA), screening 20 solvent systems for each, which enabled a highly efficient search across a broad chemical space. HT automation further enhanced the synthesis and characterization by enabling rapid screening and precise structural validation, while thoroughly exploring the chemical landscape. Experimental results confirmed 13 pairs of CA cocrystals, with 6 crystallizing in polar space groups, resulting in a polar discovery rate of 46%-nearly three times higher than the average in the Cambridge Structural Database (CSD) (∼13.2%). This integrated approach offers a new strategy in polar organic cocrystal research. The findings demonstrate the potential of this method to advance functional molecular materials and pave the way for next-generation applications using polar organic cocrystals.