Machine-Learning-Guided Discovery of 19F MRI Agents Enabled by Automated Copolymer Synthesis

• DOI: 10.1021/jacs.1c08181
• Publication Date: 2021-10-14T00:21:28Z
• Authors: Marcus Reis; Filipp Gusev; Nicholas G. Taylor; Sang Hun Chung; Matthew D. Verber; Yueh Z. Lee; Olexandr Isayev; Frank A. Leibfarth
• Keywords: Machine Learning; Solubility; Polymers; Contrast Media; Fluorine; Magnetic Resonance Imaging; 01 natural sciences; Software; 0104 chemical sciences

Modern polymer science is plagued by the curse of multidimensionality; the large chemical space imposed by including combinations of monomers into a statistical copolymer overwhelms polymer synthesis and characterization technology and limits the ability to systematically study structure–property relationships. To tackle this challenge in the context of 19F MRI agents, we pursued a computer-guided materials discovery approach that combines synergistic innovations in automated flow synthesis and machine learning (ML) method development. A software controlled, continuous polymer synthesis platform was developed to enable iterative experimental–computational cycles that resulted in the synthesis of 397 unique copolymer compositions within a six-variable compositional space. The non-intuitive design criteria identified by ML, which was accomplished by exploring less than 0.9% of overall compositional space, upended conventional wisdom in the design of 19F MRI agents and lead to the identification of >10 copolymer compositions that outperformed state-of-the-art materials.