Chemically Informed Machine Learning Approach for Prediction of Reactivity Ratios in Radical Copolymerization

Abstract Predicting monomer reactivity ratios is crucial for controlling monomer sequence distribution in copolymers and their properties. Traditional experimental methods of determining reactivity ratios are time-consuming and resource-intensive, while existing computational methods often struggle with accuracy or scalability. Here, we present a method that combines unsupervised learning with artificial neural networks to predict reactivity ratios in radical copolymerization. By applying spectral clustering to physicochemical features of monomers, we identified three distinct monomer groups with characteristic reactivity patterns. This computationally efficient clustering approach revealed specific monomer group interactions leading to different sequence arrangements including alternating, random, block, and gradient copolymers─providing chemical insights for initial exploration. Building upon these insights, we trained artificial neural networks to achieve quantitative reactivity ratio predictions. We explored two integration strategies: direct feature concatenation and cluster-specific training, which demonstrated performance enhancements for targeted chemical domains compared to general training with equivalent sample sizes. However, models utilizing complete data sets outperformed specialized models trained on focused subsets, revealing a fundamental trade-off between chemical specificity and data availability. This work demonstrates that unsupervised learning offers rapid chemical insight for exploratory analysis, while supervised learning provides the accuracy necessary for final design predictions, with optimal strategies depending on data availability and application requirements.