Predicting the formation of NADES using a transformer-based model

Abstract

Abstract The application of natural deep eutectic solvents (NADES) in the pharmaceutical, agricultural, and food industries represents one of the fastest growing fields of green chemistry, as these mixtures can potentially replace traditional organic solvents. These advances are, however, limited by the development of new NADES which is today, almost exclusively empirically driven and often derivative from known mixtures. To overcome this limitation, we propose the use of a transformer-based machine learning approach. Here, the transformer-based neural network model was first pre-trained to recognize chemical patterns from SMILES representations (unlabeled general chemical data) and then fine-tuned to recognize the patterns in strings that lead to the formation of either stable NADES or simple mixtures of compounds not leading to the formation of stable NADES (binary classification). Because this strategy was adapted from language learning, it allows the use of relatively small datasets and relatively low computational resources. The resulting algorithm is capable of predicting the formation of multiple new stable eutectic mixtures (n = 337) from a general database of natural compounds. More importantly, the system is also able to predict the components and molar ratios needed to render NADES with new molecules (not present in the training database), an aspect that was validated using previously reported NADES as well as by developing multiple novel solvents containing ibuprofen. We believe this strategy has the potential to transform the screening process for NADES as well as the pharmaceutical industry, streamlining the use of bioactive compounds as functional components of liquid formulations, rather than simple solutes.