Automated Library Generation and Serendipity Quantification Enables Diverse Discovery in Coordination Chemistry

Library generation experiments are a key part of the discovery of new materials, methods, and models in chemistry, but the question of how to generate high quality libraries to enable discovery is nontrivial. Herein, we use coordination chemistry to demonstrate the automation of many of the workflows used for library generation in automated hardware including the Chemputer. First, we explore the target-oriented synthesis of three influential coordination complexes, to validate key synthetic operations in our system; second, the generation of focused libraries in chemical and process space; and third, the development of a new workflow for prospecting library formation. This involved Bayesian optimization using a Gaussian process as surrogate model combined with a metric for novelty (or serendipity) quantification based on mass spectrometry data. In this way, we show directed exploration of a process space toward those areas with rarer observations and build a picture of the diversity in product distributions present across the space. We show that this effectively engineers serendipity into our search through the unexpected appearance of acetic anhydride, formed in situ, and solvent degradation products as ligands in an isolable series of three Co(III) anhydride complexes.

Automated summary

Library generation experiments are crucial in chemistry for discovering new materials, methods, and models. This study demonstrates the automation of workflows using coordination chemistry for library generation. Validation of key synthetic operations, generation of focused libraries in chemical and process space, and development of a new workflow for prospecting library formation were conducted. The study showcases the directed exploration of process space and the engineering of serendipity for discovering unexpected compounds.