High-throughput Supramolecular and Systems Chemistry

It is hard to create a selective host that operates in biological solutions (Chem Commun 2016 p. 2768 and p. 10093). Computer models fail at designing good hosts—partly because the guests are complicated, but mostly because we are so bad at predicting the roles of water and salts in real-world molecular recognition. Almost all synthetic approaches to host-guest chemistry up until now have been done using one-at-a-time cycles of design—make—test—repeat. The result is that most host-guest chemistry is confined to working only in organic solvents, on model systems in water, or in water using specialized, unnatural buffer conditions. We create supramolecular systems that solve critical problems in biomedicine and biological research (Anal. Chem. 2016, JACS 2018). We are developing supramolecular versions of high throughput synthesis, screening, and characterization methods, borrowing and adapting from a variety of drug development and biotechnology paradigms (JACS 2019). We also apply these newly developed methods to create innovative supramolecular therapeutics with an unusual mode of action — direct targeting and binding of other drugs in the bloodstream in order to reverse their own toxicities or unwanted activities (Angew. Chem. 2022). Students working on these projects learn cutting-edge techniques in diversity-oriented synthesis, biochemistry, analytical chemistry, screening, and/or informatics. In addition to creating novel affinity reagents for biomedical applications, we ultimately aim to learn new fundamental lessons in biomolecular recognition from these large data sets.