Professor Ryan Hili of the University of Georgia is supported by the Chemical Catalysis Program of the Division of Chemistry to develop a discovery platform for small molecule catalysts using DNA as an encoding element. Bond-forming reactions are essential to construct molecules ranging from fine chemicals used in medicine to bulk chemicals such as polymers used as plastics. Catalysts are needed to construct these bonds efficiently and selectively. This research is anticipated to greatly accelerate the discovery of new catalysts by enabling large libraries of chemicals to be screened quickly for desired catalytic activity. The information garnered from such large screens can be used to create better catalysts and to increase our understanding of the molecular interactions that contribute to catalysis. Catalysts that are more efficient and selective produce more of the desired product and, at the same time, reduce waste and time to consumer markets. This research is integrated with interdisciplinary educational and training activities and outreach at the high school, undergraduate, and graduate levels. The Hili Group is dedicated to undergraduate research, as evidenced by strong undergraduate participation in their lab, and by papers co-authored by undergraduates. Professor Hili works to rebuild the Student Affiliates of the American Chemical Society chapter at UGA to promote the impact of chemistry research on society. He also strives to increase participation in the Young Dawgs STEM Program, which is a program that identifies local area high school students and places them in University of Georgia research laboratories to gain first-hand knowledge and experience in scientific research.
The project outlines the development of an in vitro selection platform for small molecule catalysts using amphiphilic DNA, which is soluble in aqueous media and anhydrous organic solvents, as an encoding element. The ultimate goal is to couple high-throughput DNA sequencing to the discovery of small-molecule bond-forming catalysts. The immediate aims are to determine the compatibility of amphiphilic DNA as an encoding element during various catalytic reactions; to develop methods to generate and screen an amphiphilic DNA-encoded chemical library for catalytic activity in various solvents; and to apply the method to screen en masse the kinetic parameters of individual catalysts within the library. The advantages of the proposed research over existing catalyst discovery technologies are: (1) higher throughput, with libraries easily exceeding one million library members; (2) the use of small amounts of library material; (3) solution-phase kinetics; (4) the ability to easily multiplex time-points, reaction conditions, and different substrates in one sequencing experiment; and (5) the reduction of material/solvent waste that typically accompanies high-throughput screening efforts.