Fuel-Driven Dynamic Combinatorial Libraries

Christine M. E. Kriebisch, Alexander M. Bergmann, and Job Boekhoven

Journal of American Chemical Society https://doi.org/10.1021/jacs.1c0161

Abstract

In dynamic combinatorial libraries, molecules react with each other reversibly to form intricate networks underthermodynamic control. In biological systems, chemical reactionnetworks operate under kinetic control by the transduction ofchemical energy. We thus introduced the notion of energytransduction, via chemical reaction cycles, to a dynamiccombinatorial library. In the library, monomers can beoligomerized, oligomers can be deoligomerized, and oligomerscan recombine. Interestingly, we found that the dynamics of thelibrary’s components were dominated by transacylation, which isan equilibrium reaction. In contrast, the library’s dynamics weredictated by fuel-driven activation, which is a nonequilibriumreaction. Finally, we found that self-assembly can play a large role in affecting the reaction’s kinetics via feedback mechanisms. Theinterplay of the simultaneously operating reactions and feedback mechanisms can result in hysteresis effects in which the outcome ofthe competition for fuel depends on events that occurred in the past. In future work, we envision diversifying the library bymodifying building blocks with catalytically active motifs and information-containing monomers.