Fuel-Driven Dynamic Combinatorial Libraries

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