What is Dynamic Combinatorial Chemistry?
DCC methodology utilizes cyclic structures which interchange via reversible covalent bond formation to create a dynamic library of potential receptors. When this thermodynamically controlled mixture is incubated with an analyte of interest, the library responds by shifting the equilibrium towards the receptor that best binds the analyte, i.e. the best receptor is amplified relative to the non-templated state. This is best visualized with the following simple graphic:
The experiment begins with a library of “monomers”, each of which has two reactive groups on it; in the example above, the reactive groups are thiols. Prior to adding the analyte, the dithiols are oxidized and equilibrated to the complex mixture of disulfides; three are shown but statistically many hundreds are possible. An analyte is then added under conditions where the library is in equilibrium, such that the library constituents can respond to the analyte by shifting towards the best host-guest pair to establish a new equilibrium. In this competitive binding situation, the best receptor is identified by determining which compound(s) was amplified. This differs from a traditional (static) combinatorial library because the method simultaneously generates the library and dynamically amplifies/identifies the winner.
Funding for the CDCC comes from the Defense Threat Reduction Agency Basic Research program administered by the Army Research Office (W911NF04D0004)