| dc.description.abstract | Dynamic combinatorial chemistry (DCC) is a combinatorial method of synthesis utilizing complex mixtures under thermodynamic control, called dynamic combinatorial libraries (DCL). The addition of a template molecule which preferentially stabilizes one species in the complex mixture perturbs the equilibrium, amplifying that species. Although DCC is a promising method for exploring complex chemical space, it is underexplored as a method for discovering new catalysts. Here we discuss some approaches to applying DCC to the development of catalysts. In order to explore the possibility of incorporating the powerful ligand and general base characteristics of imidazole into a DCL, histidine-derived pseudopeptide monomers suitable for acid-catalyzed hydrazone-exchange-based DCC were produced. DCLs of histidine-derived pseudopeptide oligomers were produced and characterized. Although attempts at eliciting templating behavior were unsuccessful, a cyclic dimer of the histidine-derived building block was found to catalyze the hydrolysis of p-nitrophenylacetate with a tenfold greater rate enhancement than 4-methylimidazole. Dynamic libraries of Schiff-base zinc complexes were used to explore templating with transition state analogs (TSA). It was discovered that addition of phosphonate and trifluoromethylketone TSAs to equilibrating mixtures of zinc Schiff-base complexes amplifies the best catalysts for the hydrolysis of picolinate esters. A promising lead into the kinetic resolution of picolinate esters by chiral zinc Schiff-base catalysts was discovered. Efforts are under way to explore the dynamic combinatorial chemistry of enantioselective catalysts for kinetic resolution using this system. | |
