Template-Directed Synthesis of Recognition-Encoded Melamine Oligomers Using a Base-Filling Strategy.

Replication of molecular information in nature is based on the synthesis of the backbone of the copy strand by polymerization of monomers bound to a template. An alternative strategy is to use a preassembled polymer backbone devoid of sequence information as the copy strand and to attach side chains in a sequence determined by binding to a template, i.e., base-filling. Base-filling strategies were investigated for template-directed synthesis of recognition-encoded melamine oligomers (REMO) using H-bond base-pairing interactions between 4-nitrophenol and phosphine oxide side chains. A template with three 4-nitrophenol H-bond donor recognition units was used with a blank copy strand equipped with three aldehyde groups for the reversible attachment of amine recognition units via dynamic imine chemistry. Equilibration of the template and blank strands in dichloromethane in the presence of benzylamine and a phosphine oxide recognition unit equipped with an amine resulted in selective incorporation (79%) of the phosphine oxide recognition unit into the resulting copy strand. Covalent attachment of the blank strand to the template with a diester linker increased the selectivity of the base-filling process to 85%, and carrying out the experiment in toluene further increased the selectivity to 92%. The imines in the copy strand were trapped by reduction, and cleavage of the ester linkages allowed recovery of the template strand along with the kinetically stable tris-phosphine oxide copy. Fidelity of templating is determined by the concentration of the template strand, the association constant for the base-pairing interaction, and the effective molarities of the intramolecular interactions in the duplex.