Ultra-sensitive pH control of supramolecular polymers and hydrogels: pKa matching of biomimetic monomers

Achieving self-assembly in water with small molecules that disassemble in response to minimal changes in environmental conditions is important for the development of many promising materials. We report the most sensitive possible pH control of a supramolecular polymer assembly - demonstrated with hydrogel-forming monomers that mimic nucleic acid base pairing. Bidirectional pH-responsive supramolecular polymers are formed upon the self-assembly of three monomers with two pK(a)-matched recognition units (one acidic and one basic). These supramolecular assemblies are most stable when the pH equals the pK(a) of the monomers, but disassemble in response to small pH changes near neutrality (exhibiting the theoretical limit for pH-dependent stability). At pH 7 a hydrogel forms in solutions that are 0.7% by weight in monomer, however, the hydrogel dissolves at pH 6 and pH 8. Additionally, we show that hydrogel stability is finely tuned by employing monomer mixtures that frustrate formation of insoluble aggregates. These results illustrate the advantages of using pK(a)-matched recognition elements and polymer heterogeneity in the development of responsive materials. Finally, these same recognition elements have recently been proposed as possible ancestors of the current bases of RNA. In this context, the assemblies described here might also provide clues to how the first genetic polymers were driven between states of base pairing and non-base pairing by periodic changes in environmental pH.