Model-driven engineering of supramolecular buffering by multivalency

A supramolecular system in which the concentration of a molecule is buffered over several orders of magnitude is presented. Molecular buffering is achieved as a result of competition in a ring–chain equilibrium of multivalent ureidopyrimidinone monomers and a monovalent naphthyridine molecule which acts as an end-capper. While we previously only considered divalent ureidopyrimidinone monomers we now present a model-driven engineering approach to improve molecular buffering using multivalent ring–chain systems. Our theoretical models reveal an odd–even effect where even-valent molecules show superior buffering capabilities. Furthermore, we predict that supramolecular buffering can be significantly improved using a tetravalent instead of a divalent molecule, since the tetravalent molecule can form two intramolecular rings with different “stabilities” due to statistical effects. Our model predictions are validated against experimental ¹H NMR data, demonstrating that model-driven engineering has considerable potential in supramolecular chemistry.