Significance The ability of chemists to regulate the concentration of molecules is extremely important. However, as reactions are slowly superseded by more complex reaction networks, new ways of regulating molecular concentrations are needed. Recently, we described a system in which the concentration of a monovalent molecule with catalytic activity was buffered over a wide concentration range by its binding to a divalent molecule. Guided by model predictions, we are able to experimentally optimize the system by increasing the valency of the buffer, with even-numbered valencies displaying superior buffering capabilities. These results allow us to understand and gain more control over the activities of molecules in complex molecular systems, thereby obtaining insights into natural systems as well as creating adaptive artificial systems.