Within assemblies prepared by metal-templated imine condensation, one amine residue (subcomponent) may be replaced with another through substitution reactions. Proton transfer from a more to a less acidic amine may be used as the driving force for substitution. Herein, we detail the development of a set of selectivity rules to predict the outcome of subcomponent substitution reactions when several different substrates are present. When both iron and copper complexes were present, substitution occurred preferentially at imines bound to copper. This preference was kinetic in nature in the absence of a chelating amine subcomponent: The different amine residues were found to scramble between the copper and iron complexes following an initial clean substitution at the copper-bound imine. When both chelating and nonchelating amine subcomponents were present, the preference became thermodynamic in nature. Only the nonchelating amine was substituted and no evidence of scrambling was found after the reaction mixture was heated to 50 degrees C for several days. This thermodynamic selectivity, based on the chelate effect, operated in mixtures of Cu(I) and Fe(II) complexes, and in systems containing only Fe(II) complexes.