To take one example, trialdehyde U has four aromatic rings and was defined as 'rigid', with U21, the largest computationally predicted cage for Tri 4 Di 6 , Tri 6 Di 9 and Tri 8 Di 12 topologies, therefore being a RR precursor combination with a total of 6 aromatic rings -only one combination with U resulted in the clean formation of a cage (U18, Tri 2 Di 3 ), but when paired with a complimentary diamine such as 21, the precursor may have the desired level of preorganisation to promote formation of the three larger topologies. However, we may not experimentally observe any of these cages under the HT screening conditions due to the large number of aromatic rings decreasing the precursor and intermediate solubilities, leading to precipitation and removal of these species from the dynamic reaction in solution. Altering the reaction conditions, such as changing the solvent or further decreasing the overall reaction concentration, may result in accessing these predicted larger, shape-persistent cages. In contrast, I23 was a combination that went to full conversion but also formed insoluble precipitate and a mixture of topologies, but resulted in both the largest Tri 6 Di 9 and Tri 8 Di 12 experimentally observed cages. Trialdehye I has a single aromatic ring and was defined as 'rigid', while diamine 23 has no aromatic rings and was defined as 'flexible', following the observation that a degree of flexibility can promote cage formation. In this specific reaction there may be a thermodynamic preference for one cage topology, however, the precipitation of intermediates and oligomeric species may have perturbed the 'error-correction' mechanism preventing equilibration towards a single cage topology -a change in the reaction conditions such as the solvent, concentration, or reaction time, may therefore result in a change in the topological outcome.