A laboratory experiment was developed that connects the interpretation of computer-generated models to the self-assembly of macrocycles. Students compare the reactions of terephthalaldehyde and isophthalaldehyde by reacting each with (R,R)-(-)-1,2-diaminocyclohexane. These isomeric systems serve as the foundation for a discussion about the impact of entropy and enthalpy on macrocycle formation. This experiment requires students to use multiple data sources to develop evidence-based explanations about the impact of the startingmaterial geometry on macrocyclization. Results from laboratory implementation indicate that a majority of students were able to successfully demonstrate competency of the learning goals.