The experimental CS structure of risperidone in the ZnI 2 framework (EZEXAL) contains two guest molecules in the asymmetric unit and enables a quantification of the effect of multiple guests in the pore. Guest B has an increased induced intramolecular strain compared to guest A (∆E strain =12.35 kJ/mol and 18.43 kJ/mol, respectively), which is most likely due to experiencing stronger interactions in its exchange site. Configurations where only one molecule of risperidone is present have also been considered to investigate the interactions between guests. The calculated ∆E con f of guest A and B is the same in all configurations, regardless of the total number of guests present. When considering only Guest B in the pore, the strain energy is unaffected: the calculated ∆E strain of 18.13 kJ/mol is only 0.30 kJ/mol less than configurations where both guests A and B are present (Table ), corresponding to a small RMS deviation in atomic positions of * We have excluded the structures CENBUV and EZEWOY from averaging values due to their unusually high respective framework and guest energies.