The conformations of larger molecules with more flexible degrees of freedom are more substantially influenced by the CS environment. Ignoring the outlier, doxorubicinone, calculated ∆E total of guests in CS structures range up to 41 kJ/mol. Examples of the highest energy guests include nifedipine (REC-JAN, ∆E total =32.7 kJ/mol), fluoxetine (CENBOP, ∆E total =33.7 kJ/mol), and tenebrathin (COQBIW, ∆E total =41.0 and 36.2 kJ/mol in the two distinct guest sites), which all show significant geometric distortion from their gas phase conformation in the CS (see Figs. and).