Cyclic host molecules 12H and 22H, having a chiral N-methylporphyrin unit, include C76 in their asymmetrically distorted π-electronic cavity and are capable of spectral discrimination of the enantiomers of C76 by means of 1H NMR. Although the only structural difference between 12H and 22H is in the para-substituents R on their meso-phenyl groups, the association constant of C76 with 12H is more than twice as large as that with 22H. The ΔH values for the association of C76 with these hosts are hardly different from one another, but a rather big difference exists in their ΔS values (12H, −17.7 ± 0.7 J mol−1; 22H, −26.3 ± 1.0 J mol−1). The difference in ΔS is most likely due to a steric effect of the substituents on the conformational freedom of the hexamethylene linkers. Although the R groups are topologically remote from the binding site, they also affect the resolution of the diastereoisomerically split N-Me signals in the 1H NMR spectra of the hosts upon inclusion of C76. Chirality, 2008.