Although adding substituents to either face of β-CD, as done here, creates the possibility of new, attractive interactions that might in principle lead to stronger binding, we found that adding these substituents either reduced or at best maintained the affinities, relative to β-CD. We speculate that the reductions in affinity stem, at least in part, from partial blockage of binding by the substituents, without compensating stabilizing interactions. Guests with substituents that project further from the binding cavity may be better suited to forming stabilizing interactions with these β-CD substituents.