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Currently, we rationalize the difference between 6 and 7 vs 8 to a competitive interplay between conformational and electrostatic effects. On one hand, macrocycle 6 is more conformationally flexible than 7 due to the smaller size of its constituent furan subunits relative to the thiophene present in 7; this flexibility is helpful in accommodating bound anions and is expected to be manifest in terms of an increase in the binding affinity. On the other hand, the electrostatic repulsion effect between the furan oxygen or thiophene sulfur atom lone pairs (or between these heterocyclic subunits and the bound anion) is also expected to be bigger in the case of 6; this electrostatic repulsion is expected to reduce the anion binding and leads to the prediction that macrocycle 7 will be a more effective anion receptor than 6. In the case of macrocycle 8, both a reduced level of electrostatic repulsion relative to 6 and a greater degree of flexibility relative to 7 is expected, an optimization of features that could account for its relatively enhanced anion binding affinities. Theoretical calculations designed to confirm or refute this hypothesis are currently underway.
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