Ion‐Pair Binding: Is Binding Both Binding Better?

It is often tempting to explain chemical phenomena on the basis of intuitive principles, but this practice can frequently lead to biased analysis of data and incorrect conclusions. One such intuitive principle is brought into play in the binding of salts by synthetic receptors. Following the heuristic concept that “binding both is binding better”, it is widely believed that ditopic receptors capable of binding both ionic partners of a salt are more effective than monotopic receptors because of a cooperative effect. Using a newly designed ditopic receptor and a generalized binding descriptor, we show here that, when the problem is correctly formulated and the appropriate algorithm is derived, the cooperativity principle is neither general nor predictable, and that competition between ion binding and ion pairing may even lead to inhibition rather than enhancement of the binding of an ion to a ditopic receptor. Binding both is not always binding better: Cooperativity in the binding of an ion pair by synthetic ditopic receptors is neither general nor predictable and may even operate in opposite directions for the two partners of the ion pair. Competition between ion binding and ion pairing may even lead to inhibition rather than enhancement of binding to a ditopic receptor.